Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In damaged liver, TLR4 expression is upregulated, leading to hepatic inflammation and injury. We tried to investigate the role of the two most common single-nucleotide polymorphisms (SNPs) of TLR4 in HCC-genesis. Aged > 18 years old, cirrhotic patients were included in this study. Exclusion criteria were non-HCC tumors and HIV co-infection. TLR4 SNPs association with HCC occurrence was the primary endpoint, and associations with all-cause and liver-related mortality, as well as time durations between diagnosis of cirrhosis and HCC development or death and diagnosis of HCC and death were secondary endpoints. A total of 52 out of 260 included patients had or developed HCC. TLR4 SNPs showed no correlation with primary or secondary endpoints, except for the shorter duration between HCC development and death in patients with TLR4 mutations. Overall, TLR4 SNPs showed no correlation with carcinogenesis or deaths in patients with liver cirrhosis; patients with TLR4 SNPs that developed HCC had lower survival rates, a finding that should be further evaluated

Differential Effects in Vivo of Thyroid Hormone on the Expression of Surfactant Phospholipid, Surfactant Protein mRNA and Antioxidant Enzyme mRNA in Fetal Rat Lung

Antenatal administration of triiodo-L-thyronine (T3) to late gestation rats resulted in decreased lung antioxidant enzyme (AOE) activity but increased surfactant phospholipids. In fetal rat lung explant cultures, T3 decreased the expression of surfactant proteins (SP) A and B. There have been no reported studies of the simultaneous in vivo developmental influence of T3 on both pulmonary AOE and SP gene expression. We hypothesized that antenatal T3 treatment would cause differential regulation of surfactant phospholipid, SP, and AOE genes in the late gestation fetal rat. Timed pregnant rats received intramuscular injections of either T3 (7 mg/kg) or placebo on days 19 and 20 of gestation and fetuses were delivered on day 21. Fetal lung SP-A, SP-B, SP-C, and AOE mRNA levels were studied by Northern analysis. AOE mRNA levels were further quantitated by solution hybridization. Total lung phospholipids (TPL) and disaturated phosphatidylcholine (DSPC) content were quantitated by a phosphorus assay. T3 significantly increased TPL and DSPC content, and significantly decreased the expression of SP-A, SP-C, CuZnSOD, and catalase genes. Because of a crucial interplay of these factors for normal lung function at the time of birth, the molecular mechanisms by which these apparently opposing changes are accomplished warrant further investigatio

Clinical predictors of outcome in patients with inflammatory dilated cardiomyopathy

Objectives The study objectives were to identify predictors of outcome in patients with inflammatory dilated cardiomyopathy (DCMi). Methods From 2004 to 2008, 55 patients with biopsy-proven DCMi were identified and followed up for 58.2 +/- 19.8 months. Predictors of outcome were identified in a multivariable analysis with a Cox proportional hazards analysis. The primary endpoint was a composite of death, heart transplantation and hospitalization for heart failure or ventricular arrhythmias. Results For the primary endpoint, a QTc interval > 440msec (HR 2.84; 95% CI 1.03-7.87; p = 0.044), a glomerular filtration rate (GFR) <60ml/min/1.73m(2) (HR 3.19; 95% CI 1.35-7.51; p = 0.008) and worsening of NYHA classification during follow-up (HR 2.48; 95% CI 1.01-6.10; p = 0.048) were univariate predictors, whereas left ventricular ejection fraction at baseline, NYHA class at entry, atrial fibrillation, treatment with digitalis or viral genome detection were not significantly related to outcome. After multivariable analysis, a GFR < 60ml/min/1.73m(2) (HR 3.04; 95% CI 1.21-7.66; p = 0.018) remained a predictor of adverse outcome. Conclusions In patients with DCMi, a prolonged QTc interval > 440msec, a GFR <60ml/min/1.73m(2) and worsening of NYHA classification during follow-up were univariate predictors of adverse prognosis. In contrast, NYHA classification at baseline, left ventricular ejection fraction, atrial fibrillation, treatment with digitalis or viral genome detection were not related to outcome. After multivariable analysis, a GFR < 60ml/min/1.73m(2) remained independently associated with adverse outcome

Clinical predictors of outcome in patients with inflammatory dilated cardiomyopathy

<div><p>Objectives</p><p>The study objectives were to identify predictors of outcome in patients with inflammatory dilated cardiomyopathy (DCMi).</p><p>Methods</p><p>From 2004 to 2008, 55 patients with biopsy-proven DCMi were identified and followed up for 58.2±19.8 months. Predictors of outcome were identified in a multivariable analysis with a Cox proportional hazards analysis. The primary endpoint was a composite of death, heart transplantation and hospitalization for heart failure or ventricular arrhythmias.</p><p>Results</p><p>For the primary endpoint, a QTc interval >440msec (HR 2.84; 95% CI 1.03–7.87; p = 0.044), a glomerular filtration rate (GFR) <60ml/min/1.73m² (HR 3.19; 95% CI 1.35–7.51; p = 0.008) and worsening of NYHA classification during follow-up (HR 2.48; 95% CI 1.01–6.10; p = 0.048) were univariate predictors, whereas left ventricular ejection fraction at baseline, NYHA class at entry, atrial fibrillation, treatment with digitalis or viral genome detection were not significantly related to outcome. After multivariable analysis, a GFR <60ml/min/1.73m² (HR 3.04; 95% CI 1.21–7.66; p = 0.018) remained a predictor of adverse outcome.</p><p>Conclusions</p><p>In patients with DCMi, a prolonged QTc interval >440msec, a GFR<60ml/min/1.73m² and worsening of NYHA classification during follow-up were univariate predictors of adverse prognosis. In contrast, NYHA classification at baseline, left ventricular ejection fraction, atrial fibrillation, treatment with digitalis or viral genome detection were not related to outcome. After multivariable analysis, a GFR <60ml/min/1.73m² remained independently associated with adverse outcome.</p></div

Baseline characteristics of study patients (N = 55).

<p>Baseline characteristics of study patients (N = 55).</p

Hazard ratio for the composite end-point all-cause mortality, heart transplantation and hospitalization for heart failure or ventricular arrhythmias.

<p>Hazard ratio for the composite end-point all-cause mortality, heart transplantation and hospitalization for heart failure or ventricular arrhythmias.</p

Characteristics of patients with or without LVEF improvement^*.

<p>Characteristics of patients with or without LVEF improvement^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188491#t002fn002" target="_blank">*</a>}.</p

(a-k). Unadjusted survival free from death, heart transplantation and hospitalization for heart failure or ventricular arrhythmias in relation to clinical, laboratory, electrocardiographic, echocardiographic parameters and immunohistochemical parameters.

<p>a: gender; b: NYHA functional class; c: left ventricular ejection fraction (LVEF); d: QTc interval; e: treatment with digitalis; f: atrial fibrillation; g: mitral regurgitation; h: glomerular filtration rate (GFR), i: myocardial fibrosis, j: inflammatory cell count on endomyocardial biopsy, k: viral genome detection.</p