Increased liver stiffness in extrahepatic cholestasis caused by choledocholithiasis

Background

Extrahepatic cholestasis that is caused by benign and malignant diseases has been reported to increase liver stiffness (LS), as measured by transient elastography (TE).

Objectives

The aim of this study was to evaluate LS in patients with extrahepatic cholestasis due to choledocholithiasis before and after endoscopic sphincterotomy and stone removal.

Patients and Methods

LS was measured by TE (Fibroscan) in patients with extrahepatic cholestasis that was caused by choledocholithiasis before and 1 month after endoscopic sphincterotomy and successful stone removal.

Results

We studied 12 patients (7 females, 5 males), aged 36 to 76 years (mean age 57.1 ± 11.6 years), with extrahepatic cholestasis that was caused by choledocholithiasis. LS was increased in all patients (range: 6.2-18.4 kPa; mean: 8.9 ± 3.5 kPa) before endoscopic therapy. Successful biliary drainage was effected by sphincterotomy and stone removal in all patients, which led to a significant decline in LS to 3.9-8.1 kPa (Mean: 5.6 ± 1.2 kPa; p < 0.001) within a mean observation time of 29 days. The decrease in LS values correlated significantly with a decline in serum total bilirubin levels (r = 0.691; p < 0.0001).

Conclusions

Extrahepatic cholestasis due to choledocholithiasis increases LS and should be excluded before assesing liver fibrosis by transient elastography.     

Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia

There is consensus that ischemia/reperfusion injury associated with preeclampsia (PE) promotes both placental damage and the release of factors leading to maternal endothelium dysfunction, a hallmark of this potentially life-threatening syndrome. These factors include plasminogen activator inhibitor-1 (PAI-1) and soluble fms-like tyrosine kinase-1 (sFlt-1). The goal of this study was to further characterize placental factors involved in the pathophysiology of PE. Thus, DNA microarray gene profiling was utilized to identify mRNA differentially regulated in placentas from women with severe PE compared to both preterm (PC) and term control (TC) groups. Microarray studies detected an upregulation of mRNA for ceruloplasmin, a copper-containing iron transport protein with antioxidant ferroxidase properties, in PE compared to PC and TC placentas, respectively. Quantitative real-time PCR confirmed these results by demonstrating significant increases in ceruloplasmin mRNA in PE vs PC and TC placentas. Supporting previous reports, the expression of sFlt-1 and PAI-1 were also upregulated in PE placentas. Immunohistochemistry localized ceruloplasmin to the intervillous space in PE and PC placentas, whereas stronger syncytial staining was noted in PE. Western blotting confirmed a significant increase in ceruloplasmin levels in placental tissue in PE compared to PC groups. PCR identified the presence of mRNA for ceruloplasmin in primary cultures of syncytiotrophoblasts, but not villous-derived fibroblasts, suggesting that syncytium is the site of ceruloplasmin synthesis in placenta. Hypoxic treatment (1% O(2)) of syncytiotrophoblasts enhanced levels of ceruloplasmin mRNA approximately 25-fold, a significantly greater upregulation than that noted for PAI-1 and sFlt-1, suggesting that enhanced ceruloplasmin expression is a sensitive marker of syncytial hypoxia. We suggest that syncytial ceruloplasmin and its associated ferroxidase activity, induced by the hypoxia accompanying severe PE, is important in an endogenous cellular program to mitigate the damaging effects of subsequent reperfusion injury at this site.     

Promoter methylation of E-cadherin, p16, and RAR-β(2) genes in breast tumors and dietary intake of nutrients important in one-carbon metabolism

Aberrant DNA methylation plays a critical role in carcinogenesis, and the availability of dietary factors involved in 1-carbon metabolism may contribute to aberrant DNA methylation. We investigated the association of intake of folate, vitamins B(2), B(6), B(12), and methionine with promoter methylation of E-cadherin, p16, and RAR-β(2) genes in archived tumor tissues from incident, primary breast cancer cases in a population-based case-control study. Real-time methylation-specific PCR was performed on 803 paraffin-embedded samples; usual dietary intake was queried from a food frequency questionnaire. Unconditional logistic regression was used to derive adjusted odds ratios and 95% confidence intervals for likelihood of promoter methylation for high compared to low intake of those 1-carbon nutrients. Overall, in case-case comparisons, dietary intakes of folate, vitamins B(2), B(6), B(12), and methionine were not associated with likelihood of promoter methylation of E- cadherin, p16, and RAR-β(2) for all cases combined or within strata defined by menopausal status and estrogen receptor status in this study. This finding, however, does not exclude the possibility that intake of such nutrients might have the ability to modulate promoter methylation in normal or premalignant (dysplastic) breast tissue.     

Associations between use of prasugrel vs clopidogrel and outcomes by type of acute coronary syndrome: an analysis from the PROMETHEUS registry

Journal of Thrombosis and Thrombolysis - Left atrial contrast computed tomography (LA-CT) as well as transesophageal echocardiography (TEE) can exclude left atrial appendage (LAA) thrombus, but is...