Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity.

Human and animal studies show that suboptimal intrauterine environments lead to fetal programming, predisposing offspring to disease in later life. Maternal obesity has been shown to program offspring for cardiovascular disease (CVD), diabetes, and obesity. MicroRNAs (miRNAs) are small, noncoding RNA molecules that act as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of cardiac development and etiology of cardiac pathology; however, little is known about their role in the fetal cardiac response to maternal obesity. Our aim was to sequence and profile the cardiac miRNAs that are dysregulated in the hearts of baboon fetuses born to high fat/high fructose-diet (HFD) fed mothers for comparison with fetal hearts from mothers eating a regular diet. Eighty miRNAs were differentially expressed. Of those, 55 miRNAs were upregulated and 25 downregulated with HFD. Twenty-two miRNAs were mapped to human; 14 of these miRNAs were previously reported to be dysregulated in experimental or human CVD. We used an Ingenuity Pathway Analysis to integrate miRNA profiling and bioinformatics predictions to determine miRNA-regulated processes and genes potentially involved in fetal programming. We found a correlation between miRNA expression and putative gene targets involved in developmental disorders and CVD. Cellular death, growth, and proliferation were the most affected cellular functions in response to maternal obesity. Thus, the current study reveals significant alterations in cardiac miRNA expression in the fetus of obese baboons. The epigenetic modifications caused by adverse prenatal environment may represent one of the mechanisms underlying fetal programming of CVD.

Transjugular Intrahepatic Portosystemic Shunt Reduction Techniques.

Transjugular intrahepatic portosystemic shunt (TIPS) creation treats complications of portal hypertension in appropriately selected patients by lowering the portal venous pressure. While this can be a lifesaving intervention, portal venous flow diversion is not without potential consequences. Overshunting can lead to hepatic decompensation and encephalopathy. TIPS reduction and TIPS occlusion are therapeutic options used to mitigate overshunting, with reduction being the initial alternative due to retained shunt patency and lower potential for venous thrombosis. Patient selection, techniques for TIPS reduction, and patient outcomes are reviewed in this article.

Hyaluronic acid-bound letrozole nanoparticles restore sensitivity to letrozole-resistant xenograft tumors in mice.

Letrozole is a potent aromatase inhibitor and superior to other defined selective estrogen receptor modulators such as tamoxifen in treating hormone-responsive postmenopausal breast cancer patients. Patients who receive this drug may become insensitive to the effects of estrogen deprivation induced by letrozole. Letrozole has known side effects on bone metabolism due to systemic ablation of estrogen production. The purpose of this study was to examine the therapeutic efficacy of hyaluronic acid-bound letrozole nanoparticles (HA-Letr-NPs) in restoring sensitivity to letrozole-resistant (LTLT-Ca) cells. To target letrozole to LTLT-Ca cells, hyaluronic acid-bound letrozole nanoparticles were prepared by nanoprecipitation using biodegradable PLGA-PEG co-polymer. Binding specificity of HA to CD44 on the cell surface was analyzed in vitro using FITC-CD44 Ab and CD44 siRNA by flow cytometry. Effects on in vitro cytotoxicity and aromatase enzymatic activity of HA-Letr-NPs were performed in MCF-7 breast cancer cells, MCF-7 cells over-expressing aromatase (MCF-7/Aro), and LTLT-Ca cells resistant to letrozole. Preclinical efficacy of HA-Letr-NPs was examined in mice using LTLT-Ca xenograft tumors. HA-Letr-NPs were restricted to a maximum size of 100 nm. The in vitro drug release assay showed that the highest released concentration of letrozole occurred after 23 hours at 37 degrees C in phosphate-buffered saline. HA-Letr-NPs on MCF-7/Aro and LTLT-Ca cells showed an IC50 of 2 microM and 5 microM, respectively. HA-Letr-NPs were more efficacious in inhibiting tumor growth, reducing in vitro cellular and in vivo tumor aromatase enzyme activity more than the corresponding Letr-NPs or letrozole. HA-Letr-NPs restored and maintained a prolonged sensitivity and targeted delivery of letrozole in letrozole-resistant tumors in vivo.

Time-resolved lower extremity MRA with temporal interpolation and stochastic spiral trajectories: preliminary clinical experience.

PURPOSE: To assess added value of a new time-resolved technique with temporal interpolation and stochastic spiral trajectory through k-space and parallel imaging (TR-MRA) to conventional bolus chase MRA (BC-MRA) for infragenual peripheral artery evaluation. MATERIALS AND METHODS: An institutional review board-approved retrospective review of peripheral arterial disease patients was performed. Infragenual TR-MRA and BC-MRA were performed in 26 patients over four months. Two readers individually assessed image quality, diagnostic confidence, and stenosis severity and length in 13 defined below knee segments, first with BC-MRA alone, and then with a combined BC-MRA and TR-MRA reading (BC+TR-MRA). Perceived contribution of TR-MRA was rated by each reader. The reference standard was a consensus reading of both sequences. Catheter angiographic (CA) correlation was available in 6 patients. RESULTS: A total of 646 infragenual segments in 51 extremities were evaluated. Image quality and diagnostic confidence were superior for BC+TR-MRA compared with BC-MRA alone (P < 0.001). Adding TR-MRA improved sensitivity (85.7% versus 80.7%; P < 0.05) and diagnostic accuracy (88.1% versus 85.4%; P < 0.05) for hemodynamically significant stenosis. Venous contamination (0% versus 13.1% segments) and motion (0.9% versus 8.0%) were decreased for BC+TR-MRA versus BC-MRA alone, P < 0.01. For BC+TR-MRA, TR-MRA was rated more useful than BC-MRA in 30/51 legs (58.8%). TR-MRA identified retrograde flow in 5 segments. Where available, there was high concordance between CA and BC+TR-MRA (91.6%) for stenosis. CONCLUSION: Adding TR-MRA with temporal interpolation and stochastic spiral trajectories to bolus chase MRA improves image quality, diagnostic confidence and accuracy. It provides hemodynamic information and minimizes venous contamination and patient motion.

Percutaneous microwave ablation for control of massive portal venous bleeding.

We present a case of a 46 years old female with decompensated liver cirrhosis who developed severe intraperitoneal hemorrhage secondary to inadvertent liver puncture during a paracentesis which resulted in a combined hepatic arterial and portal venous injury. The arterial injury was managed with transarterial embolization. The portal venous injury was managed with percutaneous microwave ablation. This article also highlights the importance of evaluating both arterial injury as well as portal venous injury in the setting of hepatic bleeding, particularly in patients with portal hypertension.

Endovascular transsplenic recanalization with angioplasty and stenting of an occluded main portal vein in an adult liver transplant recipient.

Endovascular transshepatic access has limitations that can be exacerbated in the posttransplantation setting. Although several techniques are available for portal venous system catheterization, the transsplenic approach offers a direct pathway for accessing the portal venous system, as well as associated varices or shunts, while avoiding potential injury to the liver transplant. The purpose of this report is to present the diagnostic and interventional management of main portal vein occlusion in a 56-year-old female after liver transplantation. Endovascular transsplenic recanalization with stenting and shunt embolization is a viable method for treatment of main portal vein thrombosis in an adult liver transplant recipient.