Effect of a Diet Enriched with Fresh Coconut Saturated Fats on Plasma Lipids and Erythrocyte Fatty Acid Composition in Normal Adults

Objective: The objective of this study was to compare the effects of increased saturated fatty acid (SFA) (provided by fresh coconut) versus monounsaturated fatty acid (MUFA) intake (provided by a combination of groundnuts and groundnut oil) on plasma lipids and erythrocyte fatty acid (EFA) composition in healthy adults.

Material and Methods: Fifty-eight healthy volunteers, randomized into 2 groups, were provided standardized diet along with 100 g fresh coconut or groundnuts and groundnut oil combination for 90 days in a Yoga University. Fasting blood samples were collected before and after the intervention period for the measurement of plasma lipids and EFA profile.

Results: Coconut diet increased low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels significantly. In contrast, the groundnut diet decreased total cholesterol (TC), mainly due to a decrease in HDL levels. There were no differences in the major SFA of erythrocytes in either group. However, coconut consumption resulted in an increase in C14:0 and C24:0 along with a decrease in levels of C18:1 n9 (oleic acid). There was a significant increase in levels of C20:3 n6 (dihomo-gamma linolenic acid, DGLA).

Conclusions: Consumption of SFA-rich coconut for 3 months had no significant deleterious effect on erythrocytes or lipid-related factors compared to groundnut consumption. On the contrary, there was an increase in the anti-atherogenic HDL levels and anti-inflammatory precursor DGLA in erythrocyte lipids. This suggests that coconut consumption may not have any deleterious effects on cardiovascular risk in normal subjects.     

Acceleration of viral replication and up-regulation of cytokine levels by antimalarials: implications in malaria-endemic areas.

Antimalarial drugs are widely used in malaria endemic areas, both for chemoprophylaxis and also empirically to treat patients presenting with fever. Previously, we have reported that chloroquine enhances the severity of Semliki forest virus (SFV) and encephalomyocarditis virus infection. The studies presented herein show that a broad spectrum of antimalarial drugs augmented the replication of SFV in mice, concomitant with greater tissue damage and up-regulation of mRNA levels of various inflammatory cytokine genes, including interleukin-1 receptor antagonist (IL-1Ra), II-1alpha, IL-1beta, IL-6, IL-12p40, and interferon-gamma inducing factor. Furthermore, chloroquine enhances IL-1Ra production in RAW cells in vitro. Since IL-1Ra is known to be up-regulated in a number of viral infections, we propose that a further enhancement of its expression by antimalarials may be responsible for the increased severity of viral infection in our studies. Thus, the widespread use of antimalarials in malaria-endemic areas may predispose the population to viral infections. Further studies are in progress to delineate mechanism(s) involved in cytokine up-regulation and acceleration of viral replication.     

Co-treatment with vorinostat synergistically enhances activity of Aurora kinase inhibitor against human breast cancer cells

Aurora kinases (AKs) regulate multiple components of mitotic cell division in eukaryotic cells. Aurora A is frequently amplified or overexpressed in breast cancer cells leading to aberrant chromosome segregation, genomic instability, and activation of oncogenic pathways. In the present studies, we determined the effects of treatment with the pan-AK inhibitor MK-0457 and/or the pan-histone deacetylase inhibitor vorinostat against human breast cancer cells that were either ER-, PR-, and HER2- (MDA-MB-468 and MDA-MB-231) or exhibited Aurora A amplification (BT-474 and MDA-MB-231 cells). Treatment with MK-0457 depleted p-AKs levels and their activity, as well as induced G2/M accumulation, DNA endoreduplication, multipolar mitotic spindles, and apoptosis of the breast cancer cells. Similar apoptotic effects were observed with treatment with the Aurora A-specific inhibitor, MLN8237. Treatment with vorinostat induced hsp90 acetylation and inhibited its chaperone association with AKs, leading to depletion of AKs and Survivin. Exposure of the siRNA to AK A also induced apoptosis, which was augmented by co-treatment with MK-0457 and vorinostat. Co-treatment with vorinostat enhanced MK-0457-mediated inhibition of the activities of Aurora A and Aurora B, leading to synergistic in vitro activity against human breast cancer cells. Co-treatment with MK-0457 and vorinostat also caused greater tumor growth inhibition and superior survival of mice bearing MDA-MB-231 xenografts. These pre-clinical findings indicate that combined treatment with a pan-AK inhibitor or an Aurora A-specific inhibitor and vorinostat represents a novel therapeutic strategy for the treatment of Aurora A-amplified and/or triple negative breast cancers.     

Preliminary Results of the New 6F TrapEase Inferior Vena Cava Filter

The TrapEase filter is a permanent, symmetric nitinol filter that can be deployed through a low-profile sheath. Although the TrapEase is enjoying an increasing market share of inferior vena cava (IVC) filters, there are still limited clinical follow-up data on its use. This study is a retrospective review of 189 consecutive infrarenal TrapEase filters placed at our institution. The study included 80 men and 109 women, with an average age of 73 years (24-102). The most common indication for filter placement was a contraindication to warfarin. In total, 13% of the patients were treated with warfarin. The filter was successfully deployed in all cases, via the right femoral vein in 57% of the patients, via the left femoral vein in 32%, and via the right internal jugular vein in 11%. Follow-up studies were performed as clinically indicated. During the investigation, there were three cases of IVC thrombosis (1.5%) and one case of retroperitoneal hemorrhage potentially caused by filter placement. Two of the thrombosis cases resulted in serious sequelae. This study also represents the first report of a symptomatic pulmonary embolism (PE) after TrapEase filter placement. While this investigation does demonstrate a low overall complication rate of this new device, it raises the concern of an increase in IVC thrombosis rate.