Increased homocysteine levsls in patients with ischaemic heart disease and hypertension

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Cholestin inhibits cholesterol synthesis and secretion in human hepatic cells (HepG2)

Conference Theme: Intersection and Integratio

Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2)

Hyperlipidemia is a well-known risk factor for atherosclerosis and statins are widely used to treat patients with elevated levels of lipids in their plasma. Notwithstanding the proven benefits of statin drugs on both primary and secondary prevention of heart disease, the high cost of statin treatment, in addition to possible side effects such as liver function abnormalities, may limit their widespread use. We conducted a study on a natural product as an alternative to statin treatment. Cholestin, a dietary supplement, is prepared from rice fermented with red yeast (Monascus purpureus), which has been shown to significantly decrease total cholesterol levels in hyperlipidemic subjects. Our objective was to determine the cellular effect of Cholestin on cholesterol synthesis in human hepatic cells (HepG2) and the mechanism by which it caused a change in lipid metabolism. Cholestin had a direct inhibitory effect on HMG-CoA reductase activity (78-69% of control). Cholesterol levels in HepG2 cells treated with Cholestin (25-100 μg/mL) were significantly reduced in a dose-dependent manner (81-45% of control, respectively). This reduction was associated with decreased synthesis and secretion of both unesterified cholesterol (54-31 and 33-14% of control, respectively) and cholesteryl ester (18-6 and 37-19% of control, respectively). These results indicate that one of the anti-hyperlipidemic actions of Cholestin is a consequence of an inhibitory effect on cholesterol biosynthesis in hepatic cells and provide the first documentation of a biomolecular action of red yeast rice.link_to_subscribed_fulltex

Safety and systemic availability of intravenous and oral arsenic trioxide (As2O3) in children with relapsed / refractory neuroblastoma

Objective: We conducted a phase I study to evaluate the safety and bioavailability of intravenous (IV) and per oral (PO) As2O3 in children with neuroblastoma. Method: Eleven children with neuroblastoma were recruited (mean age 2.5 yrs [range 2.1 to 5 yrs, M:F=5:6]). All were previously treated with modified N6/N7 chemotherapy regimen, 3F8 immunotherapy, local irradiation plus auto-PBSCT (n=6), topotecan (n=2) & others (n=1). A maximum of 5 courses would be given and each consisted of 14 days of daily As2O3 alternated with 14 days of rest. In course one, 0.15mg/Kg As2O3 was given as 1 hour IV infusion and then shifted to PO route on Day 2, the rest of the course was by IV route. Blood samples for pharmacokinetic study were taken 0,1,2,4,6 & 8 hours on Days 1 & 2 and 0 hour on Day 3. Blood plasma and cellular fractions were freshly separated and arsenic concentrations were determined in duplicate by inductively coupled plasma-mass spectrometry. Results: A total of 33 courses of As2O3 were given (3 received 5 courses). The estimated 3 yrs progression free survival was 18% by Kaplan-Meier estimation (2/11 survived at 3yrs, median survival 11 months). In 5/11 tested, plasma and cell samples showed comparable area under the curve attributable to IV or PO dosing. However, the profile of concentrations (peak 400-600 nM) suggested that higher dosage is needed to achieve adequate anti-tumor effect based on in-vitro data for neuroblastoma (2000 nM). No significant side effects were found. Conclusions: Children could achieve similar plasma and cellular concentration of As2O3 by either IV or PO route. Using the current dosage, the peak and trough concentration of As2O3 were lower than anticipated concentrations required in-vitro