Raised low-density lipoprotein

The consumption of foods high in TFA has been shown to raise low-density lipoprotein cholesterol (LDL or bad cholesterol), which increases the risk of developing coronary heart disease (CHD). This prompted the Food and Drug Administration (FDA) to require mandatory labeling of the fran -fat content in foods. Food manufacturers have to comply by January 1, 2006. The FDA s chemical definition of TFA or trans-fats (TF) is unsaturated fatty acids that contain one or more isolated (i.e., nonconjugated) double bonds in the frani-configuration. ... 

Scientific reports have confirmed the relationship between trans fat and an increased risk of coronary heart disease. Trans fat, like saturated fat and dietary cholesterol, can raise low-density lipoprotein (LDL or bad cholesterol) levels in the blood. An elevated LDL cholesterol level increases the risk of developing coronary heart disease. Unlike saturated fat, trans fat also lowers high-density lipoprotein (HDL or good ) cholesterol in the blood. 

An exploratory study in Japan treated 15 patients with chronic hepatitis C (genotype lb) infection with telaprevir alone [77=]. They were treatment naive and received telaprevir 750 mg eight hourly for 24 weeks. 93% (n=14) of the patients experienced adverse events (AEs) with a total of 80 AEs. The most common events were rash (53.3%, n=8), anaemia (46.7%, n=7), raised low-density lipoprotein (40%, n=6), increased blood uric acid (26.7%, n=4), and pruritus (26.7%, n=4). There was a decrease in haemoglobin in all 15 patients, described as anaemia in seven patients. 

The simple health message has been to eat less saturated fat and more unsaturated fat. SFA, in general, increase the risk of cardiovascular disease (CVD) by raising low-density lipoprotein (LDL) cholesterol. However, not all SFA are equal in this respect lauric (12 0), myristic (14 0), and palmitic acids are more harmful than stearic acid which appears to be neutral in its effect on LDL cholesterol... 

An impressive example for the successful use of domino reactions for the synthesis of pharmacological lead structures was described by Paulsen et al1241 Recently, the difluoro compound 57 has been identified as highly potent inhibitor of the cholesterin-ester-transferprotein (CETP), which is responsible for a transfer of cholesterin from high-density lipoprotein (HDL) to low-density lipoprotein (LDL). This clearly results in an increase of LDL and a decrease of HDL which raise the risk of coronary heart desea-ses. The core structure of 57 is now accessible efficiently by a combination of a Mukaiyama-MichaeL... 

The adverse effects of trans fatty acids on serum lipids and lipoproteins are thought to be mediated by alterations in lipid catabolism and metabolism. Trans fatty acids increase the catabolism rates of apolipoprotein A-I and decrease apolipoprotein B catabolism rates (Matthan et al., 2004), reduce LDL-C particle size (Mauger et al., 2003), and can increase cholesteryl ester transfer protein (CETP) activity (van Tol et al., 1995). CETP mediates the transfer of cholesterol esters from HDL- to LDL- and very-low-density lipoprotein (VLDL)-C, thereby offering a potential explanation for the LDL-C-raising and HDL-C-lowering effect of trans fatty acids. 

One new approach that is being developed to enhance tumour specificity used monoclonal antibodies (mAb), raised against a particular type of tumour, as a kind of molecular "guided missile", with a porphyrin attached to the mAb as the light-activated "warhead." Tumour cells have different surface antigens to normal cells, and it is possible to raise mAbs specific for these antigens. Tumour cells also differ from normal cells in that they express a large number of low-density lipoprotein receptors. Hydrophobic photosensitisers may then be incorporated into a lipid moiety of such a receptor, and taken into the tumour cell via lysosomes. 

---