Intestinal cholesterol secretion: future clinical implications.

Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues in the body to the faeces. In humans, faecal cholesterol elimination via the RCT pathway is considered to be restricted to excretion via the hepatobiliary route. Recently, however, direct trans-intestinal excretion of plasma-derived cholesterol (TICE) was shown to contribute substantially to faecal neutral sterol (FNS) excretion in mice. TICE was found to be amenable to stimulation by various pharmacological and dietary interventions in mice, offering new options to target the intestine as an inducible, cholesterol-excretory organ. The relevance of TICE for cholesterol elimination in humans remains to be established. There is, however, emerging evidence for the presence of TICE in human (patho) physiology. This review discusses our current understanding of TICE and its novel therapeutic potential for individuals at increased risk of cardiovascular disease.

Antisense oligonucleotides in the treatment of lipid disorders: pitfalls and promises.

Dyslipidaemia is one of the pivotal risk factors for cardiovascular disease (CVD), and lipid-lowering therapy is therefore the cornerstone in cardiovascular risk management. With the currently available treatment options the relative risk reduction in CVD is approximately 30%, leaving a large residual risk. This calls for the development of additional therapeutic moieties and antisense oligonucleotides (ASOs) have proven to be such a new and effective treatment. ASOs are short single strands of DNA that intracellularly bind mRNA of specific proteins. This induces the degradation of the mRNA through which the protein cannot be produced. Based on knowledge of lipid metabolism several targets of ASO therapy can be identified. This review offers a summary of current developments in ASO therapy regarding lipid disorders.

[Increasing use of social benefits by young people with chronic illness or disability in the Netherlands]. / Zunahme der Inanspruchnahme von Sozialleistungen bei jungen Personen mit einer chronischen Erkrankung bzw. Behinderung in den Niederlanden.

Young handicapped citizens in the Netherlands have increasingly been receiving social benefits or special services during the last five years. Dutch governmental departments have therefore commissioned an applied social policy research. We analyzed six benefits (for example special education, psychological healthcare, and Wajong benefits for young disabled). The usage of all these provisions is increasing. In particular we focus on "Wajong" (a sort of pension for Dutch young disabled people) and its social consequences. The number of Wajong benefits is growing strongly. In 2006 every 22nd person aged 18 (4.5%) claimed and received this disability benefit. Also, the statistical trend is that people with a handicap are less often employed and are more often unemployed. So there is an ongoing political discussion about these provisions with special attention to Wajong.

Method for the safe and rapid pretransfusion warming of stored blood: an in vitro and in vivo evaluation of a radiofrequency (RF) instrument.

Inadvertent hypothermia due to massive infusion of stored blood can be prevented by pretransfusion warming. One approach is the heating of individual packs by means of electromagnetic conduction, which is a method safely used over the last 25 years. The prototype instrument, which has now been re-engineered, can effectively raise the temperature of a unit of blood to approximately 33 degrees C in less than 3 minutes. Using this new model, we found, in vitro, a modest increase in free plasma haemoglobin, but this was not accompanied by any change in potassium or lactic dehydrogenase levels and the mean red cell fragility was unaltered. In vivo, the survival of autologous red cells that had been stored for 33 days and then infused as a concentrate, having a mean haematocrit of 0.60, was measured at 24 hours and 21 days. Each donor acted as his own control. In paired studies, pretransfusion radiofrequency heating was shown to have no deleterious effect when compared to measurements using the unwarmed blood pack. It is concluded that this method can be recommended as safe.