Nuevos tratamientos para la hipercolesterolemia / New agents for hypercholesterolemia

Una alta proporción de pacientes de alto riesgo cardiovascular no alcanzan los objetivos terapéuticos del c-LDL. Ello se debe a un uso inadecuado o insuficiente de los fármacos hipolipidemiantes por parte de los facultativos, y también a una mala tolerancia o al incumplimiento terapéutico por parte de los pacientes. Sin embargo, otra causa de esta situación es la potencia insuficiente de los fármacos actuales para disminuir el colesterol, incluyendo las estatinas y la ezetimiba. Entre los nuevos agentes hipocolesteremiantes, los inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 se están mostrando como unos agentes seguros y con una alta eficacia para disminuir el c-LDL en los numerosos ensayos clínicos que se han realizado o están en curso, y nos permitirán lograr el control óptimo de la hipercolesterolemia en la gran mayoría de los pacientes. Los fármacos que inhiben la síntesis de apolipoproteína B y los inhibidores de la proteína microsómica transferidora son otros fármacos que aportan un nuevo potencial de disminuir el colesterol en los pacientes con hipercolesterolemias graves y, en particular, en la hipercolesterolemia familiar homocigótica. Por último, los inhibidores de la proteína transferidora de esteres de colesterol han mostrado potentes efectos sobre el c-HDL y el c-LDL, pero su eficacia en prevención cardiovascular y su seguridad aún no han sido probadas. En este artículo se sintetizan las principales características de los fármacos para el tratamiento de la hipercolesterolemia que han sido recientemente aprobados o que están en fase avanzada de investigación (AU)

An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians’ inappropriate or insufficient use of cholesterol lowering medications or to patients’ bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage (AU)

An apolipoprotein B100 mimotope prevents obesity in mice.

Although apolipoprotein B100 (ApoB100) plays a key role in peripheral fat deposition, it is not considered a suitable therapeutic target in obesity. In the present study we describe a novel ApoB100 mimotope, peptide pB1, and the use of pB1-based vaccine-like formulations (BVFs) against high-fat diet (HFD)-induced obesity. In HFD- compared with chow-fed adolescent mice, BVFs reduced the 3-month body-weight gains attributable to increased dietary fat by 44-65%, and prevented mesenteric fat accumulation and liver steatosis. The body-weight reductions paralleled the titres of pB1-reactive immunoglobulin G (IgG) antibodies, and pB1-reactive antibodies specifically recognized native ApoB100 and a synthetic peptide from the C-terminal half of ApoB100. In cultured 3T3L1 adipocytes, anti-pB1 antibodies increased lipolysis and inhibited low-density lipoprotein (LDL) uptake. In cultured RAW 264.7 macrophages, the same antibodies enhanced LDL uptake (without causing foam cell formation). These findings make ApoB100 a promising target for an immunization strategy against HFD-induced obesity.

[Effect of fenformin and miscleron on the delayed hypersensitivity reaction in breast cancer patients]. / Vliianie fenformina i misklerona na reaktsiiu giperchuvstvitel'nosti zamedlennogo tipa u bol'nykh rakom molochnoi zhelezy.

Some preliminary results of using phenformin and miscleron in 17 breast cancer patients, previously radically operated upon, have been assessed as being characterized by metabolic disturbances associated with the reduced cell immunity level. The treatment of patients during 15--7 months was shown to result both in the correction of endocrine-metabolic disorders and stimulation of delayed hypersensitivity response, determined by skin tests with dinitro-chlorbenzene, tuberculin and Candida. The necessity to liquidate metabolic metabolic immunodepression with the aim of prophylaxis and treatment of the tuumor process is discussed. Some other routes of metabolic immunotherapy in addition to using phenformin and miscleron are considered. It seems rational to study the effect of a continuous administration of such kind of drugs on the results of treatment of oncological patients.