Search results for "MTP"
showing 10 items of 13 documents
Clinical experience of lomitapide therapy in patients with homozygous familial hypercholesterolaemia.
2014
The microsomal triglyceride transfer protein (MTP) inhibitor lomitapide is a licenced adjunct to a low-fat diet and other lipid-lowering medication, with or without low-density lipoprotein apheresis, for the treatment of adults with homozygous familial hypercholesterolaemia (HoFH). In a recently published phase 3 study, patients with HoFH received lomitapide in addition to maximally tolerated lipid-lowering therapy. Treatment with lomitapide resulted in a mean approximate 50% reduction in LDL-C levels after 26 weeks compared with baseline levels (p < 0.0001). This decrease in LDL-C was maintained at Weeks 56 and 78 (44% [p < 0.0001] and 38% [p = 0.0001], respectively). This paper offers cli…
Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis
2011
International audience; The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but …
Therapeutic options for homozygous familial hypercholesterolemia: the role of Lomitapide
2020
Background:Lomitapide (Juxtapid® in US and Lojuxta® in Europe) is the first developed inhibitor of the Microsomal Triglyceride Transfer Protein (MTP) approved as a novel drug for the management of Homozygous Familial Hypercholesterolemia (HoFH). It acts by binding directly and selectively to MTP thus decreasing the assembly and secretion of the apo-B containing lipoproteins both in the liver and in the intestine.Aims:The present review aims at summarizing the recent knowledge on lomitapide in the management of HoFH.Results:The efficacy and safety of lomitapide have been evaluated in several trials and it has been shown a reduction of the plasma levels of Low-Density Lipoprotein Cholesterol …
Analysis of voltage dips propagation in MV distribution networks by using ATP-EMTP code
2003
In this paper, voltage dips simulation in electric power MV distribution networks by using an improved ATP circuit-breaker model are reported. An equivalent circuit of a MV distribution system is employed. The circuit-breaker is simulated by using a tool written in MODELS language and by arranging a time-variable differential arc-conductance based on the combination of Mayr's and Cassie's equations. The simulations carried out have shown how the amplitude of the voltage dips depends on the type and location of the fault and their duration is strictly related to the circuit-breaker parameters.
Maximum Torque per Ampere Control strategy for low-saliency ratio IPMSMs
2019
This paper deals with electrical drives employing low-saliency ratio interior permanent magnet synchronous motors. In particular, in order to help the designers choosing the best control algorithm, the performances of the Maximum Torque Per Ampere Control (MTPA) and the Field Orientation Control (FOC) are here both theoretically and experimentally assessed and compared, by using, as performance indicators, the torque-current ratio and the power losses. The tests are carried out on a low-power motor for various speeds and loads by implementing the two control strategies in a dSPACE® rapid prototyping system. The results show that the Maximum Torque Per Ampere algorithm has some appreciable a…
Molecular diagnosis of hypobetalipoproteinemia: an ENID review.
2007
Abstract Primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CRD), with a recessive transmission, and familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission. ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively. Heterozygous FHBL is much more frequent. FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption. FHBL may be linked or not to the APOB gene. Most mutations in APOB gene cause the formation of truncated forms of apoB which may or may be not secreted into the plasma. Truncated apoBs with a size below that of apoB-3…
Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm,…
2013
Summary Background Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in adults with this disease. Methods We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline …
Mutations in MTP gene in abeta- and hypobeta-lipoproteinemia.
2005
Abstract Familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL) are inherited disorders of apolipoprotein B (apo B)-containing lipoproteins that result from mutations in apo B and microsomal triglyceride transfer protein (MTP) genes, respectively. Here we report three patients with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. Two of them (probands F.A. and P.E.) had clinical and biochemical phenotype consistent with ABL. Proband F.A. was homozygous for a minute deletion/insertion (c.1228delCCCinsT) in exon 9 of MTP gene predicted to cause a truncated MTP protein of 412 amino acids. Proband P. E. was heterozygous for a mutation in intron 9 (IVS9-1G>A),…
New Lipid Modulating Drugs: The Role of Microsomal Transport Protein Inhibitors
2011
Microsomal triglyceride transfer protein (MTP) is involved in the synthesis of very low density lipoprotein in the liver. Its deficiency results in abetalipoproteinemia. MTP inhibitors target the assembly and secretion of apolipoprotein B-containing lipoproteins. These agents may potentially play a role, alone or in combination, in the treatment of hypercholesterolemia or hypertriglyceridemia. Clinical applications of MTP inhibitors initially focused primarily on high-dose monotherapy in order to produce substantial reductions in LDL-cholesterol levels but these proved to induce significant hepatic steatosis and transaminase elevations. However, likely orphan indications for MTP inhibitors,…
Baltijas valstu OCTA apdrošināšanas tirgus attīstība un to ietekmējošie faktori
2017
OCTA apdrošināšanas tirgus zaudējumi ir novērojami jau kopš 2010. g. Septiņu gadu laikā apdrošināšanas nozare nav nonākusi pie risinājuma, kā rezultātā OCTA apdrošināšanas tirgus varētu veiksmīgi strādāt. Bakalaura darba mērķis ir, pamatojoties uz finanšu rādītājiem, statistikas analīzi un Eiropas Savienības regulējumu, pierādīt, ka zaudējumu attīstības faktors ietekmē OCTA apdrošināšanas tirgu. Mērķa īstenošanai tiks pētīta literatūra un zinātniskie darbi par apdrošināšanu un tās aspektiem, tiks izpētīti Baltijas valstu OCTA apdrošināšanas tirgus rezultāti. Kā arī, ar zaudējumu attīstības modeli, tiks analizēts OCTA apdrošināšanas tirgus, sniedzot secinājumus, kā zaudējumu attīstības fakto…