Lomitapide and Mipomersen —Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis

AbstractPurpose of ReviewThe goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100.Recent FindingsThe pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy.SummaryThe mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplement...
Source: Current Atherosclerosis Reports - Category: Cardiology Source Type: research

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The objective of this study was to investigate the nutritional functions of highland barley subjected to heat-moisture treatment (HMT) and dry heat treatment (DHT) in vitro and in vivo. In vitro test indicated HMT and DHT play part in the reduced glycemic potency of highland barley. Meanwhile, in vivo results showed that thermally-processed highland barley (THB) supplementation significantly decreased the body weight and serum glucose, improved oxidation resistance and altered the composition of gut microbiota. Bifidobacteria, Fusicatenibacter and Desulfovibrio were identified as types of bacteria that might related to the...
Source: Food Chemistry - Category: Food Science Source Type: research
Applied Physiology, Nutrition, and Metabolism, e-First Articles. We are currently facing an “obesity epidemic” worldwide. Promoting inefficient metabolism in muscle represents a potential treatment for obesity and its complications. Sarco(endo)plasmic reticulum (SR) Ca2+-ATPase (SERCA) pumps in muscle are responsible for maintaining low cytosolic Ca2+ concentration through the ATP-depe ndent pumping of Ca2+ from the cytosol into the SR lumen. SERCA activity has the potential to be a critical regulator of body mass and adiposity given that it is estimated to contribute upwards of 20% of daily energy expenditure....
Source: Applied Physiology, Nutrition, and Metabolism - Category: Physiology Authors: Source Type: research
Conclusions: In this family with autosomal dominant hereditary intestinal neuropathy, the disorder is linked to a 9.7 Mb region in Ch9 including a 1.2 Mb duplication. There is a significant difference in disease expressivity between family branches, seemingly related to separate maternal ancestors. PMID: 31814461 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
Publication date: Available online 11 December 2019Source: Life SciencesAuthor(s): Qingting Wang, Wenhua Shi, Qianqian Zhang, Wei Feng, Jian Wang, Cui Zhai, Xin Yan, Manxiang LiAbstractAimsIt has been shown that up-regulation of E3 ubiquitin ligase seven-in-absentia-homolog 2 (Siah2) and activation of Hippo signaling pathway effector yes-associated protein (YAP) are involved in the development of pulmonary arterial hypertension (PAH). However, it is still unclear whether Siah2 activates YAP in MCT-induced PAH rat model.Main methodsIntraperitoneal injection of monocrotaline (MCT) was used to induce PAH rat models. The right...
Source: Life Sciences - Category: Biology Source Type: research
We reported higher values of hematocrit, hemoglobin, Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Volume (MCV), White Blood Cell (WBC), Red Blood Cell (RBC) and lymphocytes for treated groups. Innate immune responses (Alternative complement activity (ACH50) in M2 and M3 group, total Immunoglobulin (Ig) and lysozyme in M3), mucosal immune parameters (ACH50, total Ig for M2 and M3 group and lysozyme in all treated groups) were enhanced. Activities of digestive enzymes (protease in all treated groups, amylase for 3 and 5%, while lipase only for 5%) and lower activity of liver ALT enzyme in individuals treated with high...
Source: Fish and Shellfish Immunology - Category: Biology Source Type: research
Publication date: Available online 10 December 2019Source: Fish &Shellfish ImmunologyAuthor(s): HamidrezaAhmadniaye Motlagh, Omid Safari, Yahya Selahvarzi, Ali Baghalian, Elham KiaAbstractIn the present study, the effect of aqueous garlic (Allium sativum) extract on skin mucus immune parameters of Poecilia reticulata was evaluated. A total of 240 P. reticulate juveniles, weighing 0.013 ± 0.001 g, were randomly stocked in 12 experimental glass tanks at a density of 30 fish per tank. The fish were fed with diets supplemented with garlic extract at the concentrations of 0, 0.10, 0.15, and 0.20 ml kg&minus...
Source: Fish and Shellfish Immunology - Category: Biology Source Type: research
Publication date: Available online 10 December 2019Source: Biological ControlAuthor(s): Qiya Yang, Junwei Diao, Ngolong Ngea Guillaume Legrand, Boateng Nana Adwoa Serwah, Marui Zhu, Bo Pang, Hongyin ZhangAbstractAscorbic acid (vitamin C, Vc) is a well-known antioxidant, which can eliminate reactive oxygen species (ROS) in order to protect yeasts subjected oxidative stress. In our previous research, Pichia caribbica, one of the antagonistic yeasts showed an activity against postharvest diseases of apples, and Vc enhanced the tolerance to oxidative stress of P. caribbica, and improved its biocontrol efficacy to postharvest b...
Source: Biological Control - Category: Biology Source Type: research
Publication date: Available online 10 December 2019Source: Microvascular ResearchAuthor(s): Mengjiao Liu, Kate Lycett, Melissa Wake, Mingguang He, Jessica A. Kerr, Richard Saffery, Markus Juonala, Tim Olds, Terry Dwyer, David P. Burgner, Tien Yin WongAbstractTraditional retinal microvascular parameters (smaller arteriolar and greater venular caliber) are associated with cardiovascular risk factors, pre-clinical vascular phenotypes and clinical cardiovascular events in adults. Although novel retinal microvascular geometric parameters showed analogous associations in adults, less is known whether these parameters are associa...
Source: Microvascular Research - Category: Biochemistry Source Type: research
In conclusion, clinical characteristics of vitamin B12 deficiency are broad and nonspecific and may not be associated with anemia and increased mean corpuscular volume. Since different clinical characteristics can be seen without anemia, awareness and cautious approach are essential in order to avoid severe clinical disease, especially in children from underdeveloped countries. PMID: 31819326 [PubMed - in process]
Source: Acta Clinica Croatica - Category: General Medicine Tags: Acta Clin Croat Source Type: research
In conclusion, positive statistical association between serum cholesterol (total cholesterol, LDL-c and HDL-c) and chloride levels may suggest their similar modulation by AHF pathophysiology. Serum levels of total cholesterol, LDL-c and chloride contribute to patient survival. PMID: 31819314 [PubMed - in process]
Source: Acta Clinica Croatica - Category: General Medicine Tags: Acta Clin Croat Source Type: research
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