Optical coherence tomography of retinal and choroidal layers in patients with familial hypercholesterolaemia treated with lipoprotein apheresis

PURPOSE: Detect and quantify morpho-functional alterations of the retina and choroid in patients affected by familial hypercholesterolemia (FH) treated with lipoprotein apheresis (LA) using optic coherence tomography (OCT) and optic coherence tomography-angriography (OCTA). DESIGN: Observational study. SUBJECTS: To be diagnosed: A group of 20 patients (40 eyes) being clinically and genetically diagnosed as FH and under treatment (FH-Group)", for at least 2 years, was compared to a control group of 20 healthy subjects (40 eyes), with a normal lipid profile and no ocular disease (CT-Group). METHODS: Participants were studied with the slit lamp, binocular indirect fundoscopy, OCT and OCTA. MAIN OUTCOME MEASURES: Best corrected visual acuity (BVCA), spherical equivalent (SE), intraocular pressure (IOP), central macular thickness (CMT), choroidal thickness (CHT), retinal nerve fiber layer in four quadrants (RNFL (Superior = Sup; Inferior = Inf; Nasal = Nas Temporal = Temp), and the mean value across the four quadrants (RNFL G), foveal avascular zone (FAZ) and vascular density (VD). RESULTS: FH subjects had smaller RNFL superiorly (108 ± 19,38 μm OD/111 ± 16,56 μm OS FH-Group vs 127 ± 7,42 μm OD/129 ± 14,64 μm OS CT-Group; P < 0,001 for both OD and OS) and inferiorly (108 ± 23,58 μm OD/115 ± 17,33 μm OS FH-Group vs 128 ± 18,15 μm OD/133 ± 17,38 μm OS CT-Group; P = 0,002 OD; P = 0,001 OS). G RNFL was consequently smaller (93 ± 12,94 μm OD/94 ± 10,49 μm OS FH-Group vs 101 ± 9,01 μm OD/101 ± 10,20 μm OS CT-Group; P = 0,03 OD; P = 0,02 OS). FH subjects had a larger FAZ (0,31 ± 0,08 mm2 OD/0,33 ± 0,10 mm2 in OS FH-Group vs 0,21 ± 0,05 mm2 OD/0,21 ± 0,07 mm2 OS CT-Group; P < 0,001 OD; P = 0,002 OS). CONCLUSIONS: Early signs of retinal vessel damage in FH patients can be detected and quantified with OCT and OCTA

High-Throughput Sequencing to Reveal Genes Involved in Reproduction and Development in Bactrocera dorsalis (Diptera: Tephritidae)

BACKGROUND: Tephritid fruit flies in the genus Bactrocera are of major economic significance in agriculture causing considerable loss to the fruit and vegetable industry. Currently, there is no ideal control program. Molecular means is an effective method for pest control at present, but genomic or transcriptomic data for members of this genus remains limited. To facilitate molecular research into reproduction and development mechanisms, and finally effective control on these pests, an extensive transcriptome for the oriental fruit fly Bactrocera dorsalis was produced using the Roche 454-FLX platform. RESULTS: We obtained over 350 million bases of cDNA derived from the whole body of B. dorsalis at different developmental stages. In a single run, 747,206 sequencing reads with a mean read length of 382 bp were obtained. These reads were assembled into 28,782 contigs and 169,966 singletons. The mean contig size was 750 bp and many nearly full-length transcripts were assembled. Additionally, we identified a great number of genes that are involved in reproduction and development as well as genes that represent nearly all major conserved metazoan signal transduction pathways, such as insulin signal transduction. Furthermore, transcriptome changes during development were analyzed. A total of 2,977 differentially expressed genes (DEGs) were detected between larvae and pupae libraries, while there were 1,621 DEGs between adults and larvae, and 2,002 between adults and pupae. These DEGs were functionally annotated with KEGG pathway annotation and 9 genes were validated by qRT-PCR. CONCLUSION: Our data represent the extensive sequence resources available for B. dorsalis and provide for the first time access to the genetic architecture of reproduction and development as well as major signal transduction pathways in the Tephritid fruit fly pests, allowing us to elucidate the molecular mechanisms underlying courtship, ovipositing, development and detailed analyses of the signal transduction pathways

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk

Monascus purpureus for statin and ezetimibe intolerant heterozygous familial hypercholesterolaemia patients: A clinical study

Background Hypercholesterolaemia is a major risk factor for cardiovascular disease and requires effective therapy in affected patients. Statins, the mainstay of lipid-lowering therapy, can cause side effects, including myalgia, in some patients. Ezetimibe, is frequently used as an add-on therapy for statins, and is also used as a monotherapy in statin-intolerant patients, however elevations in liver transaminases can occur. We examined the lipid-lowering efficacy of the natural fungal product Monascus purpureus (MP), which contains the natural statin monacolin K. Methods Fifty-five patients with familial hypercholesterolaemia who had discontinued statins due to muscle symptoms. Patients were placed on a lipid-lowering diet cholesterol-lowering diet (1500–1800 kcal daily, 30% lipids, 19% proteins and 52% carbohydrates). MP was added to the diet at a dose of 300 mg (providing monacolin K 10 mg). Patients were followed for 12 months. Lipid profiles and adverse event data were collected in the normal course of patient care. Results After 6 months of treatment with MP and diet therapy, statistically significant changes in low-density lipoprotein cholesterol were evident (−17% for males, −16% for females; p < 0.005) Levels fell to −24% and −27% respectively at 12 months. No patients experienced elevated serum aminotransferases or C-reactive protein levels. Conclusions MP is a viable option for lipid-lowering therapy in statin-intolerant patients with hypercholesterolaemia, with good efficacy and safety profiles

Lipoprotein(a) concentration, genetic variants, apo(a) isoform size, and cellular cholesterol efflux in patients with elevated Lp(a) and coronary heart disease submitted or not to lipoprotein apheresis: An Italian case-control multicenter study on Lp(a)

Background: Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking. Objective: The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a). Methods: We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA. Results: Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 \ub1 0.9 \u3bcg/mg vs 16.01 \ub1 0.98 \u3bcg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 \ub1 0.8 \u3bcg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A Conclusions: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a)