RESUMO
5-hydroxyindole acetic acid, a metabolite of serotonin, is used in the diagnosis and monitoring of patients with neuroendocrine tumours, in particular patients with small intestinal neuroendocrine tumours associated with the carcinoid syndrome. Analysis of 5-hydroxyindole acetic acid was commonly performed in urine, but blood-based assays are now becoming available. The objective of this study was to assess how 5-hydroxyindole acetic acid compares in plasma and serum as a biochemical marker of neuroendocrine tumours. Twenty-four-hour urine, plasma and serum samples were obtained from 80 patients with neuroendocrine tumours and 30 healthy volunteers. We developed a liquid chromatography tandem mass spectrometry assay for plasma and serum 5-hydroxyindole acetic acid. Comparison was made between them, and their cut-off was determined using a receiver-operating characteristic curve. A close correlation was shown between plasma and serum 5-hydroxyindole acetic acid. At a cut-off of 135 nmol/l, a sensitivity of 91.2% with a specificity of 61.9% was obtained for both compared to the urinary assay. A statistically significant agreement was shown when plasma and serum 5-hydroxyindole acetic acid were compared with the currently used urine assay in patients with neuroendocrine tumours; κ = 0.675 (95% CI 0.49 to 0.86), p < 0.001 and healthy volunteers; 0.967 (95% CI 0.828 to 0.999), p = <0.001. In conclusion, 5-hydroxyindole acetic acid in plasma and serum were comparable, hence either sample type can be used interchangeably.
Assuntos
Tumores Neuroendócrinos , Humanos , Ácido Hidroxi-Indolacético , Cromatografia Líquida/métodos , Biomarcadores/urina , AcetatosRESUMO
Hyperlipidaemia is a major risk factor for the development of atherosclerosis and cardiovascular disease. Statins are the mainstay of therapy and new guidelines focus on the use of these agents without specific targets for low-density lipoprotein (LDL)-cholesterol or non high-density lipoprotein (HDL)-cholesterol. However, patients remain at risk of cardiovascular disease despite statin therapy so new drugs are required. This article reviews therapies in development to further lower LDL-cholesterol (Proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors), raise HDL-holesterol (cholesterol ester transfer protein inhibitors (CETPIs)) and reduce triglycerides (novel peroxisome proliferator-activated receptor (PPAR)-agonists and omega-3 fatty acid preparations). Specialised therapies are in development for treatment of orphan disoders such as homozygous familial hypercholesterolaemia (lomitapide) or familial chylomicroaemia (alipogene tiparvovec). These novel lipid-lowering agents are likely to find uses in treating patients at the highest cardiovascular risk.
Assuntos
Doenças Cardiovasculares , Inibidores Enzimáticos , Hiperlipidemias , Aterosclerose , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , HDL-Colesterol/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias/complicações , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/fisiopatologia , Pró-Proteína Convertase 9 , Pró-Proteína Convertases/antagonistas & inibidores , Serina Endopeptidases , Triglicerídeos/sangueRESUMO
The global burden of diabetes and cardiovascular disease (CVD) is increasing. Obesity is rapidly increasing worldwide and is associated with dyslipidaemia, metabolic syndrome (MetS) and type 2 diabetes (T2DM). Excess risks of T2DM and CVD are found in migrant Indian Asian and West African populations but with increasing urbanization similar changes are occurring in the original populations and are likely to predispose to a large increase in worldwide burden of CVD. Genetic and environmental factors interacting together play a role in the lipid patterns observed. Dyslipidaemia in the MetS associated with insulin resistance is characterised by an atherogenic lipid profile comprising elevated triglycerides, low high density lipoprotein cholesterol (HDL-C) and increased numbers of small dense low density lipoprotein particles. The pattern of dyslipidaemia varies across different ethnic groups with increases in triglycerides and a reduction in HDL-C being the commonest pattern in non-Caucasians. This review surveys the literature on dyslipidaemia in Indian Asian and West African populations and how it relates to CVD risk in those populations. It is important that dyslipidaemia and other conventional risk factors for CVD are adequately addressed and managed especially in high-risk populations.
Assuntos
Doenças Cardiovasculares , Dislipidemias , Resistência à Insulina , África Ocidental/epidemiologia , Ásia/epidemiologia , Povo Asiático , População Negra/genética , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etnologia , Dislipidemias/epidemiologia , Dislipidemias/etnologia , Dislipidemias/etiologia , Dislipidemias/genética , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/etnologia , Fatores de RiscoRESUMO
The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia--the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented.