Dissertations / Theses on the topic 'Lipoprotein kinetics'
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Ooi, Esther M. M. "Regulation of lipoprotein transport in the metabolic syndrome : impact of statin therapy." University of Western Australia. School of Medicine and Pharmacology, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0125.
Full textSun, Feifei. "Measurement of Endogenous and Exogenous Triacylglycerol Kinetics in the fed and fasted state using stable isotopes." Thesis, University of Surrey, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492925.
Full textAlshayji, Iqbal. "Development and application of a novel method to determine large very low density lipoprotein (VLDL1) kinetics." Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/253/.
Full textHirata, Rosario Dominguez Crespo. "Efeito da apolipoproteína B no metabolismo de emulsões semelhantes à fase lipídica da LDL, em ratos." Universidade de São Paulo, 1991. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-13052008-155801/.
Full textThe effects of apolipoprotein B (apo B) on the metabolism of emulsions constituted of cholesteryl oleate (29%), phosphatidycholine (69%) and triolein (2%) were studied in rats. After intra-arterial injection of the radiolabelled emulsions, plasma removal of the emulsions was reduced in presence of apo B. On the other hand, the cholesteryl ester moiety of the apob B emulsion was removed at the same rate as native LDL. Emulsions and LDL were taken up mainly by the liver 24 h after the injection. However, the hepatic uptake of the apo B emulsion was similar to LDL and lower than that of the apo B-free emulsion. These differences in metabolic behaviour were probably due to the lower hepatic B, E, receptor affinity to apo B contained in the emulsions associated to apo B and in LDL, compared to the apo B-free emulsions. The latter, as confirmed in the in vitro experiments, is capable of adsorbing more apo E, and this apolipoprotein has higher affinity for the receptor. Enhanced receptor activity induced by pre-treatment of the rats with 17 α-ehymylestradiol resulted in augmented plasma removal of both emulsions but nonetheless the cholesteryl ester plasma removal of the apo B-containing particles was still lower, compared to that of the apo B-free emulsion. These data indicate that apo B-containing emulsion exhibits metabolic behaviour similar to that of LDL, and this emulsion can be an adequate tool to test LDL metabolism.
Mason, Susan Leigh. "Metabolism of triacylglycerol-rich lipoproteins in sheep." Lincoln University, 1991. http://hdl.handle.net/10182/1756.
Full textUliaque, Cugat Katia. "Implementation of stable isotopes lipoprotein kinetic studies: effects on HDL metabolism of a Mediterranean type diet rich in MUFAs from virgin olive oil." Doctoral thesis, Universitat Rovira i Virgili, 2007. http://hdl.handle.net/10803/8658.
Full textfatty acids (MUFAs) from virgin olive oil are due, partly, to an increase in, or maintenance of,
plasma concentrations of high density lipoprotein (HDL) cholesterol. However, the underlying
mechanisms that may explain these concentrations are not well characterised, to-date.
Apolipoprotein (apo) A-I (apoA-I) is the major HDL apo and its kinetic parameters, such as
production rate and catabolic rate, reflect the kinetics of the HDL particle. Our working
hypothesis is as follows: a Mediterranean-type diet rich in MUFAs from virgin olive oil,
compared to a STEP II diet, increases or preserves HDL cholesterol concentrations due to an
increase in apoA-I production and not to a decrease in apoA-I catabolism. Kinetic studies
using stable isotopes are, perhaps, the best approach in physiologically evaluating apo
production and catabolism in humans. This methodology has not as yet been implemented in
Spain. Objectives: to implement the necessary methodology to perform kinetic studies of apo
B-100 and, especially, of apoA-I and apoA-II in volunteers in vivo using stable isotopes to
label proteins in vivo. Further, we used this methodology to analyse the overall effects of a
Mediterranean-type diet rich in monounsaturated fatty acids from virgin olive oil compared
with a low-fat, STEP II diet, on HDL and low density lipoprotein (LDL) metabolism. Design:
we conducted a crossover, randomised study with dietary intervention periods of 4 weeks,
interspersed with a washout period between diets. A total of 10 healthy, moderately
hypercholesterolaemic, male volunteers consumed the two diets. The project was approved
by the Clinical Research Ethical Committee of the Hospital Universitari de Sant Joan, Reus.
Instrumentation: kinetic studies were performed at the end of each diet using a 16h primed
constant infusion of stable isotope
2
H3-L-leucine. Lipoprotein fractions were separated using
ultracentrifugation technique. Stable isotope incorporated into proteins was measured using
GC-MS. The data obtained were analysed applying multi-compartmental modelling technique
with the SAAM II program. ApoA-I and A-II kinetic studies were conducted in our Research
Unit in Reus. Apo B-100 kinetic studies and kinetic parameter modelling were performed in
collaboration with Dr. Caslake and Professor Packard of the Vascular Biochemistry Section,
Division of Cardiovascular & Medical Sciences, Royal Infirmary, University of Glasgow,
Glasgow, Scotland. Results: the Mediterranean diet, compared to the STEP II diet,
significantly increases apoA-I plasma concentrations. A total of 17 kinetic studies have been
performed but, due to methodological complexity, only the results of 7 kinetic studies (4
following a Mediterranean diet and 3 following a STEP II diet) that have been analysed in a
GC-MS to-date, are presented in this thesis. Despite the limitation of the low number of
kinetic studies analysed, we are able to document that the Mediterranean diet induces a high
apoA-I HDL production rate compared to the STEP II diet. Also, the Mediterranean diet
induces a high apo B-100 LDL production rate and fractional catabolic rate compared to the
STEP II diet. Conclusions: we have, for the first time in Spain, implemented the necessary
methodology to perform apo B-100, apoA-I and A-II kinetic studies in vivo using stable
isotopes in human subjects. A high apoA-I production rate is the main determinant of high
plasma concentrations of apoA-I, and not variations in its catabolism. Lipoprotein kinetic
studies enable the monitoring of lipoprotein metabolic parameters and the investigation of
nutritional and pharmacologic interventions in the primary and secondary prevention of
cardiovascular disease targets.
Els efectes antiaterogènics atribuïts a una dieta de tipus mediterrani, rica en àcids grassos
monoinsaturats (AGM), aportats per oli d'oliva verge, són deguts, en part, a l'augment o al
manteniment de les concentracions plasmàtiques de colesterol de les lipoproteïnes d'alta
densitat (HDL). No obstant i fins al moment, no es coneixen del tot els mecanismes que
expliquen aquestes concentracions. L'apolipoproteïna (apo) A-I (apoA-I) és l'apolipoproteïna
majoritària de les HDL i els seus paràmetres cinètics, com ara la taxa de producció i la taxa
de catabolisme, reflexen la cinètica de les partícules d'HDL. La nostra hipòtesi de treball és la
següent: una dieta Mediterrània rica en AGM aportats per oli d'oliva verge, comparada amb
una dieta STEP II, incrementa o manté els nivells de colesterol de les HDL degut a un
augment de la producció i no a una disminució de la degradació d'apoA-I. Possiblement, la
realització d'estudis de cinètiques utilitzant isòtops estables és la forma més fisiològica
d'avaluar la producció i la degradació d'apolipoproteïnes en l'home. Objectiu: Implementar la
metodologia necessària per realitzar cinètiques d'apo B-100 i, especialment, d'apoA-I i
d'apoA-II en voluntaris in vivo utilitzant isòtops estables com a marcatge de les proteïnes.
Aplicar aquesta metodologia per comparar els efectes d'una dieta Mediterrània rica en oli
d'oliva verge amb una dieta pobra en greixos STEP II sobre el metabolisme de les HDL i de
les lipoproteïnes de baixa densitat (LDL). Disseny: Estudi creuat randomitzat de 4 setmanes
d'intervenció dietètica, amb un període de rentat entre elles. 10 voluntaris, homes sans,
moderadament hipercolesterolèmics van seguir ambdues dietes. Aquest estudi va ser
aprovat pel Comitè d'Ètica i d'Investigació Clínica de l'Hospital Universitari de Sant Joan de
Reus. Instrumentalització: Estudi cinètic mitjançant la injecció i perfusió d'isòtop estable 2H3-
L-leucina en forma d'un bolus inicial i de perfusió durant 16h al final de cada dieta. Les
diferents fraccions lipoproteïques es van separar per ultracentrifugació. La detecció d'isòtop
incorporat va ser mitjançant GC-MS. Les dades obtingudes es van analitzar amb models
multicompartimentals i el programa SAAM II. Els estudis cinètics d'apoA-I i d'apoA-II es van
posat a punt i realitzat a la nostra Unitat de Recerca a Reus. Els estudis d'apo B-100 i la
modelització de les dades cinètiques es van realitzar en colClaboració amb el grup de recerca
de la Vascular Biochemistry Section, Division of Cardiovascular & Medical Sciences, Royal
Infirmary, University of Glasgow, Glasgow). Resultats: La dieta Mediterrània, comparada
amb la dieta STEP II, incrementa significativament la concentració plasmàtica d'apoA-I.
S'han realizat 17 cinètiques però, degut a la complexitat de la metodologia, en aquesta tesis
es presenten els resultats de les 7 cinètiques (4 després de la dieta Mediterrània i 3 després
de la dieta STEP II) analitzades per GC-MS fins ara. A pesar de l'escàs nombre de cinètiques,
s'observen certes tendències. La dieta Mediterrània, comparada amb la dieta STEP II,
presenta una major taxa de producció d'apoA-I de les HDL, així com una major taxa de
producció i de catabolisme de l'apo B-100 de les LDL. Conclusions: S'ha implementat la
metodologia dels estudis de cinètiques amb isòtops estables de l'apoA-I i l'apoA-II de les
HDL i de l'apo B-100 de les VLDL1, VLDL2, IDL i LDL. El determinant de les concentracions
més elevades d'apoA-I en plasma és una major taxa de producció d'aquesta apo i no
diferències en el seu catabolisme. Les aportacions de las cinètiques de les lipoproteïnes
permetran avançar en els mecanismes lipídics involucrats en les malalties vasculars i aportar
nous aspectes sobre les dianes nutricionals i farmacològiques.
Barrett, P. Hugh R. "The kinetic analysis and computer modelling of lipoprotein metabolism in man." Title page, table of contents and abstract only, 1989. http://web4.library.adelaide.edu.au/theses/09PH/09phb274.pdf.
Full textBertato, Marina da Paz. "Cinética plasmática do colesterol livre e do colesterol esterificado e transferência in vitro de lípides para a HDL, utilizando uma nanoemulsão lipídica artificial, em indivíduos com intolerância à glicose." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-24062010-142720/.
Full textIndividuals with diabetes mellitus type 2 are 2 to 4 times more susceptible to cardiovascular disease (CVD) than non-diabetic individuals. This increased risk is also observed for glucose intolerance (GI) which appears in the initial stages of diabetes. The presence of the metabolic syndrome (MS), present in most DM2 and GI patients, is also an important factor contributing to the development of CVD in these individuals. Various MS component studies emphasize dyslipidemia as one of the main contributors for this risk factor. The dyslipidemia commonly associated to GI is characterized by hypertriglyciridemia, low HDL-C and the presence of a small and dense LDL. However, since associated LDL-C levels with the development of premature atherosclerosis in non diabetic individuals is for the most part not observed in GI patients, it is questioned whether other lipid metabolism alterations such as cholesterol kinetics or the lipid transfer to HDL could be related to a greater CVD risk in these individuals. A previous study using an artificial LDL nanoemulsion showed a faster removal rate of the free cholesterol in normolipidemic with coronary artery disease (CAD) patients when compared to control individuals. In this study an artificial lipid nanoemulsion was used to evaluate both these processes involved in the metabolism of LDL and HDL which are both altered in patients with GI that expose them to CAD, and relating the results to CVD factors such as insulin resistance, obesity and dyslipidemia. 14 GI and 15 control individuals participated in this study. All without manifestations of CVD, none using any oral antidiabetic medication or hypolipimeants, paired for age, sex, race, BMI, smoking, alcoholic consumption, physical activity and comorbidities. For the kinetic study, a labeled nanoemulsion was interveneously injected and blood samples collected at determined intervals over a 24 hour period to determine the radiactive plasma decay curves and fractional clearance rate (FCR) of the labeled nanoemulsion lipids through a compartmental analysis model. Plasma esterification rate of the 3H-free cholesterol of the nanoemulsion was measured as was the in vitro transfer from the nanoemulsion to HDL fraction. Insulin resistance was obtained by the glycemic homeostasis mathematical model (HOMA) and abdominal adipose by a computerized tomography of the abdomen. No differences were observed for total cholesterol plasmatic concentrations, LDL-C, HDL-C, triglycerides or apolipoproteins between the two groups. The anthropometric profile related to weight, BMI and abdominal circumference was similar for both groups. The GI group presented higher fasting insulin concentration (p=0.01), less insulin sensitivity (p=0.01) and a greater insulin resistance (p=0.01). The TFR 14C-CE was similar in both groups, although the TFR 3H-CL was faster in the GI group compared to the control group (p=0.04). The esterification percentage of the nanoemulsions 3H-colesterol, as well as the lipid transfer from the nanoemulsion to HDL fraction were similar for both groups. The faster 3H-free cholesterol removal shows that a dissociation of the cholesterol particles of the lipidic nanoemulsion occurred in those patients with GI. This dissociation could possibly reflect alterations in the intravascular LDL lipoprotein metabolism which in turn, may favor atherogenesis in these patients
Padoveze, Amanda Felippe. "Cinética plasmática e biodistribuição de colesterol livre e colesterol esterificado de uma nanoemulsão (LDE) que se liga aos receptores de LDL em animais controle e com indução de aterosclerose." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-25062009-120520/.
Full textI n previously studies, it was shown that free cholesterol (FC) and cholesterol ester (CE) of a cholesterol-rich nanoemulsion (LDE) behaves differently in patients with coronary artery disease (CAD). The FC plasma clearance and arterial deposition is greater than CE. In the present study we evaluate the plasma kinetics, estimated by the fractional clearance rate (FCR), and the tissue uptake of 3H-free cholesterol (3H FC) and of 14C cholesterol ester (14C - CE) of LDE by arterial segments and organs of rabbits with (n=13) and without atherosclerosis (n=17). Furthermore, it was evaluated the in vitro uptake of 3H FC and 14C - CE by rabbit aortic endothelial cells. Finally, it was evaluated the inhibition of the enzyme lecithin-cholesterol acyltransferase (LCAT), and indirectly, the FC esterification in rats non-treated (n=9) and treated with diazepam (n=9). In rabbits without atherosclerosis that received an standard diet there was no difference between the plasma clearance of 3H FC and 14C CE. In rabbits with hyperlipidemia and atherosclerosis induced by the cholesterol-rich diet the 3H - FC was removed faster than 14C - CE (p<0.05), however the arch aortic uptake of 14C CE was greater than of 3H - FC (0p<0.05). In both groups, liver, lungs, adrenals and spleen were the principal sites of LDE cholesterol uptake. The FCR and tissue uptake were smaller in rabbits with than those without atherosclerosis. In rabbit aortic endothelial cells the 3H - FC uptake was greater than 14C CE independently of incubated LDE mass (p<0.01). In control rats there was no difference on the arterial uptake of both cholesterol forms of LDE, but when the LCAT activity was diminished by the diazepam treatment, the arterial uptake of 3H FC were greater than 14C CE (p< 0.01). The hyperlipidemia and cholesterol stability alterations may lead to dissociation between lipoproteins FC and CE. This dissociation may increase the risk for atherosclerosis and likewise enhance the severity of atherosclerosis.
Oliveira, Carolina Piras de. "Estudo da cinética plasmática do colesterol livre e esterificado em pacientes diabéticos tipo 2 com ou sem doença coronariana diagnosticada." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-10032010-100945/.
Full textINTRODUTION: The diabetic dyslipidemia is one of the most important risk factor in the development of coronary artery disease (CAD). The LDL-like nanoemulsion is being used to study the clearance of cholesteryl ester(CE) and free cholesterol(FC) from intravascular in patients with advanced CAD and it was shown a higher removal of FC and higher deposit in vases. OBJECTIVE: The aim of this study is to analyze the plasma kinetics of FC and CE in Type 2 Diabetes Mellitus (T2DM); and identify if there are any differences in the removal of FC in the presence of subclinical atherosclerosis in asymptomatic patients with T2DM. METHODS: It was studied 12 T2DM and 09 controls paired by age and gender. The LDL-like nanoemulsion labeled with radioactive: 14C- cholesterol ester (CE), 3H-cholesterol free (CF) was used on plasma kinetics. The nanoemulsion was injected intravenously in all participants and blood sample was collected over 24 hours for radioactivity measurement. The intravascular lipid removal was calculated through compartmental analysis. The intravascular esterification of FC contained in the nanoemulsion was calculated. The ability of HDL to received lipids from LDL-simile were observed in vitro essays. Coronary Calcium Score was detected to identify subclinical atherosclerosis. RESULTS: T2DM patients had a bigger BMI, waist and waist/hip than control, respectively 31.9 ± 4.6 vs. 27.1± 2.4, p<0.05; 104.9 ± 9.8 vs. 94.2±7.3, p<0.05; 0.98± 0.09 vs. 0.89 ± 0.06,p<0.01. Fasting glycemia (171 ± 96 vs. 83 ± 7.5 mg/dl, p <0.05) and glycated hemoglobin( 8.9 ± 2.1 vs. 5.6 ± 0.4%,p<0.05) was higher in T2DM, and there was no differences in the concentration of Total cholesterol, HDL, LDL, Triglycerides and apolipoproteins A1, B and E concentrations. The Fractional Clearance rate (FCR) 14C CE in T2DM was 22% bigger than control ( 0.07 ± 0.02 vs. 0.05± 0.01 h-1, p<0.01). FCR 3H-CF was similar between the groups. The CAC in T2DM did not show differents TFR in CE and FC in these group. In Both groups there was no statistical difference in FC esterification rate. The HDL ability to received CE (4.2 ± 0,8vs. 3.5 ± 0,6 %, p=0,03) and TG (6.8 ± 1.6 vs. 5.0 ± 1.1, p=0.03) from LDL-like nanoemulsion was higher in T2DM. CONCLUSIONS: The higher removal of 14C-CE and similar removal of FC in T2DM can be related to the genese of the diabetic dyslipidemia. The similar removal of FC between the control group and T2DM asymptomatic CAD, with and without subclinical atherosclerosis, could possibly signalize to the relation of FC and the atherosclerotic plaque stability.
Rodrigues, Alina Coutinho. "Avaliação do metabolismo de lipídes em diabéticos tipo 1, normolipidêmicos e sem complicações microvasculares e macrovasculares significativas através de nanoemulsão lipídica artificial." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-15062009-125934/.
Full textINTRODUTION: people with type 1 diabetes mellitus (DM1) have progressively neuro-vascular complications. Factors that increase the risk of coronary artery disease hypertension, dislipidemia and advanced age explains part of increased cardiovascular mortality, however some DM1 died of early coronary artery disease and often do not have atherosclerosis classical risk factors. Structural and functional changes in lipoproteins, altering their composition and activities of lipid exchange could justify the increase in vascular events but these changes are generally not detected by routine clinical laboratory plasma lipid exams. OBJETIVES: in normolipidemic DM1, intensively treated and without significant complications of disease we evaluated, by an artificial lipid nanoemulsion that resembles the lipid structure of LDL, rates of cholesterol esterification, nanoemulsion removal of the circulation, HDL particle size and lipid transfer from nanoemulsion to HDL. Secondarily, we determine the influence of glycemic control, insulin resistance (IR) and insulinization on lipid metabolism. METHODS: we studied 36 diabetics and 37 non-diabetic controls paired by age, sex and body mass index. Artificial lipid nanoemulsion labeled with radioactive lipids cholesterol ester (CE), cholesterol (CL), phospholipids (PL) and triglycerides (TG) was used for studies. Intravenous infusion of nanoemulsion 14C-CE e 3H-CL was injected in participants and blood was sampled over 24 hours for radioactivity measurement. Circulation lipid removal was calculated through compartmental analysis. Rate of cholesterol esterification was calculated after lipid extraction and separation by thin-layer chromatography. Nanoemulsion was incubated with plasma and radioactivity of lipids 14C-EC, 3H-CL, 14C-PL and 3H-TG transferred to the HDL was quantified after the precipitation of other apoB lipoproteins. The HDL diameter was measured by laser light scattering. The insulin resistance in diabetic patients was measured by formula that estimates the rate of uptake of glucose. RESULTS: glycated hemoglobin was 8,8±1,3 mg/dl and LDL concentrations were lower in diabetic patients (85 ± 22 vs. 98 ± 26 mg / dl), p = 0035. There were no differences between groups regarding rates of cholesterol esterification, lipids transfer from nanoemulsion to HDL and HDL particle size. We found no relationship between the kinetic analyses and HbA1c, blood glucose, measures of IR and dose of insulin. The rate of removal of 14C-EC was faster in diabetics type 1 than controls (0.059 ± 0.022 vs.0.039 ± 0.022 h- 1), p = 0.019. CONCLUSIONS: despite suboptimal glycemic control in diabetics, lipids transfer from nanoemulsion to HDL, rate of cholesterol esterification and removal of 3H-CL are similar to those of non-diabetic individuals. Glycemic control, lipid profile, measures of IR and dose of insulin did not influence lipids transfer and rate of cholesterol esterification. Removal of 14C-EC from diabetic circulation is faster than controls which could justify the 18 lower LDL concentration found in this population. We believe that intensive insulin therapy could explain these findings
Padilla, Nadège. "Effets des différentes techniques de chirurgie bariatrique sur le métabolisme des lipoprotéines riches en triglycérides(LRT) intestinales et hépatiques chez le patient obèse." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5020/document.
Full textIntroduction and objective: The dyslipidemia of insulin-resistant obese patients is widely characterised by the elevation of plasma triglyceride-rich lipoproteins (TRL) of both hepatic (TRL-apoB-100) and intestinal (TRL-apoB-48) origin. Bariatric surgery is a well-established and effective modality for the treatment of obesity, and is associated with improvements in a number of metabolic abnormalities that are associated with obesity. Here, we have investigated the effect of bariatric surgery on intestinal and hepatic TRL metabolism. Approach and Results: Twenty two non-diabetic, obese subjects undergoing bariatric surgery: sleeve gastrectomy (SG; n=12) and gastric bypass (BP; n=10) were studied using a stable isotope (D3-L-Leucine) enrichment methodology, in the constant fed state. Each subject underwent two lipoprotein turnover studies: 1 month before and 6 months after surgery. The main finding was a reduction in TRL-apo-B100 concentration following both SG and BP procedures (P<0.01 for both), explained by an increase in TRL-apo-B100 fractional catabolic rate (P<0.05 for SG) without a reduction in production rate. TRL-apo-B48 concentration was significantly reduced following SG, with no clear explanation other than a trend towards reduction in production rate. The reduction of TRL-apo-B100 concentration was significantly associated with a reduction of plasma apo-CIII in the pooled group of patients undergoing bariatric surgery. Conclusions: This is the first human kinetic study to explore the mechanism of improvement of TRL metabolism following bariatric surgery. These effects may contribute to the decrease of cardiovascular mortality after surgery
Lu, Mengxiao. "Structural stability and fusion of human low-density lipoproteins." Thesis, 2014. https://hdl.handle.net/2144/14323.
Full textAdams, Tiffany S. "Synthesis and characterization of artificial lipoprotein for targeted drug delivery ; influence of formulation factors on the drug release kinetics of whole and half controlled-release trazodone HCL tablets." 2004. http://purl.galileo.usg.edu/uga%5Fetd/adams%5Ftiffany%5Fs%5F200412%5Fphd.
Full textDirected by James Price. Includes articles submitted to International journal of pharmaceutics, Journal of pahrmaceutical research, and Journal of pharmaceutical science. Includes bibliographical references.
Estronca, Luís Miguel Beicinha Branco. "Primary chemical processes in atherogenesis : kinetics and thermodynamics of amphiphile exchange between serum albumin, lipoproteins and lipid bilayer membranes." Doctoral thesis, 2008. http://hdl.handle.net/10316/7486.
Full text