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1.
J Clin Lipidol ; 14(6): 850-858, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33011137

RESUMO

BACKGROUND: Accumulation of lipoprotein X (LpX) in blood can cause severe hypercholesterolemia and cutaneous xanthomas. Monocytes sensitively sense lipid changes in circulation and contribute to inflammation. However, how monocytes respond to LpX is undefined. OBJECTIVE: We examined the phenotype of monocytes from a patient, who had LpX, severe hypercholesterolemia, and extensive cutaneous xanthomas, and effects of semiselective plasmapheresis therapy (SPPT). METHOD: Fluorescence-activated cell sorting and adhesion assays were used to examine monocyte phenotype and ex vivo oxidized low-density lipoprotein uptake and adhesion in the patient before and after treatment with SPPT. Effects of plasma from the patient on the phenotype and adhesion of monocytes from a healthy participant were determined. RESULTS: SPPT improved hypercholesterolemia and cutaneous xanthomas. Before treatment, the patient had lower frequency of nonclassical monocytes but higher frequency of intermediate monocytes than the control participant. Before treatment, monocytes from the patient with LpX showed more intracellular lipid accumulation, alterations in several cell surface markers and intracellular cytokines, as well as enhanced oxidized low-density lipoprotein uptake and reduced adhesion compared with control. After SPPT, the phenotypes of monocytes from the patient with LpX were similar to control monocytes. Incubation with plasma from the patient before treatment as compared with plasma from the control participant or the patient after treatment increased CD11c expression and adhesion of monocytes from a healthy participant. CONCLUSION: LpX-induced hypercholesterolemia increased lipid accumulation and altered the phenotype of monocytes, which may contribute to cutaneous xanthoma development. Removal of LpX by SPPT reduced lipid accumulation and improved monocyte phenotype, likely contributing to xanthoma resolution.


Assuntos
Lipoproteína-X/sangue , Monócitos/citologia , Fenótipo , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/imunologia
2.
Pharmacol Res Perspect ; 8(1): e00554, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31893124

RESUMO

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease characterized by low HDL-C levels, low plasma cholesterol esterification, and the formation of Lipoprotein-X (Lp-X), an abnormal cholesterol-rich lipoprotein particle. LCAT deficiency causes corneal opacities, normochromic normocytic anemia, and progressive renal disease due to Lp-X deposition in the glomeruli. Recombinant LCAT is being investigated as a potential therapy for this disorder. Several hepatic disorders, namely primary biliary cirrhosis, primary sclerosing cholangitis, cholestatic liver disease, and chronic alcoholism also develop Lp-X, which may contribute to the complications of these disorders. We aimed to test the hypothesis that an increase in plasma LCAT could prevent the formation of Lp-X in other diseases besides FLD. We generated a murine model of intrahepatic cholestasis in LCAT-deficient (KO), wild type (WT), and LCAT-transgenic (Tg) mice by gavaging mice with alpha-naphthylisothiocyanate (ANIT), a drug well known to induce intrahepatic cholestasis. Three days after the treatment, all mice developed hyperbilirubinemia and elevated liver function markers (ALT, AST, Alkaline Phosphatase). The presence of high levels of LCAT in the LCAT-Tg mice, however, prevented the formation of Lp-X and other plasma lipid abnormalities in WT and LCAT-KO mice. In addition, we demonstrated that multiple injections of recombinant human LCAT can prevent significant accumulation of Lp-X after ANIT treatment in WT mice. In summary, LCAT can protect against the formation of Lp-X in a murine model of cholestasis and thus recombinant LCAT could be a potential therapy to prevent the formation of Lp-X in other diseases besides FLD.


Assuntos
1-Naftilisotiocianato/efeitos adversos , Colestase Intra-Hepática/tratamento farmacológico , Lipoproteína-X/sangue , Fosfatidilcolina-Esterol O-Aciltransferase/uso terapêutico , Animais , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/metabolismo , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Humanos , Lipoproteína-X/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Fosfatidilcolina-Esterol O-Aciltransferase/farmacologia
3.
J Lipid Res ; 60(5): 1050-1057, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30808683

RESUMO

Familial LCAT deficiency (FLD) patients accumulate lipoprotein-X (LP-X), an abnormal nephrotoxic lipoprotein enriched in free cholesterol (FC). The low neutral lipid content of LP-X limits the ability to detect it after separation by lipoprotein electrophoresis and staining with Sudan Black or other neutral lipid stains. A sensitive and accurate method for quantitating LP-X would be useful to examine the relationship between plasma LP-X and renal disease progression in FLD patients and could also serve as a biomarker for monitoring recombinant human LCAT (rhLCAT) therapy. Plasma lipoproteins were separated by agarose gel electrophoresis and cathodal migrating bands corresponding to LP-X were quantified after staining with filipin, which fluoresces with FC, but not with neutral lipids. rhLCAT was incubated with FLD plasma and lipoproteins and LP-X changes were analyzed by agarose gel electrophoresis. Filipin detects synthetic LP-X quantitatively (linearity 20-200 mg/dl FC; coefficient of variation <20%) and sensitively (lower limit of quantitation <1 mg/ml FC), enabling LP-X detection in FLD, cholestatic, and even fish-eye disease patients. rhLCAT incubation with FLD plasma ex vivo reduced LP-X dose dependently, generated HDL, and decreased lipoprotein FC content. Filipin staining after agarose gel electrophoresis sensitively detects LP-X in human plasma and accurately quantifies LP-X reduction after rhLCAT incubation ex vivo.


Assuntos
Filipina/química , Deficiência da Lecitina Colesterol Aciltransferase/tratamento farmacológico , Lipoproteína-X/sangue , Lipoproteínas/sangue , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Biomarcadores/sangue , Géis/química , Humanos , Deficiência da Lecitina Colesterol Aciltransferase/sangue , Deficiência da Lecitina Colesterol Aciltransferase/enzimologia , Lipoproteína-X/síntese química , Lipoproteína-X/química , Proteínas Recombinantes/sangue
4.
Nutr Metab Cardiovasc Dis ; 29(1): 4-8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503707

RESUMO

AIMS: To review the formation, catabolism, and the possible atherogenic properties of Lp-X. DATA SYNTHESIS: The conversion of cholesterol to bile acids is regulated by several mechanisms including cholesterol 7 alpha hydroxylase, fibroblast growth factor 19, and farnesoid X receptors. During cholestasis these mechanisms are altered and there is an accumulation of bile acids and cholesterol in plasma. The hypercholesterolemia observed in cholestasis is due to the presence of an anomalous lipoprotein called lipoprotein-X (Lp-X). Lp-X is a lipoprotein rich in phospholipid and free cholesterol present in plasma of patients with cholestasis and, with some variations, in patients with lecithin-cholesterol-acyl-transferase deficiency (LCAT), and after lipid infusion. Lp-X is formed from a bile lipoprotein moving to the blood vessels where it incorporates small quantities of triglycerides, apo-C and esterified cholesterol and becomes a "mature" Lp-X. The activity of the phosphatidilcholine canalicular transporter Mdr2 P-glycoprotein (homologous to the human ABCB4) is essential for LpX appearance, since its suppression abolishes Lp-X formation. However, the concentration of Lp-X in plasma is determined also by the degree of the cholestasis, the residual liver function, and the LCAT deficiency. The Lp-X catabolism seems to be mediated by the reticuloendothelial system and possibly the kidney. CONCLUSIONS: Lp-X might be considered a defense mechanism against the toxic effect of free cholesterol in cholestasis. The frequency of cardiovascular events in patients affected by primary biliary cholangitis, in whom the Lp-X is present in high concentration, are not increased. Further studies could now clarify the remaining open questions on the role of Lp-X in the dyslipidemia of cholestasis.


Assuntos
Colestase/sangue , Hipercolesterolemia/sangue , Lipoproteína-X/sangue , Fígado/metabolismo , Animais , Transporte Biológico , Colestase/epidemiologia , Colestase/história , História do Século XX , História do Século XXI , Humanos , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/história , Deficiência da Lecitina Colesterol Aciltransferase/sangue , Deficiência da Lecitina Colesterol Aciltransferase/epidemiologia , Lipoproteína-X/história , Prognóstico , Fatores de Risco
5.
J Clin Lipidol ; 12(4): 888-897.e2, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29937398

RESUMO

BACKGROUND: Recessive inherited disorder lecithin-cholesterol acyltransferase (LCAT) deficiency causes severe hypocholesterolemia and nephrotic syndrome. Characteristic lipoprotein subfractions have been observed in familial LCAT deficiency (FLD) with renal damage. OBJECTIVE: We described a case of acquired LCAT deficiencies with literature review. METHODS: The lipoprotein profiles examined by gel permeation-high-performance liquid chromatography (GP-HPLC) and native 2-dimensional electrophoresis before and after prednisolone (PSL) treatment. RESULTS: Here we describe the case of a 67-year-old man with severely low levels of cholesterol. The serum LCAT activity was undetectable, and autoantibodies against it were detected. The patient developed nephrotic syndrome at the age of 70 years. Renal biopsy revealed not only membranous glomerulonephritis but also lesions similar to those seen in FLD. We initiated PSL treatment, which resulted in remission of the nephrotic syndrome. In GP-HPLC analysis, lipoprotein profile was similar to that of FLD although lipoprotein X level was low. Acquired LCAT deficiencies are extremely rare with only 7 known cases including ours. Patients with undetectable LCAT activity levels develop nephrotic syndrome that requires PSL treatment; cases whose LCAT activity levels can be determined may also develop nephrotic syndrome, but spontaneously recover. CONCLUSION: Lipoprotein X may play a role in the development of renal impairment in individuals with FLD. However, the effect might be less significant in individuals with acquired LCAT deficiency.


Assuntos
Deficiência da Lecitina Colesterol Aciltransferase/diagnóstico , Fosfatidilcolina-Esterol O-Aciltransferase/imunologia , Idoso , Anti-Inflamatórios/uso terapêutico , Autoanticorpos/sangue , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel Bidimensional , Humanos , Rim/patologia , Deficiência da Lecitina Colesterol Aciltransferase/tratamento farmacológico , Deficiência da Lecitina Colesterol Aciltransferase/imunologia , Lipoproteína-X/sangue , Lipoproteínas/sangue , Masculino , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Prednisolona/uso terapêutico
8.
Rinsho Byori ; 63(3): 312-8, 2015 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-26524853

RESUMO

The LDL-C level measures with homogeneous (direct) assays in almost of clinical laboratories. Several reports however showed differences in measured values among the assay reagents. We investigated the differences in LDL-C values among direct assays and Friedewald formula (F-f) in 58 LP-X positive serum samples from jaundice patients by comparing LDL-C values measured by anion-exchange chromatography (AEX-HPLC), largely comparable to ultracentrifugation method. Changes in LDL-C values during the treatment of 8 patients were also investigated. Direct assay reagents from Sekisui Medical (S-r), Denka-Seiken (D-r), Wako Chemical (W-r), and Kyowa Medics (K-r) were used for comparison. F-f, S-r, and D-r correlated with AEX-HPLC with r values < 0.6 while W-r and K-r correlated with AEX-HPLC with r-vales > 0.6. Two samples in which F-f values provided 500 mg/dL plus bias to AEX-HPLC (LDL-C value of 220 mg/dL) demonstrated increased levels of IDL-C before treatment. LDL-C values (S-r and D-r) of the 2 samples were relatively high and near to F-f data while LDL-C values (W-r and K-r) were relatively low and close to AEX-HPLC data. The jaundice treatment decreased LDL-C values (S-r and D-r) and converged to 220 mg/dL, indicating that S-r and D-r might react markedly to IDL. These changes were consistent with decreases in serum free cholesterol and phospholipid in support of LP-X. By contrast, W-r and K-r data showed upward tendency and also converged to 220 mg/dL. These results suggest that LDL-C direct assay reagents would be classified into 2 groups with respect to the reagent reactivity to LP-X.


Assuntos
LDL-Colesterol/sangue , Colesterol/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia por Troca Iônica/métodos , Lipoproteína-X/sangue , Kit de Reagentes para Diagnóstico , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Kit de Reagentes para Diagnóstico/classificação
10.
Ann Hepatol ; 14(6): 924-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26436366

RESUMO

Lipoprotein X (LpX) is an abnormal lipoprotein associated with cholestasis. It is a significant cause of severe hypercholesterolemia and should always be considered in patients with cholestatic liver disease. This case highlights the significance of LpX as a cause of severe hypercholesterolemia in a patient with cholestasis secondary to a granulomatous hepatitis attributed to tuberculosis. Lipoprotein agarose gel electrophoresis and gradient gel electrophoresis were performed for the detection of LpX. The liver function tests, electrolytes, lipid profile and bile acids were also determined. Anti-tuberculous therapy was initiated and the liver functions improved with normalisation of the lipid profile.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Colestase/etiologia , Hepatite/etiologia , Hipercolesterolemia/etiologia , Lipoproteína-X/sangue , Tuberculose Gastrointestinal/complicações , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Biomarcadores/sangue , Biópsia , Colestase/sangue , Colestase/diagnóstico , Eletroforese em Gel de Ágar , Feminino , Hepatite/sangue , Hepatite/diagnóstico , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Testes de Função Hepática , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/tratamento farmacológico , Tuberculose Gastrointestinal/microbiologia
11.
Acta Biochim Pol ; 62(3): 621-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26317127

RESUMO

Hypercholesterolemia is a common disorder in adult population, but total cholesterol concentrations beyond 1000 mg/dl occur rarely, and are found in patients with homozygous familial hypercholesterolemia and familial lecithin-cholesterol acyltransferase deficiency, in chronic graft-versus-host disease of the liver, after intravenous infusion of fat emulsion (intralipid), in newborn infants with immature liver function, and in obstructive biliary cholestasis. Cholestasis induces a dramatic increase in plasma cholesterol and the appearance of an abnormal lipoprotein, lipoprotein X (LpX), in the plasma. We report a case of severe hypercholesterolemia mediated by LpX in a patient transplanted for primary biliary cirrhosis (PBC), who was qualified for liver re-transplantation (re-LTx) due to chronic cholestasis. Four months after re-LTx, the cholesterol concentration was normal. The problems in diagnosis and treatment are discussed.


Assuntos
Hipercolesterolemia/metabolismo , Lipoproteína-X/sangue , Cirrose Hepática Biliar/metabolismo , Transplante de Fígado/efeitos adversos , Colestase/sangue , Colesterol/sangue , Emulsões , Feminino , Doença Enxerto-Hospedeiro/complicações , Homozigoto , Humanos , Hipercolesterolemia/complicações , Infusões Intravenosas , Lipídeos/química , Cirrose Hepática Biliar/complicações , Pessoa de Meia-Idade , Reoperação , Resultado do Tratamento
12.
J Clin Lipidol ; 9(2): 260-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25911084

RESUMO

Pseudohyponatremia has been reported in association with severe hypertriglyceridemia and hyperparaproteinemia, but its association with severe hypercholesterolemia is not well-known. We report a 43-year-old woman with refractory primary biliary cirrhosis who presented with asymptomatic hyponatremia (121 mmol/L; normal range: 135-145 mmol/L). She was ultimately found to have a total serum cholesterol level of 2415 mg/dL (normal range: 120-199 mg/dL) - secondary to accumulation of lipoprotein-X-causing pseudohyponatremia. The diagnosis was confirmed by measurement of serum osmolality (296 mOsm/kg H2O; normal range: 270-300 mOsm/kg H2O) and serum sodium by direct potentiometry (141 mmol/L). Furthermore, following 16 sessions of plasmapheresis over a 4-month period, there was marked lowering of serum cholesterol to 200 mg/dL and normalization of serum sodium (139 mmol/L) as measured by indirect potentiometry. This case shows that extreme hypercholesterolemia from elevation of lipoprotein-X particles in cholestasis can be a rare cause of pseudohyponatremia. It highlights the need to measure serum sodium with direct potentiometry in the setting of extreme hypercholesterolemia and consider this possibility before initiating treatment of hyponatremia.


Assuntos
Colestase/sangue , Hipercolesterolemia/sangue , Hiponatremia/sangue , Cirrose Hepática Biliar/sangue , Adulto , Colestase/complicações , Colestase/patologia , Colesterol/sangue , Feminino , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/patologia , Hiponatremia/complicações , Hiponatremia/patologia , Lipoproteína-X/sangue , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/patologia
13.
Rinsho Byori ; 63(11): 1271-6, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26995872

RESUMO

Lipoprotein-X (LP-X) in cholestatic jaundice causes abnormal reaction in assays for low-density lipoprotein-cholesterol, but the effects on other test items are unknown. Here, we report an infant with biliary atresia showing abnormal reaction in total serum protein assay using the biuret method, and lipoprotein-X (LP-X) was then detected. In this 11-month-old female infant, jaundice was observed at 2 months old, and a diagnosis of biliary atresia was made. On biochemical tests at 12 months old, the total serum protein concentrations detected by the biuret method were very high, and the response curve and linearity of dilution were abnormal. LP-X was detected by agar electrophoresis. In addition and recovery experiments with normal serum fractionation of the patient's LP-X-rich lipoprotein fraction prepared by ultracentrifugation, normal γ-globulin fractionation showed an abnormal reaction by the biuret method. In infants with biliary atresia, we showed that the total serum protein assay by the biuret method was influenced by LP-X-rich lipoprotein, which may be caused by abnormal reaction of LP-X and γ-globulin. [Case Report].


Assuntos
Atresia Biliar/diagnóstico , Proteínas Sanguíneas/análise , Lipoproteína-X/sangue , Atresia Biliar/sangue , Biomarcadores/sangue , Feminino , Humanos , Lactente , gama-Globulinas
14.
Clin Chim Acta ; 439: 29-37, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25286006

RESUMO

BACKGROUND: We investigated the reaction specificity toward cholesterol in lipoprotein X (Lp-X) and abnormal LDL among 6 homogeneous assays for low-density lipoprotein cholesterol (LDL-C) based on different measurement principles. METHODS: The homogeneous LDL-C assays used were based on the liquid selective detergent, selective solubilization, elimination, enzyme-selective protection, calixarene complex, and phosphate complex inhibition methods. The fraction with a density of 1.006-1.063 kg/l was isolated from cholestatic sera, and the reactivity of cholesterol in the lipoprotein fractions by gel filtration for each homogeneous LDL-C assay was determined. RESULTS: The liquid selective detergent and elimination methods showed increased cholesterol reactivity in the Lp-X fraction in a concentration-dependent manner, while the selective solubilization and phosphate complex inhibition methods were less reactive toward Lp-X cholesterol. Meanwhile, the homogeneous LDL-C assays showed decreased reactivity against cholesterol in abnormal LDL, with increased ratios of phospholipids and triglycerides against cholesterol. CONCLUSION: The homogeneous LDL-C assays showed differential reactivity toward Lp-X and abnormal LDL. Our findings enable accurate interpretation of the LDL-C values in these homogeneous assays, and suggest that these methods should be improved to distinguish between normal LDL and abnormal LDL or Lp-X.


Assuntos
Análise Química do Sangue/métodos , LDL-Colesterol/sangue , Hipercolesterolemia/sangue , Lipoproteína-X/sangue , Humanos , Especificidade por Substrato
15.
Nutr Hosp ; 29(4): 953-5, 2014 Apr 01.
Artigo em Espanhol | MEDLINE | ID: mdl-24679041

RESUMO

Patients with cholestatic diseases can present secondary hypercholesterolemia, as a result of the accumulation of lipoprotein X (Lp-X); an abnormal LDL form, considered as the biochemical parameter more sensitive and specific for the diagnosis of cholestasis intra or extrahepatic cholestasis. The aim of this clinical communication is to illustrate this association. A 54-year-old male with severe cholestatic liver disease which in turn presents a progressive total cholesterol rise and LDL with presence of lipoprotein X. Total and LDL cholesterol were down to normal, also coinciding with the improvement of cholestatic liver disease conferring cardiovascular protection pattern.


Los pacientes con colestasis hepática pueden presentar hipercolesterolemia secundaria, como consecuencia de la acumulación de la lipoproteína X (Lp-X); una forma anómala de LDL, considerada como el parámetro bioquímico más sensible y específico para el diagnóstico de colestasis intra o extrahepática. El objetivo de esta comunicación clínica es ilustrar esta asociación. Se trata de un varón de 54 años con hepatopatía colestásica severa que a su vez presenta una elevación progresiva de colesterol total y LDL con presencia de lipoproteína X. El colesterol total y LDL, descendieron progresivamente hasta normalizarse, coincidiendo con la mejoría de la función hepática, confiriendo un patrón de protección cardiovascular.


Assuntos
Dislipidemias/sangue , Lipoproteína-X/sangue , Colestase/etiologia , LDL-Colesterol/sangue , Dislipidemias/complicações , Humanos , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade
17.
Ann Clin Biochem ; 50(Pt 2): 173-5, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23431481

RESUMO

Hypertriglyceridaemia is an established cause of acute pancreatitis and responds to insulin therapy in addition to lipid lowering medication. We report a case of severe hypertriglycaeridemia of 149 mmol/L in a 36-year-old man with type 2 diabetes who presented to the surgical ward with abdominal pain due to pancreatitis and developed acute cholestasis, jaundice and eruptive xanthomata. His triglycerides improved to 3.8 mmol/L with sliding scale insulin within two weeks of in-hospital stay. However, his total cholesterol remained raised at 23.7 mmol/L. The lipoprotein electrophoresis confirmed the presence of lipoprotein X associated with bile obstruction, which contributed to an increase in total cholesterol. The total cholesterol normalized on improvement of his cholestasis.


Assuntos
Colestase/sangue , Colestase/complicações , Hipertrigliceridemia/complicações , Lipoproteína-X/sangue , Adulto , Colestase/terapia , Diabetes Mellitus Tipo 2/complicações , Humanos , Masculino
18.
Intern Med ; 51(6): 619-23, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22449671

RESUMO

Although the appearance of abnormal lipoproteins in liver diseases is well known, the precise analyses of abnormal lipoproteins remain elusive. Here, we report a 71-year-old woman with type 2 diabetes whose serum cholesterol levels were elevated to 560 mg/dL over a 4-month period. High-performance liquid chromatography demonstrated the presence of lipoprotein-X and lipoprotein-Y and sigmoid colon cancer and multiple liver metastases were found by colonoscopy and computed tomography. Remission of the primary colon cancer and liver lesions was achieved by chemotherapy with oxaliplatin and fluorouracil and her serum cholesterol went back to basal levels associated with the disappearance of abnormal lipoproteins.


Assuntos
Adenocarcinoma/secundário , Diabetes Mellitus Tipo 2/sangue , Hipercolesterolemia/etiologia , Lipoproteína-X/sangue , Lipoproteínas/sangue , Neoplasias Hepáticas/secundário , Neoplasias do Colo Sigmoide/sangue , Adenocarcinoma/sangue , Adenocarcinoma/complicações , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Fluoruracila/administração & dosagem , Humanos , Hipertensão/complicações , Hipoglicemiantes/uso terapêutico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/complicações , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Indução de Remissão , Neoplasias do Colo Sigmoide/complicações
19.
Gastroenterology ; 141(4): 1509-19, 1519.e1-3, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21762662

RESUMO

BACKGROUND & AIMS: Chronic, progressive hepatobiliary disease is the most severe complication of erythropoietic protoporphyria (EPP) and can require liver transplantation, although the mechanisms that lead to liver failure are unknown. We characterized protoporphyrin-IX (PPIX)-linked hepatobiliary disease in BALB/c and C57BL/6 (Fechm1Pas) mice with mutations in ferrochelatase as models for EPP. METHODS: Fechm1Pas and wild-type (control) mice were studied at 12-14 weeks of age. PPIX was quantified; its distribution in the liver, serum levels of lipoprotein-X, liver histology, contents of bile salt and cholesterol phospholipids, and expression of genes were compared in mice of the BALB/c and C57BL/6 backgrounds. The in vitro binding affinity of PPIX for bile components was determined. RESULTS: Compared with mice of the C57BL/6 background, BALB/c Fechm1Pas mice had a more severe pattern of cholestasis, fibrosis with portoportal bridging, bile acid regurgitation, sclerosing cholangitis, and hepatolithiasis. In C57BL/6 Fechm1Pas mice, PPIX was sequestrated mainly in the cytosol of hepatocytes and Kupffer cells, whereas, in BALB/c Fechm1Pas mice, PPIX was localized within enlarged bile canaliculi. Livers of C57BL/6 Fechm1Pas mice were protected through a combination of lower efflux of PPIX and reduced synthesis and export of bile acid. CONCLUSIONS: PPIX binds to bile components and disrupts the physiologic equilibrium of phospholipids, bile acids, and cholesterol in bile. This process might be involved in pathogenesis of sclerosing cholangitis from EPP; a better understanding might improve diagnosis and development of reagents to treat or prevent liver failure in patients with EPP.


Assuntos
Colangite Esclerosante/prevenção & controle , Hepatócitos/metabolismo , Células de Kupffer/metabolismo , Porfiria Eritropoética/metabolismo , Protoporfirinas/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Colangite Esclerosante/genética , Colangite Esclerosante/metabolismo , Colangite Esclerosante/patologia , Colesterol/metabolismo , Modelos Animais de Doenças , Ferroquelatase/genética , Ferroquelatase/metabolismo , Regulação da Expressão Gênica , Genótipo , Hepatócitos/patologia , Células de Kupffer/patologia , Lipoproteína-X/sangue , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fenótipo , Fosfolipídeos/metabolismo , Mutação Puntual , Porfiria Eritropoética/complicações , Porfiria Eritropoética/genética , Porfiria Eritropoética/patologia , Índice de Gravidade de Doença
20.
J Clin Lipidol ; 5(4): 324-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21784379

RESUMO

Lipoprotein X (Lp-X) is an abnormal lipoprotein which may form in patients with intra- and extra-hepatic cholestasis. The presence of very high levels of Lp-X has been shown to be a rare cause of pseudohyponatremia. We present a patient with severe obstructive cholestasis secondary to pancreatic cancer leading to very high Lp-X concentrations resulting in pseudohyponatremia, pseudohypokalemia, pseudohypochloremia and interference with the selective micellary solubilization direct low density lipoprotein cholesterol assay. These spurious laboratory anomalies impeded the initial clinical management of the patient including the attempted correction of the electrolyte abnormalities. After relief of obstruction following biliary stent placement, the patient's lipid levels normalized. Clinicians must be wary of laboratory artifacts and remember to correlate the laboratory values with the clinical presentation of the patient. Assays employing direct ion-selective electrodes such as those in blood gas analyzers are not subject to the interference of high concentrations of lipids or proteins, and maybe useful in situations where such interference is suspected. Furthermore the Vertical Auto Profile (VAP®) ultracentrifugation assay may be useful to detect lipoprotein X and low density lipoprotein cholesterol levels when the selective micellary solubilization technique fails to detect or quantify these lipid moieties.


Assuntos
Colestase/sangue , Erros de Diagnóstico , Eletrólitos/sangue , Lipoproteína-X/sangue , Neoplasias Pancreáticas/complicações , Artefatos , Gasometria , Colestase/diagnóstico , Colestase/etiologia , Técnicas de Laboratório Clínico , Feminino , Humanos , Eletrodos Seletivos de Íons , Icterícia Obstrutiva/etiologia , Pessoa de Meia-Idade , Plasma/química , Solubilidade , Ultracentrifugação/métodos
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