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[PMID]: 28625503 [Au] Autor: Othman RA; Myrie SB; Mymin D; Roullet JB; DeBarber AE; Steiner RD; Jones PJH [Ad] Endereço: Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada. [Ti] Título: Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe. [So] Source: J Pediatr;188:198-204.e1, 2017 Sep. [Is] ISSN: 1097-6833 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVES: To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE). STUDY DESIGN: Eight patients with sitosterolemia (16-56 years of age) were studied during 14 weeks off EZE therapy and 14 weeks on EZE (10 mg/day). Serum thyroid biomarkers (free triiodothyronine [FT3], free thyroxine [FT4], FT3/FT4 ratio, thyroid-stimulating hormone), 5α-stanols (sitostanol and cholestanol), and cholestanol precursors (total cholesterol and its synthesis marker lathosterol, and 7α-hydroxy-4-cholesten-3-one cholestenol) were measured at baseline and during the 14 weeks off EZE and on EZE. RESULTS: EZE increased FT3/FT4 (10% ± 4%; P = .02). EZE reduced plasma and red blood cells sitostanol (-38% ± 6% and -20% ± 4%; all P < .05) and cholestanol (-18% ± 6% and -13% ± 3%; all P < .05). The change in plasma cholestanol level on EZE inversely correlated with the change in FT3/FT4 (r = -0.86; P = .01). EZE lowered total cholesterol (P < .0001) and did not affect 7α-hydroxy-4-cholesten-3-one cholestanol. EZE increased (P < .0001) lathosterol initially, but the level was not sustained, resulting in similar levels at week 14 off EZE and on EZE. CONCLUSION: In patients with STSL, 5α-stanols levels might be associated with thyroid function. EZE reduces circulating 5α-stanols while increasing FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status. TRIAL REGISTRATION: ClinicalTrials.govNCT01584206. [Mh] Termos MeSH primário: Anticolesterolemiantes/uso terapêutico Ezetimiba/uso terapêutico Hipercolesterolemia/sangue Hipercolesterolemia/tratamento farmacológico Enteropatias/sangue Enteropatias/tratamento farmacológico Erros Inatos do Metabolismo Lipídico/sangue Erros Inatos do Metabolismo Lipídico/tratamento farmacológico Fitosteróis/efeitos adversos [Mh] Termos MeSH secundário: Adolescente Adulto Colestanol/sangue Colestenonas/sangue Colesterol/sangue Feminino Seres Humanos Masculino Meia-Idade Fitosteróis/sangue Sitosteroides/sangue Tireotropina/sangue Tiroxina/sangue Tri-Iodotironina/sangue Adulto Jovem [Pt] Tipo de publicação: CLINICAL TRIAL; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anticholesteremic Agents); 0 (Cholestenones); 0 (Phytosterols); 0 (Sitosterols); 06LU7C9H1V (Triiodothyronine); 3862-25-7 (7 alpha-hydroxy-4-cholesten-3-one); 80-99-9 (lathosterol); 8M308U816E (Cholestanol); 9002-71-5 (Thyrotropin); 97C5T2UQ7J (Cholesterol); C2NJ9WO6O7 (stigmastanol); EOR26LQQ24 (Ezetimibe); Q51BO43MG4 (Thyroxine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170911 [Lr] Data última revisão: 170911 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170620 [St] Status: MEDLINE

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[PMID]: 28190002 [Au] Autor: Mast N; Anderson KW; Lin JB; Li Y; Turko IV; Tatsuoka C; Bjorkhem I; Pikuleva IA [Ad] Endereço: From the Departments of Ophthalmology and Visual Sciences and. [Ti] Título: Cytochrome P450 27A1 Deficiency and Regional Differences in Brain Sterol Metabolism Cause Preferential Cholestanol Accumulation in the Cerebellum. [So] Source: J Biol Chem;292(12):4913-4924, 2017 Mar 24. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Cytochrome P450 27A1 (CYP27A1 or sterol 27-hydroxylase) is a ubiquitous, multifunctional enzyme catalyzing regio- and stereospecific hydroxylation of different sterols. In humans, complete CYP27A1 deficiency leads to cerebrotendinous xanthomatosis or nodule formation in tendons and brain (preferentially in the cerebellum) rich in cholesterol and cholestanol, the 5α-saturated analog of cholesterol. In mice, xanthomas are not formed, despite a significant cholestanol increase in the brain and cerebellum. The mechanism behind cholestanol production has been clarified, yet little is known about its metabolism, except that CYP27A1 might metabolize cholestanol. It also is unclear why CYP27A1 deficiency results in preferential cholestanol accumulation in the cerebellum. We hypothesized that cholestanol might be metabolized by CYP46A1, the principal cholesterol 24-hydroxylase in the brain. We quantified sterols along with CYP27A1 and CYP46A1 in mouse models ( , , , and two wild type strains) and human brain specimens. experiments with purified P450s were conducted as well. We demonstrate that CYP46A1 is involved in cholestanol removal from the brain and that several factors contribute to the preferential increase in cholestanol in the cerebellum arising from CYP27A1 deficiency. These factors include (i) low cerebellar abundance of CYP46A1 and high cerebellar abundance of CYP27A1, the lack of which probably selectively increases the cerebellar cholestanol production; (ii) spatial separation in the cerebellum of cholesterol/cholestanol-metabolizing P450s from a pool of metabolically available cholestanol; and (iii) weak cerebellar regulation of cholesterol biosynthesis. We identified a new physiological role of CYP46A1, an important brain enzyme and cytochrome P450 that could be activated pharmacologically. [Mh] Termos MeSH primário: Encéfalo/metabolismo Colestanotriol 26-Mono-Oxigenase/metabolismo Colestanol/metabolismo Colesterol/metabolismo [Mh] Termos MeSH secundário: Animais Cerebelo/metabolismo Colestanotriol 26-Mono-Oxigenase/genética Colestenonas/metabolismo Colesterol 24-Hidroxilase/metabolismo Feminino Técnicas de Inativação de Genes Seres Humanos Masculino Camundongos Camundongos Endogâmicos C57BL Camundongos Knockout [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cholestenones); 3862-25-7 (7 alpha-hydroxy-4-cholesten-3-one); 8M308U816E (Cholestanol); 97C5T2UQ7J (Cholesterol); EC 1.14.14.25 (Cholesterol 24-Hydroxylase); EC 1.14.15.15 (CYP27A1 protein, human); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase); EC 1.14.15.15 (Cyp27a1 protein, mouse) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170613 [Lr] Data última revisão: 170613 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170213 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M116.774760

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[PMID]: 27840382 [Au] Autor: Koyama S; Kato T [Ad] Endereço: Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University Faculty of Medicine. [Ti] Título: Pathophysiology of cerebrotendinous xanthomatosis. [So] Source: Rinsho Shinkeigaku;56(12):821-826, 2016 12 28. [Is] ISSN: 1882-0654 [Cp] País de publicação: Japan [La] Idioma: jpn [Ab] Resumo: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal-recessive lipid storage disease caused by mutations in the CYP27A1 gene, which lead to deficiency of the mitochondrial enzyme, sterol 27-hydroxylase, resulting in the accumulation of cholestanol in the serum and many affected lesions. To date, more than 50 different CYP27A1 mutations, including missense mutations, frameshifts, and splice site mutations, have been reported worldwide in patients with CTX. Clinical presentation is characterized by neonatal jaundice or cholestasis, refractory diarrhea, juvenile cataracts, tendon xanthomas, osteoporosis, coronary heart disease, and progressive neuropsychiatric disturbances; however, combinations of symptoms vary from patient to patient. Neuropsychiatric abnormalities include mental retardation or dementia, psychiatric symptoms, cerebellar signs, pyramidal signs, progressive myelopathy, peripheral neuropathy, extrapyramidal manifestations, and seizures. Replacement treatment with chenodeoxycholic acid in the early stage of the disease has been reported to improve or even prevent clinical symptoms of CTX. After significant neurological pathology is established, the effect of the treatment is limited and the deterioration of clinical manifestations may continue; therefore, early diagnosis of CTX is crucial. [Mh] Termos MeSH primário: Xantomatose Cerebrotendinosa [Mh] Termos MeSH secundário: Ácido Quenodesoxicólico/administração & dosagem Colestanotriol 26-Mono-Oxigenase/genética Colestanol/metabolismo Diagnóstico Diferencial Progressão da Doença Diagnóstico Precoce Seres Humanos Mutação Índice de Gravidade de Doença Xantomatose Cerebrotendinosa/diagnóstico Xantomatose Cerebrotendinosa/genética Xantomatose Cerebrotendinosa/fisiopatologia Xantomatose Cerebrotendinosa/terapia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0GEI24LG0J (Chenodeoxycholic Acid); 8M308U816E (Cholestanol); EC 1.14.15.15 (CYP27A1 protein, human); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 171012 [Lr] Data última revisão: 171012 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161115 [St] Status: MEDLINE [do] DOI: 10.5692/clinicalneurol.cn-000962

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[PMID]: 27680221 [Au] Autor: Koge J; Hayashi S; Yamaguchi H; Tateishi T; Murai H; Kira JI [Ad] Endereço: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University. [Ti] Título: A case of cerebrotendinous xanthomatosis mimicking the clinical phenotype of mitochondrial disease with a novel frame-shift mutation (c. 43_44 delGG) in CYP27A1 gene exon 1. [So] Source: Rinsho Shinkeigaku;56(10):667-671, 2016 10 28. [Is] ISSN: 1882-0654 [Cp] País de publicação: Japan [La] Idioma: jpn [Ab] Resumo: A 37-old-male with a history of early childhood mental retardation was admitted to our hospital. He experienced recurrent syncopes at 23 years old, and at age 35 gait disturbance and hearing impairment developed gradually and worsened over time. His grandparents were in a consanguineous marriage. He was of short stature and absent of tendon xanthomas. Neurological examinations revealed scanning speech, dysphagia, right sensorineural hearing loss, spasticity in both upper and lower extremities, and spastic gait. Tendon reflexes were brisk throughout, and Babinski and Chaddock reflexes were both positive bilaterally. Laboratory tests revealed elevated lactate and pyruvate concentrations in both serum and cerebrospinal fluid. Fluid attenuated inversion recovery magnetic resonance imaging showed high intensity lesions in the bilateral cerebellar hemispheres, pyramidal tracts in the brainstem, and internal capsules symmetrically. Brain magnetic resonance spectroscopy measurements revealed an elevated lactate/creatine plus phosphocreatine ratio and a decreased N-acetyl-aspartate/creatine plus phosphocreatine ratio in the cerebellum. At this point, mitochondrial diseases, particularly myoclonic epilepsy with ragged-red fibers (MERRF), to be the most likely cause. We performed a biopsy of his left biceps brachii muscle, showing variations in fiber size with occasional central nuclei and very few ragged-red fibers. Blood mitochondrial respiratory enzyme assays showed normal values with elevated citrate synthase activity, and mitochondrial DNA analyses for MERRF revealed no pathogenic mutations. We then explored other possibilities and detected an elevated serum cholestanol concentration of 20.4 µg/ml (reference value <4.0) and genetic analysis by direct sequencing method disclosed a novel frame-shift mutation (c. 43_44delGG) in CYP27A1 gene exon1, leading to a diagnosis of cerebrotendinous xanthomatosis (CTX). This case emphasizes importance of awareness of CTX as a possibility when patients present with clinical phenotypes mimicking mitochondrial diseases, but with negative results for muscle pathology or genetic analyses. The measurements of serum cholestanol concentrations might be useful in diagnosing such atypical cases. [Mh] Termos MeSH primário: Colestanotriol 26-Mono-Oxigenase/genética Diagnóstico Diferencial Mutação da Fase de Leitura Mitocôndrias/genética Xantomatose Cerebrotendinosa/diagnóstico por imagem Xantomatose Cerebrotendinosa/genética [Mh] Termos MeSH secundário: Adulto Biomarcadores/sangue Encéfalo/diagnóstico por imagem Encéfalo/patologia Colestanol/sangue Seres Humanos Síndrome MERRF Imagem por Ressonância Magnética Masculino Fenótipo [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers); 8M308U816E (Cholestanol); EC 1.14.15.15 (CYP27A1 protein, human); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 171012 [Lr] Data última revisão: 171012 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160930 [St] Status: MEDLINE

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[PMID]: 27236269 [Au] Autor: Mattis CE; Mootoo DR [Ad] Endereço: Department of Chemistry, Hunter College and The Graduate Center of the City University of New York, New York, NY 10016, USA. [Ti] Título: A ring closing metathesis strategy for carbapyranosides of xylose and arabinose. [So] Source: Carbohydr Res;429:143-7, 2016 Jun 24. [Is] ISSN: 1873-426X [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: The synthesis of ß-carba-xylo and arabino pyranosides of cholestanol is described. The synthetic strategy, which is analogous to the Postema approach to C-glycosides, centers on the ring closing metathesis of an enol ether-alkene precursor to give a cyclic enol ether that is elaborated to a carba-pyranoside via hydroboration-oxidation on the olefin. The method, which is attractive for its modularity and stereoselectivity, may find wider applications to carba-hexopyranosides and other complex cycloalkyl ether frameworks. [Mh] Termos MeSH primário: Arabinose/química Colestanol/química Glicosídeos/síntese química Xilose/química [Mh] Termos MeSH secundário: Alcenos/química Técnicas de Química Sintética Ciclização Éteres/química Oxirredução [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alkenes); 0 (Ethers); 0 (Glycosides); 8M308U816E (Cholestanol); A1TA934AKO (Xylose); B40ROO395Z (Arabinose) [Em] Mês de entrada: 1701 [Cu] Atualização por classe: 170119 [Lr] Data última revisão: 170119 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160530 [St] Status: MEDLINE

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[PMID]: 27207024 [Au] Autor: Frena M; Souza MRR; Damasceno FC; Madureira LAS; Alexandre MR [Ad] Endereço: Universidade Federal de Sergipe, Departamento de Química, São Cristóvão, Sergipe, SE 49100-000, Brazil; Universidade Federal de Santa Catarina, Departamento de Química, Campus Universitário Trindade, Florianópolis, Santa Catarina, SC 88040-900, Brazil. Electronic address: morganafrena09@gmail.com. [Ti] Título: Evaluation of anthropogenic contamination using sterol markers in a tropical estuarine system of northeast Brazil. [So] Source: Mar Pollut Bull;109(1):619-623, 2016 Aug 15. [Is] ISSN: 1879-3363 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The São Francisco River estuarine system, located in the Northeast coast of Brazil, has great economic, tourist and social importance. Its waters are used for activities such as agriculture, aquaculture, navigation and fishery, which supplies the surrounding communities. In this study, sterols markers were determined in twenty-eight sediment samples from São Francisco River estuary by gas chromatography - mass spectrometry (GC-MS). Sterol analysis was useful to distinguish between anthropogenic and biogenic organic matter (OM) sources in the studied area. Six sterols were quantified, suggesting different sources. Concentrations of fecal sterol (coprostanol) were lower than 500ngg(-1), suggesting no indicative of severe sewage contamination.However, two stations showed concentrations around 100ngg(-1) and the values for the coprostanol/(coprostanol+cholestanol) and coprostanol/cholesterol ratios indicates sewage contamination. The results in this study may be considered as baseline concentrations to be used as future reference for monitoring programs to prevent anthropogenic impacts. [Mh] Termos MeSH primário: Monitoramento Ambiental/métodos Estuários Sedimentos Geológicos/química Esteróis/análise Poluentes Químicos da Água/análise [Mh] Termos MeSH secundário: Biomarcadores/análise Brasil Colestanol/análise Fezes/química Cromatografia Gasosa-Espectrometria de Massas Sedimentos Geológicos/análise Rios/química Esgotos/análise Esgotos/química Clima Tropical [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers); 0 (Sewage); 0 (Sterols); 0 (Water Pollutants, Chemical); 8M308U816E (Cholestanol) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170911 [Lr] Data última revisão: 170911 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160522 [St] Status: MEDLINE

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[PMID]: 26874877 [Au] Autor: Matic Bujagic I; Grujic S; Jaukovic Z; Lausevic M [Ad] Endereço: University of Belgrade, Faculty of Technology and Metallurgy, Karnegijeva 4, 11000 Belgrade, Serbia. [Ti] Título: Sterol ratios as a tool for sewage pollution assessment of river sediments in Serbia. [So] Source: Environ Pollut;213:76-83, 2016 Jun. [Is] ISSN: 1873-6424 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: In this work, source pollution tracing of the sediments of the Danube River and its tributaries in Serbia was performed using sterol ratios. Improved liquid chromatography-tandem mass spectrometry method, which enabled complete chromatographic separation of four analytes with identical fragmentation reactions (epicoprostanol, coprostanol, epicholestanol and cholestanol), was applied for the determination of steroid compounds (hormones, human/animal and plant sterols). A widespread occurrence of sterols was identified in all analyzed samples, whereas the only detected hormones were mestranol and 17α-estradiol. A human-sourced sewage marker coprostanol was detected at the highest concentration (up to 1939 ng g(-1)). The ratios between the key sterol biomarkers, as well as the percentage of coprostanol relative to the total sterol amount, were applied with the aim of selecting the most reliable for distinction between human-sourced pollution and the sterols originated from the natural sources in river sediments. The coprostanol/(cholesterol + cholestanol) and coprostanol/epicoprostanol ratios do not distinguish between human and natural sources of sterols in the river sediments in Serbia. The most reliable sterol ratios for the sewage pollution assessment of river sediments in the studied area were found to be coprostanol/(coprostanol + cholestanol), coprostanol/cholesterol and epicoprostanol/coprostanol. For the majority of sediments, human-derived pollution was determined. Two sediment samples were identified as influenced by a combination of human and natural biogenic sources. [Mh] Termos MeSH primário: Monitoramento Ambiental/métodos Poluição Ambiental/análise Sedimentos Geológicos/análise Rios/química Esgotos/análise [Mh] Termos MeSH secundário: Animais Colestanol/análise Colestanóis/análise Colesterol/análise Cromatografia Líquida Estradiol/análise Seres Humanos Mestranol/análise Sérvia Espectrometria de Massas em Tandem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cholestanols); 0 (Sewage); 0 (epicoprostanol); 4TI98Z838E (Estradiol); 8M308U816E (Cholestanol); 97C5T2UQ7J (Cholesterol); B2V233XGE7 (Mestranol) [Em] Mês de entrada: 1701 [Cu] Atualização por classe: 170802 [Lr] Data última revisão: 170802 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160215 [St] Status: MEDLINE

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[PMID]: 26871580 [Au] Autor: Antharam VC; McEwen DC; Garrett TJ; Dossey AT; Li EC; Kozlov AN; Mesbah Z; Wang GP [Ad] Endereço: Department of Medicine, Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL, United States of America. [Ti] Título: An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection. [So] Source: PLoS One;11(2):e0148824, 2016. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism. [Mh] Termos MeSH primário: Colestanol/metabolismo Colesterol/metabolismo Clostridium difficile/isolamento & purificação Enterocolite Pseudomembranosa/metabolismo Enterocolite Pseudomembranosa/microbiologia Fezes/microbiologia Microbioma Gastrointestinal [Mh] Termos MeSH secundário: Adulto Idoso Colestanol/análise Colesterol/análise Clostridium difficile/genética Clostridium difficile/metabolismo Enterocolite Pseudomembranosa/diagnóstico Fezes/química Feminino Trato Gastrointestinal/metabolismo Trato Gastrointestinal/microbiologia Seres Humanos Masculino Metaboloma Microbiota Meia-Idade RNA Ribossômico 16S/genética Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nome de substância: 0 (RNA, Ribosomal, 16S); 8M308U816E (Cholestanol); 97C5T2UQ7J (Cholesterol) [Em] Mês de entrada: 1607 [Cu] Atualização por classe: 170220 [Lr] Data última revisão: 170220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160213 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0148824

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[PMID]: 26806364 [Au] Autor: Whiteside W; Tan M; Ostlund RE; Yu S; Ma L; Rocchini A [Ad] Endereço: The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Electronic address: wendy.whiteside@cchmc.org. [Ti] Título: Altered Cholesterol Metabolism and Hypocholesterolemia in Patients with Single Ventricle following Fontan Palliation. [So] Source: J Pediatr;171:73-7, 2016 Apr. [Is] ISSN: 1097-6833 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To assess whether an abnormality in cholesterol absorption or synthesis may be associated with hypocholesterolemia in patients with single ventricle anatomy following Fontan palliation. STUDY DESIGN: This is a cross-sectional study of 21 patients with hypocholesterolemia following Fontan procedure and age/sex-matched healthy controls, with median age of 13.4 (IQR 10.6-16.1) years. Laboratory values of several biomarkers, including phytosterols and 5-α-cholestanol (for cholesterol absorption) and lathosterol (for cholesterol biosynthesis), as well as cholesterol levels, inflammatory markers, and indices of liver function were compared between patients following Fontan procedure and controls. RESULTS: The Fontan cohort had significantly lower total cholesterol (mean 117 ± SD 13.9, vs 128 ± 19.2 mg/dL, P = .03) and free cholesterol (35.5 ± 4.5 vs 39.2 ± 5.4 mg/dL, P = .02) compared with control patients. There was an increase in normalized 5-α-cholestanol (1.51 ± 0.6 vs 1.14 ± 0.37 µg/mL, P = .02), and a significantly lower lathosterol/5-α-cholestanol ratio (0.70 ± 0.38 vs 1.11 ± 0.76, P = .04). There was a strong correlation (r = 0.78, P < .0001) between lathosterol and cholesterol levels in the Fontan cohort, not seen in controls (r = 0.47, P = .04). The Fontan cohort also had significantly higher C-reactive protein, transaminases, total bilirubin, and gamma-glutamyl transferase levels. CONCLUSIONS: Patients with hypocholesterolemia following Fontan procedure have evidence of increased cholesterol absorption and decreased cholesterol synthesis. As cholesterol absorption efficiency is a regulated process, this finding suggests an upregulation of cholesterol absorption as a result of decreased cholesterol production. In the setting of elevated liver indices and possible inflammation, this finding supports a growing body of data suggesting development of liver disease in patients receiving Fontan. [Mh] Termos MeSH primário: Colesterol/sangue Colesterol/metabolismo Técnica de Fontan/métodos Hipolipoproteinemias/terapia [Mh] Termos MeSH secundário: Adolescente Biomarcadores/metabolismo Proteína C-Reativa/análise Criança Colestanol/sangue HDL-Colesterol/sangue Estudos Transversais Feminino Seres Humanos Inflamação Fígado/metabolismo Testes de Função Hepática Masculino Fitosteróis/sangue Regulação para Cima Adulto Jovem [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Biomarkers); 0 (Cholesterol, HDL); 0 (Phytosterols); 80-99-9 (lathosterol); 8M308U816E (Cholestanol); 9007-41-4 (C-Reactive Protein); 97C5T2UQ7J (Cholesterol) [Em] Mês de entrada: 1608 [Cu] Atualização por classe: 170403 [Lr] Data última revisão: 170403 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 160126 [St] Status: MEDLINE

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[PMID]: 26778497 [Au] Autor: Rada JPA; Duarte AC; Pato P; Cachada A; Carreira RS [Ad] Endereço: LabMAM, Chemistry Department, Pontifical Catholic University, 22451-900, Rio de Janeiro, Brazil. [Ti] Título: Sewage contamination of sediments from two Portuguese Atlantic coastal systems, revealed by fecal sterols. [So] Source: Mar Pollut Bull;103(1-2):319-324, 2016 Feb 15. [Is] ISSN: 1879-3363 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Fecal sterols in sediments were used to assess the degree of sewage contamination in Ria de Aveiro lagoon and Mondego River estuary for the first time. Coprostanol, the major fecal sterol, averaged 1.82 ± 4.12 µg g(-1), with maxima of 16.6 µg g(-1). The northwestern sector of the Ria and a marina at Mondego estuary showed the highest level of sewage contamination. This scenario was confirmed by several diagnostic ratios based on fecal sterols and other phytosterols. Our data revealed that in spite of the improvements achieved in the last decades, there is still a need for control the organic inputs into the aquatic environment in the studied regions. [Mh] Termos MeSH primário: Monitoramento Ambiental/métodos Fezes/química Sedimentos Geológicos/química Rios/química Esgotos/análise Esteróis/análise [Mh] Termos MeSH secundário: Oceano Atlântico Colestanol/análise Estuários Portugal [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Sewage); 0 (Sterols); 8M308U816E (Cholestanol) [Em] Mês de entrada: 1610 [Cu] Atualização por classe: 170821 [Lr] Data última revisão: 170821 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160119 [St] Status: MEDLINE

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