RESUMEN
Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.
Asunto(s)
Antineoplásicos Fitogénicos , Colestanol , Simulación del Acoplamiento Molecular , Rizoma , Saponinas , Rizoma/química , Humanos , Saponinas/aislamiento & purificación , Saponinas/farmacología , Saponinas/química , Estructura Molecular , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Colestanol/farmacología , Colestanol/química , Colestanol/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Melanthiaceae/química , China , Liliaceae/químicaRESUMEN
OBJECTIVE: To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health. DESIGN: A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients. RESULTS: Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut. CONCLUSION: The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota. TRIAL REGISTRATION NUMBER: NCT02099032 and NCT02146339; Results.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/farmacología , Sobrepeso/metabolismo , Esfingomielinas/metabolismo , Animales , Apolipoproteína A-I/sangre , Apolipoproteína B-100/sangre , Colestanol/metabolismo , Colesterol/metabolismo , HDL-Colesterol/sangre , Estudios Cruzados , Suplementos Dietéticos , Método Doble Ciego , Emulsionantes/farmacología , Heces/química , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Ileostomía , Absorción Intestinal/efectos de los fármacos , Lípidos/administración & dosificación , Lípidos/análisis , Persona de Mediana Edad , Leche/química , Posmenopausia , Factores de RiesgoRESUMEN
OBJECTIVE: Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of ß-sitosterol (SI) in hamsters fed a high cholesterol diet. METHODS AND RESULTS: Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter. CONCLUSION: DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Colestanol/uso terapéutico , Colesterol/sangre , Hiperlipoproteinemia Tipo II/dietoterapia , Absorción Intestinal/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/patología , Alimentación Animal/análisis , Animales , Anticolesterolemiantes/administración & dosificación , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/prevención & control , Aterosclerosis/etiología , Aterosclerosis/patología , Aterosclerosis/prevención & control , Ácidos y Sales Biliares/análisis , Colestanol/administración & dosificación , Colesterol en la Dieta/administración & dosificación , Colesterol en la Dieta/farmacocinética , Cricetinae , Evaluación Preclínica de Medicamentos , Heces/química , Perfilación de la Expresión Génica , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/complicaciones , Lípidos/sangre , Lipoproteínas/sangre , Hígado/química , Hígado/patología , Masculino , Mesocricetus , Redes y Vías Metabólicas/genética , Micelas , Estructura Molecular , Tamaño de los Órganos/efectos de los fármacos , Placa Aterosclerótica/patología , ARN Mensajero/biosíntesis , Distribución Aleatoria , Sitoesteroles/administración & dosificación , Sitoesteroles/uso terapéutico , Esteroles/análisis , Vísceras/efectos de los fármacos , Vísceras/patologíaRESUMEN
Analyses of faecal steroids in coastal sediments from Cienfuegos Bay Cuba indicate chronic sewage contamination at the main outfalls from the city, where concentrations of coprostanol up to 5400ngg(-)(1) (dry wt) were measured. In contrast, steroid concentrations and compositions from sites from the south part of the Bay are characteristic of uncontaminated sewage environments. The levels of coprostanol in the Cienfuegos sediments compares to the lower to mid-range of concentrations reported for coastal sediments on a world-wide basis, with sedimentary levels markedly below those previously reported for heavily impacted sites. This study delivers baseline data for further investigation of the effectiveness of the proposed sewerage plan promoted by the GEF project in Cienfuegos. Investigations on the correlations between faecal steroids and other organic contaminants confirmed that the major source of petroleum hydrocarbons within the bay was associated with the sewage effluents from the Cienfuegos city.
Asunto(s)
Bahías/química , Colestanol/análisis , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Petróleo/análisis , Aguas del Alcantarillado/química , Esteroides/análisis , Cuba , Monitoreo del Ambiente/estadística & datos numéricos , Heces/química , Hidrocarburos/análisisRESUMEN
OBJECTIVES: We prospectively evaluated incidence of prolonged (>28 days) parenteral nutrition (PN), associated complications, and significance of parenteral plant sterols (PS) in neonatal intestinal failure-associated liver disease (IFALD) compared with children. METHODS: We recruited 28 neonates (mean age 50 days, range 28-126) and 11 children (6.9 y, 2.1-16.6) in all of Finland. Patients underwent repeated measurements of serum cholesterol, noncholesterol sterols, including PS, cholestanol and cholesterol precursors, and liver biochemistry during and 1 month after discontinuation of PN. Healthy matched neonates (n=10) and children (n=22) served as controls. RESULTS: IFALD occurred more frequently among neonates (63%) than children (27%; P<0.05). Ratios of serum PS, including stigmasterol, sitosterol, avenasterol, and campesterol, and total PS were increased among neonates compared with healthy controls and children on PN by 2- to 22- and 2- to 5-fold (P<0.005), respectively. Neonates with IFALD had significantly higher ratios of serum PS and cholestanol compared with neonates without IFALD (P<0.05). Total duration of PN associated with serum cholestanol, stigmasterol, avenasterol, alanine aminotransferase, and aspartate aminotransferase (r=0.472-0.636, P<0.05). Cholestanol and individual serum PS, excluding campesterol, reflected direct bilirubin (r=0.529-0.688, P<0.05). IFALD persisted after discontinuation of PN in 25% of neonates with 4.2- and 2.2-times higher ratios of serum stigmasterol and cholestanol compared with neonates without IFALD (P<0.05). CONCLUSIONS: Frequent occurrence of IFALD among neonates on PN displays an association to duration of PN and markedly increased serum PS, especially stigmasterol, in comparison to healthy neonates and children on PN. Striking accumulation of parenteral PS may contribute to IFALD among neonates.
Asunto(s)
Factores de Edad , Colestanol/sangre , Enfermedades Intestinales/complicaciones , Hepatopatías/etiología , Nutrición Parenteral/efectos adversos , Fitosteroles/sangre , Aceites de Plantas/efectos adversos , Adolescente , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Niño , Preescolar , Colesterol/análogos & derivados , Colesterol/sangre , Grasas de la Dieta/efectos adversos , Grasas de la Dieta/sangre , Emulsiones Grasas Intravenosas/efectos adversos , Emulsiones Grasas Intravenosas/química , Femenino , Finlandia/epidemiología , Humanos , Lactante , Recién Nacido , Enfermedades Intestinales/sangre , Enfermedades Intestinales/terapia , Hepatopatías/sangre , Hepatopatías/epidemiología , Masculino , Aceite de Oliva , Nutrición Parenteral/métodos , Aceites de Plantas/química , Prevalencia , Estudios Prospectivos , Aceite de Soja/efectos adversos , Aceite de Soja/química , Estigmasterol/sangreRESUMEN
BACKGROUND: Previous human studies on the effect of dietary calcium supplementation on faecal excretion of bile acids (BA) and faecal water concentrations of animal neutral sterols (NSt, cholesterol and its metabolites) lack detailed information about single BA and NSt. AIM OF THE STUDY: We investigated whether single BA and NSt in faeces and especially in faecal water are affected by calcium supplementation and whether this affects genotoxicity of faecal water. In addition, we differentiated between men and women with regard to the concentrations of BA and NSt in faecal water. METHODS: Thirty-one healthy volunteers consumed a calcium supplemented bread (1.0 g/day) and a placebo bread, respectively, for 4 weeks in a double-blind, randomised cross-over trial. Faeces were collected quantitatively for 5 days in the last week of each period. NSt and BA were analysed by GC-MS. RESULTS: Due to calcium supplementation faecal concentrations of lithocholic acid (LCA, 14%, P = 0.008), deoxycholic acid (DCA, 19%, P < 0.001) and 12 keto-deoxycholic acid (12 keto DCA, 29%, P = 0.049) significantly increased whereas BA concentrations in faecal water were only marginally affected. In contrast, concentrations of cholesterol (30%, P = 0.020) and its metabolites coprostanol (43%, P = 0.004), coprostanone (36%, P = 0.003), cholestanol (44%, P = 0.001) and cholestenone (32%, P = 0.038) in faecal water significantly decreased. Total NSt concentration in faecal water was found to be significantly higher in women compared to men (P = 0.018). The genotoxicity of faecal water was neither affected by calcium supplementation nor were there gender-specific differences. CONCLUSIONS: Dietary calcium supplementation diversely affects BA and NSt in faeces and in faecal water but does not influence the genotoxicity of faecal water in healthy adults.
Asunto(s)
Pan , Calcio de la Dieta/administración & dosificación , Heces/química , Alimentos Fortificados , Caracteres Sexuales , Esteroles/análisis , Adulto , Ácidos y Sales Biliares/análisis , Colestanos/análisis , Colestanol/análisis , Colestanonas/análisis , Colestenonas/análisis , Colesterol/análisis , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , PlacebosRESUMEN
Two experiments were performed to compare the effect of pectin and its hydrophobic derivatives on homeostasis of cholesterol and cecal metabolism in male young rats. Control rats were fed a diet supplemented with palm fat and cholesterol (50 and 10 g/kg, respectively). Rats of other groups were fed the same diet containing citrus pectin or octadecylpectinamide (60 g/kg). Diets were fed for 4 weeks. In experiment I, pectinamide of lower degree of amidation (30 %) increased serum HDL cholesterol from 1.20 to 1.43 micromol/ml (p>0.05) at the expense of other cholesterol fractions. In experiment II, pectinamide of a higher degree of amidation (53 %) significantly decreased total serum cholesterol from 2.08 to 1.67 micromol/ml. Amidated pectins at both levels of substitution significantly decreased hepatic concentrations of cholesterol and fat. In both experiments the relative weight of cecum in the pectinamide group was significantly lower than in pectin group. The highest cecal concentrations of short-chain fatty acids (SCFA) were found in rats fed a diet with pectin (133.2 and 129.3 micromol/g in experiment I and II, respectively). In other groups, cecal SCFA was significantly (pectinamide groups) or non-significantly (controls) lower. In wet feces, SCFA concentrations were higher and butyrate molar proportions lower than in corresponding cecal contents. Pectinamide of a lower or higher degree of substitution significantly increased fecal content of cholesterol from 18.5 and 17.3 micromol/g in controls to 31.8 and 28.0 micromol/g, respectively. Corresponding concentrations of coprostanol were decreased. Effects of pectin on cholesterol homeostasis were absent or marginal. Histological examination revealed that hepatic tissue of control and pectin-fed rats was infiltrated with lipids. The Sudan black-positive material was absent in the liver of rats fed pectinamides. No pathological changes of liver tissue were apparent. In summary, hydrophobic amidated pectins significantly altered cholesterol homeostasis in rats and might be considered as a clinically effective hypocholesterolemic agent. Low cecal SCFA concentrations in rats fed pectinamides suggest that amidation of pectin had decreased its fermentability.
Asunto(s)
Amidas/farmacología , Anticolesterolemiantes/farmacología , Ciego/efectos de los fármacos , Colesterol en la Dieta/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Pectinas/farmacología , Animales , Peso Corporal/efectos de los fármacos , Ciego/metabolismo , Ciego/patología , Colestanol/metabolismo , Colesterol en la Dieta/administración & dosificación , Colesterol en la Dieta/sangre , HDL-Colesterol/sangre , Ácidos Grasos Volátiles/metabolismo , Heces/química , Fermentación/efectos de los fármacos , Homeostasis , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis, caused by impaired hydroxylation of cholesterol side chains due to deficiency of the mitochondrial enzyme sterol 27-hydroxylase (CYP27A1), leading to accumulation of cholestanol and cholesterol in brain and other tissues. Elevated plasma cholestanol serves as a key marker for the clinical diagnosis of CTX. In the present report we describe a young man with CTX who was on high dose steroids for a misdiagnosed chronic inflammatory demyelinating polyneuropathy (CIDP) and had normal level of serum cholestanol. When steroids were discontinued, markedly elevated serum cholestanol was measured concomitant with marked clinical worsening. This observation may imply that steroids can lower plasma cholestanol, possibly by directly inducing residual CYP27A1 activity or by inducing alternative pathways for cholestanol elimination.
Asunto(s)
Colestanol/sangre , Errores Diagnósticos/prevención & control , Esteroide Hidroxilasas/efectos de los fármacos , Esteroides/farmacología , Xantomatosis Cerebrotendinosa/sangre , Xantomatosis Cerebrotendinosa/diagnóstico , Tendón Calcáneo/efectos de los fármacos , Tendón Calcáneo/patología , Tendón Calcáneo/fisiopatología , Adulto , Encéfalo/metabolismo , Encéfalo/fisiopatología , Ácido Quenodesoxicólico/uso terapéutico , Colestanotriol 26-Monooxigenasa , Colesterol/metabolismo , Diagnóstico Diferencial , Progresión de la Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Humanos , Masculino , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Prednisona/farmacología , Prednisona/uso terapéutico , Simvastatina/uso terapéutico , Esteroide Hidroxilasas/deficiencia , Esteroide Hidroxilasas/genética , Esteroides/uso terapéutico , Resultado del Tratamiento , Regulación hacia Arriba/fisiología , Xantomatosis Cerebrotendinosa/tratamiento farmacológicoRESUMEN
In our previous study, we demonstrated that retrograded starch, a kind of resistant starch, of beans reduced serum lipid levels in rats. In this study, we examined whether retrograded starch in potato pulps could reduce serum lipid concentrations. Rats were given diets containing 15 g of retrograded starch in potato pulps from the Benimaru potato (BM) or Hokkaikogane potato (HK) in a 100 g diet for 4 wk. At the 4th week, the total cholesterol level in the serum in the BM group and serum triglyceride (TG) level in the HK group were significantly lower than those in the control group. In the BM group, the contents of fecal bile acids were significantly higher than those in the control group. On the other hand, in the HK group, the hepatic mRNA level of fatty acid synthase (FAS) was significantly lower than that in the control group. The FAS mRNA level correlated with the mRNA level of sterol regulatory element-binding protein-1c (SREBP-1c), a regulator of expression of FAS, positively. These results suggested that BM pulp promoted the excretion of bile acids, which resulted in a low concentration of serum cholesterol. On the other hand, HK pulp inhibited the synthesis of fatty acids at the mRNA levels of FAS and SREBP-1c, which might lead to a reduction of the serum TG level.
Asunto(s)
Colesterol/sangre , Solanum tuberosum , Almidón/farmacología , Triglicéridos/sangre , Animales , Ácidos y Sales Biliares/metabolismo , Peso Corporal/efectos de los fármacos , Colestanol/metabolismo , Dieta , Ácido Graso Sintasas/efectos de los fármacos , Ácido Graso Sintasas/metabolismo , Heces , Concentración de Iones de Hidrógeno , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Almidón/administración & dosificación , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/efectos de los fármacos , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Factores de TiempoRESUMEN
We investigated the effects of pectin with different degrees of methylation (34.5, 70.8, and 92.6%, respectively) on the composition and concentration of intestinal and fecal bile acids and neutral sterols in conventional and germfree rats. Diets containing 6.5% pectin (galacturonan) were given for 3 weeks. High concentrations of free and secondary bile acids appeared in cecum and colon of conventional rats. With increasing degree of methylation, more bile acids were transported into lower parts of intestinal tract and excreted whereas the proportion of secondary bile acids decreased. In contrast, the composition of bile acids in intestinal contents and feces was relatively unchanged in germfree rats. Exclusively cholesterol was found as a neutral sterol in germfree rats. Coprostanol appeared in cecum of conventional rats and additionally coprostanone in colon. Amounts of neutral sterols increased with increasing degree of methylation of pectin. Additionally, concentrations of bile acids in plasma decreased if the pectin-containing diets were given. Besides the degree of methylation, the molecular weight of pectin used in the diets influenced concentration and composition of intestinal and fecal steroids in rats.
Asunto(s)
Intestinos/química , Pectinas/química , Pectinas/farmacología , Esteroides/análisis , Animales , Ácidos y Sales Biliares/análisis , Colestanos/análisis , Colestanol/análisis , Dieta , Heces/química , Vida Libre de Gérmenes , Masculino , Metilación , Peso Molecular , Pectinas/administración & dosificación , Ratas , Esteroles/análisis , Relación Estructura-ActividadRESUMEN
Cholestanol, not cholesterol, is a minor component in the human body and in foods, but an increase in cholestanol concentration in serum induces a pathological condition named cerebrotendinous xanthomatosis (CTX). In our investigation of this disease for more than 25 years, a procedure for quantification of cholestanol by high-performance liquid chromatography and an assay method for sterol 27-hydroxylase were established, and several mutations of the CYP 27 gene in 10 CTX families were identified. We also established experimental animal models with symptoms of CTX by feeding a high cholestanol diet. Corneal dystrophy and gallstones were produced in mice, and an apoptosis of cerebellar neuronal cells was observed in rats. We propose the following underlying mechanism of CTX pathogenesis: When cholesterol in the plasma membrane is replaced by cholestanol to some extent, the membrane fluidity is reduced, and the calcium channel fails to open, inducing cell death. CTX patients are treated with oral administration of chenodeoxycholic acid, which reduces the cholestanol concentration in serum. Cholestanol has a toxic effect, and an imbalance of the cholesterol/cholestanol ratio in plasma membrane is suspected to cause the disturbance of calcium channel function of the membrane.
Asunto(s)
Colestanol/metabolismo , Mutación , Xantomatosis Cerebrotendinosa/patología , Animales , Canales de Calcio/metabolismo , Membrana Celular/química , Ácido Quenodesoxicólico/uso terapéutico , Colestanotriol 26-Monooxigenasa , Colestanol/análisis , Colesterol/análisis , Colesterol/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratas , Esteroide Hidroxilasas/deficiencia , Esteroide Hidroxilasas/genética , Esteroide Hidroxilasas/metabolismo , Xantomatosis Cerebrotendinosa/tratamiento farmacológico , Xantomatosis Cerebrotendinosa/genéticaRESUMEN
The content of phytosterol oxidation products was determined in samples of crude vegetable oils: peanut, sunflower, maize, palm nut, and lampante olive oils that were intended for refining and not for direct consumption. The 7 alpha- and 7 beta-hydroxy derivatives of beta-sitosterol, stigmasterol, and campesterol and the 7-keto-beta-sitosterol were the principal phytosterol oxides found in almost all of the oils analyzed. In some oils, the epoxy and dihydroxy derivatives of beta-sitosterol were also found at very low levels. The highest total concentrations of phytosterol oxides, ranging from 4.5 to 67.5 and from 4.1 to 60.1 ppm, were found in sunflower and maize oils, respectively. Lower concentrations were present in the peanut oils, 2.7-9.6 ppm, and in the palm nut oil, 5.5 ppm, whereas in the lampante olive oils, only three samples of the six analyzed contained a low concentration (1.5-2.5 ppm) of oxyphytosterols. No detectable levels of phytosterol oxides were found in the samples of palm and coconut oils. Bleaching experiments were carried out on a sample of sunflower oil at 80 degrees C for 1 h with 1 and 2% of both acidic and neutral earths. The bleaching caused a reduction of the hydroxyphytosterol with partial formation of steroidal hydrocarbons with three double bonds in the ring system at the 2-, 4-, and 6-positions (steratrienes). The same sunflower oil was deodorized at 180 degrees C under vacuum for 1 h, and no dehydration products were formed with a complete recovery of the hydroxyphytosterols. A bleaching test with acidic earths was carried out also with an extra virgin olive oil fortified with 7-keto-cholesterol, dihydroxycholesterol, and alpha-epoxy-cholesterol. There was no formation of steratrienes from these compounds, but dihydroxycholesterol underwent considerable decomposition and alpha-epoxycholesterol underwent ring opening with formation of the dihydroxy derivative, whereas 7-ketocholesterol was rather stable
Asunto(s)
Manipulación de Alimentos , Óxidos/análisis , Fitosteroles/análisis , Aceites de Plantas/química , Colestanol/farmacología , Colesterol/farmacología , Cromatografía de Gases y Espectrometría de Masas , Concentración de Iones de Hidrógeno , Cetocolesteroles/farmacología , Odorantes , Aceite de Oliva , Oxidación-Reducción , Óxidos/aislamiento & purificación , Fitosteroles/aislamiento & purificación , Aceite de GirasolRESUMEN
Of the primary dementing disorders that cause frontotemporal dementia, the best-known is Pick disease. We report on a 44-year-old woman with progressive frontal lobe dementia and spastic paraplegia. Examination revealed increased serum levels of cholestanol with abnormal cholesterol metabolism and a heterozygous mutation of the sterol 27-hydroxylase gene (CYP27). Biochemical findings were compatible with cerebrotendinous xanthomatosis (CTX); however, the clinical manifestations were very dissimilar. To our knowledge, a symptomatic carrier of this mutation among CTX patients has not been reported. We speculate that the present patient has a previously undescribed neurodegenerative disease related to abnormal cholesterol metabolism with this heterozygous mutation.
Asunto(s)
Colesterol/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Demencia/genética , Lóbulo Frontal , Mutación , Esteroide Hidroxilasas/genética , Adulto , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/orina , Colestanotriol 26-Monooxigenasa , Colestanol/sangre , Colestanoles/sangre , Colestanoles/orina , Colesterol/sangre , Enzimas de Restricción del ADN/metabolismo , ADN Complementario/química , Demencia/diagnóstico , Demencia/enzimología , Femenino , Heterocigoto , Humanos , Lípidos/sangre , Lipoproteínas/sangre , Imagen por Resonancia Magnética , Fosfolípidos/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Patients with antibiotic-associated diarrhoea (AAD) show significant disturbances in short-chain fatty acid pattern. In the present study five more microflora-associated characteristics (MACs) were investigated before and after administration of an enema containing faecal microflora from a healthy person on a Western diet. METHODS: The functions of the microflora were determined with gas chromatography, electrophoresis, and spectrophotometry. RESULTS: The conversion of cholesterol to coprostanol and the concentration of urobilinogen and trypsin were significantly reduced in comparison with healthy persons. The pattern of mucin was altered, but beta-aspartylglycine remained the same as in healthy persons. Enema treatment influenced these functions to different extents. CONCLUSION: Most MACs were significantly disturbed in patients with AAD. Administration of a human faecal enema modified these changes and relieved diarrhoea, usually within 4 days.
Asunto(s)
Antibacterianos/efectos adversos , Diarrea/inducido químicamente , Diarrea/terapia , Enema , Heces/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Terapia Biológica , Colestanol/análisis , Colestanol/biosíntesis , Colesterol/análisis , Diarrea/metabolismo , Dipéptidos/análisis , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucinas/análisis , Tripsina/análisis , Urobilinógeno/análisisRESUMEN
We investigated the changes of cholesterol and non-cholesterol sterol metabolism during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects. Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2 or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas-liquid chromatography. The latter showed a small increase in sitostanol peak during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol proportions to cholesterol were significantly reduced by 5-39% (P < 0.05 or less for all) by stanol esters; the higher their baseline proportions the higher were their reductions. The precursor sterol proportions were significantly increased by 10- 46%, and their high baseline levels predicted low reduction of serum cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6-month feeding increased serum cholesterol by 5% (P < 0. 001) and serum plant sterol proportions by 8-13% (P < 0.001), but had no consistent effect on precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol exceeded that of baseline; the non-cholesterol sterol proportions suggested that stimulated synthesis with relatively weak absorption inhibition contributed to the non-responsiveness of these subjects. In conclusion, plant stanol ester feeding lowers serum cholesterol in about 88% of subjects, decreases the non-cholesterol sterols that reflect cholesterol absorption, increases the sterols that reflect cholesterol synthesis, but also slightly increases serum plant stanols. Low synthesis and high absorption efficiency of cholesterol results in the greatest benefit from stanol ester consumption.
Asunto(s)
Anticolesterolemiantes/administración & dosificación , Grasas Insaturadas en la Dieta/administración & dosificación , Ácidos Grasos Monoinsaturados , Hipercolesterolemia/sangre , Fitosteroles , Sitoesteroles/administración & dosificación , Esteroles/sangre , Índice de Masa Corporal , Colestanol/sangre , Colesterol/análogos & derivados , Colesterol/sangre , Ésteres , Humanos , Cinética , Margarina , Aceite de Brassica napus , Sitoesteroles/sangreRESUMEN
Rats were fed cholesterol-free purified diets containing casein, rice (RP), potato (PP) or soybean (SP) proteins having different amounts of methionine (25.9, 21.3, 16.2 and 10.9 g methionine/kg, respectively). Each protein was fed at 250 g/kg diet for 14 d. Growth rates of rats were the same in all groups. Serum total cholesterol concentrations were lower in rats fed SP, PP and RP than in those fed casein. Fecal bile acid plus neutral steroid excretion was significantly higher in rats fed the RP, PP and SP diets compared with those fed casein. There was a significant negative correlation between serum cholesterol concentration and fecal total steroid excretion (r = -0.490, P = 0.01). However, a stronger positive correlation was observed between serum cholesterol concentration and dietary methionine concentration (r = 0.674, P = 0.0003) or methionine:glycine ratios (r = 0.656, P = 0.0005). In a separate experiment in rats fed diets containing amino acid mixtures simulating the RP, PP and SP diets, serum total cholesterol concentrations were lower than in rats fed simulated casein. Fecal total steroid excretion was the same in all groups. A strong correlation was found between serum cholesterol concentration and dietary methionine concentration (r = 0.743, P = 0.0002) or the methionine:glycine ratio (r = 0.685, P = 0.0009) in rats fed the amino acid mixtures. Finally, we examined the hypocholesterolemic effects of 250 g SP or casein/kg diet with or without supplementation with 0.3 g/100 g sodium taurocholate (TC). Supplementation with TC did not alter the hypocholesterolemic effect of SP. These results support the view that RP, PP and SP lower serum cholesterol concentration in a similar manner.
Asunto(s)
Colesterol/metabolismo , Proteínas en la Dieta/farmacología , Metionina/farmacología , Oryza , Solanum tuberosum , Proteínas de Soja/farmacología , Aminoácidos/administración & dosificación , Aminoácidos/farmacología , Animales , Ácidos y Sales Biliares/análisis , Caseínas/administración & dosificación , Caseínas/química , Caseínas/farmacología , Colestanol/análisis , Colesterol/análisis , Colesterol/sangre , Proteínas en la Dieta/administración & dosificación , Heces/química , Hígado/anatomía & histología , Hígado/química , Masculino , Metionina/administración & dosificación , Metionina/análisis , Oryza/química , Ratas , Ratas Sprague-Dawley , Solanum tuberosum/química , Proteínas de Soja/administración & dosificación , Proteínas de Soja/químicaRESUMEN
The objective of this study was to determine the effects of diets containing non-heated and thermally oxidized olive oils on fecal endogenous lipids. Male Wistar rats were fed fat-free diets and diets supplemented with 12% non-heated, heated, and a 1:1 mixture of non-heated/heated olive oils. After a 15-day experimental period two groups of fecal lipids from major endogenous sources were quantitated: neutral sterols and fatty acids associated with intestinal microflora action. Fecal endogenous sterols, particularly cholesterol, were significantly higher when diets contained oil, and excretion increased as the dietary oil alteration increased. Similar results were obtained for endogenous fatty acids. Increments of fecal sterols, dependent on oil alteration, could be explained by impairments in triglyceride hydrolysis and subsequent effect on cholesterol micellar solubilization. Moreover, high concentrations of poorly digestible lipids may have led to intestinal microbial modifications.
Asunto(s)
Grasas Insaturadas en la Dieta/administración & dosificación , Heces/química , Metabolismo de los Lípidos , Aceites de Plantas/administración & dosificación , Animales , Colestanol/metabolismo , Colesterol/metabolismo , Ácidos Grasos/metabolismo , Calor , Masculino , Aceite de Oliva , Ratas , Ratas Wistar , Sitoesteroles/metabolismoRESUMEN
We studied the effect of the degree of fatty acid saturation on cholesterol metabolism in rats fed either a low cholesterol-low fat diet (control group), high cholesterol-low fat diet (Chol group), high cholesterol-high saturated fat diet (Chol-SF) or high cholesterol-high PUF diet (Chol-PUF). The highest serum cholesterol levels were found in the Chol-SF group. No significant difference in serum cholesterol was found between the Chol and Chol-PUF groups. The Chol-PUF group showed the greatest accumulation of cholesterol in the liver. There was no significant difference in fecal excretion of acidic sterols, cholesterol and coprostanol between the Chol-PUF and Chol-SF groups. We conclude that in chronic feeding experiments in rats: a) high dietary cholesterol intake results in hypercholesterolemia; b) the hypercholesterolemia is accentuated by high dietary SF but is unaffected by PUF; c) addition of PUF to high cholesterol diet leads to massive cholesterol accumulation in the liver which can partly account for the apparent hypocholesterolemic effect of PUF relative to SF; and d) differences in serum and tissue cholesterol levels between SF and PUF supplemented groups are unlikely to be due to their effects on fecal sterol excretion.
Asunto(s)
Colesterol/análisis , Ácidos Grasos/farmacología , Heces/análisis , Esteroles/análisis , Animales , Colestanol/análisis , HDL-Colesterol/análisis , Masculino , Ratas , Ratas Endogámicas , Distribución Tisular , Triglicéridos/análisisRESUMEN
The establishment of a functionally active intestinal flora was followed in 17 healthy Swedish children from birth up to 6 months of age. Utilizing gas chromatography, spectrophotometry, and gel electrophoresis, feces were analyzed on certain biochemical markers that reflect the action of the intestinal flora in vivo. The establishment of the following five flora-related functions was investigated: production of short chain fatty acids (SCFAs), degradation of mucin, conversion of bilirubin to urobilinogen and of cholesterol to coprostanol, and inactivation of fecal tryptic activity (FTA). Production of SCFAs was the first function to be established, followed by bilirubin conversion and mucin degradation. No child showed conversion of cholesterol. The values of FTA were lower than in adults. This study indicates that the establishment of a functionally active flora is a slow process and that some functions are almost fully established before other functions have started to develop. Environmental factors, such as the diet, seem to be of importance. In general, the functions seem to develop slower in those children receiving breast milk exclusively than in those receiving formula supplements.
Asunto(s)
Recién Nacido/metabolismo , Intestinos/microbiología , Bilirrubina/metabolismo , Colestanol/metabolismo , Colesterol/metabolismo , Ácidos Grasos Volátiles/biosíntesis , Heces/análisis , Femenino , Estudios de Seguimiento , Humanos , Lactante , Estudios Longitudinales , Masculino , Mucinas/metabolismo , Tripsina/metabolismo , Urobilinógeno/biosíntesisRESUMEN
The effect of glycolipid (GL) and phospholipid (PL) fractions obtained from Chlorella on serum lipid level and fecal excretion of steroids were examined in cholesterol-fed rats. The increase of the level of serum lipids were inhibited by the feeding of GL, PL and Chlorella powder almost the same degree. Fecal excretion of steroids (mostly of cholesterol, deoxycholic and lithocholic acid) were increased by feeding of GL and PL fractions. It is concluded that the feeding of each fraction inhibits the absorption of exogenous steroids and promotes turnover of bile acids in liver to suppress the increase of serum cholesterol level caused by administration of high cholesterol diet.