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1.
Reprod Biol Endocrinol ; 21(1): 41, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37165411

RESUMEN

BACKGROUND: To evaluate the association of serum advanced glycation end-products (AGEs) and its soluble receptor of AGE (sRAGE) levels with dysglycaemia and metabolic syndrome in women with polycystic ovary syndrome (PCOS). METHODS: This was an analysis of a cohort of women with PCOS who were prospectively recruited for a longitudinal observational study on their endocrine and metabolic profile between January 2010 and December 2013. The association of serum AGEs and sRAGE levels with dysglycaemia and metabolic syndrome at the second-year visit (the index visit) and the sixth-year visit (the outcome visit) were determined. Comparisons of continuous variables between groups were made using the Mann-Whitney U-test. Spearman test was used for correlation analysis. Multivariate binary logistic regression analysis was employed to identify the factors independently associated with the outcome events. RESULTS: A total of 329 women were analysed at the index visit. Significantly lower serum levels of sRAGE (both p < 0.001), but no significant difference in AGEs, were observed in those with dysglycaemia or metabolic syndrome. At the outcome visit, those with incident metabolic syndrome had a significantly lower initial serum sRAGE levels (p = 0.008). The association of serum sRAGE with dysglycaemia and metabolic syndrome at the index visit was no longer significant in multivariate logistic regression after controlling for body mass index, free androgen index and homeostatic model assessment for insulin resistance (HOMA-IR). sRAGE was also not significantly associated with incident metabolic syndrome at the outcome visit on multivariate logistic regression. CONCLUSIONS: Serum sRAGE levels are significantly lower in women with PCOS who have dysglycaemia or metabolic syndrome, and in those developing incident metabolic syndrome in four years. However, it does not have a significant independent association with these outcome measures after adjusting for body mass index, free androgen index and HOMA-IR.


Asunto(s)
Resistencia a la Insulina , Síndrome Metabólico , Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/complicaciones , Receptor para Productos Finales de Glicación Avanzada , Productos Finales de Glicación Avanzada , Andrógenos , Reacción de Maillard
2.
Nephrol Dial Transplant ; 36(9): 1648-1656, 2021 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-32617578

RESUMEN

BACKGROUND: The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. METHODS: In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3-4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. RESULTS: Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. CONCLUSION: Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.


Asunto(s)
Insuficiencia Renal Crónica , Renina , Adulto , Anciano , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Tasa de Filtración Glomerular , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico
3.
Epidemiol Infect ; 147: e279, 2019 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-31556360

RESUMEN

Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339-428) vs. 713 (95% CI 641-792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018-2019 winter influenza epidemic, our results corroborated the epidemic subtype.


Asunto(s)
Anticuerpos Antivirales/sangre , Susceptibilidad a Enfermedades , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Gripe Humana/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Niño , Preescolar , Hong Kong/epidemiología , Humanos , Lactante , Recién Nacido , Gripe Humana/epidemiología , Persona de Mediana Edad , Adulto Joven
4.
J Biol Chem ; 292(11): 4755-4763, 2017 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-28053091

RESUMEN

Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone. Notably, in animals lacking FAH, transient withdrawal of NTBC can be used to induce liver damage and a concomitant regenerative response that stimulates the growth of healthy hepatocytes. Among other things, this model has raised tremendous interest for the in vivo expansion of human primary hepatocytes inside these animals and for exploring experimental gene therapy and cell-based therapies. Here, we report the generation of FAH knock-out rabbits via pronuclear stage embryo microinjection of transcription activator-like effector nucleases. FAH-/- rabbits exhibit phenotypic features of HT1 including liver and kidney abnormalities but additionally develop frequent ocular manifestations likely caused by local accumulation of tyrosine upon NTBC administration. We also show that allogeneic transplantation of wild-type rabbit primary hepatocytes into FAH-/- rabbits enables highly efficient liver repopulation and prevents liver insufficiency and death. Because of significant advantages over rodents and their ease of breeding, maintenance, and manipulation compared with larger animals including pigs, FAH-/- rabbits are an attractive alternative for modeling the consequences of HT1.


Asunto(s)
Hidrolasas/genética , Tirosinemias/genética , Animales , Modelos Animales de Enfermedad , Femenino , Técnicas de Inactivación de Genes , Hepatocitos/trasplante , Humanos , Hidrolasas/metabolismo , Riñón/metabolismo , Riñón/patología , Hígado/metabolismo , Hígado/patología , Fallo Hepático/etiología , Fallo Hepático/metabolismo , Fallo Hepático/patología , Fallo Hepático/terapia , Masculino , Conejos , Tirosinemias/complicaciones , Tirosinemias/metabolismo , Tirosinemias/patología
5.
Clin Endocrinol (Oxf) ; 89(5): 634-641, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30019416

RESUMEN

OBJECTIVE: This study aimed at investigating the association of serum vitamin D (25(OH)D) and anti-Mullerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) as well as non-PCOS healthy ovulatory women and the possible confounding effects of adiposity and androgen. METHOD: This was a cross-sectional study conducted on serum samples collected from 451 women diagnosed with PCOS as well as 244 age-matched healthy ovulatory women in a tertiary gynaecology out-patient clinic and a family planning clinic. RESULTS: Serum 25(OH)D level was significantly higher in women recruited during summer and autumn than those recruited in winter and spring. Both serum 25(OH)D and AMH levels peaked during summer in women with PCOS. In ovulatory women, only serum 25(OH)D but not AMH level showed such seasonal variation. Serum 25(OH)D level in women with PCOS significantly correlated positively with AMH, AMH/antral follicle count (AFC) ratio, serum total testosterone, sex-hormone-binding globulin and quantitative insulin-sensitivity check index and inversely with body mass index (BMI), insulin, triglycerides and homeostatic model assessment of insulin resistance. After controlling for BMI, 25(OH)D level remained significantly correlated positively with serum AMH, AMH/AFC and total testosterone, and inversely with triglycerides. 25(OH)D level was an independent predictor of serum AMH level after controlling for age, BMI and free androgen index in women with PCOS. CONCLUSION: Serum 25(OH)D level is an independent factor significantly associated with AMH level in women with PCOS but not in ovulatory women.


Asunto(s)
Hormona Antimülleriana/sangre , Síndrome del Ovario Poliquístico/sangre , Vitamina D/sangre , Adiposidad/fisiología , Adulto , Andrógenos/sangre , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos
6.
Arch Environ Contam Toxicol ; 73(3): 410-420, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28770280

RESUMEN

Bisphenol A (BPA) glucuronide and sulfate conjugates are major products of Phase II metabolism of BPA in humans. In the past, their determination in body fluids usually involves tedious enzymatic hydrolysis and multiresidual analysis. The recent availability of authentic standards of these conjugates enables our better understand of the human metabolism of BPA and the distribution of their metabolites in body fluids. In this work, we report the chemical synthesis and purification of BPA mono- and di-glucuronide and BPA mono- and di-sulfate. Their levels, as well as that of BPA, in 140 paired human plasma and urine samples collected randomly from voluntary donors in Hong Kong SAR, China, were determined by solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). BPA was found in more than 135 human plasma and urine samples. Its Phase II metabolites, ranging from N.D. to 36.7 µg g-1-creatinine, also were detected in 139 of the 140 urine samples. Good correlation (r = 0.911) between molar concentration of BPA in the plasma and that of "total urinary BPA" (i.e., ln [(BPA + ∑ BPA phase II conjugate)molar concentration]) was observed. Direct quantification of Phase II metabolites of BPA in human urine can be a useful assessment tool for population exposure to this potent endocrine disrupting chemical.


Asunto(s)
Compuestos de Bencidrilo/metabolismo , Disruptores Endocrinos/metabolismo , Fenoles/metabolismo , Compuestos de Bencidrilo/sangre , Compuestos de Bencidrilo/orina , Disruptores Endocrinos/sangre , Disruptores Endocrinos/orina , Glucurónidos/sangre , Glucurónidos/metabolismo , Glucurónidos/orina , Hong Kong , Humanos , Fase II de la Desintoxicación Metabólica/fisiología , Fenoles/sangre , Fenoles/orina , Extracción en Fase Sólida , Sulfatos
7.
Gynecol Endocrinol ; 32(5): 390-4, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26699091

RESUMEN

OBJECTIVE: To evaluate the association of serum adiponectin level with the metabolic syndrome in Chinese women with polycystic ovary syndrome (PCOS). METHODS: This was a cross-sectional study carried out in Hong Kong Chinese women with PCOS at a university-affiliated tertiary hospital between January 2010 and January 2011. Clinical and biochemical parameters of the women were analysed. Prediction of the metabolic syndrome was determined by receiver-operator characteristic (ROC) curves, univariate and multivariate logistic regression analyses. RESULTS: A total of 116 women diagnosed to have PCOS were analysed. The area under the ROC curve of adiponectin for the prediction of metabolic syndrome was 0.820, 95% confidence interval (CI) 0.737-0.886. Univariate binary logistic regression showed that testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), waist circumference, body mass index (BMI), quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment of insulin resistance (HOMA-IR) and adiponectin were significantly associated with the metabolic syndrome. On multivariate logistic regression analysis, adiponectin (p = 0.020), HOMA-IR, age (p = 0.011) and BMI (p = 0.019) were independently associated with the metabolic syndrome, but not FAI (p = 0.256). CONCLUSIONS: Serum adiponectin is independently associated with the metabolic syndrome in Chinese women with PCOS. Further longitudinal follow-up studies are needed to determine whether serum adiponectin adds to the prediction of long-term cardiometabolic morbidity conferred by age, BMI and measures of insulin resistance.


Asunto(s)
Adiponectina/sangre , Síndrome Metabólico/sangre , Obesidad/sangre , Síndrome del Ovario Poliquístico/sangre , Adulto , Glucemia , Índice de Masa Corporal , Estudios Transversales , Femenino , Hong Kong , Humanos , Insulina/sangre , Síndrome Metabólico/complicaciones , Obesidad/complicaciones , Síndrome del Ovario Poliquístico/complicaciones , Testosterona/sangre , Circunferencia de la Cintura
8.
J Clin Microbiol ; 53(12): 3750-9, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26378277

RESUMEN

Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n = 46) with those of community-acquired pneumonia (CAP) patients (n = 30) and controls without active infection (n = 30) using ultrahigh-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(R)-HETE], ceramide (d18:1/16:0), cholesterol sulfate, and 4α-formyl-4ß-methyl-5α-cholesta-8-en-3ß-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve (AUC) values of 0.914, 0.912, 0.905, and 0.856, sensitivities of 84.8%, 84.8%, 87.0%, and 89.1%, specificities of 90.0%, 86.7%, 86.7%, and 80.0%, and fold changes of 4.19, 26.15, 6.09, and 1.83, respectively. In a comparison of TB and CAP patients, the four metabolites demonstrated AUC values of 0.793, 0.717, 0.802, and 0.894, sensitivities of 89.1%, 71.7%, 80.4%, and 84.8%, specificities of 63.3%, 66.7%, 70.0%, and 83.3%, and fold changes of 4.69, 3.82, 3.75, and 2.16, respectively. 4α-Formyl-4ß-methyl-5α-cholesta-8-en-3ß-ol combined with 12(R)-HETE or cholesterol sulfate offered ≥70% sensitivity and ≥90% specificity for differentiating TB patients from controls or CAP patients. These novel plasma biomarkers, especially 12(R)-HETE and 4α-formyl-4ß-methyl-5α-cholesta-8-en-3ß-ol, alone or in combination, are potentially useful for rapid and noninvasive diagnosis of TB. The present findings may offer insights into the pathogenesis and host response in TB.


Asunto(s)
Biomarcadores/sangre , Metaboloma , Plasma/química , Tuberculosis/diagnóstico , Tuberculosis/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cromatografía Liquida , Femenino , Humanos , Masculino , Espectrometría de Masas/métodos , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Adulto Joven
9.
Eur J Haematol ; 94(4): 330-5, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25135740

RESUMEN

BACKGROUND: Serum lactate dehydrogenase (LDH) has been an adverse prognostic factor for myeloma but does not feature in the International Staging System (ISS). We examined whether elevated serum LDH at diagnosis remains an adverse risk factor independent of ISS for survivals transplant-eligible myeloma patients receiving early/frontline bortezomib-based induction, followed by autologous stem cell transplantation (ASCT). PATIENTS: Seventy-seven transplant-eligible Chinese patients received three induction regimens [staged approach (N = 25), PAD (N = 19), VTD (N = 33)], followed by ASCT and thalidomide maintenance. RESULTS: Five-year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was no difference in demographics, complete remission/near complete remission (CR/nCR rates postinduction or ASCT, and survivals among patients induced by the three induction regimens. Elevated LDH was associated with male gender (P = 0.006), ISS III (P = 0.042) and serum ß2-microglobulin (P = 0.040). Univariate analysis showed that elevated LDH, ISS III, high ß2-microglobulin, and failure to attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS. Multivariate analysis showed that elevated LDH was the only factor impacting both OS (P = 0.007) and EFS (P = 0.008). CONCLUSION: In this uniformly treated cohort of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT regimen had not abolished the adverse impact of elevated LDH.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Lactato Deshidrogenasas/sangre , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Bortezomib/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Estadificación de Neoplasias , Pronóstico , Inducción de Remisión , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento
10.
Anal Bioanal Chem ; 407(25): 7765-74, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26374566

RESUMEN

Aldosterone is a mineralocorticoid steroid hormone, the measurement of which in the clinical laboratory is principally performed for the investigation of primary hyperaldosteronism. Primary hyperaldosteronism is a specifically treatable and potentially curable form of hypertension, which typically presents as drug-resistant hypertension and, in up to 37% of cases, hypokalemia. Accurate measurement of aldosterone concentration is essential for correct diagnosis. The serum concentrations of aldosterone are in the picomolar range and therefore sensitive aldosterone assays are required. With the advancement in instrumentation of LC-MS/MS, the picomolar range of aldosterone can be easily measured by the newer models, but for those with a less sensitive instrument, special technique for sample preparation to enhance assay sensitivity is required. This work described the use of charge-tagging for the picomolar measurement of serum aldosterone in a less sensitive LC-MS/MS instrument. The assay was linear up to 3000 pmol/L with lower limit of quantitation at 80 pmol/L. The mean relative recovery was 96.5% with a range of 89.3-101.6% for aqueous calibrators and the mean relative recovery was 94.8% with a range of 87.5-101.4% for serum calibrators. Intra-assay CVs range from 8.2% to 11.3%, and inter-assay CVs ranged from 8.5% to 13.5% at concentration range from 229 to 1720 pmol/L. The LC-MS/MS method compared well (y = 1.04x + 8.97) with the in-use radioimmunoassay method. There was no significant difference found (p = 0.7135) between results determined by LC-MS/MS and radioimmunoassay method.


Asunto(s)
Aldosterona/sangre , Hiperaldosteronismo/sangre , Espectrometría de Masas en Tándem/métodos , Adulto , Anciano , Calibración , Cromatografía Liquida/métodos , Femenino , Humanos , Hiperaldosteronismo/diagnóstico , Límite de Detección , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto Joven
11.
FASEB J ; 27(10): 4122-35, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23825225

RESUMEN

Previously, exchange protein directly activated by cAMP 2 (Epac2) and PKA were known to play a role in glucose-stimulated insulin secretion (GSIS) by pancreatic ß cells. The present study shows that Epac1 mRNA is also expressed by ß cells. Therefore, we generated mice and embryonic stem (ES) cells with deletion of the Epac1 gene to define its role in ß-cell biology and metabolism. The homozygous Epac1-knockout (Epac1(-/-)) mice developed impaired glucose tolerance and GSIS with deranged islet cytoarchitecture, which was confirmed by isolated islets from adult Epac1(-/-) mice. Moreover, Epac1(-/-) mice developed more severe hyperglycemia with increased ß-cell apoptosis and insulitis after multiple low-dose streptozotocin (MLDS; 40 mg/kg) treatment than Epac1(+/+) mice. Interestingly, Epac1(-/-) mice also showed metabolic defects, including increased respiratory exchange ratio (RER) and plasma triglyceride (TG), and more severe diet-induced obesity with insulin resistance, which may contributed to ß-cell dysfunction. However, islets differentiated from Epac1(-/-) ES cells showed insulin secretion defect, reduced Glut2 and PDX-1 expression, and abolished GLP-1-stimulated PCNA induction, suggesting a role of Epac1 in ß-cell function. The current study provides in vitro and in vivo evidence that Epac1 has an important role in GSIS of ß cells and phenotype resembling metabolic syndrome.


Asunto(s)
Factores de Intercambio de Guanina Nucleótido/metabolismo , Células Secretoras de Insulina/metabolismo , Síndrome Metabólico/metabolismo , Animales , Glucemia , Diabetes Mellitus Experimental , Grasas de la Dieta/efectos adversos , Células Madre Embrionarias , Factores de Intercambio de Guanina Nucleótido/genética , Ratones , Ratones Noqueados , Obesidad/etiología , Obesidad/genética
12.
BMC Cardiovasc Disord ; 14: 24, 2014 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-24559092

RESUMEN

BACKGROUND: Previous studies suggested that high dietary carbohydrate intake is associated with increased cardiovascular risk through raised triglyceride and decreased high-density lipoprotein-cholesterol levels. However, the relation between carbohydrate intake and arterial stiffness has not been established. The purpose of this study was to examine this relation among high-risk cardiovascular patients. METHODS: We studied the relation between dietary macronutrient intake and arterial stiffness in 364 patients with documented cardiovascular diseases or risk equivalent (coronary artery diseases 62%, ischemic stroke 13%, diabetes mellitus 55%) and in 93 age-and-sex matched control subjects. Dietary macronutrient intake was assessed using a validated food-frequency questionnaire (FFQ) for Chinese. Heart-ankle pulse wave velocity (PWV) was measured non-invasively with a Vascular Profiling System (VP2000, Colin Corp. USA). A dietary pattern with ≥60% total energy intake derived from carbohydrates was defined as a high-carbohydrate diet according to the Dietary Reference Intakes (DRI) for Chinese. RESULTS: Subjects who consumed a high-carbohydrate diet had significantly higher mean PWV than those who did not consume a high-carbohydrate diet (P = 0.039). After adjustment for potential confounders, high-carbohydrate diet was associated with significantly increased PWV [B = 73.50 (10.81 to 136.19), P = 0.022]. However, there was no significant association between high-carbohydrate diet and PWV in controls (P = 0.634). CONCLUSIONS: High-carbohydrate diet is associated with increased arterial stiffness in patients with established cardiovascular disease or risk equivalent.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Carbohidratos de la Dieta/efectos adversos , Conducta Alimentaria , Rigidez Vascular , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Estudios de Casos y Controles , China , Estudios Transversales , Ingestión de Energía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Análisis de la Onda del Pulso , Factores de Riesgo , Encuestas y Cuestionarios
13.
Hong Kong Med J ; 19(3): 272-5, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23732435

RESUMEN

Dihydropyrimidinase deficiency is an autosomal recessive inborn error of metabolism characterised by the presence of dihydropyrimidinuria. Its clinical presentation is variable and has also been reported in asymptomatic subjects. We report the first case of dihydropyrimidinase deficiency in Hong Kong, which is also the first reported in a Chinese subject. The patient was a 32-month-old boy who presented with language development delay. Biochemical analysis confirmed markedly increased urinary excretion of dihydrouracil and dihydrothymine, whilst DNA testing confirmed that the patient was compound heterozygous for two missense mutations, one known (p.R302Q) and the other was novel (p.N16K).


Asunto(s)
Deficiencia de Dihidropirimidina Deshidrogenasa/diagnóstico , Errores Innatos del Metabolismo/diagnóstico , Preescolar , China , Deficiencia de Dihidropirimidina Deshidrogenasa/etiología , Hong Kong , Humanos , Masculino , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/genética , Mutación Missense , Uracilo/análogos & derivados , Uracilo/orina
14.
Anal Chem ; 84(22): 9881-8, 2012 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-23075377

RESUMEN

Bromophenol glucuronide and sulfate conjugates have been reported to be products of mammalian metabolism of polybrominated diphenyl ethers (PBDEs), a group of additive flame-retardants found ubiquitously in the environment. In order to explore their occurrence in human urine, four water-soluble bromophenol conjugates, namely, 2,4-dibromophenyl glucuronide, 2,4,6-tribromophenyl glucuronide, 2,4-dibromophenyl sulfate, and 2,4,6-tribromophenyl sulfate, were synthesized, purified, and characterized. An analytical protocol using solid-phase extraction and ion-paired liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) quantification has been developed for the direct and simultaneous determination of these glucuronide and sulfate conjugates in human urine samples. The limit of detections for all analytes were below 13 pg mL(-1), with 73-101% analyte recovery and 7.2-8.6% repeatability. The method was applied to analyze 20 human urine samples collected randomly from voluntary donors in Hong Kong SAR, China. All the samples were found to contain one or more of the bromophenol conjugates, with concentration ranging from 0.13-2.45 µg g(-1) creatinine. To the best of our knowledge, this is the first analytical protocol for the direct and simultaneous monitoring of these potential phase II metabolites of PBDEs in human urine. Our results have also suggested the potential of these bromophenol conjugates in human urine to be convenient molecular markers for the quantification of population exposure to PBDEs.


Asunto(s)
Cromatografía Liquida/métodos , Exposición a Riesgos Ambientales/análisis , Glucurónidos/química , Glucurónidos/orina , Éteres Difenilos Halogenados/toxicidad , Fenoles/química , Espectrometría de Masas en Tándem/métodos , Biomarcadores/química , Biomarcadores/orina , Técnicas de Química Sintética , Femenino , Glucurónidos/síntesis química , Glucurónidos/aislamiento & purificación , Humanos , Masculino , Extracción en Fase Sólida , Sulfatos
15.
Nephrol Dial Transplant ; 27(2): 613-8, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21680850

RESUMEN

BACKGROUND: Aliskiren is a relatively new oral direct renin inhibitor (DRI) that has been increasingly used for the treatment of diabetic nephropathy and hypertension. Its potential efficacy in nondiabetic chronic kidney diseases that are driven by renin-angiotensin system activation remains to be explored. METHODS: From a teaching and regional hospital in Hong Kong between July 2009 and March 2010, patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in whom the ratio of protein to creatinine, as measured in early morning urine samples, remained >113 mg/mmol (1000 mg/g), despite receiving the maximum recommended dose of losartan (100 mg daily) were recruited to receive additional DRI treatment. They were followed prospectively for 12 months with changes in proteinuria as the main outcome measure. RESULTS: Twenty-five consecutive patients were enrolled. Treatment with aliskiren for 12 months reduced the mean urinary protein-to-creatinine ratio by 26.3% (95% confidence interval, 20.1-43.6; P = 0.001 versus baseline), with a reduction of ≥ 50% in 24% of patients. There were significant reductions in plasma renin activity (P < 0.0001) and serum interleukin-6 (P < 0.05) and transforming growth factor-ß (P = 0.01) levels, compared with baseline. Two patients (8%) developed mild allergic reactions and six (24%) had transient hyperkalemia (K >5.5 mmol/L) during the study. CONCLUSION: Aliskiren confers an antiproteinuric effect in IgAN patients with significant residual proteinuria, despite receiving the recommended renoprotective treatment. Further prospective randomized trials are warranted to examine its long-term renoprotective potential. This trial is registered with the ClinicalTrials.gov number NCT00922311.


Asunto(s)
Amidas/uso terapéutico , Fumaratos/uso terapéutico , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/tratamiento farmacológico , Losartán/uso terapéutico , Adulto , Amidas/efectos adversos , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Intervalos de Confianza , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Fumaratos/efectos adversos , Hong Kong , Humanos , Interleucina-6/análisis , Interleucina-6/metabolismo , Pruebas de Función Renal , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Proyectos Piloto , Estudios Prospectivos , Proteinuria/prevención & control , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Factor de Crecimiento Transformador beta/análisis , Factor de Crecimiento Transformador beta/metabolismo , Resultado del Tratamiento , Urinálisis
16.
Circ J ; 76(11): 2572-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22813696

RESUMEN

BACKGROUND: Exercise training improves endothelial function in patients with coronary artery disease (CAD) through unclear mechanisms. We hypothesized that mitochondrial dysfunction related to a lower habitual physical activity level (PAL) is associated with endothelial dysfunction. METHODS AND RESULTS: We assessed habitual PAL by a validated International Physical Activity Questionnaire, brachial flow-mediated dilation (FMD) and serum lactate, pyruvate, fasting glucose and lipid profiles in 105 CAD patients (age 68±10; 87% men). As defined by the lactate/pyruvate ratio (LP ratio) ≥75(th) percentile of the age-and sex-matched controls (ie, ≥18), mitochondrial dysfunction was observed in 33/105 (31%) patients. With decreasing PAL tertiles, there were significant linear trends of lower FMD (P=0.004) and higher LP ratio (P=0.009). Multivariate logistic regression found that the lowest compared with the highest PAL tertile (adjusted odds ratio=3.78, P=0.02) had more patients with high LP ratio. After adjustment for cardiovascular risk factors and medications, the lowest compared to the highest PAL tertile had significantly lower FMD (absolute decrease 1.25%, P=0.03); and high LP ratio was associated with impaired FMD (absolute reduction 1.09%, P=0.03). CONCLUSIONS: In CAD patients, a lower level of habitual PAL is associated with impaired FMD and increased prevalence of mitochondrial dysfunction as defined by high LP ratio. Moreover, high LP ratio predicts a lower FMD, suggesting that the occurrence of mitochondrial dysfunction with lower habitual PAL is associated with endothelial dysfunction in CAD patients.


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Endotelio Vascular/metabolismo , Estilo de Vida , Mitocondrias/metabolismo , Actividad Motora , Anciano , Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/fisiopatología , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Femenino , Humanos , Ácido Láctico/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad , Mitocondrias/patología , Ácido Pirúvico/sangre , Factores de Riesgo
17.
J Hum Genet ; 56(8): 617-21, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21697855

RESUMEN

Influenza-associated encephalopathy (IAE) is a potentially fatal neurological complication of influenza infection usually in the presence of high and persistent fever. Thermolabile carnitine palmitoyltransferase II enzyme (CPT-II) predisposes IAE, so far only described in Japanese. As the genetic origins of Japanese and Chinese are alike, similar genetic risk factors in CPT-II are expected. We report the first two unrelated Chinese patients of thermolabile CPT-II variants that underlain the persistent high fever-triggered viral infection-associated encephalopathy, multi-organ failure and death. Elevated (C16:0+C18:1)/C2 acylcarnitines ratio and the CPT2 susceptibility variant allele [p.Phe352Cys; p.Val368Ile] were detected. The asymptomatic family members of one patient also had abnormal long-chain acylcarnitines. In our experience of biochemical genetics, the elevated (C16:0+C18:1)/C2 acylcarnitines ratio is unusual and specific for thermolabile CPT-II variants. Allele frequency of [p.Phe352Cys; p.Val368Ile] among Hong Kong Chinese was 0.104, similar to Japanese data, and [p.Phe352Cys] has not been reported in Caucasians. This may explain the Asian-specific phenomenon of thermolabile CPT-II-associated IAE. We successfully demonstrated the thermolabile CPT-II variants in patients with viral infection-associated encephalopathy in another Asian population outside Japanese. The condition is likely under-recognized. With our first cases, it is envisaged that more cases will be diagnosed in subsequent years. The exact pathogenic mechanism of how other factors interplay with thermolabile CPT-II variants and high fever leading to IAE, is yet to be elucidated. Fasting and decreased intake during illness may aggravate the disease. Further studies including high risk and neonatal screening are warranted to investigate its expressivity, penetrance and temperature-dependent behaviors in thermolabile CPT-II carriers. This may lead to discovery of the therapeutic golden window by aggressive antipyretics and L-carnitine administration in avoiding the high mortality and morbidity of IAE.


Asunto(s)
Carnitina O-Palmitoiltransferasa/metabolismo , Encefalitis Viral/enzimología , Gripe Humana/complicaciones , Sustitución de Aminoácidos , Secuencia de Bases , Carnitina/análogos & derivados , Carnitina/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Preescolar , Análisis Mutacional de ADN , Encefalitis Viral/complicaciones , Encefalitis Viral/genética , Estabilidad de Enzimas , Salud de la Familia , Resultado Fatal , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Datos de Secuencia Molecular , Mutación , Linaje , Factores de Riesgo , Temperatura
18.
Clin Endocrinol (Oxf) ; 74(2): 206-13, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21054477

RESUMEN

OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 gene (APOA5) are associated with hypertriglyceridaemia in our population. We studied the associations of SNPs in APOA5 with the metabolic syndrome (MetS) in the Hong Kong and Guangzhou Chinese. METHODS: We genotyped five tagging SNPs in 1330 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort with follow-up after a median interval of 6·4 years; 1952 subjects from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort were used to replicate the findings. The MetS was defined according to the consensus criteria proposed jointly by several organizations in 2009. RESULTS: The SNP rs662799 (-1131T>C) was associated with the MetS (odds ratio = 1·47, P = 0·00082) and the number of its components present (regression coefficient = 0·204, P = 4·6 × 10(-5) ) after adjusting for age, sex, smoking, drinking and education in Hong Kong subjects at baseline. Similar association of this SNP was found in Hong Kong subjects at follow-up (P = 0·010 and 0·00021, respectively) and in Guangzhou subjects (P = 0·0041 and 0·017, respectively). The association of rs662799 with the number of the MetS components was significant regardless of age, sex, obesity and alcohol drinking, but almost disappeared after further adjusting for plasma triglycerides. CONCLUSION: Our results showed that the -1131T>C polymorphism in APOA5 was associated with the MetS because of its strong effect on plasma triglycerides. This may partly explain the higher cardiovascular risk in people with this polymorphism.


Asunto(s)
Apolipoproteínas A/genética , Síndrome Metabólico/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Anciano de 80 o más Años , Apolipoproteína A-V , Pueblo Asiatico/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad
19.
Eur J Cardiovasc Prev Rehabil ; 18(3): 360-8, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21450646

RESUMEN

Endogenous estrogen is known to positively influence the level and functionality of endothelial progenitor cells (EPC). However, the effect of phytoestrogen on EPC is unknown. Isoflavone is a major component of phytoestrogen. This study aims to investigate if the intake of isoflavone has any impact on the circulating level of EPC. We studied 102 consecutive patients (mean age: 66.5 ± 9.5 years, 78% male, all female post-menopausal) with cardiovascular disease (atherothrombotic stroke 62%, coronary artery disease 38%). Circulating levels of CD133(+) EPC were determined by flow cytometry. Non-invasive pulse wave velocity (PWV) was measured. Long-term intake of isoflavone was determined by a validated food frequency questionnaire. Isoflavone intake was positively associated with circulating CD133(+) EPC (r = 0.31, p = 0.001). Patients with circulating CD133(+) EPC <10th percentile had significantly lower isoflavone intake than patients with CD133(+)EPC ≥10th percentile (4.6 ± 3.7 mg/day versus 19.3 ± 30.2 mg/day, p < 0.001). A significant overall linear trend of circulating EPC across increasing tertiles of isoflavone intake was observed (p = 0.004). Adjusted for potential confounders, increased isoflavone intake from the 1st to the 3rd tertile independently predicted increased circulating CD133(+) EPC level by 221 cells/µl (95%CI: 71.4 to 369.8, relative increase 160%, p = 0.004). Gender was not a significant factor (p > 0.05). Furthermore, circulating CD133(+) EPC <10th percentile was independently predictive of increased PWV by 261.7 cm/s (95% CI: 37.1 to 486.2, p = 0.024). The study demonstrated that circulating EPC increased by more than one fold in patients with cardiovascular disease who had higher intake of isoflavone, suggesting that isoflavone may confer vascular protection through enhanced endothelial repair.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Suplementos Dietéticos , Células Endoteliales/fisiología , Endotelio Vascular/fisiología , Fitoestrógenos/administración & dosificación , Células Madre/fisiología , Anciano , Enfermedades Cardiovasculares/dietoterapia , Enfermedades Cardiovasculares/prevención & control , Células Endoteliales/citología , Endotelio Vascular/citología , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Encuestas y Cuestionarios
20.
Pharmacology ; 88(5-6): 260-5, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21996640

RESUMEN

Metformin is a widely used antidiabetic agent that is generally considered safe. However, metformin-associated lactic acidosis (MALA), though not common, occurs from time to time and results in significantly high mortality. A series of 23 MALA cases in a local major hospital in Hong Kong is reported in this article to demonstrate the epidemiological data, risk factors, clinical features as well as the clinical outcomes for better understanding of this disease entity. It is the first MALA case series in which plasma metformin levels were assessed. However, the results show that plasma metformin levels in MALA bear no diagnostic and prognostic values. Risk factors of mortality were identified as shock and high plasma lactate levels. The majority of patients were found to have significantly raised creatinine versus a normal baseline value before the acute illness. Concomitant illnesses taking place alongside MALA were common. With a high utility rate of renal replacement therapy (82.6%) in the study group, the mortality rate was 30.4%.


Asunto(s)
Acidosis Láctica/inducido químicamente , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Acidosis Láctica/sangre , Acidosis Láctica/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Amilasas/sangre , Pueblo Asiatico , China/epidemiología , Creatinina/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Sobredosis de Droga , Femenino , Cardiopatías/epidemiología , Humanos , Hipertensión/epidemiología , Hipoglucemiantes/sangre , Enfermedades Renales/epidemiología , Masculino , Metformina/sangre , Persona de Mediana Edad , Terapia de Reemplazo Renal , Factores de Riesgo , Accidente Cerebrovascular/epidemiología
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