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1.
J Tradit Chin Med ; 44(5): 1017-1023, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39380233

RESUMO

OBJECTIVE: To investigate the value of relative exchangeable copper (REC) in diagnosing Wilson's disease (WD) and to determine its significance in the differentiation of Traditional Chinese Medicine (TCM) syndrome. METHODS: A total of 78 patients with WD were recruited on the same day of the medical visit, and among them, 32 were suffering from non-WD (N-WD) and 37 were heterozygous ATP7B carriers (HC) enrolled as controls. Molecular genetic testing was performed for diagnosing WD and HC. Additionally, REC levels in different TCM syndromes were investigated. The correlation between REC and serum ceruloplasmin (Cp), serum copper oxidase (CO), and 24-h urinary copper was analyzed using the Global Assessment Scale and Unified Wilson's Disease Rating Scale and the significance of REC in WD diagnosis was investigated. Resting-state functional magnetic resonance imaging was used to assess the clinical symptoms of WD and analyze its severity in different TCM syndromes. RESULTS: REC determination helped in significantly distinguishing patients with N-WD or HC from those with WD with a cut-off of 21.15%. Furthermore, the comparative analysis of REC ratios among different TCM syndromes showed markedly high REC levels in the dampness-heat internal accumulation syndrome group. Additionally, the seed-based functional connectivity value from the putamen to the cerebellum was significantly correlated with TCM syndromes. CONCLUSION: REC level is a high-quality biomarker for diagnosing WD that effectively reflects disease severity and plays an essential role in deciding on treatment strategies and prognosis. Furthermore, REC levels are closely related to TCM syndromes in WD; thus, it is a potential objective quantitative indicator for distinguishing TCM syndromes in WD.


Assuntos
Biomarcadores , Cobre , Degeneração Hepatolenticular , Medicina Tradicional Chinesa , Humanos , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/diagnóstico , Feminino , Masculino , Cobre/sangue , Cobre/urina , Cobre/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Adulto , Adulto Jovem , Adolescente , Diagnóstico Diferencial , Criança , Pessoa de Meia-Idade
2.
Sci Rep ; 14(1): 21972, 2024 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304680

RESUMO

The recent investigation targets to use adapted carbon paste (CP) with copper nanoparticles (CuNs) operating in a phosphate buffer (PBS) medium with a pH range of 5.0-8.0, to synthesize a novel, susceptible, and simple electrochemical sensor for the detection of one of the most important drugs, vitamin B6. Copper (Cu) is one of the most three common essential trace elements found in the bodies of both humans and animals, along with iron and zinc for all crucial physiological and biochemical functions. Its properties, which are assessed using a variety of methods including scanning electron microscopy (SEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS), have also drawn a lot of attention recently. We considered the effects of pH, buffer, scan rate, interference, and calibration curve. The susceptible electrode's linear calibration curve encompassed concentration values between 8.88 and 1000.0 µM. The calculated limits of detection and quantification were 32.12 and 107.0 µM, respectively. Furthermore, this method was established in real human urine samples and drug validation which have been shown satisfactory results for vitamin B6 detection.


Assuntos
Carbono , Cobre , Técnicas Eletroquímicas , Eletrodos , Vitamina B 6 , Carbono/química , Humanos , Técnicas Eletroquímicas/métodos , Vitamina B 6/análise , Vitamina B 6/urina , Cobre/análise , Cobre/urina , Piridoxina/análise , Piridoxina/urina , Nanopartículas Metálicas/química , Concentração de Íons de Hidrogênio , Limite de Detecção , Espectroscopia Dielétrica/métodos
3.
BMC Pediatr ; 24(1): 576, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267050

RESUMO

BACKGROUND: Wilson disease (WD) is an autosomal recessive inherited disease caused by ATP7B variants and characterized by copper metabolism defects. However, children with WD are often asymptomatic, making the clinical diagnosis difficult. Therefore, more accurate methods are required for clinical diagnosis. The objective of this study was to highlight the phenotypic and genetic characteristics of children with WD in northeast China. METHODS: We retrospectively analyzed the clinical data and gene sequencing results of 65 children with WD from January 1, 2014, to December 31, 2022, at the Shengjing Hospital of China Medical University. All data refer to the time of diagnosis before treatment. RESULTS: The median age at diagnosis was 5 years (range 1.2-15 years). In 50 cases (50/65, 76.9%) patients, routine physical examinations revealed only abnormal liver function. However, they had a significantly negative (p < 0.05) Kayser-Fleischer ring (KF). Children with acute liver failure had significantly increased 24 h urinary copper excretion (p < 0.05). We detected 46 genetic variants of ATP7B, including seven novel variants. The most frequent variant was p.R778L with an allele frequency of 38.7%. Phenotype-genotype correlation analysis suggested that p.R778L was significantly associated with lower serum ceruloplasmin levels and higher zinc levels (p < 0.05). The loss-of-function (LOF) variant was associated with significantly lower albumin levels (p < 0.05). CONCLUSION: Most children with WD are asymptomatic, which makes early diagnosis of WD difficult. Therefore, clinical and laboratory characteristics as well as genetic testing are essential. p.R778L is the most frequent variant of ATP7B in China and may play an important role in lowering serum ceruloplasmin levels.


Assuntos
ATPases Transportadoras de Cobre , Degeneração Hepatolenticular , Fenótipo , Humanos , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/diagnóstico , Criança , Masculino , ATPases Transportadoras de Cobre/genética , Feminino , China , Adolescente , Pré-Escolar , Estudos Retrospectivos , Lactente , Cobre/urina , Cobre/sangue , Ceruloplasmina/genética , Ceruloplasmina/análise , Mutação , Estudos de Associação Genética
4.
Ecotoxicol Environ Saf ; 285: 117034, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39270475

RESUMO

BACKGROUND: Vitamin D deficiency is prevalent worldwide and associated with worse outcomes in various lung diseases. This study examines the association between vitamin D deficiency and pulmonary function in healthy young adults. METHODS: This prospective cohort study (2017-2019) explored the impact of vitamin D deficiency on pulmonary function in a community-based young adult population. Pulmonary function was assessed via spirometry, with serum 25-hydroxyvitamin D [25(OH)D] and urinary copper levels quantified. Multivariate regression was used to estimate the relationship between vitamin D levels and lung function, with mediation analysis evaluating copper's role. RESULTS: The study included 1034 participants, average age 33.45 years, 41.93 % male. The median 25(OH)D level was 19.20 ng/mL (Interquartile Range: 13.48-24.90 ng/mL). Over half (54.74 %) had 25(OH)D levels below 20 ng/mL. Higher 25(OH)D levels were associated with better forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). Trends suggested subgroup differences, but these were not statistically significant, indicating a consistent effect of 25(OH)D on pulmonary function across groups. SEM analysis suggested urinary copper as a mediator between 25(OH)D levels and FVC. CONCLUSION: Vitamin D deficiency is significantly associated with reduced pulmonary function in young adults in Taiwan.


Assuntos
Cobre , Pulmão , Deficiência de Vitamina D , Vitamina D , Humanos , Deficiência de Vitamina D/epidemiologia , Masculino , Cobre/sangue , Cobre/urina , Feminino , Adulto , Estudos Prospectivos , Taiwan/epidemiologia , Vitamina D/sangue , Vitamina D/análogos & derivados , Pulmão/fisiopatologia , Pulmão/efeitos dos fármacos , Adulto Jovem , Testes de Função Respiratória , Capacidade Vital , Espirometria , Volume Expiratório Forçado , Estudos de Coortes
5.
J Am Coll Cardiol ; 84(16): 1545-1557, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39297845

RESUMO

BACKGROUND: Exposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression. OBJECTIVES: The authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis). METHODS: We analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (µg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. RESULTS: At baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%, 74%) higher at baseline and 75% (95% CI: 47%, 107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%, 71%), 39% (95% CI: 17%, 64%), and 47% (95% CI: 25%, 74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors. CONCLUSIONS: Exposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doença da Artéria Coronariana/urina , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etnologia , Aterosclerose/urina , Aterosclerose/etnologia , Aterosclerose/epidemiologia , Cádmio/urina , Calcificação Vascular/urina , Calcificação Vascular/epidemiologia , Calcificação Vascular/diagnóstico por imagem , Estudos Longitudinais , Idoso de 80 Anos ou mais , Tungstênio/urina , Tungstênio/efeitos adversos , Cobalto/urina , Cobre/urina , Fatores de Risco , Zinco/urina , Progressão da Doença , Estados Unidos/epidemiologia , Metais/urina , Etnicidade
6.
ACS Sens ; 9(9): 4898-4905, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39236153

RESUMO

Copper ions, implicated in processes such as oxidative stress and inflammation, are believed to play a crucial role in cardiovascular disease, a prevalent and deadly disease. Despite this, current diagnostic methods fail to detect early stage cardiovascular disease or track copper ion accumulation, limiting our understanding of the disease's progression. Therefore, the development of noninvasive techniques to image copper ions in cardiovascular disease is urgently needed to enhance diagnostic precision and therapeutic strategies. In this study, we report the successful synthesis and application of a copper ion-activated photoacoustic probe, CS-Cu, which exhibits high sensitivity and selectivity toward copper ions both in vitro and in vivo. CS-Cu was able to noninvasively monitor the changes in copper ion levels and differentiate between different mice based on copper ions in urine. Furthermore, the probe demonstrated good photoacoustic stability and exhibited no significant toxicity in the mice. These findings suggest that CS-Cu could be a promising tool for early detection and monitoring of Cu2+ levels in vivo and urine, providing a new perspective on the role of copper ions in cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Cobre , Técnicas Fotoacústicas , Cobre/química , Cobre/urina , Animais , Técnicas Fotoacústicas/métodos , Camundongos , Humanos , Íons , Raios Infravermelhos
7.
J Pediatr Gastroenterol Nutr ; 79(4): 807-817, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39113473

RESUMO

BACKGROUND AND OBJECTIVES: Wilson's disease (WD) in children and adolescents is predominantly asymptomatic or oligo-symptomatic. The symptoms are nonspecific and difficult to distinguish from other hepatic or neuropsychiatric disorders. In this study, we present the experience of a pediatric referral center for WD diagnosis and treatment. PATIENTS AND METHODS: We retrospectively analyzed clinical and laboratory data from 99 patients with WD of Sardinian origin, including physical examination, laboratory biochemical testing, liver biopsy, and genetic analysis. RESULTS: Patients were prevalently oligo-symptomatic or asymptomatic. The median age of diagnosis was 8.78 years. Ceruloplasmin values were lower than normal values in all analyzed patients. Twenty-four-hour urinary copper levels were higher than 40 µg/24-h in 92/96 patients. In all analyzed patients with the exception of one, liver copper was higher than 250 µg/g of dry weight but all had >75 µg/g of dry weight. Statistical analysis showed correlation between the age at diagnosis, serum copper, and 24-h urinary copper. Correlation was also found between serum copper and 24-h urinary copper. Molecular analysis of ATP7B gene allowed complete characterization in all the analyzed patients. CONCLUSION: A high index of clinical suspicion and biochemical tests including liver tests, serum ceruloplasmin, and basal 24-h urinary copper excretion and genotype determination are key to WD diagnosis. The long experience that a referral center for WD possesses is an important factor in making WD diagnosis a more accurate process. Studies in animal models on WD could be used as a guide to further investigate the molecular mechanisms that regulate copper metabolism and influence the natural history of WD.


Assuntos
Ceruloplasmina , ATPases Transportadoras de Cobre , Cobre , Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/sangue , Criança , Masculino , Feminino , Estudos Retrospectivos , Adolescente , Cobre/urina , Cobre/sangue , Cobre/metabolismo , Ceruloplasmina/metabolismo , Ceruloplasmina/análise , Pré-Escolar , Itália , ATPases Transportadoras de Cobre/genética , Fígado/patologia , Fígado/metabolismo , Encaminhamento e Consulta , Adenosina Trifosfatases/genética , Proteínas de Transporte de Cátions/genética
8.
Circulation ; 150(10): 758-769, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39087344

RESUMO

BACKGROUND: Exposure to metals has been associated with cardiovascular disease (CVD) end points and mortality, yet prospective evidence is limited beyond arsenic, cadmium, and lead. In this study, we assessed the prospective association of urinary metals with incident CVD and all-cause mortality in a racially diverse population of US adults from MESA (the Multi-Ethnic Study of Atherosclerosis). METHODS: We included 6599 participants (mean [SD] age, 62.1 [10.2] years; 53% female) with urinary metals available at baseline (2000 to 2001) and followed through December 2019. We used Cox proportional hazards models to estimate the adjusted hazard ratio and 95% CI of CVD and all-cause mortality by baseline urinary levels of cadmium, tungsten, and uranium (nonessential metals), and cobalt, copper, and zinc (essential metals). The joint association of the 6 metals as a mixture and the corresponding 10-year survival probability was calculated using Cox Elastic-Net. RESULTS: During follow-up, 1162 participants developed CVD, and 1844 participants died. In models adjusted by behavioral and clinical indicators, the hazard ratios (95% CI) for incident CVD and all-cause mortality comparing the highest with the lowest quartile were, respectively: 1.25 (1.03, 1.53) and 1.68 (1.43, 1.96) for cadmium; 1.20 (1.01, 1.42) and 1.16 (1.01, 1.33) for tungsten; 1.32 (1.08, 1.62) and 1.32 (1.12, 1.56) for uranium; 1.24 (1.03, 1.48) and 1.37 (1.19, 1.58) for cobalt; 1.42 (1.18, 1.70) and 1.50 (1.29, 1.74) for copper; and 1.21 (1.01, 1.45) and 1.38 (1.20, 1.59) for zinc. A positive linear dose-response was identified for cadmium and copper with both end points. The adjusted hazard ratios (95% CI) for an interquartile range (IQR) increase in the mixture of these 6 urinary metals and the corresponding 10-year survival probability difference (95% CI) were 1.29 (1.11, 1.56) and -1.1% (-2.0, -0.05) for incident CVD and 1.66 (1.47, 1.91) and -2.0% (-2.6, -1.5) for all-cause mortality. CONCLUSIONS: This epidemiological study in US adults indicates that urinary metal levels are associated with increased CVD risk and mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Metais , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aterosclerose/urina , Aterosclerose/mortalidade , Cádmio/urina , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/urina , Cobalto/urina , Cobre/urina , Etnicidade , Incidência , Metais/urina , Estudos Prospectivos , Fatores de Risco , Tungstênio/urina , Estados Unidos/epidemiologia , Urânio/urina , Zinco/urina
9.
Cardiovasc Toxicol ; 24(10): 1005-1017, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134881

RESUMO

The impact of metal exposure on cardiovascular diseases has become an increasingly concerning topic. To date, few studies have investigated the relationship between the copper-to-zinc ratio and CVD (Cardiovascular disease). This China multi-ethnic cohort study explored the association between the copper-to-zinc ratio and CVD in Chinese adults. The study included a sample size of 9878 people. Logistic regression analysis was used to examine the correlation between urinary copper, urinary zinc, and the copper-to-zinc ratio and CVD prevalence. Restricted cubic spline (RCS) analysis was used to investigate the potential dose-response relationships among copper-to-zinc ratio, urinary copper, urinary zinc, and CVD prevalence. In addition, the least absolute shrinkage and selection operator (LASSO) regression method was used to identify significant risk factors associated with CVD, leading to the development of a nomogram. The predictive performance of the nomogram model for CVD was assessed using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Compared with the copper-to-zinc ratio in Q1, the copper-to-zinc ratio in Q4 was associated with CVD after adjusting for all potential confounders (Model 3) (Q4, odds ratio [OR] 0.608, 95% confidence interval [CI] 0.416-0.889, P = 0.010). After adjusting for all potential confounders (Model 3), urinary copper levels in Q4 were associated with CVD (Q4, odds ratio [OR] 0.627, 95% confidence interval [CI] 0.436-0.902, P = 0.012). No significant difference was found between urinary zinc levels and CVD. The RCS showed a linear dose-response relationship between the copper-to-zinc ratio and CVD (P for overall = 0.01). The nomogram based on the influencing factors examined with LASSO showed good predictive power, and the AUC was 76.3% (95% CI 73.7-78.9%). Our results suggest that there is a significant linear negative correlation between the copper-to-zinc ratio and CVD in Chinese adults and that it has good predictive value for CVD.


Assuntos
Doenças Cardiovasculares , Cobre , Zinco , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/urina , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/urina , China/epidemiologia , Cobre/urina , População do Leste Asiático , Fatores de Risco de Doenças Cardíacas , Nomogramas , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores de Risco , Zinco/urina
10.
Ecotoxicol Environ Saf ; 283: 116764, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39067081

RESUMO

BACKGROUND: Previous studies have indicated a correlation between maternal imbalances in essential trace elements during pregnancy and the occurrence of spontaneous abortion (SA). Nonetheless, the impact of these elements from both partners and during the preconception period remains unexplored. OBJECTIVE: This study sought to evaluate the relationship between preconception essential trace elements and spontaneous abortion (SA) based on husband-wife dyads. METHODS: This study selected 390 couples with spontaneous abortion (SA) and 390 matched couples with live births from a preconception cohort of 33,687 couples. Urine samples collected prior to pregnancy were analyzed for ten essential trace elements (Se, Cr, Mo, Cu, Zn, Fe, Mn, V, Co, and Ni) using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Multivariate conditional logistic regression analysis identified that elevated concentrations of Zn (OR = 0.73) and Ni (OR = 0.69) in couples were associated with a reduced risk of SA, whereas elevated levels of Cr (OR = 1.30) and Mn (OR = 1.39) were linked to an increased risk. Restricted cubic spline models suggested a U-shaped association between couples' Cu and Co concentrations and SA. Bayesian Kernel Machine Regression further supported a U-shaped relationship between the mixture of ten elements and SA, showing significant protection at the 50th and 55th percentiles compared to the 10th percentile. Additionally, the effects of Cr, Zn, Mn, and Ni on SA varied when the concentrations of the other nine elements were held constant at their 25th, 50th, and 75th percentiles. Stratified analysis revealed that maternal Cu (OR = 0.43) and Fe (OR = 0.63) reduced the risk of SA when paternal Cu and Fe were in the lower quartile. Conversely, maternal Cu (OR = 2.03) and Fe (OR = 1.77) increased the risk of SA when paternal concentrations were in the higher quartile. Similar patterns were observed for Cr, Mn, Co, and Zn. CONCLUSION: Elevated urinary concentrations of Zn and Ni in couples were associated with a reduced risk of SA, while higher levels of Cr and Mn were linked to an increased risk. Cu, Co, and a mixture of ten essential trace elements exhibited a U-shaped relationship with SA. The impact of certain essential trace elements (Cu, Fe, Cr, Mn, Co, and Zn) on SA in one partner was influenced by their concentrations in the other partner.


Assuntos
Aborto Espontâneo , Oligoelementos , Humanos , Feminino , Oligoelementos/urina , Oligoelementos/análise , Estudos de Casos e Controles , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/urina , Adulto , Gravidez , Masculino , Zinco/urina , Adulto Jovem , Cobre/urina , Cônjuges/estatística & dados numéricos , Níquel/urina , Poluentes Ambientais/urina
11.
J Trace Elem Med Biol ; 85: 127496, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39032317

RESUMO

BACKGROUND: The essential mineral elements play important roles in proper growth, development and maintenance of physiological homeostasis of an organism. Women are at greater risk of mineral deficiency during pregnancy. However, the predictors of mineral element levels in pregnant women remain unclear. This study was conducted to determine the urinary levels of calcium (Ca), iron (Fe), copper (Cu), manganese (Mn) and selenium (Se) in women during early pregnancy and to explore the predictors of urinary exposure to each mineral element and high co-exposure to mineral element mixture. METHODS: 298 pregnant women in first trimester were recruited when they attended antenatal care in a hospital in Jinan, Shandong Province, China. We collected their spot urine samples and questionnaire data on their sociodemographic characteristics, lifestyle habits, food and dietary supplement intake, and residential environment. The concentrations of Ca, Fe, Cu, Mn and Se in all urine samples were measured. LASSO regression, multiple linear regression and binary logistic regression were used to analyze the predictors affecting mineral element levels. RESULTS: The geometric means of creatinine-corrected Ca, Fe, Cu, Mn and Se concentrations were 99.37 mg/g, 1.75 µg/g, 8.97 µg/g, 0.16 µg/g and 16.83 µg/g creatinine, respectively. Factors that influenced the concentrations of individual mineral element were as follows: (1) Se and Ca concentrations increased with maternal age; (2) women taking tap water as family drinking water had higher Ca levels and those taking polyunsaturated fatty acids intermittently had higher Cu levels; (3) Fe was adversely related to consumption frequency of barbecued foods; (4) Pregnant women with more frequent consumption of shellfish/shrimp/crab and living near green spaces or parks had higher Mn exposure, and those with higher frequency of meat consumption had lower Mn exposure. In addition, maternal age and the frequency of egg consumption were associated with odds of exposure to a mixture of high Ca, Fe, Cu and Se. CONCLUSIONS: The pregnant women in this study had comparable concentrations of urinary Cu and Se but lower concentrations of Ca, Fe and Mn compared with those in other areas. Predictors of urinary mineral elements included maternal age (Se and Ca), type of domestic drinking water (Ca), consumption frequency of barbecued food (Fe), polyunsaturated fatty acid use (Cu), the presence of urban green spaces or parks near the home and frequency of meat and shellfish/shrimp/crab intake (Mn). Moreover, maternal age and egg consumption frequency were significant predictors of high-level co-exposure to urinary Ca, Fe, Cu and Se.


Assuntos
Oligoelementos , Humanos , Feminino , China , Gravidez , Adulto , Oligoelementos/urina , Minerais/urina , Adulto Jovem , Cálcio/urina , Manganês/urina , Cobre/urina , Ferro/urina , Selênio/urina
12.
BMJ Case Rep ; 17(7)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39074939

RESUMO

A female adolescent presented with a 9 month history of progressive involuntary movements, initially manifesting as finger tremors and evolving into flinging motions of the extremities, resulting in an inability to walk over the last 4 months. Concurrently, she developed dysarthria. Neurologically, she exhibited normal power, rigidity and brisk deep tendon reflexes, with a downgoing plantar reflex. Contrast-enhanced MRI revealed hyperintensity in bilateral caudate lobes, basal ganglia and pons, indicative of Wilson's disease. Liver function tests and ultrasound were normal while Kayser-Fleischer rings were confirmed by slit lamp examination. Serum ceruloplasmin was low, 24-hour urine copper was elevated (125.5 mcg) and whole exome sequencing identified a heterozygous ATP7B mutation, confirming the diagnosis. Isolated neurological involvement without hepatic involvement is an extremely rare presentation and needs clinical expertise to delineate Wilson's disease as a possible aetiology.


Assuntos
ATPases Transportadoras de Cobre , Degeneração Hepatolenticular , Imageamento por Ressonância Magnética , Humanos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/complicações , Feminino , Adolescente , ATPases Transportadoras de Cobre/genética , Cobre/urina , Mutação , Ceruloplasmina
13.
Biometals ; 37(3): 721-737, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642266

RESUMO

BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.


Assuntos
Biomarcadores , Exposição Ambiental , Oligoelementos , Humanos , Biomarcadores/urina , Biomarcadores/metabolismo , Criança , Masculino , Feminino , Oligoelementos/análise , Oligoelementos/urina , Exposição Ambiental/efeitos adversos , Estudos Transversais , Adolescente , Lipocalina-2/urina , Taxa de Filtração Glomerular , Cobre/urina , Cobre/análise , Selênio/urina , Selênio/análise , Nefropatias/induzido quimicamente , Nefropatias/urina , Nefropatias/metabolismo , Rim/metabolismo , Pré-Escolar , Níquel/urina
14.
BMC Pediatr ; 24(1): 253, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622515

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) and Wilson's disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is rarely encountered in clinical practice, making it challenging to diagnose. CASE REPORT: We present the case of a 9-year-old girl who initially presented with proteinuria, haematuria, pancytopenia, hypocomplementemia, and positivity for multiple autoantibodies. She was diagnosed with SLE, and her blood biochemistry showed elevated liver enzymes at the time of diagnosis. Despite effective control of her symptoms, her liver enzymes remained elevated during regular follow-up. Laboratory tests revealed decreased serum copper and ceruloplasmin levels, along with elevated urinary copper. Liver biopsy revealed chronic active hepatitis, moderate inflammation, moderate-severe fibrosis, and a trend towards local cirrhosis. Genetic sequencing revealed compound heterozygous mutations in the ATP7B gene, confirming the diagnosis of SLE with WD. The girl received treatment with a high-zinc/low-copper diet, but her liver function did not improve. Upon recommendation following multidisciplinary consultation, she underwent liver transplantation. Unfortunately, she passed away on the fourth day after the surgery. CONCLUSIONS: SLE and WD are diseases that involve multiple systems and organs in the body, and SLE complicated with WD is rarely encountered in the clinic; therefore, it is easy to misdiagnose. Because penicillamine can induce lupus, it is not recommended. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment with WD. However, further research is needed to determine the optimal timing of liver transplantation for patients with SLE complicated with WD.


Assuntos
Degeneração Hepatolenticular , Lúpus Eritematoso Sistêmico , Criança , Feminino , Humanos , Ceruloplasmina/metabolismo , Ceruloplasmina/uso terapêutico , Cobre/urina , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Penicilamina/uso terapêutico
15.
Neurology ; 102(3): e208078, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38175989

RESUMO

A 13-year-old boy of nonconsanguineous parents presented with abnormal body movements, gait difficulty, and slurring of speech for 2 years. On examination, he had rigidity, dystonia, dysarthria, and drooling. Ophthalmologic examination revealed bilateral Kayser-Fleischer rings. He had elevated serum "free" copper levels (41.2 µg/dL [range:10-15]), 24-hour urine copper levels (895.7 µg/d [range:<60]), and reduced serum ceruloplasmin levels (4.3 mg/dL (range:20-40]). MRI revealed "face of giant panda" appearance (Figure A), T2-fluid attenuated inversion recovery hyperintensities (Figure, B and C), and frontal cystic encephalomalacic changes (Figure D), suggestive of Wilson disease (WD). Face of giant panda in WD, first described by Hitoshi et al.,1 is due to high signal intensity in tegmentum with normal signals in red nuclei forming the eyes, normal signals of pars reticulata (lateral portion) of substantia nigra forming the ears, and hypointensity of superior colliculus forming the chin.2 Bilateral cystic changes are less commonly reported in WD.3 Recognizing diverse neuroimaging signatures beyond well-known findings in WD enhances diagnostic accuracy.


Assuntos
Degeneração Hepatolenticular , Adolescente , Humanos , Masculino , Cobre/urina , ATPases Transportadoras de Cobre , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/diagnóstico por imagem , Neuroimagem
16.
Biol Trace Elem Res ; 201(2): 529-538, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35247137

RESUMO

Hispanics/Latinos have higher rates of type 2 diabetes (T2D), and the origins of these disparities are poorly understood. Environmental endocrine-disrupting chemicals (EDCs), including some metals and metalloids, are implicated as diabetes risk factors. Data indicate that Hispanics/Latinos may be disproportionately exposed to EDCs, yet they remain understudied with respect to environmental exposures and diabetes. The objective of this study is to determine how metal exposures contribute to T2D progression by evaluating the associations between 8 urinary metals and measures of glycemic status in 414 normoglycemic or prediabetic adults living in Starr County, Texas, a Hispanic/Latino community with high rates of diabetes and diabetes-associated mortality. We used multivariable linear regression to quantify the differences in homeostatic model assessments for pancreatic ß-cell function, insulin resistance, and insulin sensitivity (HOMA-ß, HOMA-IR, HOMA-S, respectively), plasma insulin, plasma glucose, and hemoglobin A1c (HbA1c) associated with increasing urinary metal concentrations. Quantile-based g-computation was utilized to assess mixture effects. After multivariable adjustment, urinary arsenic and molybdenum were associated with lower HOMA-ß, HOMA-IR, and plasma insulin levels and higher HOMA-S. Additionally, higher urinary copper levels were associated with a reduced HOMA-ß. Lastly, a higher concentration of the 8 metal mixtures was associated with lower HOMA-ß, HOMA-IR, and plasma insulin levels as well as higher HOMA-S. Our data indicate that arsenic, molybdenum, copper, and this metal mixture are associated with alterations in measures of glucose homeostasis among non-diabetics in Starr County. This study is one of the first to comprehensively evaluate associations of urinary metals with glycemic measures in a high-risk Mexican American population.


Assuntos
Arsênio , Cobre , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Molibdênio , Adulto , Humanos , Arsênio/urina , Glicemia , Cobre/urina , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/urina , Insulinas/sangue , Americanos Mexicanos , Molibdênio/urina , Texas
17.
J Diabetes Investig ; 13(8): 1412-1425, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35340117

RESUMO

AIMS/INTRODUCTION: Metals play an important role in diabetes mellitus. This cross-sectional study aimed to evaluate the overall, individual and interactive effects of multi-metal exposure on the prevalence of diabetes mellitus, impaired fasting glucose (IFG) rate and fasting blood glucose (FBG) levels. MATERIALS AND METHODS: The FBG levels of a study population from a cadmium (Cd)-polluted area (n = 250) and an unpolluted area (n = 204), and the metal levels, including magnesium, calcium (Ca), iron (Fe), zinc (Zn), arsenic (As), Cd, copper and lead (Pb) in blood and urine were detected. The study population was divided into a normal fasting glucose group, an IFG group and a diabetes mellitus group on the basis of FBG levels. RESULTS: The IFG rate and diabetes mellitus prevalence were negatively associated with blood Cd and urine Zn levels (IFG rate: odds ratio [OR] 0.780, 95% confidence interval [CI] 0.655-0.928; OR 0.622, 95% CI 0.465-0.831. Diabetes mellitus prevalence: OR 0.506, 95% CI 0.288-0.888; OR 0.609, 95% CI 0.395-0.939), the IFG rate was positively associated with urine Fe levels (OR 1.876, 95% CI 1.290-2.778), and diabetes mellitus prevalence was positively associated with urine Pb and blood Fe levels (OR 1.185, 95% CI 1.022-1.376; OR 1.008, 95% CI 1.001-1.014). A linear negative correlation was observed between FBG levels and blood Cd, and non-linear inverted U-shaped associations were found between FBG levels and Zn, Pb and copper in urine. CONCLUSIONS: This research suggests that multi-metal exposure, especially Cd, Fe, Zn, copper and Pb, is linked to diabetes mellitus, and the interactive effects of multiple metals require further exploration.


Assuntos
Diabetes Mellitus , Estado Pré-Diabético , Glicemia , Cádmio/urina , China/epidemiologia , Cobre/urina , Estudos Transversais , Diabetes Mellitus/epidemiologia , Jejum , Humanos , Chumbo , Zinco
18.
Open Heart ; 9(1)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35169044

RESUMO

BACKGROUND: Disturbances of copper (Cu) homeostasis can lead to hypertrophic cardiac phenotypes (eg, Wilson's disease). We previously identified abnormal Cu homeostasis in patients with hypertrophic cardiomyopathy (HCM) and, therefore, hypothesised that Cu2+-selective chelation with trientine dihydrochloride may slow or reverse disease progression in HCM. The aim of this study was, therefore to explore the clinical efficacy, safety and tolerability of trientine in HCM. METHODS: In this medicines and healthcare products regulatory agency (MHRA) registered open-label pilot study, we treated 20 HCM patients with trientine for 6 months. Patients underwent a comprehensive assessment schedule including separate cardiac magnetic resonance imaging (CMR) and CMR 31P-spectroscopy at baseline and end of therapy. Predefined end points included changes in left ventricular mass (LVM), markers of LV fibrosis, markers of LV performance and myocardial energetics. Ten matched patients with HCM were studied as controls. RESULTS: Trientine treatment was safe and tolerated. Trientine caused a substantial increase in urinary copper excretion (0.42±0.2 vs 2.02±1.0, p=0.001) without affecting serum copper concentrations. Treatment was associated with significant improvements in total atrial strain and global longitudinal LV strain using both Echo and CMR. LVM decreased significantly in the treatment arm compared with the control group (-4.2 g v 1.8 g, p=0.03). A strong trend towards an absolute decrease in LVM was observed in the treatment group (p=0.06). These changes were associated with a significant change in total myocardial volume driven by a significant reduction in extracellular matrix (ECM) volume (43.83±18.42 mL vs 41.49±16.89 mL, p=0.04) as opposed to pure cellular mass reduction and occurred against a background of significant ECM volume increase in the control group (44.59±16.50 mL vs 47.48±19.30 mL, p=0.02). A non-significant 10% increase in myocardial phosphocreatine/adenosine triphosphate (PCr/ATP) ratio with trientine therapy (1.27±0.44 vs 1.4±0.39) was noted. CONCLUSIONS: Cu2+-selective chelation with trientine in a controlled environment is safe and a potential future therapeutic target. A phase 2b trial is now underway.


Assuntos
Cardiomiopatia Hipertrófica , Cobre , Trientina , Disponibilidade Biológica , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/etiologia , Cardiomiopatia Hipertrófica/fisiopatologia , Quelantes/administração & dosagem , Quelantes/farmacocinética , Cobre/metabolismo , Cobre/urina , Monitoramento de Medicamentos/métodos , Matriz Extracelular/patologia , Feminino , Fibrose , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Projetos Piloto , Resultado do Tratamento , Trientina/administração & dosagem , Trientina/farmacocinética
19.
Anal Bioanal Chem ; 414(4): 1651-1662, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34988586

RESUMO

A sensing platform with both ratiometric fluorescence and colorimetric responses towards copper(II) ions (Cu2+) and D-penicillamine (D-pen) was constructed based on carbon dots (CDs). o-Phenylenediamine (OPD) was employed as a chromogenic development reagent for reaction with Cu2+ to generate the oxidation product 2,3-diaminophenazine (oxOPD), which not only emits green fluorescence at 555 nm, but also quenches the blue fluorescence of CDs at 443 nm via the inner filter effect (IFE) and Förster resonance energy transfer (FRET). Additionally, oxOPD exhibits obvious absorption at 420 nm. Since the intense chelation affinity of D-pen to Cu2+ greatly inhibits the oxidation of OPD, the intensity ratio of fluorescence at 443 nm to that at 555 nm (F443/F555) and the absorbance at 420 nm (A420) were conveniently employed as spectral response signals to represent the amount of D-pen introduced into the testing system. This dual-signal sensing platform exhibits excellent selectivity and sensitivity towards both Cu2+ and D-pen, with low detection limits of 0.019 µM and 0.092 µM, respectively. In addition, the low cytotoxicity of the testing reagents involved in the proposed sensing platform facilitates its application for live cell imaging.


Assuntos
Colorimetria/métodos , Cobre/análise , Penicilamina/análise , Espectrometria de Fluorescência/métodos , Células A549 , Carbono , Colorimetria/instrumentação , Cobre/sangue , Cobre/urina , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Humanos , Microscopia Eletrônica de Transmissão , Oxirredução , Penicilamina/urina , Fenilenodiaminas/química , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Espectrometria de Fluorescência/instrumentação , Espectrofotometria Ultravioleta
20.
J Clin Lab Anal ; 36(2): e24191, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34951059

RESUMO

BACKGROUND: Wilson's disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000 live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24-hour urinary copper, and ceruloplasmin using the Leipzig criteria. METHODS: Adhering to PRISMA guidelines, databases including PubMed/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along with normal populations were included with adult and pediatric group. The sensitivity, specificity, negative predictive value and positive predictive value were computed using RevMan 5.4. RESULTS: Nine studies were included. The best practice evidence for 24-hour urinary copper test ranged from a cutoff value of 0.64-1.6 µmol/24 h (N = 268; sensitivity = 75.6%, specificity = 98.3%). Hepatic copper test was optimally cutoff based on the ROC curve analysis at 1.2 µmol/g yielding a power of 96.4% sensitivity and 95.4% specificity (N = 1,150); however, the tried and tested 4 µmol/g cutoff, with 99.4% sensitivity and 96.1% specificity, is more widely accepted. The ceruloplasmin test cutoff value was found to be ranging from 0.14 to 0.2 g/L (N = 4,281; sensitivity = 77.1%-99%, specificity = 55.9%-82.8%). CONCLUSION: This paper provides a large-scale analysis of current evidence pertaining to the biochemical diagnosis of WD employing the Leipzig criteria. The laboratory values are typically based on specific subgroups based on age, ethnicity, and clinical subgroups. The findings of this systematic review must be used with caution, given the over- or under-estimation of the index tests.


Assuntos
Ceruloplasmina/análise , Cobre/urina , Degeneração Hepatolenticular/diagnóstico , Fígado/química , Cobre/análise , Córnea/patologia , Humanos , Sensibilidade e Especificidade
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