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1.
Biometals ; 35(5): 921-933, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35781862

RESUMO

Serum copper (Cu) and zinc (Zn), essential micronutrients that have important immunomodulatory and antimicrobial properties, are biomarkers of ageing. Serum Cu/Zn-ratio may be a more reliable marker for age-related degenerative conditions compared with serum Cu or Zn alone. We aimed to assess the association between Cu/Zn-ratio and the risk of incident pneumonia in a prospective cohort study. Serum levels of Cu and Zn were measured at baseline using atomic absorption spectrometry in 2503 men aged 42-61 years in the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident pneumonia using Cox regression models. A total of 599 cases of pneumonia occurred during a median follow-up of 26.1 years. Serum Cu/Zn-ratio and Cu were each linearly associated with incident pneumonia. A unit increase in Cu/Zn-ratio was associated with an increased risk of pneumonia in analysis adjusted for potential confounders including C-reactive protein (HR 1.65; 95% CI 1.17-2.33). The corresponding adjusted HR (95% CI) was 2.04 (1.22-3.40) for serum Cu. The association between serum Zn and pneumonia was curvilinear. Compared to the bottom tertile of Zn, the multivariable adjusted HRs (95% CIs) for incident pneumonia were 0.68 (0.55-0.83) and 0.96 (0.79-1.16) for the middle and top tertiles of Zn, respectively. Further analysis in the same participants showed that Cu/Zn-ratio might be a stronger risk indicator for pneumonia than serum C-reactive protein. In middle-aged and older Finnish men, increased serum Cu/Zn-ratio and Cu concentrations are each linearly associated with an increased risk of incident pneumonia.


Assuntos
Cobre , Pneumonia , Zinco , Adulto , Biomarcadores , Proteína C-Reativa , Cobre/sangue , Finlândia , Humanos , Masculino , Micronutrientes , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Estudos Prospectivos , Zinco/sangue
2.
Front Public Health ; 10: 924103, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832281

RESUMO

Background: Preeclampsia (PE) is a common multi-system disorder in pregnancy and a major cause of maternal and perinatal morbidity and mortality globally. Copper is a crucial micronutrient for human health. Methods: A systematic review was performed according to Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) guidelines to synthesize the best available evidence regarding the correlation between maternal copper levels and PE from women with different geographical and economic backgrounds. Results: A total of 34 studies containing 2,471 women with PE and 2,888 healthy pregnant controls across 16 countries were included for research. All studies were systematically reviewed and assessed with the Newcastle-Ottawa Scale (NOS), The Agency of Healthcare for Research and Quality (AHRQ) assessment tools according to the study types. Globally, there was no significant difference in maternal serum copper levels between women with PE and control (Mean difference 5.46, 95% CI -9.63, 20.54). Sub-group analysis from geographical and economic perspectives revealed contrasting results. In conclusion, copper is associated with PE, but the levels of copper leading to increased risk of PE varied across regions and economic development. Conclusions: The deranged maternal copper levels are correlated with risks of PE, but it presents variously across different geographical and economic contexts. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=306536. Identifier: CRD42022306536.


Assuntos
Cobre/sangue , Pré-Eclâmpsia/sangue , Gravidez/sangue , Feminino , Humanos , Pré-Eclâmpsia/etiologia
3.
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
4.
Nutrients ; 14(2)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35057415

RESUMO

Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness. Methods: We employed a two-sample Mendelian Randomization (MR) analysis. Our genetic variants derived from European-ancestry GWAS reflected circulating levels of Zn, Cu, Se in red blood cells as well as Se and vitamin K1 in serum/plasma. For the COVID-19 outcome GWAS, we used infection, hospitalization or critical illness. Our inverse-variance weighted (IVW) MR analysis was complemented by sensitivity analyses including a more liberal selection of variants at a genome-wide sub-significant threshold, MR-Egger and weighted median/mode tests. Results: Circulating micronutrient levels show limited evidence of association with COVID-19 infection, with the odds ratio [OR] ranging from 0.97 (95% CI: 0.87-1.08, p-value = 0.55) for zinc to 1.07 (95% CI: 1.00-1.14, p-value = 0.06)-i.e., no beneficial effect for copper was observed per 1 SD increase in exposure. Similarly minimal evidence was obtained for the hospitalization and critical illness outcomes with OR from 0.98 (95% CI: 0.87-1.09, p-value = 0.66) for vitamin K1 to 1.07 (95% CI: 0.88-1.29, p-value = 0.49) for copper, and from 0.93 (95% CI: 0.72-1.19, p-value = 0.55) for vitamin K1 to 1.21 (95% CI: 0.79-1.86, p-value = 0.39) for zinc, respectively. Conclusions: This study does not provide evidence that supplementation with zinc, selenium, copper or vitamin K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.


Assuntos
COVID-19/genética , Cobre/sangue , Selênio/sangue , Vitamina K 1/sangue , Zinco/sangue , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Razão de Chances , Gravidez , SARS-CoV-2 , Adulto Jovem
5.
Biometals ; 35(1): 125-145, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34993712

RESUMO

The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%-36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients' low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.


Assuntos
COVID-19/sangue , Cobre/sangue , SARS-CoV-2/patogenicidade , Selênio/sangue , Zinco/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Proteína C-Reativa/metabolismo , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Contagem de Células , Colecalciferol/sangue , Humanos , Linfócitos/imunologia , Linfócitos/virologia , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/virologia , Neutrófilos/imunologia , Neutrófilos/virologia , Análise de Regressão , SARS-CoV-2/crescimento & desenvolvimento , Índice de Gravidade de Doença , Superóxido Dismutase/sangue , Vitamina A/sangue , Vitamina E/sangue
6.
Am J Epidemiol ; 191(1): 85-92, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34132328

RESUMO

Irritable bowel syndrome (IBS) has been associated with copper and zinc imbalance and a zinc-deficient diet. Mendelian randomization was used in this study to evaluate if genetically determined copper and zinc levels play a causal role in the development of IBS. Three single-nucleotide polymorphisms (SNPs; rs1175550, rs2769264, and rs2769270) associated with erythrocyte copper levels, and 3 SNPs associated with erythrocyte zinc levels (rs11638477, rs1532423, and rs2120019) in the Australian Twin Study (1993-1996 and 2001-2005) were used as instrumental variables for levels of these metals. The association of these SNPs with IBS was tested using summary statistics computed from data on 340,331 individuals from the UK Biobank, 5,548 of whom had IBS (2006-2010). Genetically predicted high serum copper levels were associated with a lower risk of IBS (odds ratio = 0.89; 95% confidence interval: 0.80, 0.98). Genetically predicted, high serum zinc levels were nonsignificantly associated with a higher risk of IBS (odds ratio = 1.06; 95% confidence interval: 0.95, 1.18). Sensitivity analysis did not suggest the presence of pleiotropy. These results suggest that high erythrocyte copper levels may be protective against IBS development. Targeting higher levels, therefore, may provide an avenue to reduce the likelihood of IBS development in high-risk individuals.


Assuntos
Cobre/sangue , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/genética , Zinco/sangue , Austrália , Humanos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
7.
Biol Trace Elem Res ; 200(5): 2040-2052, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34263421

RESUMO

The aim of this study is to investigate the relationship between IL-18 (- 607 C/A), IL-18 (- 137 G/C), and MMP-2 (- 1306 C/T) gene variations and serum trace element levels in patients diagnosed with CRF. Genotype distributions of IL-18 (- 607 C/A, - 137 G/C) gene variations were determined by polymerase chain reaction (PCR) method. PCR-restriction fragment length polymorphism (RFLP) methods were used to determine the MMP-2 (- 1306 C/T) gene variation genotype distributions. Serum trace element levels were determined by atomic absorption spectrophotometer method. A significant difference was found between the CRF patient and healthy control groups in terms of genotype distributions of IL-18 (- 607 C/A) and MMP-2 (- 1306 C/T) gene variations (p < 0.05). The significant difference was found between the patient and control groups in terms of serum copper and zinc levels and copper/zinc ratio (p < 0.05). The significant difference was detected between patient and control groups in terms of copper and zinc levels and copper/zinc ratio according to IL-18 (- 607 C/A), IL-18 (- 137 G/C), and MMP-2 (- 1306 C/T) gene variations and genotype distributions (p < 0.05). In addition, significant difference was determined in terms of serum copper and zinc levels and copper/zinc ratio according to haplotypes of IL-18 (- 607 C/A), IL-18 (- 137 G/C), and MMP-2 (- 1306 C/T) gene variations between patient and control groups (p < 0.05). In conclusion, evaluation of IL-18 (- 607 C/A, - 137 G/C) and MMP-2 (- 1306 C/T) gene variations and serum trace element levels together is extremely important in terms of obtaining important biomarkers in CRF early diagnosis and progression.


Assuntos
Interleucina-18 , Falência Renal Crônica , Metaloproteinase 2 da Matriz , Oligoelementos , Estudos de Casos e Controles , Cobre/sangue , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-18/genética , Falência Renal Crônica/sangue , Falência Renal Crônica/genética , Masculino , Metaloproteinase 2 da Matriz/genética , Oligoelementos/sangue , Zinco/sangue
8.
Anal Biochem ; 639: 114525, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34929153

RESUMO

A Fluorescence probe was designed based on 8-hydroxyquinoline chitosan silica precursor (HQCS) for selective detection of Al3+, Cu2+. The HQCS has no observable fluorescence signal, but after the addition of Al3+, a huge fluorescence signal appeared, and the selective quenching was absorbed after the addition of Cu2+. The effect of other different cations, including Cu2+, Mg2+, Ca2+, Pb2+, Zn2+, Hg2+, Ag+, Fe3+, and K+ was studied. The addition of Cu2+ to the probe (HQCSAL) decreased the fluorescence very repeatable, and the variation of the fluorescence vs. Cu2+ was monotonic and linear. Therefore, the prepared probe was used to determine Cu2+ ions in real samples. The mechanism of fluorescence variation by adding cations to the probe solution was studied using the Stern-Volmer equation. Under the optimum conditions, the linear range and detection limit were 3.5-31 µM and 1 µM, respectively. The probe accuracy on the copper determination in the blood and tap waters was comparable to the ICP-OES results. The circuit logic gate mimic was designed for the fluorescence behavior of the probe constituents.


Assuntos
Cobre/sangue , Corantes Fluorescentes/química , Cátions Bivalentes/análise , Cátions Bivalentes/sangue , Quitosana/análogos & derivados , Cobre/análise , Humanos , Oxiquinolina/química , Espectrometria de Fluorescência/métodos , Água/análise
9.
Rejuvenation Res ; 25(1): 16-24, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34913745

RESUMO

Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases A2 (PLA2) are hydrolases with several functions in the brain, nevertheless their deregulation contributes to neurodegeneration. We evaluated platelet total PLA2 activity (ptotPLA2) in healthy elderly subjects (HE, n = 102), patients suffering from mild cognitive impairment (MCI, n = 90) and AD (n = 91). Platelets are considered "circulating neurons" and ptotPLA2 appears to mirror the cerebral activity. ptotPLA2 of the three cohorts was similar, but in MCI the higher ptotPLA2 the worse the global cognitive status (Mini Mental State Examination score [MMSE]) and in AD the lower ptotPLA2 the more severe the pathology stage (Clinical Dementia Rating [CDR]). Accordingly, MCI with MMSE ≥26 overlapped HE, in MCI with MMSE <26 and in AD with CDR 1 ptotPLA2 increased, in AD with CDR 2 ptotPLA2 decreased. In MCI ptotPLA2 positively correlated with blood oxidation and inflammation, in AD it was the opposite. Finally, Discrimination Index (DI)-calculated multiplying ptotPLA2, oxidative level and Cu/Zn ratio (an inflammation parameter)-differentiated MCI patients who progressed to dementia in the following 24 months and AD patients with the worse pathology development. Summarizing, ptotPLA2 changes during MCI and AD progression, is linked, in opposite way, to oxidative/inflammatory status in MCI and AD and might help, when included in DI, to identify MCI converters to dementia and AD patients with the more severe prognosis. ptotPLA2 may have a diagnostic/prognostic value and be a potential therapeutic target.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Fosfolipases A2/metabolismo , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Biomarcadores , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Cobre/sangue , Progressão da Doença , Humanos , Estresse Oxidativo , Zinco/sangue
10.
Inorg Chem ; 60(23): 18048-18057, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34781677

RESUMO

Gly-His-Lys (GHK) is a tripeptide present in the human bloodstream that exhibits a number of biological functions. Its activity is attributed to the copper-complexed form, Cu(II)GHK. Little is known, however, about the molecular aspects of the mechanism of its action. Here, we examined the reaction of Cu(II)GHK with reduced glutathione (GSH), which is the strongest reductant naturally occurring in human plasma. Spectroscopic techniques (UV-vis, CD, EPR, and NMR) and cyclic voltammetry helped unravel the reaction mechanism. The impact of temperature, GSH concentration, oxygen access, and the presence of ternary ligands on the reaction were explored. The transient GSH-Cu(II)GHK complex was found to be an important reaction intermediate. The kinetic and redox properties of this complex, including tuning of the reduction rate by ternary ligands, suggest that it may provide a missing link in copper trafficking as a precursor of Cu(I) ions, for example, for their acquisition by the CTR1 cellular copper transporter.


Assuntos
Complexos de Coordenação/metabolismo , Cobre/metabolismo , Glutationa/metabolismo , Oligopeptídeos/metabolismo , Compostos de Sulfidrila/metabolismo , Complexos de Coordenação/sangue , Complexos de Coordenação/química , Cobre/sangue , Cobre/química , Glutationa/sangue , Glutationa/química , Humanos , Estrutura Molecular , Oligopeptídeos/sangue , Oligopeptídeos/química , Oxirredução , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/química
11.
Nutrients ; 13(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34836302

RESUMO

Trace elements play an important role in metabolism. We compared the daily intake and serum concentrations of copper (Cu), selenium (Se), and zinc (Zn) across a spectrum of glucose tolerance status in a representative U.S. population. Daily intake and serum concentrations of Cu, Zn and Se in 5087 adults from the 2011-2016 National Health and Nutrition Examination Survey (NHANES) were examined and compared to normal (NGT) and abnormal (AGT) glucose tolerance and the presence of diabetes mellitus (DM). Other than Zn deficiency (21.15%), the prevalence of Zn, Se, and Cu excess and Se and Cu deficiency were low (<4.00%). As compared to the NGT group, Cu and Se supplementation was higher in the AGT and DM groups (p < 0.0001 for all). Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake (p < 0.0001 for both). As compared to the NGT group, serum Cu concentration was highest in the AGT group (p = 0.03), serum Se concentration was highest in the DM group (p < 0.0001), and serum Zn concentration was highest in the AGT group (p < 0.0001). Serum Se and Zn concentration was correlated with daily Se and Zn intake. Even within the reference range for serum Cu, Se, and Zn concentrations, a higher serum concentration of Cu, Se, and Zn was associated with abnormal glucose metabolism. Although the casual relationship remains to be elucidated, these data suggest caution in Cu, Se and Zn supplementation in non-deficient individuals.


Assuntos
Cobre/sangue , Ingestão de Alimentos , Glucose/metabolismo , Selênio/sangue , Adulto , Estudos Transversais , Diabetes Mellitus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estado Nutricional , Oligoelementos/sangue , Zinco/sangue
12.
Nutrients ; 13(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684579

RESUMO

Copper is an essential micronutrient for humans. A cross-sectional and comparative study was done to assess serum Cu levels and serum copper/zinc (Cu/Zn) ratio and its association with nutritional indicators in a series of children and adolescents with chronic diseases. Anthropometric, biochemical, dietary, body composition, and bone densitometry assessments were carried out. Serum Cu and Zn were measured by atomic absorption spectrophotometry. Seventy-eight patients (55% women) participated. The mean serum Cu in the entire series and by nutritional status through body mass index (BMI) was normal. Serum Cu decreased significantly with age and was meaningfully higher in children than in adolescents. The risk of finding altered Cu levels in children and men was higher than in adolescents and women, respectively. Twenty-two per cent of patients had abnormal serum copper levels, 13 had hypercupremia, and four had hypocupremia. The Cu/Zn ratio was greater than 1.00 for 87% of the patients, which is an indicator of an inflammatory state. All patients with hypozincemia and hypocupremia had deficient Zn intake, but only 65% of the patients with hypercupremia had dietary Zn deficiency. Consequently, the Cu/Zn ratio could indicate an inflammatory state and a high risk of zinc deficiency in this specific child population.


Assuntos
Doença Crônica , Cobre/sangue , Zinco/sangue , Sedimentação Sanguínea , Índice de Massa Corporal , Condução Óssea , Proteína C-Reativa/metabolismo , Criança , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Masculino , Estado Nutricional , Análise de Regressão
13.
Nutrients ; 13(8)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34444662

RESUMO

The serum copper (Cu) to zinc (Zn) ratio could be an important determinant of Type 2 diabetes (T2D) risk, but prospective epidemiological data are scarce. We aimed to investigate the association between T2D incidence and the dietary Cu/Zn ratio. A total of 70,991 women from the E3N cohort study were followed for 20 years. The intakes of copper and zinc were estimated at baseline using a validated food frequency questionnaire. We identified and validated 3292 incident T2D cases. Spline analysis showed that a Cu/Zn ratio < 0.55 was associated with a lower risk of T2D. Subgroup analyses comparing women in the highest versus the lowest quintile of Cu/Zn ratio showed the same pattern of association for obese women and those with zinc intake ≥8 mg/day. However, for women with zinc intake <8 mg/day, higher Cu/Zn ratio appeared to be associated with higher T2D risk. Our findings suggest that a lower dietary Cu/Zn ratio is associated with a lower T2D risk, especially among obese women and women with zinc intake >8 mg/day. Further studies are warranted to validate our results.


Assuntos
Cobre/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Obesidade/epidemiologia , Zinco/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , França/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo
14.
Nutrients ; 13(8)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34444889

RESUMO

Cardiometabolic risk (CMR) factors increase the likelihood of developing cardiovascular diseases (CVD). In Qatar, 24% of the total deaths are attributed to CVDs. Several nutritional disturbances have been linked to high risk of CVD. Many studies have discussed the effects of zinc (Zn) and copper (Cu) on CMR factors; however, evidence has been controversial. This investigated the association between CMR factors and the status of Zn and Cu, in addition to Zn/Cu ratio. A total of 575 Qatari men and women aged 18 years and older were obtained from Qatar Biobank. Plasma levels of Zn and Cu were determined using inductively coupled plasma mass spectrometry (ICP-MS). Anthropometric data and CMR factors were determined using standard methods. Adjusted associations between trace minerals and CMR were estimated by logistic regression. Partial correlation was performed to test the strength of the associations. Zn was not strongly correlated (p-value ˃ 0.01) or significantly associated with CMR factors and metabolic syndrome (MetS). Cu levels correlated positively with body mass index (BMI) (0.23; p ˂ 0.001), pulse rate (PR) (0.18; p ˂ 0.001), total cholesterol (0.13; p = 0.01), and high-density lipoproteins (HDL) (0.27; p ˂ 0.001); and negatively with diastolic blood pressure (DBP) (-0.13; p = 0.01). High plasma Cu significantly decreased the risk of metabolic syndrome (MetS) (0.121; p ˂ 0.001). Furthermore, Zn/Cu ratio positively correlated with waist circumference (0.13; p = 0.01), systolic blood pressure (0.13; p ˂ 0.01), and DBP (0.14; p ˂ 0.01); and negatively with BMI (-0.19; p ˂ 0.001), PR (-0.17; p ˂ 0.001), and HDL (-0.27; p ˂ 0.001). High Zn/Cu ratio increased the prevalence of low HDL (4.508; p ˂ 0.001) and MetS (5.570; p ˂ 0.01). These findings suggest that high plasma Cu levels are associated with a protective effect on DBP, HDL and MetS and that high plasma Zn/Cu ratio is associated with the risk of having low HDL and MetS.


Assuntos
Doenças Cardiovasculares/epidemiologia , Cobre/sangue , Síndrome Metabólica/epidemiologia , Zinco/sangue , Adolescente , Adulto , Bancos de Espécimes Biológicos , Pressão Sanguínea , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/sangue , Feminino , Humanos , Lipoproteínas HDL/sangue , Modelos Logísticos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Prevalência , Catar/epidemiologia , Adulto Jovem
15.
Mol Neurobiol ; 58(11): 6020-6031, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34435331

RESUMO

This study aims to identify neuropsychiatric manifestations in neurological Wilson disease (NWD), and their correlation with MRI changes and glutamate excitotoxicity. Forty-three consecutive patients with NWD from a tertiary care teaching hospital were evaluated prospectively who fulfilled the inclusion criteria. The neuropsychiatric evaluation was done using Neuropsychiatric Inventory (NPI) battery that assesses 12 domains including delusion, hallucination, agitation/aggression, dysphoria/depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, appetite change, and abnormal nighttime behavior. Cranial MRI was done using a 3 T machine, and locations of signal changes were noted including the total number of MRI lesions. Serum glutamate level was measured by a fluorescence microplate reader. Abnormal NPI in various domains and total NPI scores were correlated with MRI lesions, serum and urinary copper, and glutamate level. The median age of the patients was 16 years. Forty-one (48.8%) patients had cognitive impairment and 37 (86%) had movement disorder. Neurobehavioral abnormality was detected in all-commonest being agitation (90.7%) followed by appetite change (81.4%), elation (74.4%), irritability (69.8%), anxiety (67.4%), depression (65.1%), apathy (44.2%), night time abnormal behavior (32.6%), aberrant motor behavior (20.9%), delusions (16.3%), and hallucination (18.6%). The thalamic lesion was associated with depression, globus pallidus with depression and anxiety, caudate with anxiety and agitation, brainstem with irritability, and frontal cortex with apathy. Serum glutamate level was higher in NWD. NPI sum score correlated with MRI load and glutamate level. Varying severity of neurobehavioral abnormalities are common in the patients with NWD and correlate with the location of MRI lesion and glutamate level.


Assuntos
Sintomas Comportamentais/etiologia , Transtornos Cognitivos/etiologia , Ácido Glutâmico/sangue , Degeneração Hepatolenticular/complicações , Imageamento por Ressonância Magnética , Transtornos dos Movimentos/etiologia , Neuroimagem , Adolescente , Adulto , Sintomas Comportamentais/sangue , Sintomas Comportamentais/diagnóstico por imagem , Mapeamento Encefálico , Transtornos Cognitivos/sangue , Transtornos Cognitivos/diagnóstico por imagem , Cobre/sangue , Cobre/urina , Transtornos da Alimentação e da Ingestão de Alimentos/sangue , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Feminino , Alucinações/diagnóstico por imagem , Alucinações/tratamento farmacológico , Alucinações/etiologia , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/metabolismo , Humanos , Fígado/diagnóstico por imagem , Masculino , Transtornos do Humor/sangue , Transtornos do Humor/diagnóstico por imagem , Transtornos do Humor/etiologia , Transtornos dos Movimentos/sangue , Transtornos dos Movimentos/diagnóstico por imagem , Neurotransmissores/metabolismo , Fumarato de Quetiapina/uso terapêutico , Índice de Gravidade de Doença , Adulto Jovem
16.
Toxicol Ind Health ; 37(9): 528-534, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34388958

RESUMO

Automobile technicians in resource-poor settings often work in poor environments and are exposed to chemicals that put them at risk of ill health and disease. These chemical exposures could affect blood coagulation, leading to bleeding disorders or thrombosis. The present study is aimed at assessing prothrombin test (PT) and activated partial thromboplastin test (aPTT) values, serum zinc (Zn) and copper (Cu) concentrations, and blood lead level (BLL) among occupationally exposed automobile technicians compared to unexposed controls. A total of 140 consenting participants comprising 70 automobile technicians and 70 unexposed controls were recruited for this case-control study. A 6-mL blood sample was drawn from each participant for estimation of BLL, serum Zn and Cu concentrations, and PT and aPTT values. Blood lead level, and serum Zn and Cu concentrations were determined using atomic absorption spectrophotometry, while PT and aPTT values were determined using Innovin PT and Actin FS Activated PTT reagents on the Sysmex CA-101 coagulation analyser. Data were analysed using t-tests, chi-square tests, and logistic and multiple linear regression analyses with statistical significance set at p < 0.05. The mean BLL, serum Zn concentration, and PT and aPTT values were significantly higher in automobile technicians compared to controls. Binary logistic regression showed that automobile technicians had higher odds of elevated PT value (OR = 21.769; p = 0.000), aPTT value (OR = 1.348; p = 0.018), BLL (OR = 1.261; p = 0.000) and serum Zn concentration (OR = 1.063; p = 0.005) than unexposed controls. Linear regression showed significant positive association of PT value with BLL and with serum Zn concentration. Higher PT and aPTT values reflect prolonged blood coagulation time among automobile technicians, which indicates impairment of extrinsic and intrinsic coagulation pathways associated with work-related exposures.


Assuntos
Automóveis , Transtornos da Coagulação Sanguínea/induzido quimicamente , Coagulação Sanguínea/efeitos dos fármacos , Metais Pesados/efeitos adversos , Exposição Ocupacional/efeitos adversos , Adulto , Cobre/efeitos adversos , Cobre/sangue , Humanos , Chumbo/efeitos adversos , Chumbo/sangue , Modelos Logísticos , Masculino , Metais Pesados/sangue , Nigéria , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Zinco/efeitos adversos , Zinco/sangue
17.
Nutrients ; 13(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206577

RESUMO

BACKGROUND: In recent years, trace elements (TEs) have gained considerable attention in the course of treatment and diagnosis of ischemic stroke. The purpose of the conducted research was to determine the trace mineral status (Se, Cu, Zn, Cu/Zn ratio, and Cu/Se ratio) in patients with acute ischemic stroke compared to the population of healthy people in the northeastern region of Poland. MATERIALS AND METHODS: 141 patients with acute ischemic stroke (AIS) and 69 healthy control subjects were examined. The serum concentrations of mineral components were assessed by the atomic absorption spectrometry method. Clinical parameters were updated based on medical records. RESULTS: The serum Se and Zn concentrations were significantly decreased (p < 0.0001; p < 0.0001) in patients with AIS compared with healthy control subjects. However, no significant differences were revealed in terms of the serum Cu concentration (p = 0.283). As expected, we found that the serum Cu/Zn and Cu/Se molar ratios were significantly higher (p = 0.001; p < 0.0001) in patients with AIS compared with healthy control subjects. CONCLUSIONS: Disturbed metal homeostasis is a significant contributor to AIS pathogenesis. Furthermore, marked disruption of the serum Cu/Zn and Cu/Se molar ratios could serve as a valuable indicator of AIS patients' nutritional status and oxidative stress levels.


Assuntos
Cobre/sangue , AVC Isquêmico/sangue , Selênio/sangue , Oligoelementos/sangue , Zinco/sangue , Doença Aguda , Adulto , Idoso , Estudos de Casos e Controles , Deficiências Nutricionais/complicações , Deficiências Nutricionais/epidemiologia , Deficiências Nutricionais/fisiopatologia , Feminino , Humanos , AVC Isquêmico/etiologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estresse Oxidativo , Polônia/epidemiologia , Espectrofotometria Atômica
18.
J Inherit Metab Dis ; 44(5): 1099-1112, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34286869

RESUMO

Wilson disease (WD) is a rare genetic condition that results from a build-up of copper in the body. It requires life-long treatment and is mainly characterized by hepatic and neurological features. Copper accumulation has been reported to be related to the occurrence of heart disease, although little is known regarding this association. We have conducted a systematic review of the literature to document the association between WD and cardiac involvement. Thirty-two articles were retained. We also described three cases of sudden death. Cardiac manifestations in WD include cardiomyopathy (mainly left ventricular (LV) remodeling, hypertrophy, and LV diastolic dysfunction, and less frequently LV systolic dysfunction), increased levels of troponin, and/or brain natriuretic peptide, electrocardiogram (ECG) abnormalities, and rhythm or conduction abnormalities, which can be life-threatening. Dysautonomia has also been reported. The mechanism of cardiac damage in WD has not been elucidated. It may be the result of copper accumulation in the heart, and/or it could be due to a toxic effect of copper, resulting in the release of free oxygen radicals. Patients with signs and/or symptoms of cardiac involvement or who have cardiovascular risk factors should be examined by a cardiologist in addition to being assessed by their interdisciplinary treating team. Furthermore, ECG, cardiac biomarkers, echocardiography, and 24-hours or more of Holter monitoring at the diagnosis and/or during the follow-up of patients with WD need to be evaluated. Cardiac magnetic resonance imaging, although not always available, could also be a useful diagnostic tool, allowing assessment of the risk of ventricular arrhythmias and further guidance of the cardiac workup.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatias/etiologia , Morte Súbita Cardíaca/etiologia , Degeneração Hepatolenticular/complicações , Disautonomias Primárias/etiologia , Adulto , Arritmias Cardíacas/fisiopatologia , Autopsia , Cardiomiopatias/fisiopatologia , Cobre/sangue , Cobre/metabolismo , Ecocardiografia , Eletrocardiografia Ambulatorial , Feminino , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Disautonomias Primárias/fisiopatologia
19.
J Mater Chem B ; 9(29): 5869-5876, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34259308

RESUMO

A highly selective and sensitive photoelectrochemical (PEC) detection method has been developed for the analysis of copper (Cu2+) ions using nanoflower-like ZnO@CdS heterojunctions, of which ZnO was first in situ grown onto the indium tin oxide electrodes by a hydrothermal method and then coated with CdS through the chemical bath deposition route. It was discovered that the ZnO@CdS heterojunction so formed could serve as a photosensitive catalyst with improved charge separation for visible-light-driven PEC responses. Enhanced visible-light harvesting of nanocomposites could also be expected with CdS as the visible-light sensitizer. Furthermore, the introduction of Cu2+ ions could cause a rational decrease in the photocurrents of nanocomposites through the specific interaction between CdS and Cu2+ ions. A ZnO@CdS heterojunction-based PEC sensor was thereby developed for the detection of Cu2+ ions in blood in the linear concentrations ranging from 0.50 to 80 nM, with a limit of detection of 0.18 nM. Such a heterojunction-based PEC detection platform constructed using two photocatalytic materials with matched band structures are promising for a wide range of applications for sensing Cu2+ ions in clinical diagnostics, food monitoring, and environmental analysis.


Assuntos
Compostos de Cádmio/química , Cobre/sangue , Nanocompostos/química , Sulfetos/química , Compostos de Estanho/química , Óxido de Zinco/química , Técnicas Biossensoriais , Técnicas Eletroquímicas , Eletrodos , Humanos , Íons/sangue , Processos Fotoquímicos
20.
Biomolecules ; 11(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209820

RESUMO

Evidence indicates that patients with Alzheimer's dementia (AD) show signs of copper (Cu) dyshomeostasis. This study aimed at evaluating the potential of Cu dysregulation as an AD susceptibility factor. We performed a meta-analysis of 56 studies investigating Cu biomarkers in brain specimens (pooled total of 182 AD and 166 healthy controls, HC) and in serum/plasma (pooled total of 2929 AD and 3547 HC). We also completed a replication study of serum Cu biomarkers in 97 AD patients and 70 HC screened for rs732774 and rs1061472 ATP7B, the gene encoding for the Cu transporter ATPase7B. Our meta-analysis showed decreased Cu in AD brain specimens, increased Cu and nonbound ceruloplasmin (Non-Cp) Cu in serum/plasma samples, and unchanged ceruloplasmin. Serum/plasma Cu excess was associated with a three to fourfold increase in the risk of having AD. Our replication study confirmed meta-analysis results and showed that carriers of the ATP7B AG haplotype were significantly more frequent in the AD group. Overall, our study shows that AD patients fail to maintain a Cu metabolic balance and reveals the presence of a percentage of AD patients carrying ATP7B AG haplotype and presenting Non-Cp Cu excess, which suggest that a subset of AD subjects is prone to Cu imbalance. This AD subtype can be the target of precision medicine-based strategies tackling Cu dysregulation.


Assuntos
Doença de Alzheimer/metabolismo , ATPases Transportadoras de Cobre/genética , Cobre/metabolismo , Adenosina Trifosfatases/genética , Doença de Alzheimer/genética , Biomarcadores/análise , Encéfalo/metabolismo , Proteínas de Transporte de Cátions/genética , Ceruloplasmina/análise , Cobre/sangue , Suscetibilidade a Doenças , Haplótipos/genética , Homeostase , Humanos , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
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