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1.
Dis Markers ; 2020: 8848225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670436

RESUMO

Background: Urolithiasis is the process of stone formation in the urinary tract. Its etiology is only partly known, and efficient therapeutic approaches are currently lacking. Metabolomics is increasingly used in biomarkers discovery for its ability to identify mediators of relevant (patho)physiological processes. Amino acids may be involved in kidney stone formation. The aim of the present study was to investigate the presence of an amino acid signature in stone former urine through a targeted metabolomic approach. Methods: A panel of 35 amino acids and derivatives was assessed in urines from 15 stone former patients and 12 healthy subjects by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to define amino acid profiles of cases and controls. Results and Discussion. Our approach led to the definition of a specific amino acid fingerprint in people with kidney stones. A urinary amino acid profile of stone formers was characterized by lower levels of α-aminobutyric acid, asparagine, ethanolamine, isoleucine, methionine, phenylalanine, serine, tryptophan, and valine. Metabolomic analysis may lend insights into the pathophysiology of urolithiasis and allow tracking this prevalent condition over time.

2.
Geroscience ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32488674

RESUMO

Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy. Two-hundred community-dwellers, 100 with PF&S and 100 non-physically frail, non-sarcopenic (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 serum analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel) analysis. Separate SO-CovSel models were constructed for the whole study population and for the two genders. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet-derived growth factor BB, heat shock protein 72 (Hsp72), myeloperoxidase, and α-aminobutyric acid defined the profile of nonPF&S participants. Gender-specific SO-CovSel models identified a "core" biomarker profile of PF&S, characterized by higher serum levels of aspartic acid and Hsp72 and lower concentrations of macrophage inflammatory protein 1ß, with peculiar signatures in men and women.SO-CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.

3.
Geroscience ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32458283

RESUMO

Dopaminergic nigrostriatal denervation and widespread intracellular α-synuclein accumulation are neuropathologic hallmarks of Parkinson's disease (PD). A constellation of peripheral processes, including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi-marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age-matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables organized in multi-block datasets. The SO-CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)-1ß, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP-1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as biomarkers for PD as well as unveil new targets for interventions.

4.
Exp Gerontol ; 128: 110766, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31666195

RESUMO

BACKGROUND AND AIM: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in old age. Neurotoxicity of dopaminergic neurons triggered by aggregation of misfolded α-synuclein is a major pathogenic trait of PD. However, growing evidence indicates that peripheral processes, including metabolic changes, may precede and contribute to neurodegeneration. The present study was undertaken to identify a metabolic signature of PD through the quantification of serum amino acids and derivatives. PARTICIPANTS AND METHODS: Twenty older adults with PD (11 men and 9 women; mean age 73.1 ±â€¯10.2 years) and 30 age-matched controls (14 men and 16 women; mean age 74.6 ±â€¯4.3 years) were enrolled. A panel of 37 serum amino acids and derivatives was assessed by ultra-performance liquid chromatography/mass spectrometry. Partial least squares - discriminant analysis (PLS-DA) followed by double cross-validation was used to characterize the relationship between amino acid profiles and PD. RESULTS: The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classifications was 99.3 ±â€¯2.5% for participants with PD and 94.7 ±â€¯3.0% for non-PD controls. Higher levels of ß-amino butyric acid, cystine, ornithine, phosphoethanolamine, and proline defined the circulating amino acid profile of older people with PD. Controls were characterized by higher concentrations of 3-methyl-histidine, citrulline, and serine. CONCLUSION: Our findings indicate the existence of a distinct metabotype in older persons with PD. Future studies will have to establish whether changes in amino acid metabolism are involved in the pathogenesis of PD. This knowledge may be harnessed to identify novel disease biomarkers as well as new targets for interventions.

5.
Ann Ist Super Sanita ; 55(3): 205-208, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553311

RESUMO

BACKGROUND: The combination of infrared spectroscopy and morphological analysis significantly improves the urinary stone analysis. In addition to common urinary stones, it is not unusual to encounter spurious or factitious stones that, if not appropriately identified, can lead to errors in the diagnosis. In this study, we show the importance of Infrared Spectroscopy and the morphological analysis, for determining the presence of drugs crystals or atypical components in the calculi. METHODS: 1041 urinary stones were analyzed by morphocostitutional analysis, in addition the rare stones were analyzed by chemical spot test analysis. RESULTS: Among 1041 calculi analyzed, 1018 had a known composition, 23 samples were stones with rare composition or fake urinary stones. CONCLUSIONS: Infrared spectroscopy (FT-IR), allows to identify, theoretically, any substance, including drug-containing calculi or calculi with unusual composition and identify false stones. This is mandatory to treat patients affected by urolithiasis with a personalized clinical approach.


Assuntos
Cálculos Urinários/química , Cálculos Urinários/ultraestrutura , Cristalização , Humanos , Microscopia , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Nutrients ; 10(11)2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30404172

RESUMO

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this initial report, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled as part as the "BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons" (BIOSPHERE) study. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares⁻Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for nonPF&S). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S participants was defined by higher concentrations of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older people with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.


Assuntos
Aminoácidos/sangue , Idoso Fragilizado , Fragilidade/sangue , Sarcopenia/sangue , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Força Muscular
7.
Molecules ; 23(10)2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30347792

RESUMO

Determination of urinary lactulose/mannitol is one of the most used tests to evaluate intestinal barrier function. High-performance liquid chromatography (HPLC) separation with electrospray ionization tandem mass spectrometry guarantees high levels of selectivity and reproducibility. In this paper we report an upgrade of the previous published liquid chromatography tandem mass spectrometry method, introducing more reliable internal standards and ultra-performance liquid chromatography with ethylene bridged hybrid amide columns. The ultra-performance liquid chromatography provided an efficient chromatographic separation of the two sugars in 5 min, compared to 15 min using the previous method. The limit of quantification was 10 µg/mL for mannitol and 2.5 µg/mL for lactulose, and the assay was linear up to 1000 µg/mL for mannitol and 1000 µg/mL for lactulose. The within-run precision and accuracy ranged from 0.7 to 2.9% and 97.2 to 101.2%, respectively. The between-run precision and accuracy ranged from 1.9 to 4.7% and 94.8 to 97.5%, respectively. Recovery was higher than 90.2% for both lactulose and mannitol, and the matrix effect for both lactulose and mannitol was lower than 15%. With this new method we have a real improvement in terms of accuracy and reproducibility, ensuring results in shorter time. The changes to the previous protocol make this method excellent for routine purposes.


Assuntos
Absorção Intestinal/fisiologia , Lactulose/isolamento & purificação , Manitol/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Humanos , Lactulose/urina , Manitol/urina , Permeabilidade , Espectrometria de Massas por Ionização por Electrospray
8.
Antioxidants (Basel) ; 7(7)2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-29996549

RESUMO

Hydrogen sulfide (H2S) is an endogenous gasotransmitter recognized as an essential body product with a dual, biphasic action. It can function as an antioxidant and a cytoprotective, but also as a poison with a high probability of causing brain damage when present at noxious levels. In a previous study, we measured toxic liquoral levels of H2S in sporadic amyotrophic lateral sclerosis (ALS) patients and in the familial ALS (fALS) mouse model, SOD1G93A. In addition, we experimentally demonstrated that H2S is extremely and selectively toxic to motor neurons, and that it is released by glial cells and increases Ca2+ concentration in motor neurons due to a lack of ATP. The presented study further examines the effect of toxic concentrations of H2S on embryonic mouse spinal-cord cultures. We performed a proteomic analysis that revealed a significant H2S-mediated activation of pathways related to oxidative stress and cell death, particularly the Nrf-2-mediated oxidative stress response and peroxiredoxins. Furthermore, we report that Na2S (a stable precursor of H2S) toxicity is, at least in part, reverted by the Bax inhibitor V5 and by necrostatin, a potent necroptosis inhibitor.

9.
Urolithiasis ; 45(3): 291-294, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27639704

RESUMO

Mutations of the CYP24A1 gene, encoding for the enzyme 25(OH)D-24-hydroxylase, can cause hypercalcemia, hypercalciuria, nephrolithiasis and nephrocalcinosis. We report the case of a 22-year-old male patient with recurrent nephrolithiasis, nephrocalcinosis, hypercalcemia with low parathyroid hormone levels, hypercalciuria and low bone mass. Gene sequencing showed that the patient had compound heterozygous mutations including a novel genotype of the CYP24A1 gene. Genetic CYP24A1 testing and biochemical analyses were offered to other family members; the father was heterozygous for the same novel genotype and was also affected with recurrent nephrolithiasis.


Assuntos
Hipercalcemia/genética , Hipercalciúria/genética , Nefrocalcinose/genética , Nefrolitíase/genética , Osteoporose/genética , Vitamina D3 24-Hidroxilase/genética , Adulto , Fosfatos de Cálcio/química , Genótipo , Humanos , Hipercalcemia/sangue , Hipercalcemia/urina , Hipercalciúria/sangue , Hipercalciúria/urina , Rim/metabolismo , Cálculos Renais/química , Masculino , Mutação , Nefrocalcinose/sangue , Nefrocalcinose/diagnóstico por imagem , Nefrocalcinose/urina , Nefrolitíase/sangue , Nefrolitíase/diagnóstico por imagem , Nefrolitíase/urina , Osteoporose/sangue , Osteoporose/urina , Hormônio Paratireóideo/sangue , Linhagem , Recidiva , Eliminação Renal , Análise de Sequência de DNA , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
Clin Biochem ; 49(13-14): 998-1003, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27208555

RESUMO

BACKGROUND: The simultaneous quantification of a steroid hormones panel provides more clinical information than a single steroid assay. Traditionally, steroids have been quantified with immunoassays which are characterized by high rate of positive results. Aim of this work, was to develop a TurboFlow-LC-MS/MS method for the simultaneous quantification of 17-hydroxyprogesterone, androstenedione, cortisol and testosterone in serum. METHODS: To 100µL of serum, 100µL of internal standard solution in methanol were added; after centrifugation the supernatant was injected in the TurboFlow for further purification. Steroids were determined using a TSQ Vantage operating with an atmospheric pressure chemical ionization source. Method was fully validated and results compared with immunoassay methods. RESULTS: Limit of quantification ranged from 0.02ng/mL to 1ng/mL. The precision was lower than 11% and accuracy ranged from 93.5 to 121.6%. The correlation was acceptable for all analytes except for low levels of testosterone. However, the Bland-Altman plots display a positive bias for androstenedione and 17-hydroxyprogesterone, and a negative bias for cortisol and testosterone. CONCLUSIONS: TurboFlow analysis provides a simple and effective clean-up procedure minimizing the interference of the matrix. The presented method is selective, precise, and sensitive being suitable in a clinical laboratory.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Androstenodiona/sangue , Cromatografia Líquida/métodos , Hidrocortisona/sangue , Espectrometria de Massas em Tandem/métodos , Testosterona/sangue , Humanos
12.
Dis Markers ; 2016: 5340386, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28070137

RESUMO

Aim. Lactulose/mannitol ratio is used to assess intestinal barrier function. Aim of this work was to develop a robust and rapid method for the analysis of lactulose and mannitol in urine by liquid chromatography coupled to tandem mass spectrometry. Lactulose/mannitol ratio has been measured in pediatric patients suffering from irritable bowel syndrome. Methods. Calibration curves and raffinose, used as internal standard, were prepared in water : acetonitrile 20 : 80. Fifty µL of urine sample was added to 450 µL of internal standard solution. The chromatographic separation was performed using a Luna NH2 column operating at a flow rate of 200 µL/min and eluted with a linear gradient from 20% to 80% water in acetonitrile. Total run time is 9 minutes. The mass spectrometry operates in electrospray negative mode. Method was fully validated according to European Medicine Agency guidelines. Results and Conclusions. Linearity ranged from 10 to 1000 mg/L for mannitol and 2.5 to 1000 mg/L for lactulose. Imprecision in intra- and interassay was lower than 15% for both analytes. Accuracy was higher than 85%. Lactulose/mannitol ratio in pediatric patients is significantly higher than that measured in controls. The presented method, rapid and sensitive, is suitable in a clinical laboratory.


Assuntos
Síndrome do Intestino Irritável/urina , Lactulose/urina , Manitol/urina , Urinálise/métodos , Adolescente , Estudos de Casos e Controles , Criança , Cromatografia Líquida/métodos , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos
13.
J Alzheimers Dis ; 44(4): 1323-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25672765

RESUMO

Widely confirmed reports were published on association between hyperhomocysteinemia, B vitamin deficiency, oxidative stress, and amyloid-ß in Alzheimer's disease (AD). Homocysteine, cysteine, cysteinylglycine and glutathione are metabolically interrelated thiols that may be potential indicators of health status and disease risk; they all participate in the metabolic pathway of homocysteine. Previous data obtained in one of our laboratories showed that B vitamin deficiency induced exacerbation of AD-like features in TgCRND8 AD mice; these effects were counteracted by S-adenosylmethionine (SAM) supplementation, through the modulation of DNA methylation and antioxidant pathways. Since the cellular response to oxidative stress typically involves alteration in thiols content, a rapid and sensitive HPLC method with fluorescence detection was here used to evaluate the effect of SAM and superoxide-dismutase (SOD) supplementation on thiols level in plasma, in TgCRND8 mice. The quantitative data obtained from HPLC analysis of mice plasma samples showed significant decrease of thiols level when the B vitamin deficient diet was supplemented with SAM + SOD and SOD alone, the latter showing the greatest effect. All these considerations point out the measurement of plasma thiols concentration as a powerful tool of relevance for all clinical purposes involving the evaluation of oxidative stress. The coupling of HPLC with fluorimetric detection, here used, provided a strong method sensitivity allowing thiols determination at very low levels.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/dietoterapia , Hiper-Homocisteinemia/induzido quimicamente , S-Adenosilmetionina/uso terapêutico , Compostos de Sulfidrila/sangue , Superóxido Dismutase/uso terapêutico , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Cromatografia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Glutationa/sangue , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação/genética
14.
Dis Markers ; 2014: 176165, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24868112

RESUMO

BACKGROUND: Kidney stones are a common illness with multifactorial etiopathogenesis. The determination of crystalline and molecular composition and the quantification of all stone components are important to establish the etiology of stones disease but it is often laborious to obtain using the chemical method. The aim of this paper is to compare chemical spot test with FT-IR spectroscopy, for a possible introduction in our laboratory. METHODS: We analyzed 48 calculi using Urinary Calculi Analysis kit in accordance with the manufacturer's instructions. The same samples were analyzed by FT-IR using the Perkin Elmer Spectrum One FT-IR Spectrometer. All FT-IR spectra of kidney stones were then computer matched against a library of spectra to generate a report on the various components. RESULTS: On the basis of FT-IR analysis, the 48 calculi were divided into three groups: pure stone, mixed stone, and pure stone with substances in trace. Results of each group were compared with those obtained with chemical spot test. A general disagreement between methods was observed. CONCLUSIONS: According to our data, the introduction of the FT-IR technique in clinical chemistry laboratory may be more responsive to clinician expectations.


Assuntos
Cálculos Urinários/diagnóstico , Adulto , Idoso , Compostos de Amônio/química , Oxalato de Cálcio/química , Feminino , Humanos , Magnésio/química , Masculino , Pessoa de Meia-Idade , Espectroscopia de Infravermelho com Transformada de Fourier , Cálculos Urinários/química , Adulto Jovem
15.
Mol Genet Metab ; 111(1): 41-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24246682

RESUMO

INTRODUCTION: Costello syndrome (CS) is a multisystemic disorder characterized by postnatal reduced growth, facial dysmorphism, cardiac defects, cognitive impairment, skin and musculo-skeletal anomalies, and predisposition to certain cancers. CS is caused by activating germline mutations in the HRAS proto-oncogene. Similar to what is observed in other RASopathies, CS causative HRAS mutations promote enhanced signal flow through the RAF-MEK-ERK and PI3K-AKT signaling cascades. While decreased bone mineralization has been documented in other RASopathies, such as neurofibromatosis type 1 and Noonan syndrome, systematic studies investigating bone mineral density (BMD) are lacking in CS. MATERIALS AND METHODS: Dual-energy X-ray absorptiometry (DXA) was utilized to assess BMD and body composition (fat and fat-free mass) in a cohort of subjects with molecularly confirmed diagnosis of CS (n = 9) and age-matched control individuals (n = 29). Using general linear regression, subtotal body (total body less head), lumbar, femoral neck and femur BMD parameters were compared considering age, sex, body mass index (BMI) and Tanner stage. Blood and urine biomarkers of bone metabolism were also assessed. RESULTS: All individuals with CS showed significantly lower mean values of subtotal, lumbar and femoral neck BMD compared to the control group (p ≤ 0.01). Similarly, mean total body mass and fat-free mass parameters were lower among the CS patients than in controls (p < 0.01). Low 25-OH vitamin D concentration was documented in all individuals with CS, with values below the reference range in two patients. No significant correlation between vitamin D levels and BMD parameters was observed. DISCUSSION: CS belongs to a family of developmental disorders, the RASopathies, that share skeletal defects as a common feature. The present data provide evidence that, similar to what is recently seen in NF1 and NS, bone homeostasis is impaired in CS. The significant decrease in BMD and low levels of vitamin D documented in the present cohort, along with the risk for pathologic fractures reported in adult individuals with CS, testifies the requirement for a preventive treatment to alleviate evolutive complications resulting from dysregulated bone metabolism.


Assuntos
25-Hidroxivitamina D 2/sangue , Absorciometria de Fóton/métodos , Composição Corporal/fisiologia , Densidade Óssea/fisiologia , Síndrome de Costello/fisiopatologia , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Feminino , Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Adulto Jovem
16.
Cell Biochem Funct ; 32(1): 1-4, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24277487

RESUMO

Two genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) can influence the plasma homocysteine (Hcy) levels, especially in the presence of an inadequate folate status. The aim of this study was to evaluate the frequencies of C677T and of A1298C MTHFR polymorphisms and their correlation with Hcy and serum folate concentrations in a population of blood donors living in a region of middle-southern Italy (the Molise Region). One hundred ninety seven blood donors were studied for total plasma Hcy, serum folate and C677T and A1298C MTHFR genotypes. The frequency of C677T genotypes was 20.8% (CC), 49.8% (CT) and 29.4% (TT); for the A1298C genotypes: 48.7% (AA), 43.7% (AC) and 7.6% (CC). Hcy and serum folate concentrations were significantly different among genotypes of the C677T polymorphism (CC versus CT versus TT: <0.0001 both for Hcy and folate), with Hcy values increasing, and serum folate decreasing, from CC to TT subjects. Regarding to A1298C polymorphism, the difference among genotypes (AA versus AC versus CC; p: 0.026 for Hcy and 0.014 for serum folate), showed an opposite trend for both parameters, with Hcy higher in the wild-type and lower in the homozygotes and serum folate higher in CC than in AA subjects. In conclusion, we found a high frequency of MTHFR allele associated with high level of Hcy and low levels of folate in an Italian southern population.


Assuntos
Ácido Fólico/sangue , Frequência do Gene , Genótipo , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adulto , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade
17.
Dis Markers ; 35(3): 141-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24167359

RESUMO

BACKGROUND: Sulfhydryl groups (SH) are considered a key factor in redox sensitive reaction of plasma, and their modification could be considered an expression of abnormal generation of oxygen free radicals. METHODS: Fifty consecutive patients with acute brain stroke were enclosed in this study. The plasma concentrations of SH groups were correlated to cytokines (IL-1b, IL-6, IL-8, TNF- α ), plasma chitotriosidase (Chit), metalloprotease (MMP2-9), intercellular adhesion molecule-1 (ICAM-1). RESULTS: The results demonstrated a significant reduction of SH groups within 24 hours from the onset of an acute ischemic stroke, a reduction of plasma IL-1b, IL-6, and IL-8, and an increase of Chit and TNF- α in relation to the stroke severity. CONCLUSION: The observation of an intense microenvironment activation that follows the stroke and the correlation between SH levels and markers of immune response suggest that, especially in stroke, is necessary to maintain the redox function to prevent the brain damage. The reduced SH levels represent an attempt to neutralize the abnormal generation of free radicals. Since the reperfusion of brain after ischemic event represents a severe oxidative stress, which must be corrected by regeneration of redox sensitive function, pharmacological intervention could be beneficial in this setting.


Assuntos
Citocinas/sangue , Acidente Vascular Cerebral/sangue , Compostos de Sulfidrila/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Hexosaminidases/sangue , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/imunologia
18.
Nutrients ; 5(5): 1531-43, 2013 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-23698160

RESUMO

BACKGROUND/OBJECTIVES: To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with "moderate" hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. SUBJECTS/METHODS: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 µg from a natural folate-rich diet, 200 µg [6S]5-methyltetrahydrofolate (5-MTHF), 200 µg folic acid or placebo. Participants were stratified according to their MTHFR genotype. RESULTS: Homocysteine (Hcy) levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002), 19.4% (p < 0.001) and 21.9% (p < 0.001), as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid). After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. CONCLUSIONS: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations.


Assuntos
Ácido Fólico/administração & dosagem , Homocisteína/sangue , Hiper-Homocisteinemia/dietoterapia , Hiper-Homocisteinemia/tratamento farmacológico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Complexo Vitamínico B/administração & dosagem , Adulto , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Ácido Fólico/farmacologia , Ácido Fólico/uso terapêutico , Genótipo , Homocisteína/genética , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Índice de Gravidade de Doença , Tetra-Hidrofolatos/genética , Tetra-Hidrofolatos/farmacologia , Tetra-Hidrofolatos/uso terapêutico , Complexo Vitamínico B/farmacologia , Complexo Vitamínico B/uso terapêutico
19.
Biomed Res Int ; 2013: 270426, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23555079

RESUMO

OBJECTIVE: 25-hydroxyvitamin D2/D3 (25-OHD2/D3) determination is a reliable biomarker for vitamin D status. Liquid chromatography-tandem mass spectrometry was recently proposed as a reference method for vitamin D status evaluation. The aim of this work is to compare two commercial kits (Chromsystems and PerkinElmer) for 25-OHD2/D3 determination by our entry level LC-MS/MS. DESIGN AND METHODS: Chromsystems kit adds an online trap column to an HPLC column and provides atmospheric pressure chemical ionization, isotopically labeled internal standard, and 4 calibrator points. PerkinElmer kit uses a solvent extraction and protein precipitation method. This kit can be used with or without derivatization with, respectively, electrospray and atmospheric pressure chemical ionization. For each analyte, there are isotopically labeled internal standards and 7 deuterated calibrator points. RESULTS: Performance characteristics are acceptable for both methods. Mean bias between methods calculated on 70 samples was 1.9 ng/mL. Linear regression analysis gave an R (2) of 0.94. 25-OHD2 is detectable only with PerkinElmer kit in derivatized assay option. CONCLUSION: Both methods are suitable for routine. Chromsystems kit minimizes manual sample preparation, requiring only protein precipitation, but, with our system, 25-OHD2 is not detectable. PerkinElmer kit without derivatization does not guarantee acceptable performance with our LC-MS/MS system, as sample is not purified online. Derivatization provides sufficient sensitivity for 25-OHD2 detection.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Vitamina D/análogos & derivados , Vitamina D/isolamento & purificação , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Kit de Reagentes para Diagnóstico , Vitamina D/sangue
20.
J Matern Fetal Neonatal Med ; 26(13): 1311-5, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23480554

RESUMO

OBJECTIVE: To test the hypothesis that lutein, compared to the placebo, would enhance the total antioxidant status (TAS) in the preterm infants. METHODS: Infants with gestational age (GA) ≤34 weeks were randomly assigned to receive a daily dose of lutein and zeaxanthin (0.5 mg + 0.02 mg/kg/d) or placebo from the 7th day of life until 40th week of postmenstrual age or until discharge. RESULTS: Seventy-seven preterm infants were randomized (38 in the Lutein group and 39 in the Placebo group) with mean GA of 30.4 (±2.3) weeks and the mean birth weight of 1415 (±457) grams. The TAS did not result statistically different between the two groups during all the study period, but a significant linear correlation was evidenced between plasma lutein concentration and TAS (r = 0.14, p = 0.012) and between plasma zeaxanthin concentration and TAS (r = 0.13, p = 0.02). CONCLUSIONS: Supplementation of preterm infants with orally lutein was ineffective in enhancing biological antioxidant capacity. Further studies need to better understand the bioavailability of lutein in the neonatal period in order to identify any best form of supplementation. TRIAL REGISTRATION NUMBER: UMIN000007041.


Assuntos
Antioxidantes/metabolismo , Recém-Nascido Prematuro , Luteína/administração & dosagem , Luteína/farmacologia , Administração Oral , Alimentação Artificial , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Nível de Saúde , Humanos , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Luteína/sangue , Masculino , Placebos , Xantofilas/sangue , Zeaxantinas
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