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1.
Leg Med (Tokyo) ; 47: 101782, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32916471

RESUMO

Chlorine gas exposure occurs in chemical warfare, industrial and household accidents. In forensic science, the generation of chlorine gas by mixing sodium hypochlorite detergent and strong acid detergent cannot be overlooked because of the possibility of suicide method (NaClO + 2HCl â†’ NaCl + H2O + Cl2). Though typical autopsy findings are obtained in chlorine exposure, such as pulmonary edema, useful biomarkers don't exist. In this research, we developed an analytical method of 3-chloro-l-tyrosine (Cl-Tyr) in blood as a novel marker of chlorine poisoning utilizing gas chromatography-mass spectrometry (GC-MS). Cl-Tyr was purified using protein precipitation and cation-exchange solid phase extraction, derivatized by the silylation agent and subjected to GC-MS. The quantification range was 10-200 ng/mL and good reproducibility was obtained. We applied the developed method to analyze Cl-Tyr in autopsy sample, which is suspected of chlorine poisoning, and detected 59.7 ng/mL Cl-Tyr in left heart blood. To our knowledge, this is the first report of determination of the chlorinated biomolecule in the human autopsy sample from chlorine poisoning.


Assuntos
Autopsia , Cloro/envenenamento , Ciências Forenses , Envenenamento/diagnóstico , Tirosina/análogos & derivados , Biomarcadores/sangue , Transtorno Depressivo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Edema Pulmonar/etiologia , Suicídio , Tirosina/sangue
2.
Intern Med ; 59(14): 1695-1704, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296001

RESUMO

Objective We aimed to investigate the association between the digit symbol test (DST) and clinical characteristics, including the nutritional status of liver cirrhosis patients. Methods Fifty-nine cirrhotic patients without a history of overt hepatic encephalopathy were retrospectively evaluated. We examined neuropsychological abnormalities (NPAs) using the DST. We also estimated the detailed nutritional status using the Food Frequency Questionnaire (FFQ). The patients were divided into two groups according to their DST status: patients with normal DST scores (DST-Nor group, n=45) and those with abnormal DST scores (DST-Abn group, n=14). The clinical and nutritional findings of the two groups were compared. Results Overall, 14 (23.7%) patients had a DST abnormality. There were significant differences between the two groups in serum albumin (Alb; p=0.0043), valine (Val; p=0.0016), leucine (Leu; p=0.0078), isoleucine (Ile; p=0.0022), the molar ratio of total branched-chain amino acids to tyrosine (BTR; p=0.00025), total-bilirubin (T-Bil; p=0.0071), prothrombin time (%) (PT; p=0.028), and serum sodium (Na; p=0.035). A multivariate analysis found the BTR to be the only independent predictor of a DST abnormality (hazard ratio, 9.24; p<0.031). An FFQ analysis, revealed that the nutritional findings of patients with and without a DST abnormality, were similar. Conclusion The BTR was useful for predicting the risk of NPAs, as defined by a DST abnormality. The risk of NPAs may be estimated by monitoring the BTR.


Assuntos
Aminoácidos de Cadeia Ramificada/sangue , Biomarcadores/sangue , Encefalopatia Hepática/sangue , Encefalopatia Hepática/fisiopatologia , Cirrose Hepática/sangue , Cirrose Hepática/fisiopatologia , Tirosina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Retrospectivos
3.
Nitric Oxide ; 99: 17-24, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32222418

RESUMO

To investigate the association between systemic nitrotyrosine (NT) levels and primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and the mechanism involved. A case control study was conducted in the Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Fudan University from April 2017 to December 2017. A total of 400 participants were consecutively recruited into this study (100 PACG, 100 POAG and 200 controls). Multivariable logistic regression analysis was performed to identify the association between serum NT level and PACG or POAG. Clinical results were validated in cell and animal models. Among 200 glaucoma patients, 101 (50.5%) were women; the age was 57.07 ± 14.51 years. 106 (53%) control participants were women and age was 58.34 ± 14.04 years. Serum levels of NT in PACG and POAG patients are significantly higher than controls (1808.53 ± 417.76 nmol/L vs. 1270.62 ± 454.60 nmol/L, p < 0.001; 1718.63 ± 437.29 nmol/L vs. 1258.38 ± 460.72 nmol/L, p < 0.001). Further, elevated serum NT level increases the risk of developing PACG (OR = 1.003, 95% CI: 1.002 to 1.004, p < 0.001) and POAG (OR = 1.002, 95% CI: 1.002 to 1.003, p < 0.001). Consistent with the clinical data, serum and aqueous humour NT levels are significantly higher in caveolin 1 knockout (Cav1 KO) mice, an animal model of glaucoma. More importantly, peroxynitrite (PN) scavenger MnTMPyP and its transduction molecule PARP inhibitor significantly reduce intraocular pressure in Cav1 KO mice. Our data show for the first time that NT is a systemic risk factor and local treatment target of glaucoma.


Assuntos
Glaucoma de Ângulo Fechado/tratamento farmacológico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Metaloporfirinas/uso terapêutico , Ácido Peroxinitroso/metabolismo , Tirosina/análogos & derivados , Adulto , Idoso , Animais , Estudos de Casos e Controles , Caveolina 1/genética , Feminino , Glaucoma de Ângulo Fechado/sangue , Glaucoma de Ângulo Fechado/metabolismo , Glaucoma de Ângulo Aberto/sangue , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Fatores de Risco , Tirosina/sangue , Tirosina/metabolismo
4.
PLoS One ; 15(3): e0227044, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203565

RESUMO

Under paradigms of combined intravenous cocaine and ethanol self-administration, the effects on behavior have been poorly explored. Numerous studies have found sex differences in amino acids profile and behavioral responses to each drug, yet few have focused on the interactions between cocaine and ethanol. The main objective of this work was to explore the acquisition and maintenance of intravenous self-administration behavior with a combination of cocaine and ethanol in male and female young adult rats. Likewise, the amino acids profile in blood plasma was quantified 48 hours after the last self-administration session. Male and female 52 days old Wistar rats were randomly assigned to one of 3 groups: i) saline control, ii) cocaine (1 mg/kg bodyweight/injection) and iii) cocaine and ethanol (1 mg + 133 mg/kg bodyweight/ injection). After 24 self-administration sessions carried out on a fixed-ratio-1 schedule, with a limit of 15 doses per session, 14 plasma amino acids were quantified by mean Capillary Electrophoresis technique. The curve of cocaine and ethanol combined self-administration was similar to that associated with cocaine administration alone, with females acquiring self-administration criterion before males. The self-administration of cocaine and ethanol altered the plasma concentration and relative ratios of the amino acid L-Tyrosine. In our intravenous self-administration model, females appeared more vulnerable to acquire abusive consumption of the cocaine and ethanol combination, which altered plasma L-Tyrosine levels.


Assuntos
Comportamento Animal/efeitos dos fármacos , Cocaína/efeitos adversos , Etanol/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/etiologia , Animais , Cocaína/administração & dosagem , Modelos Animais de Doenças , Etanol/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Masculino , Ratos , Reforço Psicológico , Autoadministração/efeitos adversos , Autoadministração/psicologia , Fatores Sexuais , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/psicologia , Tirosina/sangue
5.
JAMA Netw Open ; 3(3): e201357, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32202644

RESUMO

Importance: Alkaptonuria is an autosomal recessive disorder caused by pathogenic variants in the HGD gene. Deficiency of the HGD enzyme leads to tissue deposition of homogentisic acid (HGA), causing severe osteoarthropathies and cardiac valve degeneration. Although HGD is vital for the catabolism of tyrosine, which provides the basis for thyroid hormone synthesis, the prevalence of thyroid dysfunction in alkaptonuria is unknown. Objective: To assess thyroid structure and function in patients with alkaptonuria. Design, Setting, and Participants: A single-center cohort study was conducted in a tertiary referral center including patients with alkaptonuria followed up for a median of 93 (interquartile range, 48-150) months between February 1, 2000, and December 31, 2018. The alkaptonuria diagnosis was based on clinical presentation and elevated urine HGA levels. A total of 130 patients were considered for participation. Main Outcomes and Measures: Prevalence of thyroid dysfunction in adults with alkaptonuria compared with the general population. Thyrotropin and free thyroxine levels were measured by immunoassay and repeated in each patient a median of 3 (interquartile range, 2-22) times. Neck ultrasonographic scans were analyzed in a subset of participants. Logistic regression was used to test the association of thyroid dysfunction with age, sex, thyroid peroxidase (TPO) antibodies, serum tyrosine levels, and urine HGA levels. Results: Of the 130 patients, 5 were excluded owing to thyroidectomy as the cause of hypothyroidism. The study cohort consisted of 125 patients; the median age was 45 (interquartile range, 35-51) years. Most of the patients were men (72 [57.6%]). The prevalence of primary hyperthyroidism was 0.8% (1 of 125 patients), similar to 0.5% observed in the general population (difference, 0.003; 95% CI, -0.001 to 0.04; P = .88). The prevalence of primary hypothyroidism was 16.0% (20 of 125 patients), which is significantly higher than 3.7% reported in the general population (difference, 0.12; 95% CI, 0.10-0.24; P < .001). Women were more likely to have primary hypothyroidism than men (odds ratio, 10.99; 95% CI, 3.13-38.66; P < .001). Patients with TPO antibodies had a higher likelihood of primary hypothyroidism than those without TPO antibodies (odds ratio, 7.36; 95% CI, 1.89-28.62; P = .004). There was no significant difference in the prevalence of thyroid nodules between patients in this study (29 of 49 [59.2%]) vs the general population (68%) (difference, 0.088; 95% CI, -0.44 to 0.73; P = .20) or of cancer (7% vs 5%; difference, 0.01; 95% CI, -0.01 to 0.17; P = .86). Conclusions and Relevance: The high prevalence of primary hypothyroidism noted in patients with alkaptonuria in this study suggests that serial screening in this population should be considered and prioritized.


Assuntos
Alcaptonúria/metabolismo , Hipotireoidismo/epidemiologia , Adulto , Alcaptonúria/complicações , Alcaptonúria/genética , Autoanticorpos/sangue , Autoantígenos/imunologia , Estudos de Coortes , Feminino , Ácido Homogentísico/urina , Humanos , Hipertireoidismo/epidemiologia , Hipertireoidismo/genética , Hipotireoidismo/genética , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Testes de Função Tireóidea , Glândula Tireoide/enzimologia , Tireotropina/sangue , Tiroxina/sangue , Tirosina/sangue
6.
Int J Occup Med Environ Health ; 33(2): 173-185, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-31950931

RESUMO

OBJECTIVES: The aim of the study was to evaluate the effects of repeated Finnish sauna baths on the concentrations of nitric oxide metabolites (NOx) and 3-nitrotyrosine in relation to pro-oxidative and antioxidative status in young males with different physical activity levels. MATERIAL AND METHODS: The study was performed on healthy males (aged 20-25 years), representing the training (T, N = 10) and non-training groups (NT, N = 10). The protocol included a series of 10 sauna baths during 3 weeks. One bath consisted of three 15-min sessions, with 2 min recovery. Before the first and the 10th treatment, measurements of body composition, blood pressure, rectal temperature, and plasma concentrations of the total pro-oxidative and antioxidative status, 3-nitrotyrosine and NOx were performed. RESULTS: A significant increase in physiological parameters during sauna treatments, as well as a significant decrease in the total antioxidative status before the 10th bath, were observed in both groups. The series of sauna baths caused a significant increase in the total antioxidative status in the T group, and a decrease in the total oxidative status in the NT group. A significant decrease in 3-nitrotyrosine in both groups before the last treatment, and also in the T group after the last treatment, was noted. In both groups, a significant increase in NOx concentrations was observed after the first bath. CONCLUSIONS: A series of sauna baths contributes to the improvement in the prooxidative/ antioxidative balance. The increased production of nitric oxide may lead to a better vascular relaxation and blood flow. Int J Occup Med Environ Health. 2020;33(2):173-85.


Assuntos
Antioxidantes/metabolismo , Exercício Físico , Óxido Nítrico/sangue , Espécies Reativas de Oxigênio/metabolismo , Banho a Vapor , Tirosina/análogos & derivados , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Temperatura Corporal , Frequência Cardíaca , Humanos , Masculino , Tirosina/sangue , Adulto Jovem
7.
Anticancer Res ; 40(1): 253-259, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892574

RESUMO

BACKGROUND/AIM: The aim of the study was to compare the MDA (malonidialdehyde) plasma concentrations versus CAT (catalase)/NT (nitrotyrosine) plasma concentrations, patient satisfaction and pain score at rest/pressure to the wound area in laparotomy patients with rectus sheath block (RSB) analgesia. PATIENTS AND METHODS: Initially, 56 patients were randomized to four groups; control group (n=12), single-dose (n=16), repeated-dose (n=12) and continuous infusion (n=16) RSB analgesia groups. The plasma concentrations of CAT, NT and MDA markers were measured just before, immediately after and 24 h after operation. RESULTS: The RSB analgesia enhanced significantly patient satisfaction (p=0.001). The plasma MDA decreased immediately after operation (POP1) and the postoperative decrease between the preoperative and the POP1 values in the MDA marker were statistically significant (p<0.001). In linear mixed model, the time effect in both the single group and in the benign group in plasma NT biomarker was statistically significant (p=0.001, p=0.013, respectively). The median plasma MDA concentrations (ng/ml) following surgery were significantly lower in patients with cancer versus patients with benign disease (589 vs. 852, p=0.021). Jitterplots of the individual plasma NT versus plasma MDA showed that there was significant correlation in benign and cancer patients (r=0.347, p<0.001). CONCLUSION: Plasma MDA decreased significantly after operation in all patients and cancer patients had significantly lower MDA concentrations following surgery than patients with benign disease.


Assuntos
Analgesia , Laparotomia , Malondialdeído/sangue , Neoplasias/sangue , Bloqueio Nervoso , Catalase/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tirosina/análogos & derivados , Tirosina/sangue
8.
Biosci Biotechnol Biochem ; 84(2): 372-379, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31608804

RESUMO

Sericin is a protein component of the silkworm cocoon, and contains a high proportion of L-serine, but it has been mostly disposed of as an industrial waste. However, recent studies have revealed its unique biological functionalities beneficial to human health. This study aimed to evaluate the effect of acute oral intake of sericin on amino acid and neurotransmitter metabolism in the mouse brain. Acute administration of chemically modified sericin (0.26 g/30 g body weight) increased L-serine and L-tyrosine levels in the serum and brain, although the L-tyrosine content in the sericin was less than 3% (w/w). In addition, sericin administration led to a significant facilitation of noradrenergic turnover via enhancement of 3-methoxy-4-hydroxyphenylethyleneglycol, a principal metabolite of noradrenaline, in several of the brain regions examined. These present findings suggest that oral intake of sericin efficiently delivers L-serine and L-tyrosine to the brain, thus stimulating noradrenergic activity in the brain.Abbreviations: DA: dopamine; 5-HIAA: 5-hydroxyindoleicetic acid; 5-HT: 5-hydroxytryptamine; HVA: homovanillic acid; MHPG: 3-methoxy-4-hydroxyphenylethyleneglycol; 3-MT: 3-methoxytyramine; NA: noradrenaline; NM: normetanephrine; Veh: vehicle.


Assuntos
Encéfalo/metabolismo , Norepinefrina/metabolismo , Sericinas/administração & dosagem , Serina/metabolismo , Seda/química , Tirosina/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sericinas/farmacologia , Serina/sangue , Tirosina/sangue
9.
Brain Stimul ; 13(1): 105-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31494070

RESUMO

BACKGROUND: Recent evidence suggests that transcranial direct current stimulation (tDCS) may interact with the dopaminergic system to affect cognitive flexibility. Objective/hypotheses: We examined whether putative reduction of dopamine levels through the acute phenylalanine/tyrosine depletion (APTD) procedure and excitatory anodal tDCS of the dorsolateral prefrontal cortex (dlPFC) are causally related to cognitive flexibility as measured by task switching and reversal learning. METHOD: A double-blind, sham-controlled, randomised trial was conducted to test the effects of combining anodal tDCS and depletion of catecholaminergic precursor tyrosine on cognitive flexibility. RESULTS: Anodal tDCS and tyrosine depletion had a significant effect on task switching, but not reversal learning. Whilst perseverative errors were significantly improved by anodal tDCS, the APTD impaired reaction times. Importantly, the combination of APTD and anodal tDCS resulted in cognitive performance which did not statistically differ to that of the control condition. CONCLUSIONS: Our results suggest that the effects of tDCS on cognitive flexibility are modulated by dopaminergic tone.


Assuntos
Cognição , Dopamina/deficiência , Córtex Pré-Frontal/fisiologia , Estimulação Transcraniana por Corrente Contínua , Dopamina/sangue , Feminino , Humanos , Masculino , Tempo de Reação , Reversão de Aprendizagem , Tirosina/sangue , Tirosina/deficiência , Adulto Jovem
10.
Paediatr Drugs ; 21(6): 413-426, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31667718

RESUMO

Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires life-long dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life.


Assuntos
Cicloexanonas/efeitos adversos , Nitrobenzoatos/efeitos adversos , Tirosinemias/tratamento farmacológico , Cicloexanonas/uso terapêutico , Humanos , Nitrobenzoatos/uso terapêutico , Tirosina/sangue , Tirosinemias/complicações , Tirosinemias/dietoterapia
11.
Nutrients ; 11(10)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640267

RESUMO

The standard treatment for phenylketonuria (PKU) is a lifelong low-phenylalanine (Phe) diet, supplemented with Phe-free protein substitutes; however, adult patients often show poor adherence to therapy. Alternative treatment options include the use of large neutral amino acids (LNAA). The aim of this study was to determine the Phe, tyrosine (Tyr), and Phe/Tyr ratio in a cohort of sub-optimally controlled adult patients with classical PKU treated with a new LNAA formulation. Twelve patients received a Phe-restricted diet plus a slow-release LNAA product taken three times per day, at a dose of 1 g/kg body weight (mean 0.8 ± 0.24 g/kg/day), over a 12-month period. The product is in a microgranulated formulation, which incorporates all amino acids and uses sodium alginate as a hydrophilic carrier to prolong its release. This LNAA formulation provides up to 80% of the total protein requirement, with the rest of the protein supplied by natural food. Patients had fortnightly measurements of Phe and Tyr levels over a 12-month period after the introduction of LNAA. All patients completed the 12-month treatment period. Overall, adherence to the new LNAA tablets was very good compared with a previous amino acid mixture, for which taste was a major complaint by patients. Phe levels remained unchanged (p = 0.0522), and Tyr levels increased (p = 0.0195). Consequently, the Phe/Tyr ratio decreased significantly (p < 0.05) in the majority of patients treated. In conclusion, LNAA treatment increases Tyr levels in sub-optimally controlled adult PKU patients, while offering the potential to improve their adherence to treatment.


Assuntos
Aminoácidos Neutros/uso terapêutico , Fenilalanina/sangue , Fenilcetonúrias/sangue , Fenilcetonúrias/tratamento farmacológico , Tirosina/sangue , Adulto , Barreira Hematoencefálica , Dieta , Suplementos Nutricionais , Feminino , Humanos , Itália , Masculino , Cooperação do Paciente , Satisfação do Paciente , Fenilalanina/administração & dosagem , Fenilcetonúrias/dietoterapia , Paladar , Adulto Jovem
12.
Mikrochim Acta ; 186(8): 493, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31267341

RESUMO

Glutathione (GSH) is an important tripeptide that plays an important role in preventing damage to reactive oxygen species. An electrochemical assay was fabricated for this purpose by modification of a carbon paste electrode (CPE) with bis(1,10-phenanthroline)(1,10-phenanthroline-5,6-dione)nickel(II) hexafluorophosphate (BPPDNi) as new electro-catalyst and Pt:Co nanoparticle (Pt:CO-NPs) as highly conductive mediator. The analyses were performed at a scan rate of 10 mV/s and at a pH value of 7.4. The BPPDNi/Pt:CO-NPs/CPE showed a high sensitivity and good selectivity for electro-catalytic determination of glutathione (GSH) in nano-molar concentration range. In addition, the BPPDNi/Pt:CO-NPs/CPE was used for the determination of glutathione in the presence of doxorubicin (DOX) and tyrosine (Tyr) with three separated oxidation signals ~160 mV, ~385 mV and ~790 mV vs. Ag/AgCl/KClsat, respectively. The peak currents of the square wave voltammetric analyses were linearly dependent on glutathione, doxorubicin and tyrosine concentrations in the respective ranges of 0.001-450, 0.5-300 and 1.0-650 µM, with detection limits of 0.5 nM, 0.1 µM and 0.6 µM, respectively. Graphical abstract The first analytical sensor for simultaneous determination of glutathione, doxorubicin and tyrosine.


Assuntos
Antibióticos Antineoplásicos/análise , Doxorrubicina/análise , Glutationa/análise , Tirosina/análise , Antibióticos Antineoplásicos/sangue , Antibióticos Antineoplásicos/química , Catálise , Cobalto/química , Doxorrubicina/sangue , Doxorrubicina/química , Técnicas Eletroquímicas , Glutationa/sangue , Glutationa/química , Humanos , Nanopartículas/química , Níquel/química , Platina/química , Tirosina/sangue , Tirosina/química
13.
Mol Genet Metab ; 127(3): 184-190, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31235217

RESUMO

AIM: To study the efficacy of low dosage of nitisinone in alkaptonuria. BACKGROUND: Alkaptonuria (AKU) is a rare genetic disease which induces deposition of homogentisic acid (HGA) in connective inducing premature arthritis, lithiasis, cardiac valve disease, fractures, muscle and tendon ruptures and osteopenia. Recent studies showed that nitisinone decreases HGA and is a beneficial therapy in AKU. This treatment induces an increase in tyrosine levels which can induces adverse effects as keratopathy. METHODS: We described the evolution HGA excretion and tyrosine evolution in 3 AKU patients treated by very low dosage of nitisinone with regards to their daily protein intakes. We also described the first pregnancy in an AKU patient treated by nitisinone. RESULTS: We found mild clinical signs of alkaptonuria on vertebra MRI in two young adults and homogentisate deposition in teeth of a 5 years old girl. Very low dose of nitisinone (10% of present recommended dose: 0.2 mg/day) allowed to decrease homogentisic acid by >90% without increasing tyrosine levels above 500 µmol/ in these three patients. INTERPRETATIONS: The analysis of the follow-up data shows that, in our three patients, a low-dosage of nitisinone is sufficient to decrease urinary HGA without increasing plasma tyrosine levels above the threshold of 500 µmol/L.


Assuntos
Alcaptonúria/diagnóstico por imagem , Alcaptonúria/tratamento farmacológico , Cicloexanonas/administração & dosagem , Nitrobenzoatos/administração & dosagem , Adulto , Pré-Escolar , Dieta , Relação Dose-Resposta a Droga , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Tirosina/sangue , Adulto Jovem
14.
Biosens Bioelectron ; 140: 111356, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31163395

RESUMO

Nanometer-sized copper sulfide has remarkable properties such as metal like electrical conductivity and electrocatalytic activity. In this work, ultrathin copper sulfide nanosheets (CuS NS) were synthesized and employed to modify on surface of glassy carbon electrode (GCE) combining with chitosan (CS) and acidified multi-walled carbon nanotubes (F-MWCNTs). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the shape of CuS NS was hexagon with side length of 13.33 ±â€¯0.67 nm and thickness of 4.50 ±â€¯0.58 nm. The electrochemical characteristics of different nanocomposite modified electrodes were examined by using cyclic voltammetry (CV) and differential pulse voltammetry (DPV), indicating that the modified electrode of CuS NS-CS/F-MWCNTs/GCE possessed good electrocatalytic activity towards oxidation of L-tyrosine (L-Tyr). Under the optimal condition, the modified electrode exhibited a wide linear response range for L-Tyr (0.08-1.0 µM) with a detection limit of 4.9 nM. No obvious interferences from coexisted two-fold of L-tryptophan and 50-fold of other amino acids could be observed, indicating its relatively good selectivity. The electrode also had good repeatability, reproducibility and stability. Compared with a commercial instrument analytical method, HPLC, the electrode can be successfully applied to the determination of L-Tyr in pig serums with a recovery rate of 95.7%-102.6%, and its test results are in good agreement with that of HPLC, showing its promising application value.


Assuntos
Técnicas Biossensoriais/métodos , Cobre/química , Nanocompostos/química , Suínos/sangue , Tirosina/sangue , Animais , Quitosana/química , Técnicas Eletroquímicas/métodos , Eletrodos , Limite de Detecção , Nanocompostos/ultraestrutura
15.
Mater Sci Eng C Mater Biol Appl ; 102: 653-660, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31147037

RESUMO

This paper reports an aptamer-based green approach for the electrochemical evaluation of tyrosinamide (Tyr-NH2). In this regard, at the first step, an aqueous synthetic strategy for preparing N-acetyl-l-cysteine (NAC)-capped Ag-In-S (AIS) quantum dots (QDs) with bright yellow/orange emission was developed. The conjugation of AIS QDs to NAC-biomolecules provides opportunities for using them as luminescent contrast agents for living cell tracking and labeling or sensing studies. In the next step, the design stage of the aptasensor, the glassy carbon electrode (GCE) was modified with the AIS QDs and then the Tyr-NH2 special aptamer, which has an amine group at its end, interacts with silver and indium ions at the surface of the AIS QDs and through the formation of covalent bonding of AgN and InN, attaches to the GCE surface modified with the AIS QDs. In this approach, for the first time, NAC-capped AIS QDs have been used to modify the electrode surface in the aptamer-based electrochemical sensor. The response changes of the [Fe(CN)6]4-/3- as redox probe, during the modification of GCE surface, the fabrication and assessment of proposed aptasensing, using the cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy were recorded. The designed aptasensor for the Tyr-NH2 evaluation showed good linearity from 0.01 to 2.81 nM and 2.81-10.81 nM, and low detection limit of 3.34 pM. The obtained results of the stability, reproducibility and selectivity investigations implying that the reported aptasensor as the first aptamer-based electrochemical assay for Tyr-NH2, can be reliable for the determination of Tyr-NH2 in serum samples.


Assuntos
Acetilcisteína/química , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Carbono/química , Técnicas Eletroquímicas/métodos , Vidro/química , Pontos Quânticos/química , Tirosina/análogos & derivados , Espectroscopia Dielétrica , Eletrodos , Humanos , Índio/química , Pontos Quânticos/ultraestrutura , Reprodutibilidade dos Testes , Prata/química , Enxofre/química , Fatores de Tempo , Tirosina/sangue
16.
Methods Mol Biol ; 1985: 391-405, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069748

RESUMO

Capillary electrophoresis (CE) is a well-established and one of the most powerful separation techniques in the field of chiral separations. Its hyphenation with mass spectrometry (MS) combines both the high separation efficiency and low sample consumption of CE and the high sensitivity and structural information of MS. Thus, the outstanding chiral resolution power of CE along with the MS advantages makes CE-MS a perfect combination to achieve sensitive enantioseparations. This chapter describes three representative examples of different approaches used in the chiral analysis of amino acids in biological fluids by CE-MS. The first methodology uses the partial filling technique to avoid the entry of cyclodextrins in the MS source. The second method shows the possibility to carry out the direct coupling EKC-MS even when a relative high concentration of a native cyclodextrin is used as chiral selector. The last example illustrates an alternative strategy based on the formation of stable diastereomers between an enantiomerically pure chiral reagent and the amino acids enantiomers which can be separated in an achiral environment.


Assuntos
Eletroforese Capilar/métodos , Espectrometria de Massas/métodos , Animais , Cromatografia Capilar Eletrocinética Micelar , Fenilalanina/sangue , Fenilalanina/líquido cefalorraquidiano , Ratos , Estereoisomerismo , Tirosina/sangue , Tirosina/líquido cefalorraquidiano
17.
Medicina (Kaunas) ; 55(5)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126140

RESUMO

Background and objective: One of the reasons for thrombosis in chronic heart failure (CHF) might be reactive forms of oxygen activating platelets. The aim of this study was to evaluate the effect of oxidant hypochlorous acid (HOCl) on platelet aggregation and dityrosine concentration in CHF patients and healthy controls. Materials and Methods: CHF patients (n 67) and healthy (n 31) were investigated. Heart echoscopy, 6-min walking test, complete blood count, platelet aggregation, and dityrosine concentration were performed. Platelet aggregation and dityrosine concentration were measured in plasma samples after incubation with different HOCl concentrations (0.15, 0.0778, and 0.0389 mmol/L). Results: Platelet aggregation without oxidant was lower (p = 0.049) in CHF patients than in controls. The spontaneous platelet aggregation with oxidant added was higher in CHF patients (p = 0.004). Dityrosine concentration was also higher (p = 0.032) in CHF patients. Platelet aggregation was the highest in samples with the highest oxidant concentration in both healthy controls (p = 0.0006) and in CHF patients (p = 0.036). Platelet aggregation was higher in NYHA III group in comparison to NYHA II group (p = 0.0014). Concentration of dityrosine was significantly higher in CHF samples (p = 0.032). The highest concentration of dityrosine was obtained in NYHA IV group samples (p 0.05). Intensity of platelet aggregation, analyzed with ADP, was correlated with LV EF (r 0.42, p = 0.007). Dityrosine concentration was correlated with NYHA functional class (r 0.27, p 0.05). Conclusions: The increase in platelet aggregation in CHF and healthy controls shows the oxidant effect on platelets. The increase in dityrosine concentration in higher NYHA functional classes shows a higher oxidative stress in patients with worse condition.


Assuntos
Insuficiência Cardíaca/sangue , Ácido Hipocloroso/uso terapêutico , Agregação Plaquetária/fisiologia , Tirosina/análogos & derivados , Idoso , Feminino , Voluntários Saudáveis , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Ácido Hipocloroso/farmacocinética , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Tirosina/análise , Tirosina/sangue
18.
Nutrients ; 11(3)2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30823411

RESUMO

Introduction: In phenylketonuria (PKU), evidence suggests that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is associated with better protein utilisation and less blood phenylalanine (Phe) variability. Aim: To study the impact of CGMP-AA on blood Phe variability using 3 different dietary regimens in children with PKU. Methods: This was a 6-week randomised controlled cross-over study comparing CGMP-AA vs. Phe-free l-amino acids (l-AA) assessing blood Phe and tyrosine (Tyr) variability over 24 h in 19 children (7 boys) with PKU, with a median age of 10 years (6⁻16). Subjects were randomised to 3 dietary regimens: (1) R1, CGMP-AA and usual dietary Phe (CGMP + Phe); (2) R2, CGMP-AA - Phe content of CGMP-AA from usual diet (CGMP - Phe); and (3) R3, l-AA and usual dietary Phe. Each regimen was administered for 14 days. Over the last 48 h on days 13 and 14, blood spots were collected every 4 h at 08 h, 12 h, 16 h, 20 h, 24 h, and 04 h. Isocaloric intake and the same meal plan and protein substitute dosage at standardised times were maintained when blood spots were collected. Results: Eighteen children completed the study. Median Phe concentrations over 24 h for each group were (range) R1, 290 (30⁻580), R2, 220 (10⁻670), R3, 165 (10⁻640) µmol/L. R1 vs. R2 and R1 vs. R3 p < 0.0001; R2 vs. R3 p = 0.0009. There was a significant difference in median Phe at each time point between R1 vs. R2, p = 0.0027 and R1 vs. R3, p < 0.0001, but not between any time points for R2 vs. R3. Tyr was significantly higher in both R1 and R2 [70 (20⁻240 µmol/L] compared to R3 [60 (10⁻200) µmol/L]. In children < 12 years, blood Phe remained in the target range (120⁻360 µmol/L), over 24 h, for 75% of the time in R1, 72% in R2 and 64% in R3; for children aged ≥ 12 years, blood Phe was in target range (120⁻600 µmol/L) in R1 and R2 for 100% of the time, but 64% in R3. Conclusions: The residual Phe in CGMP-AA increased blood Phe concentration in children. CGMP-AA appears to give less blood Phe variability compared to l-AA, but this effect may be masked by the increased blood Phe concentrations associated with its Phe contribution. Reducing dietary Phe intake to compensate for CGMP-AA Phe content may help.


Assuntos
Caseínas/administração & dosagem , Caseínas/farmacologia , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Fenilalanina/sangue , Tirosina/sangue , Criança , Suplementos Nutricionais , Feminino , Humanos , Masculino , Fenilalanina/metabolismo , Fenilcetonúrias , Tirosina/metabolismo
19.
Clin Chim Acta ; 494: 100-105, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30904545

RESUMO

BACKGROUND: Availability of appropriately established reference intervals for biochemical tests can be troublesome in pediatrics. Here we establish age-specific continuous reference intervals for catecholamine O-methylated metabolites in children evaluated for catecholamine producing tumors, particularly younger children with suspected neuroblastoma. METHODS: Plasma concentrations of 3-methoxytyramine, normetanephrine, metanephrine, and 3-O-methyldopa were analyzed by liquid chromatography tandem mass spectrometry in 533 children aged 2 days to 18 years. RESULTS: Concentrations of plasma free normetanephrine, 3-methoxytyramine and 3-O-methyldopa were higher in neonates up until six months of age, but thereafter declined steeply to levels after one year that were <38% those of neonatal concentrations and to further lower concentrations in teenagers that were <23% those in neonates. In contrast, concentrations of plasma free metanephrine showed a reciprocal pattern with 50% lower concentrations in infants below one year compared to later in childhood. CONCLUSION: The dynamic reciprocal changes in plasma concentrations of normetanephrine, 3-methoxytyramine and 3-O-methyldopa compared to metanephrine during early childhood suggest underlying developmental changes in extra-adrenal and adrenal chromaffin tissue that must be considered for pediatric reference intervals, particularly in infants. With such reference intervals at hand, biochemical testing for catecholamine producing tumors in young children is substantially improved.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Envelhecimento/sangue , Dopamina/análogos & derivados , Metanefrina/sangue , Normetanefrina/sangue , Paraganglioma/sangue , Feocromocitoma/sangue , Tirosina/análogos & derivados , Adolescente , Análise Química do Sangue , Catecolaminas/biossíntese , Criança , Pré-Escolar , Cromatografia Líquida , Dopamina/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valores de Referência , Espectrometria de Massas em Tandem , Tirosina/sangue
20.
Mater Sci Eng C Mater Biol Appl ; 98: 496-502, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30813051

RESUMO

Electrochemical oxidation of l­cysteine resulted in the formation of a film on glassy carbon electrode. In a solution of levodopa (l­DOPA), l­tyrosine (Tyr) and uric acid (UA), three separated intense anodic peaks were appeared in differential pulse voltammetry regime. Experimental conditions were optimized for simultaneous determination of the three compounds. All experiments were carried out in phosphate buffer solution (0.1 M, pH 8). Calibration curves were obtained in the presence of various concentrations of l­DOPA, Tyr, and UA. Linear concentration ranges were 0.65-22 µM for l­DOPA, 3.5-96 µM for Tyr, and 1.0-19 µM for UA. The limits of detection (LODs) were calculated as 0.2, 1.1 and 0.36 µM for l­DOPA, Tyr, and UA, respectively. The electrochemical sensor was used successfully for the simultaneous determination of l­DOPA, Tyr, and UA species in human blood serum samples.


Assuntos
Carbono/química , Ácido Cisteico/química , Vidro/química , Levodopa/sangue , Tirosina/sangue , Ácido Úrico/sangue , Técnicas Eletroquímicas , Eletrodos , Humanos , Concentração de Íons de Hidrogênio , Polimerização
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