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1.
Methods Mol Biol ; 2030: 277-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347125

RESUMO

A high number of non-protein amino acids are chiral compounds that have demonstrated to be relevant in different fields. Their determination enables to obtain valuable information related to food quality and safety and has also a high interest from a biological point of view since many of them are key compounds in metabolic pathways or are related with different pathologies.In the development of analytical methodologies to perform chiral separations, capillary electrophoresis (CE) is well-established and one of the most powerful separation techniques as a consequence of its high efficiency, short analysis time, and versatility.This chapter shows, by means of three interesting examples, the application of different CE methodologies to the chiral analysis of non-protein amino acids. The first example describes different electrokinetic chromatography (EKC)-UV methodologies based on the use of negatively charged cyclodextrins as chiral selectors to carry out the stereoselective separation of ten different non-protein amino acids of relevance from a biological or food analysis point of view. The second method illustrates the EKC-UV analysis of L-citrulline and its enantiomeric impurity in food supplements using sulfated-γ-cyclodextrin as chiral selector. The last example shows the simultaneous enantiomeric separation of 3,4-dihydroxy-DL-phenylalanine and all the other chiral constituents involved in the phenylalanine-tyrosine metabolic pathway by using an EKC-MS methodology.


Assuntos
Cromatografia Capilar Eletrocinética Micelar/métodos , Citrulina/isolamento & purificação , Di-Hidroxifenilalanina/isolamento & purificação , Eletroforese Capilar/métodos , Animais , Cromatografia Capilar Eletrocinética Micelar/instrumentação , Citrulina/química , Ciclodextrinas/química , Suplementos Nutricionais/análise , Di-Hidroxifenilalanina/sangue , Di-Hidroxifenilalanina/química , Di-Hidroxifenilalanina/metabolismo , Eletroforese Capilar/instrumentação , Concentração de Íons de Hidrogênio , Ratos , Estereoisomerismo
2.
Colloids Surf B Biointerfaces ; 162: 212-219, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29190472

RESUMO

In this work, we report a fluorescence strategy for detecting dopamine (DA) and sensing tyrosinase (TYR) activity on the basis of the dual-emission carbon dots (DECDs), which contain two emitters: the blue emitters (BE, maximum emission at 385nm) and yellow emitters (YE, maximum emission at 530nm). Gold nanoparticles (AuNPs) can effectively quench the two emissions of DECDs. The addition of DA aggregates AuNPs effectively, leading to the fluorescence recovery of dual emitters gradually. This strategy exhibits a high selectivity toward DA and shows good linear ranges, such as 0.5-3µM for BE and 0.1-3µM for YE. Additionally, the proposed method is successfully applied to the determination of DA in real samples with satisfactory recoveries. Subsequently, this DECDs-AuNPs platform is further taken advantage to assess TYR activity by the aid of TYR's capability for oxidation of DA into dopaquinone, which will not induce the agglomeration of AuNPs, so the fluorescence quenching of DECDs is associated with TYR activity. Finally, the mechanism of the reaction is discussed in detail, and the results suggest that both amine and phenolic hydroxyl groups of DA bring the aggregation of AuNPs.


Assuntos
Bioensaio , Dopamina/sangue , Ouro/química , Nanopartículas Metálicas/química , Monofenol Mono-Oxigenase/sangue , Pontos Quânticos/química , Benzoquinonas/sangue , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/sangue , Floculação , Recuperação de Fluorescência Após Fotodegradação/métodos , Humanos , Cinética , Nanopartículas Metálicas/ultraestrutura , Oxirredução , Sensibilidade e Especificidade
3.
Neurol Res ; 39(5): 381-386, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28222651

RESUMO

INTRODUCTION: Homocysteine increase and glutathione derivative cysteinyl-glycine fall are indirect biomarkers for oxidative stress, for instance due to dopamine D1 receptor stimulation. OBJECTIVES: To investigate the influence of the D1 receptor agonists levodopa and rotigotine compared with placebo on homocysteine and cysteinyl-glycine in plasma of patients with Parkinson's disease. METHODS: Patients received 100 mg levodopa, 4 mg rotigotine or placebo. Cysteinyl-glycine and homocysteine were measured every 30 min over three hours. RESULTS: Homocysteine rose during levodopa- and placebo administration. Rotigotine had no effect. Cysteine-glycine only increased after placebo- but not after levodopa- or rotigotine. DISCUSSION: Homocysteine elevation results from hepatic and gastrointestinal methylation processes. Transdermal rotigotine circumvents these methylation locations. Turnover of segregated alkyl residuals from rotigotine serves as methyl group donors, which counteract homocysteine increment. The placebo-related cysteinyl-glycine increase results from reduced free radical exposure. Low levodopa dosing and antioxidants in the rotigotine patch matrix prevented cysteinyl-glycine fall.


Assuntos
Dipeptídeos/sangue , Dopaminérgicos/administração & dosagem , Homocisteína/sangue , Levodopa/administração & dosagem , Tetra-Hidronaftalenos/administração & dosagem , Tiofenos/administração & dosagem , Idoso , Análise de Variância , Cromatografia Líquida de Alta Pressão , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/sangue , Dopaminérgicos/sangue , Técnicas Eletroquímicas , Feminino , Humanos , Levodopa/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Tetra-Hidronaftalenos/sangue , Tiofenos/sangue , Fatores de Tempo , Tirosina/análogos & derivados
4.
J Cereb Blood Flow Metab ; 37(9): 3124-3134, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28156211

RESUMO

The Patlak graphical analysis (PGAREF) for quantification of irreversible tracer binding with a reference tissue model was approximated by a dual time point imaging approach (DTPREF). The DTPREF was applied to 18 [18F]-FDOPA brain scans using the occipital cortex as reference region (DTPOCC) and compared to both PGAOCC and striatal-to-occipital ratios (SOR). Pearson correlation analysis and Bland-Altman plots showed an excellent correlation and good agreement between DTPOCC and PGAOCC, while correlations between SOR and PGAOCC were consistently lower. Linear discriminant analysis (LDA) demonstrated a similar performance for all methods in differentiating patients with Parkinson's disease (PD) from healthy controls (HC). Specifically for [18F]-FDOPA brain imaging, these findings validate DTPOCC as an approximation for PGAOCC, providing the same quantitative information while reducing the acquisition time to two short static scans. For PD patients, this approach can greatly improve patient comfort while reducing motion artifacts and increasing image quality. In general, DTPREF can improve the clinical applicability of tracers with irreversible binding characteristics when a reference tissue is available.


Assuntos
Encéfalo/diagnóstico por imagem , Di-Hidroxifenilalanina/análogos & derivados , Processamento de Imagem Assistida por Computador/métodos , Modelos Teóricos , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/metabolismo , Estudos de Casos e Controles , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/metabolismo , Di-Hidroxifenilalanina/sangue , Di-Hidroxifenilalanina/metabolismo , Análise Discriminante , Radioisótopos de Flúor , Humanos , Modelos Lineares , Doença de Parkinson/metabolismo , Putamen/diagnóstico por imagem , Putamen/metabolismo , Valores de Referência , Fatores de Tempo
5.
BMJ Open ; 6(2): e009630, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26920441

RESUMO

OBJECTIVES: To compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults. DESIGN: Randomised two-condition crossover trial. SETTING: Laboratory study conducted in Melbourne, Australia. PARTICIPANTS: 19 overweight/obese adults (45-75 years). INTERVENTIONS: After an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition). PRIMARY OUTCOME MEASURES: Self-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h. SECONDARY OUTCOME MEASURES: Neuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system). RESULTS: During the active condition, fatigue levels were lower at 4 h (-13.32 (95% CI -23.48 to -3.16)) and at 7 h (-10.73 (95% CI -20.89 to -0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG). CONCLUSIONS: Interrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in this pilot study. Further research is needed to identify potential implications, particularly for the occupational health context. TRIAL REGISTRATION NUMBER: ACTRN12613000137796; Results.


Assuntos
Cognição , Fadiga/prevenção & controle , Obesidade/psicologia , Sobrepeso/psicologia , Comportamento Sedentário , Caminhada , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Estudos Cross-Over , Di-Hidroxifenilalanina/sangue , Feminino , Frequência Cardíaca , Humanos , Masculino , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Sobrepeso/sangue , Sobrepeso/fisiopatologia , Projetos Piloto
6.
Biomed Chromatogr ; 30(10): 1696-700, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26910491

RESUMO

The aim of study was to develop a suitable analytical method for simultaneous estimation of levodopa, carbidopa and 3-O-methyl dopa in rat plasma. Chromatographic separation of plasma samples was achieved using a reverse-phase C18 column. The mobile phase used consisted of a mixture of methanol and phosphate buffer (10 mM, pH 3.50) in the ratio of 90:10 v/v. All analytes were estimated by electrochemical detection at +800 mV. The developed method has been validated as per the standard guidelines. Precision study results were found to be satisfactory, with percentage relative standard deviation for repeatability and intermediate precision <3.96 and 6.56%, respectively, for all analytes detected in rat plasma. The developed method in rat plasma was found to be simple, rapid, accurate, precise and specific. The proposed method has been successfully applied for analysis of rat plasma samples obtained during an oral pharmacokinetic study of sustained release pellets of levodopa and carbidopa in rats. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Carbidopa/sangue , Cromatografia Líquida de Alta Pressão/métodos , Di-Hidroxifenilalanina/análogos & derivados , Técnicas Eletroquímicas/métodos , Levodopa/sangue , Animais , Di-Hidroxifenilalanina/sangue , Limite de Detecção , Masculino , Ratos , Ratos Wistar , Tirosina/análogos & derivados
7.
Mol Genet Metab ; 115(2-3): 91-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25956449

RESUMO

Aromatic L-amino acid decarboxylase (AADC) deficiency is an inborn error of metabolism affecting the biosynthesis of serotonin, dopamine, and catecholamines. We report a case of AADC deficiency that was detected using the Global MAPS platform. This is a novel platform that allows for parallel clinical testing of hundreds of metabolites in a single plasma specimen. It uses a state-of-the-art mass spectrometry platform, and the resulting spectra are compared against a library of ~2500 metabolites. Our patient is now a 4 year old boy initially seen at 11 months of age for developmental delay and hypotonia. Multiple tests had not yielded a diagnosis until exome sequencing revealed compound heterozygous variants of uncertain significance (VUS), c.286G>A (p.G96R) and c.260C>T (p.P87L) in the DDC gene, causal for AADC deficiency. CSF neurotransmitter analysis confirmed the diagnosis with elevated 3-methoxytyrosine (3-O-methyldopa). Metabolomic profiling was performed on plasma and revealed marked elevation in 3-methoxytyrosine (Z-score +6.1) consistent with the diagnosis of AADC deficiency. These results demonstrate that the Global MAPS platform is able to diagnose AADC deficiency from plasma. In summary, we report a novel and less invasive approach to diagnose AADC deficiency using plasma metabolomic profiling.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/sangue , Descarboxilases de Aminoácido-L-Aromático/deficiência , Dopa Descarboxilase/genética , Metabolômica/métodos , Polimorfismo de Nucleotídeo Único , Descarboxilases de Aminoácido-L-Aromático/sangue , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/sangue , Humanos , Lactente , Masculino , Tirosina/análogos & derivados , Tirosina/sangue
8.
Bioanalysis ; 7(2): 207-20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25587837

RESUMO

BACKGROUND: In this study, we developed and validated a HPLC-MS/MS method capable of simultaneously determining levodopa, carbidopa, entacapone, tolcapone, 3-O-methyldopa and dopamine in human plasma. RESULTS & METHODOLOGY: Chromatographic separation was achieved using a C8 column with a mobile phase consisting of a gradient of water and acetonitrile:methanol (90:10 v/v), both containing 0.1% formic acid. The developed method was selective, sensitive (LD<7.0 ng ml(-1)), linear (r>0.99), precise (RSD<11.3%), accurate (RE<11.8%) and free of residual and matrix effects. The developed method was successfully applied in plasma patients with Parkinson's disease using Stalevo®. CONCLUSION: The new method can be used for the clinical monitoring of these substances and applied to adjustments in drug dosages.


Assuntos
Benzofenonas/sangue , Análise Química do Sangue/métodos , Carbidopa/sangue , Catecóis/sangue , Cromatografia Líquida de Alta Pressão , Di-Hidroxifenilalanina/análogos & derivados , Dopamina/sangue , Levodopa/sangue , Nitrilas/sangue , Nitrofenóis/sangue , Espectrometria de Massas em Tandem , Benzofenonas/normas , Carbidopa/normas , Catecóis/normas , Cromatografia Líquida de Alta Pressão/normas , Di-Hidroxifenilalanina/sangue , Di-Hidroxifenilalanina/normas , Dopamina/normas , Humanos , Levodopa/normas , Nitrilas/normas , Nitrofenóis/normas , Controle de Qualidade , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/normas , Tolcapona , Tirosina/análogos & derivados
9.
Clin Neuropharmacol ; 37(4): 96-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24992088

RESUMO

BACKGROUND: According to recent investigations, the eradication of Helicobacter pylori (H. pylori) may influence levodopa (LD) pharmacokinetics (PK) and improve the motor function of infected patients with Parkinson disease (PD). The aim of this study was to compare PK of LD and its metabolite 3-O-methyldopa (3-OMD), between H. pylori-positive (HP+) and -negative (HP-) patients with PD and motor fluctuations. MATERIALS AND METHODS: Patients with the clinical diagnosis of PD, under stable LD therapy, reporting daily motor fluctuations and who had no history of previous eradication treatment were screened for the H. pylori infection with an antigen stool test. Two groups of patients-bacteria-infected and noninfected-matched demographically and clinically, were selected for the examination of PK values. Blood samples were collected after morning oral LD dose. Noncompartmental PK parameters were computed from the LD and 3-OMD plasma concentration-time data. RESULTS: Interindividual variability was seen in LD absorption curve in both groups. There were no clinically significant differences in PK parameters of LD and 3-OMD. Changes of small magnitude but with possible clinical impact were found according to tmax and Cmax that tended to be lower in HP- patients and AUC0-t that was larger in the HP+ group. The Cmax value of 3-OMD was almost identical in both groups. The HP- group had smaller AUC0-∞t of 3-OMD. CONCLUSIONS: The H. pylori infection in PD patients with motor fluctuations, despite not significantly influencing PK parameters of LD and 3-OMD, may still have important clinical implications.


Assuntos
Antiparkinsonianos/farmacocinética , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Levodopa/farmacocinética , Atividade Motora/efeitos dos fármacos , Doença de Parkinson , Adulto , Idoso , Antiparkinsonianos/uso terapêutico , Benserazida/uso terapêutico , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/sangue , Jejum , Feminino , Infecções por Helicobacter/sangue , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Índice de Gravidade de Doença , Tirosina/análogos & derivados
10.
Clin Chim Acta ; 431: 19-22, 2014 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-24513538

RESUMO

BACKGROUND: Inherited defects that affect the synthesis or metabolism of neurotransmitters cause severe motor dysfunction. The diagnosis of these diseases, including aromatic L-amino-acid decarboxylase (AADC) deficiency, typically requires cerebrospinal fluid (CSF) neurotransmitter analysis. However, 3-O-methyldopa (3-OMD), which is a catabolic product of L-dopa that accumulates in individuals with AADC deficiency, can be detected in blood. METHODS: 3-OMD concentrations were measured in dried blood spots (DBSs). One 3.2-mm punch was eluted with 90% methanol containing a deuterated internal standard (3-OMD-d3), and then analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: 3-OMD in DBSs was shown to be stable for more than 28 days at 37°C. We measured DBS 3-OMD concentrations in controls and patients with AADC deficiency. 3-OMD concentrations in normal newborns and children decreased with age. Patients with AADC deficiency revealed >15-fold increase of DBS 3-OMD concentrations. Archive newborn screening DBS samples, obtained from 6 patients with AADC deficiency, revealed more than 19-fold increase of 3-OMD concentrations. CONCLUSIONS: We demonstrated that DBS 3-OMD concentrations were highly elevated in newborns and children with AADC deficiency. Because 3-OMD is stable in DBS, this method can be used for both high risk and newborn screening of AADC deficiency.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Descarboxilases de Aminoácido-L-Aromático/deficiência , Di-Hidroxifenilalanina/análogos & derivados , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Descarboxilases de Aminoácido-L-Aromático/sangue , Calibragem , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Di-Hidroxifenilalanina/sangue , Teste em Amostras de Sangue Seco , Humanos , Lactente , Recém-Nascido , Triagem Neonatal , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Tirosina/análogos & derivados
11.
Obesity (Silver Spring) ; 22(3): 652-62, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23997009

RESUMO

OBJECTIVES: This study was conducted to examine (1) the effects of dietary weight loss on indices of norepinephrine (NE) turnover and (2) whether baseline hyperinsulinemia modulates sympathetic neural adaptations. METHODS: Obese individuals aged 56 ± 1 year, BMI 32.5 ± 0.4 kg/m(2) , with metabolic syndrome, underwent a 12-week hypocaloric diet (HCD, n = 39) or no treatment (n = 26). Neurochemical measurements comprised arterial dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylglycol (DHPG), and NE concentrations, the steady-state ratio of [3H]-DHPG to [3H]-NE, as an index of neuronal uptake, and calculated whole-body plasma NE clearance and spillover rates. RESULTS: Body weight decreased by -7.4 ± 0.5% in HCD group (P < 0.001) and was accompanied by reductions in DOPA, NE, and DHPG averaging -14 ± 5% (P = 0.001), -23 ± 4% (P <0.001), and -5 ± 4% (P = 0.03), respectively. NE spillover rate decreased by -88 ± 39 ng/min (P = 0.01), whereas neuronal uptake and NE plasma clearance were unchanged. Despite similar weight loss, hyperinsulinemic subjects exhibited greater reductions in NE and NE spillover rate, compared to normoinsulinemic subjects (group by time interaction P < 0.05). CONCLUSIONS: Weight loss is associated with down-regulation of sympathetic nervous activity but no overall alteration in disposition indices. Hyperinsulinemic subjects derive a greater sympathoinhibitory benefit during weight loss.


Assuntos
Dieta Redutora , Hiperinsulinismo/metabolismo , Norepinefrina/sangue , Perda de Peso/efeitos dos fármacos , Índice de Massa Corporal , Di-Hidroxifenilalanina/sangue , Di-Hidroxifenilalanina/farmacocinética , Regulação para Baixo , Metabolismo Energético , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Hiperinsulinismo/complicações , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/sangue , Metoxi-Hidroxifenilglicol/farmacocinética , Pessoa de Meia-Idade , Norepinefrina/farmacocinética , Obesidade/complicações , Obesidade/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos
12.
Brain Res ; 1497: 1-14, 2013 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-23206800

RESUMO

Levodopa (L-DOPA) is widely used for symptomatic management in Parkinson's disease. We recently showed that (-)-epigallocatechin-3-gallate, a tea polyphenol, not only inhibits L-DOPA methylation, but also protects against oxidative hippocampal neurodegeneration. In the present study, we sought to determine several other common dietary phenolics, namely, tea catechins [(+)-catechin and (-)-epicatechin] and a representative flavonoid (quercetin), for their ability to modulate L-DOPA methylation and to protect against oxidative hippocampal injury. A combination of in vitro biochemical assays, cell culture-based mechanistic analyses, and in vivo animal models was used. While both tea catechins and quercetin strongly inhibit human liver catechol-O-methyltransferase (COMT)-mediated O-methylation of L-DOPA in vitro, only (+)-catechin exerts a significant inhibition of L-DOPA methylation in both peripheral compartment and striatum in rats. The stronger in vivo effect of (+)-catechin on L-DOPA methylation compared to the other dietary compounds is due to its better bioavailability in vivo. In addition, (+)-catechin strongly reduces glutamate-induced oxidative cytotoxicity in HT22 mouse hippocampal neurons in vitro through inactivation of the nuclear factor-κB signaling pathway. Administration of (+)-catechin also exerts a strong neuroprotective effect in the kainic acid-induced oxidative hippocampal neurodegeneration model in rats. In conclusion, (+)-catechin is a dietary polyphenolic that may have beneficial effects in L-DOPA-based treatment of Parkinson patients by inhibiting L-DOPA methylation plus reducing oxidative neurodegeneration.


Assuntos
Catequina/farmacologia , Catecol O-Metiltransferase/metabolismo , Hipocampo/patologia , Hidroxibenzoatos/farmacologia , Degeneração Neural/prevenção & controle , Inibidores da Captação Adrenérgica/farmacologia , Análise de Variância , Animais , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/sangue , Carbidopa/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/sangue , Modelos Animais de Doenças , Agonistas de Aminoácidos Excitatórios/toxicidade , Fluoresceínas , Proteína Glial Fibrilar Ácida/metabolismo , Técnicas In Vitro , Ácido Caínico/toxicidade , Levodopa/efeitos adversos , Levodopa/sangue , Masculino , Metilação/efeitos dos fármacos , Camundongos , Degeneração Neural/induzido quimicamente , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reserpina/farmacologia , Fatores de Tempo , Tirosina/análogos & derivados
15.
J Neural Transm (Vienna) ; 116(10): 1253-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19657587

RESUMO

Chronic levodopa (LD)/dopadecarboxylase inhibitor (DDI) increases homocysteine generation as side reaction of O-methylation. Aim was to investigate the impact of the peripheral COMT inhibitor entacapone (EN) on plasma concentrations of homocysteine, LD and 3-O-methyl-dopa (3-OMD). Patients with Parkinson's disease (PD) received on two consecutive days in a standardised fashion one single dose of 200 mg retarded release LD/carbidopa (CD) or of 150 mg LD/CD/EN, since both were shown to have simultaneous pharmacokinetic LD behaviour. Homocysteine increased after retarded release LD/CD application, but not following LD/CD/EN intake. Homocysteine was lower during the LD/CD/EN condition 80 min after baseline when compared with its levels after LD/CD administration. LD levels simultaneously rose on both days. 3-OMD concentrations did not change. Acute LD/CD application caused a rise of homocysteine levels, which was prevented by LD/CD/EN intake. Therefore, peripheral COMT inhibition may have a beneficial effect on putative, controversially debated components of homocysteine-related progression of PD.


Assuntos
Antiparkinsonianos/farmacologia , Inibidores de Catecol O-Metiltransferase , Catecóis/farmacologia , Inibidores Enzimáticos/farmacologia , Homocisteína/sangue , Levodopa/farmacologia , Nitrilas/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/sangue , Carbidopa/administração & dosagem , Carbidopa/farmacologia , Preparações de Ação Retardada , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/sangue , Feminino , Humanos , Levodopa/administração & dosagem , Levodopa/sangue , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Fatores de Tempo , Tirosina/análogos & derivados
16.
Klin Med (Mosk) ; 87(4): 32-6, 2009.
Artigo em Russo | MEDLINE | ID: mdl-19514318

RESUMO

Activation of sympato-adrenal system plays an important role in the development of chronic cardiac failure (CCF). However, its relation to morpho-functional state of myocardium in CCF patients is virtually unknown. HPLC with electrochemical detection was used to determine plasma noradrenalin, adrenalin, and their precursors, 3,4-dioxyphenylalanine (DOPA) and dopamine, in patients with different morpho-functional changes in myocardium. The study demonstrated enhanced activity of sympato-adrenal system in patients with CCF. It showed for the first time that activity of sympato-adrenal system in CCF patients depends on the morpho-functional status of myocardium.


Assuntos
Glândulas Suprarrenais/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Doença Crônica , Di-Hidroxifenilalanina/sangue , Dopamina/sangue , Epinefrina/sangue , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Remodelação Ventricular
17.
Mov Disord ; 24(9): 1339-43, 2009 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-19425084

RESUMO

Levodopa (L-dopa) administered with a dopadecarboxylase inhibitor (DDI) increases homocysteine plasma levels. This may support the onset of atherosclerosis-related disorders and neuropsychiatric complications in patients with Parkinson's disease (PD). This homocysteine elevation is considered as long-term effect of chronic L-dopa/DDI treatment. Little is known about the acute effects of L-dopa/DDI intake on homocysteine generation. The objective of this trial was to investigate the relations between L-dopa and homocysteine after acute L-dopa/DDI administration in PD patients with different L-dopa metabolism. Thirty PD patients were divided into groups with superior (I) and less (II) L-dopa absorption after standardized intake of 125 mg L-dopa/benserazide with determination of L-dopa, 3-O-methyl-dopa (3-OMD) and homocysteine in plasma at baseline, 30, 60, and 90 minutes. There was a homocysteine increase in Group I (F = 5; P = 0.005) and a moderate decrease in Group II (F = 4.27; P = 0.01). A rise of 3-OMD (F = 10.51; P < 0.0001) appeared in Group I, but not in Group II (F = 0.91; P = 0.44), accordingly L-dopa accumulation was better in Group I than in Group II. Thus, in conclusion, L-dopa metabolism is an important component for homocysteine elevation after one time L-dopa/DDI administration in PD patients.


Assuntos
Antiparkinsonianos/administração & dosagem , Homocisteína/sangue , Levodopa/administração & dosagem , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Idoso , Análise de Variância , Antiparkinsonianos/sangue , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/sangue , Feminino , Humanos , Levodopa/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Estatística como Assunto , Fatores de Tempo , Tirosina/análogos & derivados
18.
Cardiology ; 113(4): 277-86, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19270454

RESUMO

BACKGROUND: It is well established that the serotonergic system (SS) plays important roles in the pathogenesis of cardiovascular diseases. However, the impact of serotonin and its inter-relation with the sympathoadrenal system (SAS) in chronic heart failure (CHF) is poorly understood. METHODS: Utilizing high-performance liquid chromatography with electrochemical detection, we determined blood plasma levels of serotonin (5-hydroxy-triptamine, [5-HT](p)), 5- hydroxy-indole-acetic acid ([5-HIAA](p)), epinephrine ([E](p)), norepinephrine ([NE](p)), 3,4-dihydroxy-L-phenyl-alanine ([DOPA](p)), dopamine ([DA](p)) and the platelet concentration of serotonin ([5-HT](pt)) in CHF patients with different morphofunctional alterations of myocardium. The morphofunctional alterations included diastolic dysfunction (DD), diastolic dysfunction with left ventricular hypertrophy (DD&LVH), and diastolic and systolic dysfunction (D&SD). RESULTS: All CHF groups showed significant rises of [5-HT](p) and [5-HT](pt). DD&LVH and D&SD individuals also had increased [5-HIAA](p). Levels of SAS blood biomarkers were also significantly changed. The correlation between SS and SAS was increased in CHF and corresponded with disease severity. CONCLUSIONS: These results clearly demonstrate that in CHF patients significant changes in SS and SAS occur, which are thought to relate to the morphofunctional alterations of myocardium. The observed changes in the levels of these biomarkers may serve as potential surrogates to monitor severity of disease, to evaluate response to drug treatment, and as a rational basis for new therapeutic approaches.


Assuntos
Glândulas Suprarrenais/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Serotonina/sangue , Sistema Nervoso Simpático/fisiopatologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Biomarcadores/sangue , Doença Crônica , Di-Hidroxifenilalanina/sangue , Progressão da Doença , Dopamina/sangue , Epinefrina/sangue , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Ácido Hidroxi-Indolacético/sangue , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Índice de Gravidade de Doença
19.
Neurochem Res ; 33(9): 1889-93, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18357519

RESUMO

This study tested whether familial dysautonomia (FD) involves progressive loss of noradrenergic nerves. Plasma levels of catechols, including dihydroxyphenylglycol (DHPG), norepinephrine (NE), dopamine (DA), and DOPA, were measured in 7 adult patients with FD and 50 healthy control subjects. FD patients were re-tested after a mean follow-up period of 13 years. Compared to controls, FD patients had low plasma levels of DHPG (P < 0.001), high DOPA and DA levels (P = 0.01, P = 0.0002), and high NE:DHPG (P < 0.0001), DA:NE (P = 0.0003), and DOPA:DHPG (P < 0.0001) ratios. At follow-up there were no changes in plasma levels of individual catechols; however, there were further increases in DOPA:DHPG ratios (mean 24 +/- 7%, P = 0.01). In FD, plasma catechol profiles are sufficiently stable, at least over a decade, to be used as a biomarker of disease involvement. An increasing DOPA:DHPG ratio suggests slight but consistent, progressive loss of noradrenergic neurons.


Assuntos
Ácido 3,4-Di-Hidroxifenilacético/sangue , Di-Hidroxifenilalanina/sangue , Dopamina/sangue , Disautonomia Familiar/sangue , Epinefrina/sangue , Norepinefrina/sangue , Adulto , Disautonomia Familiar/patologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/sangue
20.
Artigo em Inglês | MEDLINE | ID: mdl-19136729

RESUMO

A home-made nano-desorption electrospray ionization (nano-DESI) device and the kinetic method were tested in chiral analysis of model clinical samples containing enantiomers of one of three pharmaceutically important compounds: dihydroxyphenylalanine (DOPA), ephedrine and ibuprofen. The initial evaluation of chiral systems was carried out by direct infusion of solution mixtures (analyte/central metal/chiral reference ligand) to a standard electrospray ionization (ESI) source. Cu(II) was used as a central metal for all analytes, L-phenylalanine was applied as a chiral reference ligand for DOPA, whereas L-tryptophan was used for the other two analytes. Then, the ESI source was substituted by a nano-DESI source and dried spots of 1 microL samples of whole human blood spiked with individual drugs were successfully analyzed without any pre-treatment. Irrespective of a laborious initial nano-DESI set-up, the combination of the kinetic method with nano-desorption electrospray has, for the first time, been demonstrated as a promising tool for chiral analysis of drugs in blood samples.


Assuntos
Nanotecnologia/métodos , Preparações Farmacêuticas/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Di-Hidroxifenilalanina/sangue , Efedrina/sangue , Humanos , Ibuprofeno/sangue , Cinética , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Estereoisomerismo
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