RESUMEN
This research aims to study the antioxidation and anticholinesterase activities of 7'-ethoxy-trans-feruloyltyramine (ETFT), which was an alkaloid isolated from Portulaca oleracea for the first time. Furthermore, its main metabolites and metabolic pathways in rats were also explored. The antioxidation and anticholinesterase effects of ETFT were, respectively, examined using 1,1-diphenyl-2-picrylhydrazyl assay and modified Ellman's method. The results showed that ETFT exhibited both the good antioxidant and anticholinesterase effects. Its main metabolites in rats were implemented, and nine metabolites were finally found in the rat's plasma and urine, including the oxidation, reduction, hydrolysis, glucuronidation, sulfation, and glutathionylation process.
Asunto(s)
Antioxidantes/farmacología , Inhibidores de la Colinesterasa/farmacología , Cromatografía Líquida de Alta Presión , Extractos Vegetales/farmacología , Portulaca , Espectrometría de Masa por Ionización de Electrospray , Tiramina/farmacología , Administración Intravenosa , Animales , Antioxidantes/metabolismo , Biotransformación , Inhibidores de la Colinesterasa/sangre , Inhibidores de la Colinesterasa/orina , Masculino , Extractos Vegetales/sangre , Extractos Vegetales/orina , Ratas Sprague-Dawley , Tiramina/análogos & derivados , Tiramina/sangre , Tiramina/metabolismo , Tiramina/orinaRESUMEN
Hordenine, a natural constituent of germinated barley, is a biased agonist of the dopamine D2 receptor. This pilot study investigated the biokinetics of hordenine and its metabolites in four volunteers consuming beer equal to 0.075 mg hordenine/kg body weight. A new ultrahigh-performance liquid chromatography method coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method determined maximum plasma concentrations of 12.0-17.3 nM free hordenine after 0-60 min. Hordenine phase-II metabolism was first dominated by sulfation, but later by glucuronidation. The elimination half-lives in plasma were 52.7-66.4 min for free hordenine and about 60/80 min longer for hordenine sulfate and hordenine glucuronide. Urinary excretion peaked 2-3.5 h after consumption and accumulated to 3.78 µmol within 24 h, corresponding to 9.9% of the ingested dose. The observed hordenine levels in plasma seem too low to provoke direct interaction with the dopamine D2 receptor related to food reward, but synergistic or additive effects with alcohol or N-methyltyramine may occur.
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Cerveza/análisis , Agonistas de Dopamina/farmacocinética , Tiramina/análogos & derivados , Adulto , Cromatografía Líquida de Alta Presión , Agonistas de Dopamina/sangre , Agonistas de Dopamina/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptores de Dopamina D2/química , Receptores de Dopamina D2/metabolismo , Espectrometría de Masas en Tándem , Tiramina/sangre , Tiramina/farmacocinética , Tiramina/orina , Adulto JovenRESUMEN
Background Metabolic syndrome (MetS) is an important contributor to both type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Although MetS affects one third of American adults, its pathogenesis remains to be elucidated. Tyramine, a derivative of tyrosine, has been shown to act as a catecholamine releasing agent in the human body. The aim of this study is to investigate the role of tyramine as an early biomarker for nascent MetS without the confounding of T2DM, ASCVD or smoking. Patients and methods This was an exploratory study of 28 patients with nascent MetS and 20 matched controls carried out in 2018. Metabolites were evaluated from patient's frozen early morning urine samples and were correlated with biomarkers of inflammation and adipokines. They were assayed by the National Institutes of Health (NIH) Western Metabolomics Center using liquid chromatography/mass spectrometry (LC/MS) and standardized to urinary creatinine. All patients had normal hepatic and renal function. Results Tyramine concentrations were significantly reduced in patients with MetS compared to controls, p = 0.0009. In addition, tyramine was significantly inversely correlated with multiple biomarkers of inflammation and cardiometabolic risk factors such as RBP4, monocyte TLR-4 abundance and P38MAPKinase activity, body mass index (BMI) and blood pressure (BP) (both systolic and diastolic). Conclusion In conclusion, low levels of tyramine could contribute to the proinflammatorty state of MetS.
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Inflamación/orina , Síndrome Metabólico/orina , Tiramina/orina , Adulto , Anciano , Biomarcadores/metabolismo , Biomarcadores/orina , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/metabolismo , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/metabolismo , Metabolómica , Persona de Mediana Edad , Tiramina/metabolismoRESUMEN
The parasitic disease onchocerciasis is the second leading cause of preventable blindness, afflicting more than 18 million people worldwide. Despite an available treatment, ivermectin, and control efforts by the World Health Organization, onchocerciasis remains a burden in many regions. With an estimated 120 million people living in areas at risk of infection, efforts are now shifting from prevention to surveillance and elimination. The lack of a robust, point-of-care diagnostic for an active Onchocerca infection has been a limiting factor in these efforts. Previously, we reported the discovery of the biomarker N-acetyl-tyramine- O-glucuronide (NATOG) in human urine samples and its ability to track treatment progression between medicated patients relative to placebo; we also established its capability to monitor disease burden in a jird model. NATOG is a human-produced metabolite of tyramine, which itself is produced as a nematode neurotransmitter. The ability of NATOG to distinguish between active and past infection overcomes the limitations of antibody biomarkers and PCR methodologies. Lateral flow immunoassay (LFIA) diagnostics offer the versatility and simplicity to be employed in the field and are inexpensive enough to be utilized in large-scale screening efforts. Herein, we report the development and assessment of a NATOG-based urine LFIA for onchocerciasis, which accurately identified 85% of analyzed patient samples ( N = 27).
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Inmunoensayo/métodos , Enfermedades Desatendidas/diagnóstico , Enfermedades Desatendidas/orina , Onchocerca volvulus , Oncocercosis/diagnóstico , Oncocercosis/orina , Tiramina/análogos & derivados , Animales , Anticuerpos Monoclonales de Origen Murino/inmunología , Biomarcadores/orina , Exactitud de los Datos , Oro/química , Humanos , Espectrometría de Masas , Nanopartículas del Metal/química , Enfermedades Desatendidas/prevención & control , Oncocercosis/prevención & control , Pruebas en el Punto de Atención , Resonancia por Plasmón de Superficie , Tiramina/inmunología , Tiramina/orinaRESUMEN
This work reports the development of a simple and cost-effective electrochemical sensor based on electrochemically reduced graphene oxide (ErGO) bound to the surface of indium tin oxide (ITO) electrode through 3-aminopropyltriethoxysilane (APTES) monolayer (ITO/APTES/ErGO) for selective and sensitive detection of tyramine. The features of the modified electrode were studied by scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance (EIS) methods. The analytical performance of the developed sensor was evaluated with respect to linear detection range, limit of detection, stability, coexistence interference and reproducibility. The modified device exhibited electrocatalytic activity toward tyramine oxidation within two linear concentration range of 1-100â¯nM, and 1-100⯵M, with LOD of 0.1â¯nM. Finally, the sensor successfully detected tyramine in commercially available real samples with satisfactory recovery ranges. The proposed modified sensor offers distinct advantages including low cost, simple handling, good sensitivity and high selectivity.
Asunto(s)
Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Grafito/química , Propilaminas/química , Silanos/química , Compuestos de Estaño/química , Tiramina/análisis , Técnicas Biosensibles/economía , Espectroscopía Dieléctrica , Técnicas Electroquímicas/economía , Electrodos , Humanos , Límite de Detección , Oxidación-Reducción , Reproducibilidad de los Resultados , Tiramina/química , Tiramina/orinaRESUMEN
The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG's biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development.
Asunto(s)
Glucurónidos/orina , Espectrometría de Masas/métodos , Enfermedades Desatendidas/orina , Onchocerca volvulus/aislamiento & purificación , Oncocercosis/orina , Tiramina/análogos & derivados , Animales , Biomarcadores/orina , Cromatografía Liquida/métodos , Glucurónidos/metabolismo , Humanos , Límite de Detección , Metabolómica/métodos , Enfermedades Desatendidas/metabolismo , Onchocerca volvulus/metabolismo , Oncocercosis/metabolismo , Tiramina/metabolismo , Tiramina/orinaRESUMEN
BACKGROUND: Onchocerciasis, also known as river blindness is one of the neglected tropical diseases affecting millions of people, mainly in sub-Saharan Africa and is caused by the filarial nematode Onchocerca volvulus. Efforts to eliminate this disease are ongoing and are based on mass drug administration programs with the microfilaricide ivermectin. In order to monitor the efficacy of these programs, there is an unmet need for diagnostic tools capable of identifying infected patients. We have investigated the diagnostic potential of urinary N-acetyltyramine-O,ß-glucuronide (NATOG), which is a promising O. volvulus specific biomarker previously identified by urine metabolome analysis. METHODS: A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was used to assess the stability characteristics of NATOG and to evaluate the levels of NATOG in study samples. An LC-fluorescence method was also developed. RESULTS: Stability characteristics of NATOG were investigated and shown to be ideally suited for use in tropical settings. Also, an easy and more accessible method based on liquid chromatography coupled to fluorescence detection was developed and shown to have the necessary sensitivity (limit of quantification 1 µM). Furthermore, we have evaluated the levels of NATOG in a population of 98 nodule-positive individuals from Ghana with no or low levels of microfilaria in the skin and compared them with the levels observed in different control groups (endemic controls (n = 50), non-endemic controls (n = 18) and lymphatic filariasis (n = 51). Only a few (5 %) of nodule-positive individuals showed an increased level (> 10 µM) of NATOG and there was no statistical difference between the nodule-positive individuals and the control groups (P > 0.05). CONCLUSIONS: Results of the present study indicate the limited potential of NATOG as a diagnostic biomarker for O. volvulus infection in amicrofilaridermic individuals.
Asunto(s)
Glucurónidos/orina , Onchocerca volvulus/aislamiento & purificación , Oncocercosis Ocular/diagnóstico , Oncocercosis/diagnóstico , Tiramina/análogos & derivados , Animales , Biomarcadores/orina , Cromatografía Liquida , Femenino , Humanos , Microfilarias , Espectrometría de Masas en Tándem , Tiramina/orinaRESUMEN
Hordenine is an active compound found in several foods, herbs and beer. In this work, a novel sorbent was fabricated for selective solid-phase extraction (SPE) of hordenine in biological samples. The organic polymer sorbent was synthesized in one step in the plastic barrel of a syringe by a pre-polymerization solution consisting of methacrylic acid (MAA), 4-vinylphenylboronic acid (VB) and ethylene glycol dimethacrylate (EGDMA). The conditions for preparation were optimized to generate a poly(MAA-VB-EGMDA) monolith with good permeability. The monolith exhibited good enrichment efficiency towards hordenine. By using tyramine as the internal standard, a poly(MAA-VB-EGMDA)-based SPE-HPLC method was established for analysis of hordenine. Conditions for SPE, including volume of eluting solvent, pH of sample solution, sampling rate and sample volume, were optimized. The proposed SPE-HPLC method presented good linearity (R(2) = 0.9992) within 10-2000 ng/mL and the detection limits was 3 ng/mL, which is significantly more sensitive than reported methods. The method was also applied in plasma and urine samples; good capability of removing matrices was observed, while hordenine in low content was well extracted and enriched. The recoveries were from 90.6 to 94.7% and from 89.3 to 91.5% for the spiked plasma and urine samples, respectively, with the relative standard deviations <4.7%.
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Ácidos Borónicos/química , Cromatografía Líquida de Alta Presión/métodos , Glicoles de Etileno/química , Metacrilatos/química , Extracción en Fase Sólida/métodos , Tiramina/análogos & derivados , Compuestos de Vinilo/química , Humanos , Modelos Lineales , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Extracción en Fase Sólida/instrumentación , Tiramina/sangre , Tiramina/química , Tiramina/orinaRESUMEN
Onchocerciasis, also known as "river blindness", is a neglected tropical disease infecting millions of people mainly in Africa and the Middle East but also in South America and Central America. Disease infectivity initiates from the filarial parasitic nematode Onchocerca volvulus, which is transmitted by the blackfly vector Simulium sp. carrying infectious third-stage larvae. Ivermectin has controlled transmission of microfilariae, with an African Program elimination target date of 2025. However, there is currently no point-of-care diagnostic that can distinguish the burden of infection--including active and/or past infection--and enable the elimination program to be effectively monitored. Here, we describe how liquid chromatography-MS-based urine metabolome analysis can be exploited for the identification of a unique biomarker, N-acetyltyramine-O,ß-glucuronide (NATOG), a neurotransmitter-derived secretion metabolite from O. volvulus. The regulation of this tyramine neurotransmitter was found to be linked to patient disease infection, including the controversial antibiotic doxycycline treatment that has been shown to both sterilize and kill adult female worms. Further clues to its regulation have been elucidated through biosynthetic pathway determination within the nematode and its human host. Our results demonstrate that NATOG tracks O. volvulus metabolism in both worms and humans, and thus can be considered a host-specific biomarker for onchocerciasis progression. Liquid chromatography-MS-based urine metabolome analysis discovery of NATOG not only has broad implications for a noninvasive host-specific onchocerciasis diagnostic but provides a basis for the metabolome mining of other neglected tropical diseases for the discovery of distinct biomarkers and monitoring of disease progression.
Asunto(s)
Metaboloma , Neurotransmisores/orina , Onchocerca volvulus/metabolismo , Oncocercosis Ocular/orina , Tiramina/orina , Animales , Antibacterianos/uso terapéutico , Biomarcadores/orina , Doxiciclina/uso terapéutico , Femenino , Humanos , Masculino , Oncocercosis Ocular/diagnóstico , Oncocercosis Ocular/tratamiento farmacológicoRESUMEN
The biogenic amine octopamine [4-(2-amino-1-hydroxyethyl)phenol] is prohibited in sports owing to its stimulating and performance-enhancing properties. Adverse analytical findings in athletes' doping control samples commonly result from surreptitious applications; however, the occurrence of octopamine in nutritional supplements and in selected invertebrates as well as the assumption that its N-methylated analog synephrine [4-(1-hydroxyethyl-2-methylamino)phenol, not banned by anti-doping authorities but currently monitored in prevalence studies) might be converted in-vivo into octopamine have necessitated a study to investigate the elimination of synephrine and octopamine present in over-the-counter products. Urine samples collected after administration of nutritional supplements containing octopamine and/or synephrine as well as urine samples collected after therapeutic application of octopamine- or synephrine-containing drugs were analyzed using a validated solid-phase extraction-based procedure employing a weak cation exchange resin and liquid chromatographic/tandem mass spectrometric detection with electrospray ionization and multiple reaction monitoring. In the case of therapeutic octopamine application, the urinary concentration of the target compound increased from baseline levels below the lower limit of detection to 142 µg/mL, while urine samples collected after synephrine as well as dietary supplement administration did not yield any evidence for elevated renal excretion of octopamine.
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Doping en los Deportes , Octopamina/orina , Adulto , Anciano de 80 o más Años , Cromatografía Liquida , Suplementos Dietéticos/análisis , Humanos , Límite de Detección , Masculino , Persona de Mediana Edad , Octopamina/administración & dosificación , Octopamina/química , Octopamina/farmacocinética , Sinefrina/administración & dosificación , Sinefrina/química , Sinefrina/farmacocinética , Sinefrina/orina , Espectrometría de Masas en Tándem , Tiramina/orinaRESUMEN
A transient ITP-CZE system is proposed for the determination of biogenic amines in urine. The complete separation and identification of dopamine, tyramine (TA), tryptamine (T), serotonin, epinephrine, norepinephrine, and normetanephrine have been achieved in a twofold diluted urine sample (in which the analytes were below the LODs by normal CZE). The tITP preconcentration conditions were created by introducing a 30 mM solution of NaOH, containing 0.1% hydroxypropylcellulose (pH 6.5 adjusted with MES), and 0.1 M HCl before and after the sample zone to work as leading and terminating electrolytes, respectively. This allowed the LODs of direct UV absorption detection to be decreased down to the 10(-8) M level that is comparable with the sensitivity thresholds of LIF detection or inline SPE-CE. The RSDs of migration time and peak area for real-biofluid analysis were in the range of 0.1-4.5% and 0.8-16% (n=3), respectively. Quantification of dopamine, TA, T, and serotonin was performed using internal calibration. To the best of our knowledge, this is the first report on probing urinal biogenic amines and their metabolites by tITP-CZE.
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Aminas Biogénicas/orina , Electroforesis Capilar/métodos , Electroforesis/métodos , Adulto , Dopamina/orina , Electroforesis Capilar/estadística & datos numéricos , Epinefrina/orina , Humanos , Norepinefrina/orina , Normetanefrina/orina , Sensibilidad y Especificidad , Serotonina/orina , Espectrofotometría Ultravioleta , Triptaminas/orina , Tiramina/orinaRESUMEN
Liquid chromatography (LC) with fluorescence detection is described for simultaneous determination of native fluorescent bioamines (indoleamines and catecholamines). This is based on intramolecular fluorescence resonance energy transfer (FRET) in an LC system following post-column derivatization of native fluorescent bioamines' amino groups with o-phthalaldehyde (OPA). OPA fluorescence was achieved through an intramolecular FRET process when the molecules were excited at maximum excitation wavelength of the native fluorescent bioamines. Bioamines separated by reversed-phase LC on ODS column were derivatized with OPA and 2-mercaptoethanol. This method provides sufficient selectivity and sensitivity for the determination of normetanephrine, dopamine, tyrosine, 5-hydroxytryptamine, tryptamine, and tryptophan in healthy human urine without prior sample purification.
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Aminas Biogénicas/orina , Cromatografía Liquida/métodos , Transferencia Resonante de Energía de Fluorescencia/métodos , Fluorescencia , Aminas Biogénicas/química , Catecolaminas/química , Catecolaminas/orina , Cromatografía Liquida/instrumentación , Dopamina/química , Dopamina/orina , Humanos , Normetanefrina/química , Normetanefrina/orina , Reproducibilidad de los Resultados , Triptófano/química , Triptófano/orina , Tiramina/química , Tiramina/orina , Tirosina/química , Tirosina/orina , o-Ftalaldehído/química , o-Ftalaldehído/orinaRESUMEN
A liquid chromatographic (LC) method for sensitive and selective fluorometric determination of p-hydroxyphenylethylamino group containing compounds is described. This method is based on an intramolecular excimer-forming fluorescence derivatization with a pyrene reagent, 4-(1-pyrene)butanoyl chloride, followed by reversed-phase LC. The analytes, containing an amino moiety and a phenolic hydroxyl moiety in a molecule, were converted to the corresponding dipyrene-labeled derivatives by one-step derivatization. The dipyrene-labeled derivatives afforded intramolecular excimer fluorescence (440-540 nm), which can clearly be discriminated from the normal fluorescence (360-420 nm) emitted from reagent blanks. The derivatives of tyrosine and tyramine could be separated by reversed-phase LC on ODS column under conditions of isocratic elution. The detection limits (signal-to-noise ratio = 3) for tyrosine and tyramine were 4.5 and 2.6 fmol per 20 microL injection, which corresponded to analyte concentrations of 0.9 and 0.5 nM, respectively.
Asunto(s)
Cromatografía Liquida/métodos , Tiramina/orina , Tirosina/orina , Butanos/química , Humanos , Pirenos/química , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de FluorescenciaRESUMEN
Marked, dose-dependent elevations in the urinary excretion of phenylethylamine, para-tyramine, and meta-tyramine were observed in depressed patients treated for three or more weeks with 10, 30, or 60 mg/day of the partially-selective inhibitor of MAO-B, selegiline (l-deprenyl). In comparative studies with other, structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A inhibitor used in doses of 90 mg/day for three or more weeks, produced elevations in these trace amines which were similar to those found with the highest dose of selegiline studied. Clorgyline, a selective inhibitor of MAO-A used in doses of 30 mg/day for three or more weeks (a dose/time regimen previously reported to reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) > 80%, indicating a marked inhibitory effect on MAO-A in humans in vivo) produced negligible changes in trace amine excretion. In comparison to recent studies of individuals lacking the genes for MAO-A, MAO-B, or both MAO-A and MAO-B, the lack of change in trace amine excretion in individuals with a mutation affecting only MAO-A is in agreement with the observed lack of effect of clorgyline in the present study. Selegiline produced larger changes in trace amines--at least at the higher doses studied--than found in individuals lacking the gene for MAO-B, in agreement with other data suggesting a lesser selectivity for MAO-B inhibition when selegiline was given in doses higher than 10 mg/day. Overall, trace amine elevations in individuals receiving the highest dose of deprenyl or receiving pargyline were approximately three to five-fold lower than the elevations observed in individuals lacking the genes for both MAO-A and MAO-B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.
Asunto(s)
Aminas Biogénicas/orina , Clorgilina/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/orina , Inhibidores de la Monoaminooxidasa/uso terapéutico , Pargilina/uso terapéutico , Selegilina/uso terapéutico , Deleción Cromosómica , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/deficiencia , Isoenzimas/genética , Masculino , Monoaminooxidasa/deficiencia , Monoaminooxidasa/genética , Fenetilaminas/orina , Valores de Referencia , Estudios Retrospectivos , Tiramina/orina , Cromosoma XRESUMEN
There is considerable evidence that subjects vulnerable to endogenous depression excrete less tyramine sulphate after an oral dose of free tyramine than controls (the tyramine test). In this study, 26 psychiatric inpatients, exhibiting a wide range of responses to the test, and 10 normal controls were challenged with oral doses of paracetamol and tyramine on two separate occasions. Urinary output of paracetamol sulphate and paracetamol glucuronide in all subjects was monitored but there were no significant correlations with tyramine sulphate output. Thus, the output of these metabolites appears to be under complex control, and paracetamol cannot be substituted for tyramine in the "tyramine test". The basic deficit responsible for low values in the tyramine test is unlikely to stem from sulphate depletion or a generalised disturbance of the sulphation system, and remains obscure.
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Acetaminofén/farmacocinética , Agonistas alfa-Adrenérgicos/farmacocinética , Analgésicos no Narcóticos/farmacocinética , Tiramina/farmacocinética , Acetaminofén/orina , Agonistas alfa-Adrenérgicos/orina , Analgésicos no Narcóticos/orina , Cromatografía Líquida de Alta Presión , Humanos , Trastornos Mentales/metabolismo , Espectrofotometría Ultravioleta , Sulfatos/metabolismo , Tiramina/orinaRESUMEN
This study was designed to investigate tyramine sulfate conjugation in patients with migraine or tension-type headache, as defined by the newly introduced International Headache Society (IHS) criteria and to examine whether this relationship is mediated by major depression. A total of 62 subjects completed the study: 38 with migraine (22 with aura and 16 without aura), 12 with tension-type headache, and 12 controls. Patients with migraine had significantly lower urinary tyramine sulfate excretion following oral tyramine challenge than normal control. Tension-type headache was also associated with low tyramine conjugation, but only when comorbid with depression. Although mean tyramine sulfate output was lower among subjects with major depression within each of the subtypes of headache, no significant main effect emerged for depression or major subtype thereof. The lower tyramine sulfate excretion values among patients with both migraine and depression compared to those of migraine alone or depression alone in our data and those of others suggests that comorbid migraine with depression may represent a more severe form of migraine than migraine alone. The findings underscore the importance of comorbidity in clinical and epidemiological studies of migraine.
Asunto(s)
Trastorno Depresivo/metabolismo , Trastornos Migrañosos/metabolismo , Cefalea de Tipo Tensional/metabolismo , Tiramina/metabolismo , Adulto , Trastorno Depresivo/complicaciones , Trastorno Depresivo/psicología , Femenino , Humanos , Masculino , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/diagnóstico , Escalas de Valoración Psiquiátrica , Recurrencia , Cefalea de Tipo Tensional/complicaciones , Cefalea de Tipo Tensional/diagnóstico , Tiramina/orinaRESUMEN
Para-tyramine (p-TYM) is a predominant urinary amine in humans, rabbit, rat and dog, and its urinary excretion rate may reflect central nervous system pathophysiology. However, the source of urinary p-TYM is not known, nor have the mechanisms regulating its excretion been characterized. The present study, by using renal clearance techniques, examined the sources of urinary p-TYM and the mechanism of excretion in anesthetized rabbits. In all studies, the renal clearance of p-TYM was compared with that of norepinephrine (NE). Base-line delivery to the kidney of p-TYM in plasma was 8.6 +/- 1.6 ng/min (mean +/- S.E.M., n = 16), whereas the mean urinary excretion rate of p-TYM was 26.5 +/- 3.6 ng/min during the same period (P < .001 vs. delivery). In three separate series of experiments, either vehicle (n = 5) or a specific inhibitor of renal tubular organic cation secretion, cyanine 863 (6 mg/kg, n = 7), or a specific inhibitor of aromatic-amino acid-decarboxylase, alpha-mono-fluoromethyldopa (FMD, 4 mg/kg, n = 5), were infused i.v., Mean arterial pressure, glomerular filtration rate, renal plasma flow and urine flow rate were unchanged in all studies. The renal clearances of p-TYM (Cp-TYM) and NE (CNE) were unchanged only after vehicle. After cyanine 863, Cp-TYM was decreased to 36% of control (P < .01), whereas CNE decreased to 21% of its base-line value (P < .01). After FMD Cp-TYM was reduced to 2% of control (P < .05), whereas CNE decreased by 44% (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Riñón/metabolismo , Tiramina/orina , Animales , Presión Sanguínea/efectos de los fármacos , Túbulos Renales/metabolismo , Masculino , Metildopa/análogos & derivados , Metildopa/farmacología , Norepinefrina/orina , Compuestos de Quinolinio/farmacología , Conejos , Ácido p-Aminohipúrico/orinaRESUMEN
The endogenous monoamine oxidase (MAO) inhibitory activity, termed tribulin, contains several components. We have previously identified one of them, isatin, which is a selective inhibitor of MAO B. In the present study we have purified several further components of human urinary tribulin which act as selective inhibitors of MAO A. They have been identified by gas chromatography-mass spectrometry (GC-MS) as ethyl indole-3-acetate (and/or methyl indole-3-propionate), methyl indole-3-acetate and ethyl 4-hydroxyphenylacetate. IC50 values for MAO A were found to be 44 microM (105 microM for methyl indole-3-propionate), 88 microM and 120 microM, respectively, whilst those for MAO B were each greater than 1 mM. The artificial formation of these esters was excluded by carrying the parent acids, from which they are presumably synthesized, through the purification procedure. As tribulin output is increased during stress or anxiety, these results point to a possible role for tryptamine and tyramine pathways in such disorders.
Asunto(s)
Isatina , Inhibidores de la Monoaminooxidasa/orina , Plaquetas/enzimología , Cromatografía en Gel , Cromatografía de Gases y Espectrometría de Masas , Humanos , Indoles/orina , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/aislamiento & purificación , Placenta/enzimología , Receptores de GABA-A/efectos de los fármacos , Estándares de Referencia , Triptaminas/orina , Tiramina/orinaRESUMEN
Abnormally low tyramine test values are known to be markers for vulnerability to unipolar, but not bipolar, endogenous depression. In the present study, 37 women with recent postnatal depression (25 major, 12 minor) and 22 puerperal controls with no depressive disorder, all assessed by Schedule for Affective Disorder and Schizophrenia (SADS-L) interview, together with 17 other controls, underwent the test. No significant differences in tyramine sulfate output were demonstrated between the different groups. Those subjects with endogenous features according to Newcastle score (n = 7) or Research Diagnostic Criteria (RDC) (n = 6) also had normal output. Thus, the tyramine test does not appear to be a useful marker for vulnerability to postnatal depression. Over half the subjects recalled that their postnatal depression had started in the first 2 weeks postpartum. Of the total of 62 postpartum subjects interviewed with the SADS-L, ten recalled a period of euphoria in the first postpartum week, which met RDC for hypomania and eight of them went on to become depressed postnatally. An additional patient from the total group was hospitalized with mania.
Asunto(s)
Trastorno Depresivo/diagnóstico , Euforia/fisiología , Trastornos Puerperales/diagnóstico , Tiramina , Adulto , Biomarcadores , Trastorno Depresivo/psicología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Determinación de la Personalidad , Trastornos Puerperales/psicología , Valores de Referencia , Tiramina/orinaRESUMEN
5- and 6-Hydroxydopamine, which we had earlier identified as naturally occurring amines in human urine, were quantified in Parkinson's patients treated with L-DOPA, Parkinson's patients whose treatment did not include L-DOPA and in age matched controls. Analysis was carried out by GC-MS of the ditrifluoromethylbenzoyl-trimethylsilyl (DTFMB-TMS) derivatives of the compounds. The concentrations of 5- and 6-hydroxydopamine in the urine of DOPA treated Parkinson's patients were significantly higher than the concentrations from patients not treated and from normal controls. Urinary dopamine levels were greatly elevated in DOPA treated Parkinson's patients while p-tyramine levels were suppressed. No marked differences were seen between the three groups in terms of the urinary concentrations of any of the other amines measured.