RESUMO
Amino-functionalized polyhedral oligomeric silsesquioxanes (POSS-8NH2) were covalently bound to the surface of polydopamine-coated magnetized graphene oxide. It was then reacted with 4-formylphenylboronic acid to prepare a "cubic boronic acid"-bonded magnetic graphene oxide adsorbent. The new adsorbent exhibits better selectivity and much higher adsorption capacity for ortho-phenols over adsorbents where small boronic ligands are directly bound to the surface of the material. It is shown to enable selective and faster enrichment of the catecholamines epinephrine (EP), dopamine (DA) and isoprenaline (IP) with high selectivity over many potential interferents that can occur in urine. The analytes were then quantified by HPLC with fluorometric detection. Under optimal conditions, response is linear (R2 ≥ 0.9907), limits of detection are low (0.54-2.3 ng·mL-1), and reproducibility is acceptable (inter- and intra-day assay RSDs of≤10.9%). The method was successfully applied to the determination of endogenous EP and DA and exogenous IP in urine samples. Graphical abstractSchematic of boronic acid (BA)-modified polyhedral oligomeric silsesquioxanes (POSS) on polydopamine-coated magnetized graphene oxide (magGO). The material (magGO@POSS-BA) has good selectivity and higher adsorption capacity to ortho-phenols and can be applied to enrich the catecholamines in urine.
Assuntos
Ácidos Borônicos/química , Catecolaminas/isolamento & purificação , Grafite/química , Indóis/química , Compostos de Organossilício/química , Polímeros/química , Adsorção , Catecolaminas/urina , Dopamina/isolamento & purificação , Dopamina/urina , Epinefrina/isolamento & purificação , Epinefrina/urina , Isoproterenol/isolamento & purificação , Isoproterenol/urina , Limite de Detecção , Magnetismo , Reprodutibilidade dos TestesRESUMO
A novel One MoNomer dual imprinted graphene oxide/carbon black composite polymer was developed applying 'surface-grafting from' approach on the screen printed carbon electrode for the electrochemical sensing of dopamine and epinephrine. Acryloylated-graphene oxide/carbon black was synthesized for the first time. This served both as a crosslinker and monomer leading to the fast electron transfer from the redox centre to the electrode. The oxidation peak potentials of both the targets were found separated by 200â¯mV which enabled their simultaneous analysis in real world samples, without any cross reactivity, interferences, and false-positives. The detection limits realized by the proposed sensor, under optimized analytical conditions, were found to be as low as 0.028, 0.028,0.061 and 0.029â¯ngâ¯mL-1 for dopamine and 0.017, 0.018, 0.019 and 0.020â¯ngâ¯mL-1 for epinephrine (S/Nâ¯=â¯3) in aqueous, blood serum, urine and pharmaceutical samples. Such sensor could be considered suitable for the primitive diagnosis of several chronic diseases, manifested at ultra-trace level.
Assuntos
Acrilatos/química , Dopamina/análise , Epinefrina/análise , Grafite/química , Neurotransmissores/análise , Fuligem/química , Acrilatos/análise , Acrilatos/urina , Técnicas Biossensoriais/métodos , Dopamina/sangue , Dopamina/urina , Técnicas Eletroquímicas/métodos , Epinefrina/sangue , Epinefrina/urina , Humanos , Limite de Detecção , Impressão Molecular/métodos , Neurotransmissores/sangue , Neurotransmissores/urinaRESUMO
Glucose intolerance is often observed in patients with pheochromocytoma. However, it remains controversial issue that glucose intolerance on pheochromocytoma is caused by impaired insulin secretion and/or by increased insulin resistance. We aimed to reveal the mechanism of glucose intolerance on pheochromocytoma with regard to the type and amount of catecholamines released. We evaluated 12 individuals diagnosed with pheochromocytoma and who underwent surgery to remove it. We examined glycemic parameters before and after surgery and investigated the association between the change of parameters of insulin secretion (homeostasis model assessment of ß-cell function (HOMA-ß)), insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) and that of urinary levels of metanephrine/normetanephrine before and after surgery. Overall, fasting plasma glucose, glycated hemoglobin (HbA1c), HOMA-ß, and HOMA-IR were improved significantly after surgery. Regression analysis showed that the improvement in HOMA-ß from before to after surgery was significantly positively associated with an improvement in urinary levels of metanephrine from before to after surgery and showed a significantly negative association with improvement in urinary levels of normetanephrine from before to after surgery. The improvement in HOMA-IR from before to after surgery was significantly positively associated with an improvement in urinary levels of normetanephrine from before to after surgery. Our results showed that pheochromocytoma extirpation improved glycemic parameters. Furthermore, the different effects elicited by excess amounts of adrenaline and noradrenaline on glucose intolerance were demonstrated.
Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Epinefrina/urina , Intolerância à Glucose/metabolismo , Resistência à Insulina/fisiologia , Norepinefrina/urina , Feocromocitoma/cirurgia , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/metabolismo , Idoso , Glicemia/análise , Feminino , Intolerância à Glucose/complicações , Hemoglobinas Glicadas/análise , Humanos , Masculino , Metanefrina/urina , Pessoa de Meia-Idade , Normetanefrina/urina , Feocromocitoma/complicações , Feocromocitoma/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVES: To determine the incidence and preoperative risk factors of post-excisional hypoglycemia in patients undergoing pheochromocytoma resection. METHODS: Patients who underwent surgical resection of pheochromocytoma at a single institution were retrospectively enrolled in the present study. The primary end-point was the development of post-excisional hypoglycemia; that is, a serum glucose level <70 mg/dL. The serum levels of immunoreactive insulin and glucose levels during the preoperative oral glucose-tolerance test and surgery were analyzed to elucidate the mechanism of hypoglycemia. RESULTS: A total of 49 patients underwent surgical resection of pheochromocytoma, of which 21 patients (43%) developed post-excisional hypoglycemia. The incidence of hypoglycemia was not statistically different between patients with adrenal tumors and those with extra-adrenal tumors (18/41 [44%] vs 3/8 [38%], respectively, P = 0.73). There was no difference in the immunoreactive insulin/glucose ratio during the preoperative oral glucose-tolerance test between patients with and those without post-excisional hypoglycemia. The intraoperative immunoreactive insulin/glucose ratio was significantly higher in patients with hypoglycemia than in those without hypoglycemia. A higher 24-h urinary epinephrine level, but not norepinephrine level, was a predictive factor for post-excisional hypoglycemia. CONCLUSIONS: Post-excisional hypoglycemia is a frequent complication of pheochromocytoma resection, irrespective of the tumor location, and might be common in patients with epinephrine-predominant tumors. All patients undergoing resection of adrenal and extra-adrenal pheochromocytoma require intensive monitoring of serum glucose levels during and after surgery.
Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/efeitos adversos , Hipoglicemia/epidemiologia , Feocromocitoma/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Neoplasias das Glândulas Suprarrenais/urina , Adulto , Idoso , Glicemia , Epinefrina/urina , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Norepinefrina/urina , Período Perioperatório , Feocromocitoma/urina , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Background Exposure to green vegetation has been linked to positive health, but the pathophysiological processes affected by exposure to vegetation remain unclear. To study the relationship between greenness and cardiovascular disease, we examined the association between residential greenness and biomarkers of cardiovascular injury and disease risk in susceptible individuals. Methods and Results In this cross-sectional study of 408 individuals recruited from a preventive cardiology clinic, we measured biomarkers of cardiovascular injury and risk in participant blood and urine. We estimated greenness from satellite-derived normalized difference vegetation index ( NDVI ) in zones with radii of 250 m and 1 km surrounding the participants' residences. We used generalized estimating equations to examine associations between greenness and cardiovascular disease biomarkers. We adjusted for residential clustering, demographic, clinical, and environmental variables. In fully adjusted models, contemporaneous NDVI within 250 m of participant residence was inversely associated with urinary levels of epinephrine (-6.9%; 95% confidence interval, -11.5, -2.0/0.1 NDVI ) and F2-isoprostane (-9.0%; 95% confidence interval, -15.1, -2.5/0.1 NDVI ). We found stronger associations between NDVI and urinary epinephrine in women, those not on ß-blockers, and those who had not previously experienced a myocardial infarction. Of the 15 subtypes of circulating angiogenic cells examined, 11 were inversely associated (8.0-15.6% decrease/0.1 NDVI ), whereas 2 were positively associated (37.6-45.8% increase/0.1 NDVI ) with contemporaneous NDVI . Conclusions Independent of age, sex, race, smoking status, neighborhood deprivation, statin use, and roadway exposure, residential greenness is associated with lower levels of sympathetic activation, reduced oxidative stress, and higher angiogenic capacity.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Plantas , Características de Residência , Urbanização , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Ambiente Construído , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Células Progenitoras Endoteliais/patologia , Epinefrina/urina , F2-Isoprostanos/urina , Feminino , Humanos , Kentucky , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Fatores de Proteção , Medição de Risco , Fatores de Risco , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologiaRESUMO
AIMS: To inform research on the etiology and prevention of substance use among rural African American youth by (a) identifying developmental trajectory classes of cannabis use and heavy drinking across adolescence and young adulthood and (b) examining associations between trajectory class membership and multi-level assessments of risk factors. DESIGN: A prospective study spanning 9 years with assessments of cannabis use and heavy drinking, the catecholamines epinephrine and norepinephrine, perceived stress and psychosocial risk factors. SETTING: Rural communities in the southeastern United States. PARTICIPANTS: African American youth (n = 518). MEASUREMENTS: Participants were assessed for cannabis use and heavy drinking at seven assessments beginning at 16 years of age and continuing to 25 years of age. At age 19, participants provided overnight urine voids that were assayed for catecholamines, a biological marker of life stress resulting from sympathetic nervous system activation. At ages 16 and 19, participants provided information on malleable psychosocial risk factors. FINDINGS: Latent class growth models revealed three distinct trajectory classes for cannabis use and for heavy drinking. Higher levels of circulating stress hormones and perceived stress were associated with classes reporting greater substance use over time (all Ps < 0.05). A composite of selected risk factors discriminated class membership (all Ps < 0.05). Trajectory classes characterized by rapid usage increases in early adulthood exhibited the greatest increase in deviant peer affiliations between ages 16 and 19 years. CONCLUSIONS: Rural African American youth's cannabis use and heavy drinking across adolescence and young adulthood demonstrate distinct developmental courses; a small number of risk factors and measures of biological and perceived stress differentiate class membership prognostically. Variability over time in these measures, specifically an increase in deviant peer affiliation, may help to account for steep increases in young adulthood.
Assuntos
Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Uso da Maconha/epidemiologia , Estresse Psicológico/epidemiologia , Consumo de Álcool por Menores/estatística & dados numéricos , Desempenho Acadêmico/psicologia , Desempenho Acadêmico/estatística & dados numéricos , Adolescente , Adulto , Negro ou Afro-Americano/psicologia , Consumo Excessivo de Bebidas Alcoólicas/psicologia , Epinefrina/urina , Feminino , Amigos , Humanos , Análise de Classes Latentes , Masculino , Uso da Maconha/psicologia , Norepinefrina/urina , Relações Pais-Filho , Estudos Prospectivos , Racismo/psicologia , Racismo/estatística & dados numéricos , Fatores de Risco , População Rural , Sudeste dos Estados Unidos/epidemiologia , Estresse Psicológico/psicologia , Estresse Psicológico/urina , Consumo de Álcool por Menores/psicologia , Adulto JovemRESUMO
OBJECTIVE: Our objective was to improve molecular diagnostics in patients with hereditary pheochromocytoma and paraganglioma (PPGL) by using next-generation sequencing (NGS) multi-gene panel analysis. Derived from this study, we here present three cases that were diagnosed with NF1 germline mutations but did not have a prior clinical diagnosis of neurofibromatosis type 1 (NF1). DESIGN: We performed genetic analysis of known tumor predisposition genes, including NF1, using a multi-gene NGS enrichment-based panel applied to a total of 1029 PPGL patients. We did not exclude genes known to cause clinically defined syndromes such as NF1 based on missing phenotypic expression as is commonly practiced. METHODS: Genetic analysis was performed using NGS (TruSight Cancer Panel/customized panel by Illumina) for analyzing patients' blood and tumor samples. Validation was carried out by Sanger sequencing. RESULTS: Within our cohort, three patients, who were identified to carry pathogenic NF1 germline mutations, attracted attention, since none of the patients had a clinical suspicion of NF1 and one of them was initially suspected to have MEN2A syndrome due to co-occurrence of a medullary thyroid carcinoma. In these cases, one splice site, one stop and one frameshift mutation in NF1 were identified. CONCLUSIONS: Since phenotypical presentation of NF1 is highly variable, we suggest analysis of the NF1 gene also in PPGL patients who do not meet diagnostic NF1 criteria. Co-occurrence of medullary thyroid carcinoma and PPGL was found to be a clinical decoy in NF1 diagnostics. These observations underline the value of multi-gene panel NGS for PPGL patients.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Mutação em Linhagem Germinativa/genética , Neurofibromatose 1/genética , Feocromocitoma/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Sequência de Bases , Carcinoma Neuroendócrino/genética , Códon sem Sentido , Epinefrina/urina , Feminino , Genes da Neurofibromatose 1 , Predisposição Genética para Doença/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Hipertensão , Masculino , Metanefrina/urina , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/genética , Normetanefrina/urina , Paraganglioma/genética , Linhagem , Feocromocitoma/diagnóstico , Feocromocitoma/patologia , Neoplasias da Próstata , Neoplasias da Glândula Tireoide/genéticaRESUMO
BACKGROUND: Glucocorticoids influence the synthesis and metabolism of catecholamines (epinephrine and norepinephrine) and metanephrines (metanephrine and normetanephrine). The aim of this study was to measure urinary catecholamines and metanephrines in dogs with hypercortisolism before and during trilostane therapy. Urine samples were collected during initial work up and during therapy with trilostane in 14 dogs with hypercortisolism and in 25 healthy dogs. Epinephrine, norepinephrine, metanephrine and normetanephrine were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration. RESULTS: Untreated dogs with hypercortisolism had significantly higher epinephrine, norepinephrine, and normetanephrine:creatinine ratios compared to healthy dogs. During trilostane therapy, urinary catecholamines and their metabolites did not decrease significantly. However, dogs with low post-ACTH cortisol concentrations during trilostane therapy had less increased epinephrine, norepinephrine and normetanephrine:creatinine ratios compared to healthy dogs. There was no correlation of urinary catecholamines and their metabolites with baseline or post-ACTH cortisol or endogenous ACTH concentrations during trilostane therapy. CONCLUSION: Influences between steroid hormones and catecholamines seem to occur, as dogs with hypercortisolism have significantly higher urinary epinephrine, norepinephrine, and normetanephrine:creatinine ratios. Once-daily trilostane therapy does not lead to a significant decrease in catecholamines and their metabolites. Trilostane-treated dogs still have increased urinary epinephrine, norepinephrine and normetanephrine:creatinine ratios during trilostane therapy.
Assuntos
Catecolaminas/urina , Síndrome de Cushing/tratamento farmacológico , Di-Hidrotestosterona/análogos & derivados , Doenças do Cão/tratamento farmacológico , Animais , Catecolaminas/metabolismo , Síndrome de Cushing/metabolismo , Síndrome de Cushing/urina , Di-Hidrotestosterona/uso terapêutico , Doenças do Cão/urina , Cães , Epinefrina/urina , Feminino , Masculino , Metanefrina/metabolismo , Metanefrina/urina , Norepinefrina/urina , Normetanefrina/metabolismo , Normetanefrina/urina , Estudos ProspectivosRESUMO
The catecholamines, epinephrine (E) and norepinephrine (NE) are small polar, hydrophilic molecules, posing significant challenges to liquid chromatography - tandem mass spectrometry (LC-MS/MS) method development. Specifically, these compounds show little retention on conventional reversed-phase liquid chromatography columns. This work presents development and validation of an LC-MS/MS method for determining catecholamines in urine, based on a new approach to ion-pairing chromatography (IPC), in which the ion-pairing reagent (IPR), 1-Heptane Sulfonic Acid (HSA), is added to the extracted samples instead of the mobile phases. A Hamilton STARlet workstation carried out the solid phase extraction of urine samples. The extracted samples were diluted with 60mmol/L HSA and injected on a Kinetex core-shell biphenyl column with conventional LC-MS/MS suitable mobile phases. Chromatographic separation of E and NE was achieved successfully with very stable retention times (RT). In 484 injections, the RTs were steady with a CV of less than ±4%. Furthermore, HSA was separated from E and NE, allowing HSA to be diverted to waste instead of entering the mass spectrometer ion chamber. The method was validated with good analytical performance, and even though the analysis for urinary catecholamines is increasingly being replaced by plasma free metanephrines in diagnosing pheochromocytomas, this work represents the application of a new analytical technique that can be transferred to other small polar molecules, that are difficult to chromatograph on traditional reversed phase columns.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Epinefrina/urina , Norepinefrina/urina , Espectrometria de Massas em Tandem/métodos , Alcanossulfonatos , Calibragem , Cromatografia de Fase Reversa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Extração Líquido-Líquido , Propriedades de SuperfícieRESUMO
Severe hyperlactatemia (SH)/lactic acidosis (LA) after laparoscopic resection of pheochromocytoma is an infrequently reported complication. The study aims to investigate the incidence of this complication and to determine the clinical risk factors. Patients who underwent laparoscopic resection for pheochromocytoma between 2011 and 2014 at Peking Union Medical College Hospital were enrolled. LA was defined as pH < 7.35, bicarbonate <20 mmol/L, and serum lactate ≥5 mmol/L; SH as lactate ≥5 mmol/L; and moderate hyperlactatemia (MH) as lactate 2.5-5.0 mmol/L without evidence of acidosis (pH > 7.35 and/or bicarbonate >20 mmol/L). Data concerning patient demographics, clinical history, and laboratory results were collected and statistical analyses were performed. Out of 145 patients, 59 (40.7%) developed post-operative hyperlactatemia. The incidences of MH and SH/LA were 25.5% and 15.2%, respectively. Multivariate analysis demonstrated that body mass index (BMI) (odds ratio [OR], 1.204; 95% confidence interval [CI], 1.016-1.426), 24-hour urine epinephrine concentration (OR, 1.012; 95% CI, 1.002-1.022), and tumor size (OR, 1.571; 95% CI, 1.102-2.240) were independent predictors of post-operative SH/LA. The data show that post-operative SH/LA is not a rare complication after pheochromocytoma resection and may be closely associated with higher BMI, larger tumor size, and higher levels of urine epinephrine.
Assuntos
Acidose Láctica/epidemiologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Hiperlactatemia/epidemiologia , Laparoscopia/efeitos adversos , Feocromocitoma/cirurgia , Complicações Pós-Operatórias/epidemiologia , Acidose Láctica/etiologia , Neoplasias das Glândulas Suprarrenais/epidemiologia , Adulto , Índice de Massa Corporal , Epinefrina/urina , Feminino , Humanos , Hiperlactatemia/etiologia , Masculino , Pessoa de Meia-Idade , Feocromocitoma/epidemiologia , Fatores de RiscoRESUMO
Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8-15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3-29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.
Assuntos
Doenças Cardiovasculares/fisiopatologia , Ritmo Circadiano/fisiologia , Transtornos do Sono do Ritmo Circadiano/fisiopatologia , Tolerância ao Trabalho Programado/fisiologia , Actigrafia , Adulto , Pressão Sanguínea/fisiologia , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Estudos Cross-Over , Epinefrina/urina , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Polissonografia , Resistina/sangue , Fatores de Risco , Transtornos do Sono do Ritmo Circadiano/sangue , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
The article considers the technique of simultaneous detection of free catecholamines and free metanephrines in urine using inverse phase highly effective liquid chromatography with fluorimetric detection. The solid phase extraction was implemented on cartridges with 30 mg of hyper cross-linked polystyrene (Purosep-200). The simplicity, reproducibility and sufficient sensitivity of technique permit applying it in clinical practice to diagnose pheochromocytoma.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dopamina/urina , Epinefrina/urina , Metanefrina/urina , Norepinefrina/urina , Normetanefrina/urina , Adolescente , Adsorção , Adulto , Cromatografia Líquida de Alta Pressão/instrumentação , Fluorometria/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Extração em Fase Sólida/métodosRESUMO
An analytical method based on micellar liquid chromatography was developed to determine the concentration of three catecholamines (epinephrine, norepinephrine, and dopamine) in urine. The detection of these compounds in urine can be useful to diagnose several diseases, related to stress and sympathoadrenal system dysfunction, using a non-invasive collection procedure. The sample pretreatment was a simple dilution in a micellar solution, filtration, and direct injection, thus avoiding time-consuming and tedious extraction steps. Therefore, there is no need to use an internal standard. The three catecholamines were eluted using a C18 column and a mobile phase of 0.055 M sodium dodecyl sulfate-1.5% methanol buffered at pH 3.8 running at 1.5 mL/min under isocratic mode in less than 25 min. The detection was performed by amperometry applying a constant potential of +0.5 V. The procedure was validated following the guidelines of the European Medicines Agency in terms of the following: calibration range (0.09-5 µg/mL), linearity (r(2) > 0.9995), limit of detection (0.02 µg/mL), within- and between-run accuracy (-6.5 to +8.4%) and precision (<10.2%), dilution integrity, matrix effect, robustness (<8.4), and stability. The obtained values were below those required by the guide. The method was rapid, easy-to-handle, eco-friendly, and safe and provides reliable quantitative data, and is thus useful for routine analysis. The procedure was applied to the analysis of epinephrine, norepinephrine, and dopamine in urine samples from patients of a local hospital.
Assuntos
Neoplasias das Glândulas Suprarrenais/urina , Cromatografia Líquida/métodos , Dopamina/urina , Epinefrina/urina , Norepinefrina/urina , Feocromocitoma/urina , Hospitalização , HumanosRESUMO
BACKGROUND: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A-adrenoceptor agonist clonidine. METHODS: A total of 176 adolescent CFS patients (12-18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules (25 µg or 50 µg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model. RESULTS: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment. There were 14 drop-outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation of all RR-intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20° head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period. CONCLUSIONS: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance. TRIAL REGISTRATION: Clinical Trials ID: NCT01040429, date of registration 12/28/2009.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Clonidina/administração & dosagem , Síndrome de Fadiga Crônica/tratamento farmacológico , Síndrome de Fadiga Crônica/fisiopatologia , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/sangue , Clonidina/sangue , Creatinina/urina , Método Duplo-Cego , Epinefrina/sangue , Epinefrina/urina , Frequência Cardíaca/efeitos dos fármacos , Humanos , Norepinefrina/sangue , Norepinefrina/urina , Intolerância Ortostática/tratamento farmacológico , Intolerância Ortostática/fisiopatologia , Teste da Mesa InclinadaAssuntos
Neoplasias das Glândulas Suprarrenais/complicações , Biomarcadores Tumorais/urina , Epinefrina/urina , Insuficiência Cardíaca/etiologia , Miocardite/etiologia , Feocromocitoma/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/urina , Adrenalectomia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/urina , Humanos , Imageamento por Ressonância Magnética , Metanefrina/urina , Pessoa de Meia-Idade , Miocardite/diagnóstico , Miocardite/urina , Norepinefrina/urina , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Feocromocitoma/urina , Resultado do TratamentoRESUMO
OBJECTIVE: Depression and anxiety are considered risk factors for cardiovascular disease (CVD). The explanatory mechanisms, however, are still to be characterized. One proposed pathophysiological pathway is dysregulation of the autonomic nervous system, including heightened sympathetic nervous system activity. This study examined the relationship between symptoms of depression, anxiety, and sympathetic nervous system activity in individuals with untreated high blood pressure. METHODS: A total of 140 participants with untreated high blood pressure (55% white, 38.5% female, mean [standard deviation] age = 45.5 [8.55] years) collected urine over a 24-hour period on 3 separate occasions. Urine samples were assayed for mean 24-hour epinephrine (EPI24) and norepinephrine excretion. Depressive symptoms were assessed using the Beck Depression Inventory, with anxiety symptoms assessed using the Spielberger State-Trait Anxiety Inventory. RESULTS: Depression and anxiety scores were intercorrelated (r = 0.76, p < .001). EPI24 was positively correlated with anxiety (r = 0.20, p = .02) but not depression (r = 0.02, p = .77), whereas 24-hour urinary norepinephrine excretion was not correlated with anxiety (r = 0.10, p = .21) or with depression (r = 0.07, p = .39). Regression models, accounting for sex, age, body mass index, race, mean systolic ambulatory blood pressure, tobacco use, alcohol use, physical activity, and sleep efficiency confirmed that anxiety was associated with EPI24 excretion (p = .023) and that depressive symptoms were not (p = .54). CONCLUSIONS: Anxiety was associated with heightened sympathoadrenal activity, suggesting a biological pathway through which anxiety could increase CVD risk. Anxiety and depression may confer increased CVD risk via different mechanisms.
Assuntos
Ansiedade/urina , Depressão/urina , Epinefrina/urina , Hipertensão/urina , Norepinefrina/urina , Ansiedade/complicações , Depressão/complicações , Feminino , Humanos , Hipertensão/complicações , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
STUDY OBJECTIVE: To determine the relationship between preoperative catecholamine levels and intraoperative peak plasma lactate levels in patients who underwent adrenalectomy for pheochromocytoma. DESIGN: Retrospective observational study. SETTING: Operating room in one university hospital. MEASUREMENTS: The records of 27 ASA physical status 1 and 2 patients who underwent adrenalectomy for pheochromocytoma were studied. Preoperative catecholamine levels and intraoperative plasma lactate levels were recorded. MAIN RESULTS: Twenty cases had high lactate levels (>2 mmol/L). Preoperative urine epinephrine levels and urine metanephrine levels showed a moderate correlation with intraoperative peak plasma lactate levels (rs = 0.475 and rs = 0.499, respectively; Spearman's rank correlation test). Receiver operating characteristic (ROC) curve analysis for preoperative urine epinephrine levels showed good performance for prediction of high lactate levels [>2 mmol/L, area under the curve (AUC) =0.800], whereas ROC for preoperative urine norepinephrine levels showed no predictive performance for high lactate levels. CONCLUSIONS: Catecholamine release caused by surgical manipulation may be a possible cause of intraoperative transient lactic acidosis, and it should be considered as a differential diagnosis of intraoperative lactic acidosis. Intraoperative peak plasma lactate level was correlated with preoperative epinephrine-releasing activity.
Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Ácido Láctico/sangue , Feocromocitoma/cirurgia , Adulto , Epinefrina/urina , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/urina , Estudos RetrospectivosRESUMO
BACKGROUND: Stroke leads to transient immunedepression, which leads to increased incidence of poststroke infections. Because infection is one of the most common causes of increased mortality in patients with stroke, this study was undertaken to document immunedepression after stroke in our population. METHODS: A case-controlled study wherein 39 patients with acute ischemic stroke in the age group of 18 and 60 years without any evidence of previous immunedepression were included. Interleukin 6 (IL-6) and interleukin 10 (IL-10) levels were checked in plasma in both the groups on day 3 and day 45. Also Cortisol and epinephrine levels were checked in the urine samples collected on day 3 and day 8. RESULTS: No significant difference was seen between the IL-6 and the IL-10 levels in samples collected on day 3 between the controls and cases, whereas Cortisol and norepinephrine were significantly raised in samples collected on day 3 in cases who developed infection as compared with controls. CONCLUSIONS: The higher levels of urinary cortisol and norepinephrine were observed in patients with stroke who developed infections, which indirectly reflected increased amount of stroke related stress. Furthermore, the levels of plasma IL-6 and IL-10 were also elevated in the same group of patients, which means transformation of immunecompetence to immunedepression, which is responsible for higher mortality. Subsequently on recovery from infection the plasma levels of interleukins and urinary cortisol and norepinephrine did not show any difference, which indirectly means recovery of the immune system on recovery from acute stage of stroke. Mortality in the patients with infection was increased than controls.
Assuntos
Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Epinefrina/urina , Humanos , Hidrocortisona/urina , Índia , Interleucina-10/sangue , Interleucina-6/sangue , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/urina , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Medication-related interferences with measurements of catecholamines and their metabolites represent important causes of false-positive results during diagnosis of phaeochromocytomas and paragangliomas (PPGLs). Such interferences are less troublesome with measurements by liquid chromatography with tandem mass-spectrometry (LC-MS/MS) than by other methods, but can still present problems for some drugs. Levodopa, the precursor for dopamine used in the treatment of Parkinson's disease, represents one potentially interfering medication. METHODS: Plasma and urine samples, obtained from 20 Parkinsonian patients receiving levodopa, were analysed for concentrations of catecholamines and their O-methylated metabolites by LC-MS/MS. Results were compared with those from a group of 120 age-matched subjects and 18 patients with PPGLs. RESULTS: Plasma and urinary free and deconjugated (free + conjugated) methoxytyramine, as well as urinary dopamine, showed 22- to 148-fold higher (P < 0.0001) concentrations in patients receiving levodopa than in the reference group. In contrast, plasma normetanephrine, urinary noradrenaline and urinary free and deconjugated normetanephrine concentrations were unaffected. Plasma free metanephrine, urinary adrenaline and urinary free and deconjugated metanephrine all showed higher (P < 0.05) concentrations in Parkinsonian patients than the reference group, but this was only a problem for adrenaline. Similar to normetanephrine, plasma and urinary metanephrine remained below the 97.5 percentiles of the reference group in almost all Parkinsonian patients. CONCLUSIONS: These data establish that although levodopa treatment confounds identification of PPGLs that produce dopamine, the therapy is not a problem for use of LC-MS/MS measurements of plasma and urinary normetanephrine and metanephrine to diagnose more commonly encountered PPGLs that produce noradrenaline or adrenaline.
Assuntos
Levodopa/administração & dosagem , Paraganglioma/diagnóstico , Doença de Parkinson/tratamento farmacológico , Feocromocitoma/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Dopamina/análogos & derivados , Dopamina/sangue , Dopamina/urina , Epinefrina/sangue , Epinefrina/urina , Feminino , Humanos , Levodopa/efeitos adversos , Masculino , Metanefrina/sangue , Metanefrina/urina , Pessoa de Meia-Idade , Norepinefrina/sangue , Norepinefrina/urina , Normetanefrina/sangue , Normetanefrina/urina , Paraganglioma/sangue , Paraganglioma/patologia , Paraganglioma/urina , Doença de Parkinson/sangue , Doença de Parkinson/urina , Feocromocitoma/sangue , Feocromocitoma/patologia , Feocromocitoma/urina , Espectrometria de Massas em TandemRESUMO
Tumors that grow within the adrenal medulla are called pheochromocytoma; when located extra-adrenal, they are called paraganglioma. Paraganglioma of the bladder are very rare, with only 180 reported cases. Less than 30 were malignant. We report a case of a 72-years old man with bladder paraganglioma who presented with painless hematuria. Urgent transurethral resection (TUR) was performed. Definitive pathohistological diagnosis was confirmed to imunohistochemical and electron microscopy. Clinical diagnostic showed normal value of epinephrine and norepinehrine in the urine. Scintigraphy of entire body and targeted pictures of pelvis where taken 24, 48 and 72 hours after administration of RI. No loci of pathologic accumulation of 131-I MIBG where found. Computer tomography (CT) of pelvis and abdomen were normal. Considering staging and pathohistological analysis, we treated our patient with TUR and longtime follow-up afterworth.