Metabolic study of trimetazidine using ultra-high performance liquid chromatography-tandem mass spectrometry

Abstract In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known-as well as hitherto unknown-trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0-4 h, 4-8 h, 8-12 h, and 12-24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites

La determinación económica, social y laboral de la enfermedad renal crónica de causas no tradicionales (ERCnT) en la costa sur de Guatemala / The economic, social and labor determination of chronic kidney disease of non-traditional causes (CKDnT) on the southern coast of Guatemala

La flexibilidad laboral es característica de la producción estacional agroindustrial, cuyo principal problema es aprovechar con intensidad los períodos en los que se incrementa la producción. Pero, ¿cómo la demandante competitividad laboral influye en las estrategias de los trabajadores para incrementar su productividad? A partir de esta pregunta, se identificaron los aspectos económicos, sociales y laborales que inciden en la salud, así como las respuestas para disminuir el dolor físico y aumentar las exigencias de competitividad, flexibilización y desregularización del mercado de trabajo. La exposición ambiental y ocupacional en las condiciones de trabajo, el estrés térmico asociado a la deshidratación en la actividad física intensa, el limitado acceso a los servicios de salud, la mala alimentación y la pobre calidad de vida, también pueden producir otras enfermedades como diabetes e hipertensión, así como infecciones y lesiones renales. En ese contexto, en los últimos 20 años, se empezaron a reportar casos de enfermedad renal. La metodología cualitativa aplicada a este estudio, permitió llevar a cabo un proceso investigativo descriptivo e interpretativo sobre la forma en que los sujetos interactúan. Para ello se utilizaron las trayectorias laborales como técnicas en la recolección de datos. Los resultados arrojaron información relevante sobre las estrategias que los trabajadores utilizan para incrementar su rendimiento laboral, entre ellas la automedicación de vitaminas y analgésicos para tratar los espasmos musculares, que estimulan el sistema nervioso central, así como de bebidas saborizadas y energizantes con posibles repercusiones en la excreción renal.

Labor flexibility is characteristic of seasonal agroindustrial production whose main problem is to take advantage of the periods in which production increases. But, how does this demanding labor competitiveness influence workers' strategies to increase their productivity? From this question, the economic, social and labor aspects that affect health were identified, as well as the answers to reduce physical pain and increase the demands for competitiveness, flexibility and deregulation of the labor market. Environmental and occupational exposure in working conditions, thermal stress associated with dehydration in intense physical activity, limited access to health services, poor diet and quality of life, can also cause other diseases such as diabetes and hypertension, as well as infections and kidney lesions. In that context, in the last 20 years, cases of kidney disease began to be reported. The qualitative methodology applied to this study, allowed to carry out a descriptive and interpretive investigation process on the way in which the subjects interact, for this, the work trajectories were used as techniques in data collection. The results yielded relevant information on the strategies that workers use to increase their work performance, including self-medication of "vitamins" and analgesics to treat muscle spasms, drugs that stimulate the central nervous system, as well as flavored and energizing drinks with possible repercussions on renal excretion.

Augmented renal clearance

Adding to the complexity of caring for critically ill patients is the fact that many of them have a creatinine clearance that exceeds 130 mL/min/1.73 m². This phenomenon, termed augmented renal clearance (ARC), has only recently been widely recognized and its pathogenesis remains incompletely understood. However, ARC has been shown to result in increased dose requirements for drugs that are primarily eliminated by renal excretion, including many antimicrobial agents and enoxaparin. Recognition of ARC is hampered by the fact that the standard creatinine-based equations used to estimate renal function are not accurate in this clinical setting and the diagnosis is best established using both serum and urine creatinine measurements to calculate clearance. So a high index of clinical suspicion and awareness is usually required before this step is taken to confirm the diagnosis of ARC.

Determination of renal handling of marbofloxacin in Lohi sheep [Ovis aries] following a single intravenous administration

The objective of present study was to investigate renal clearance, urinary excretion and underlying excretory mechanism of marbofloxacin in Lohi sheep. For this purpose, marbofloxacin was administered intravenously [IV] as single bolus dose [2.5 mg/kg body weight] to eight healthy sheep of Lohi breed. After start of experiment, blood and urine samples were drawn at predetermined time intervals and marbofloxacin concentrations in the samples were measured by reverse phase high performance liquid chromatography [RP-HPLC] using UV/Vis detector. The mean +/- SD values of creatinine in plasma and urine were 15.37 +/- 0.65 micro g/ml and 246.7 +/- 48.05 micro g/ml, respectively. Glomerular filtration rate was 1.29 +/- 0.22 ml/min/kg whereas urinary flow rate was observed to be 0.084 +/- 0.016 ml/min/kg. The renal clearance of marbofloxacin in Lohi sheep was 9.45 +/- 2.12 ml/min/kg. Cumulative percentage dose excreted was seen to be maximum at 24 h post drug administration. It was concluded that renal handling of marbofloxacin in Lohi sheep involved both glomerular filtration and active tubular secretion

Balanço hídrico e excreção renal de metabólitos em ovinos alimentados com palma forrageira (Nopalea cochenillifera Salm Dyck) / Water balance and renal excretion of metabolites in sheep fed forage cactus (Nopalea cochenillifera Salm Dyck)

Objetivou-se avaliar balanço hídrico e excreção renal de metabólitos em borregos sem raça definida, alimentados com diferentes quantidades de palma forrageira (Nopalea cochenillifera Salm Dyck), na forma in natura e em farelo. Foram utilizados 20 borregos, com peso vivo médio inicial de 20 Kg e foram distribuídos no delineamento inteiramente casualizado, sendo cinco tratamentos e quatro repetições. As dietas experimentais consistiram em uma dieta controle à base de feno de tífton, farelo de soja, suplemento mineral e calcário, os demais tratamentos visaram testar níveis diferentes de palma forrageira corrigida com ureia em duas formas: in natura e farelada e em dois níveis de substituição (50 e 100%) da matéria seca do feno de tífton. Amostras de sangue e urina foram coletadas para determinação de diferentes metabólitos e minerais e utilização de equações para obtenção dos índices de excreção urinária destes metabólitos, taxa de depuração endógena de creatinina e reabsorção de água livre de eletrólitos, além do registro de ingestão de água e volume de urina. A ingestão voluntária de água sofreu influência das dietas, sendo que os animais submetidos às dietas contendo farelo de palma e feno e farelo de palma foram superiores aos demais tratamentos. A ingestão de água via alimentos também sofreu influência da dieta, sendo maior nos animais que receberam palma in natura e farelo mais palma in natura. Com relação à ingestão total de água foi maior para os animais alimentados com dietas contendo palma in natura em relação aos demais tratamentos. As dietas experimentais influenciaram na excreção renal de metabólitos derivados purínicos e minerais, sem alterar a função renal. A presença da palma forrageira tanto na condição de farelo como in natura proporciona aumento do volume urinário sem alterar a função renal, além de que deve ser considerado como uma excelente estratégia alimentar no semiárido.

This study aimed to assess fluid balance and renal excretion of metabolites in lambs without defined breed standard, fed different forage cactus (Nopalea cochenillifera Salm Dyck), in natura and bran. 20 lambs were used, with initial body weight of 20 kg and were distributed in a completely randomized design, with five treatments and four repetitions. The experimental diets consisted of a control diet based on Bermuda grass hay, soybean meal, limestone and mineral supplement, other treatments aimed at testing different levels of cactus pear plus urea in two forms: fresh and mash and two levels of substitution (50 and 100%) of dry matter of hay. Blood and urine samples were collected for determination of different metabolites and minerals and use of equations to determine the rates of urinary excretion of these metabolites, rate of endogenous creatinine clearance and electrolyte reabsorption of free water, in addition to recording of water intake and urine volume. The voluntary water intake was influenced by the diets, and the animals subjected to diets containing soybean meal and hay palm and cactus meal were higher than other treatments. Water intake via food was also influenced by diet, being higher in animals fed palm fresh and bran over palm in nature. With respect to total water intake was greater for cows fed diets containing palm in nature compared to the other treatments. The experimental diets influenced the renal excretion of purine metabolites and minerals derived, without changing renal function. The presence of cactus pear both as bran as in nature provides increased urine volume without changing renal function, and to be considered as an excellent food strategy in semiarid.

Therapeutic drug monitoring of vancomycin in a patient with Duchenne muscular dystrophy (DMD): A case report

Vancomycin is a widely used glycopeptide antibiotic that requires therapeutic drug monitoring (TDM) owing to its narrow therapeutic window. It is primarily eliminated by renal excretion; thus, estimating the renal function of a patient is vital in the TDM of vancomycin. In patients with Duchenne muscular dystrophy (DMD), it is difficult to estimate the glomerular filtration rate using the serum creatinine level owing to the pathophysiological nature of the disease. Here, we report a case of a patient in whom TDM of vancomycin was performed, and explore the appropriate methods for evaluating renal function in patients with DMD based on serum levels of creatinine and cystatin C.

A Case of Isolated Glycosuria Mediated by an SLC5A2 Gene Mutation and Characterized by Postprandial Heavy Glycosuria Without Salt Wasting

Familial renal glycosuria (FRG) is an inherited disorder characterized by persistent glycosuria in the absence of hyperglycemia. It is caused by mutations in the sodium-glucose co-transporter, leading to increase in the renal excretion of glucose and sodium. However, there have been no studies on the role of fasting and postprandial changes in the urinary sodium excretion in patients with FRG. We report a case of renal glycosuria, which was confirmed by a SLC5A2 mutation via gene sequencing, and compared the postprandial urinary glucose and sodium excretion. A 26-year-old man sometimes experienced glycosuria on routine screening; however, other laboratory findings were normal. His fasting and postprandial urinary glucose excretion levels were 295mg/dL and 2,170mg/dL, respectively. The fasting and postprandial urinary sodium excretion levels were 200mEq/L and 89mEq/L, respectively. In patients with FRG, excessive diuresis might be prevented by a compensatory mechanism that reduces postprandial sodium excretion.

Insuficiencia renal aguda secundaria a aciclovir: Reporte de caso y revisión de la literatura / Acute renal failure secondary to acyclovir. Case report and literature review

La excreción renal es uno de los principales mecanismos para la eliminación de medicamentos, lo cual convierte a los riñones en blanco frecuente de lesión. Distintos medicamentos han sido asociados a desarrollo de insuficiencia renal aguda. El aciclovir es un antiviral altamente efectivo en el tratamiento de infecciones por virus del complejo Herpesviridae y puede causar daño renal agudo por depósito de cristales en los túbulos contorneados distales. Se presenta el caso de un paciente, quien desarrolla insuficiencia renal aguda secundaria probablemente a tratamiento con aciclovir intravenoso administrado para manejo de herpes zóster facial.

Renal excretion is one of the main mechanisms for the elimination of drugs, which makes the kidneys a frequent target of injury. Various drugs have been associated with development of acute renal failure. Acyclovir is an antiviral highly effective in the treatment of herpes virus infections and can cause acute kidney damage for crystal deposition in the distal convo-luted tubules. Here we present a case report on a patient who developed acute renal failure likely due to intravenous acyclovir administered for the treatment of facial herpes zoster.

Adiposidad abdominal, insulino-resistencia, hipertensión y sodio urinarioen adolescentes obesos / Abdominal adiposity, insulin resistance, hypertension and urinary sodium in obese adolescents / Adiposidade abdominal, insulino-resistência, hipertensão e sódio urinário em adolescentes obesos

El objetivo de este estudio fue evaluar la relación entre adiposidad abdominal con insulino-resistencia, hipertensión arterial y excreción urinaria de sodio en adolescentes obesos. Se realizó un estudio transversal descriptivo que incluyó 107 adolescentes obesos, entre 10 y 14 años, sin restricción dietaria, provenientes del Hospital de Pediatría-Posadas, Misiones, durante los años 2011-2012. Se definió obesidad abdominal según: perímetro de cintura ≥p90, hipertensión arterial: presión arterial sistólica y/o diastólica ≥p95 y prehipertensión ≥p90 y

The aim of this study was to assess abdominal adiposity relationship with insulin resistance, high blood pressure and urinary sodium excretion in an obese adolescent population. A descriptive cross sectional study that included 107 obese teenagers from 10 to 14 years of age without any dietary restriction was performed during 2011 and 2012 at the Pediatric Hospital, in Posadas, Misiones. Abdominal obesity was defined as: waist perimeter ≥p90, hypertension: systolic and/or diastolic pressure ≥p95 and prehypertension ≥p90 and

O objetivo deste estudo foi avaliar a relação de adiposidade abdominal com insulino-resistência, hipertensão arterial e excreção urinária de sódio em adolescentes obesos. Foi realizado um estudo transversal descritivo que incluiu 107 adolescentes obesos, entre 10 e 14 anos, sem restrição na dieta, provenientes do Hospital de Pediatría Posadas, Misiones, durante os anos 2011-2012. Definiu-se obesidade abdominal conforme o perímetro de cintura ≥p90, hipertensão arterial: pressão arterial sistólica e/ou diastólica ≥p95 e pré-hipertensão ≥p90 e

Urinary Albumin Excretion Rate: Diagnostic and Prognostic Utility in Essential Hypertension.

Context : To evaluate the usefulness of urinary albumin excretion rate (UAER) i.e. Albumin/Creatinine Ratio (ACR) in diagnosis and prognosis of essential hypertension (EHT). Objectives : To find out the association of urinary albumin excretion rate with the pathophysiology of essential hypertension. Study Design : A cross-sectional analytical study. Materials & Methods : Urinary albumin excretion (UAE), urinary creatinine (UC) and UAER were analyzed and compared between hypertensive cases and age & sex matched normotensive controls of age group 30-65 years using unpaired two-tailed Student ‘t’ test. All statistical analyses were done with PASW (SPSS) v.18.0. Results : Systolic BP (SBP) and diastolic BP (DBP) of cases were found to be significantly higher (p < 0.001) than controls. Urine MAlb level (p < 0.001) and ACR (p < 0.001) in cases were significantly higher compared to controls. Correlation studies showed that SBP and DBP was significantly positively correlated with urine MAlb (SBP: r = 0.859, DBP: r = 0.733; p < 0.001) and ACR (SBP: r = 0.830, DBP: r = 0.739; p < 0.001). Sex-wise comparison in cases revealed that males had statistically non-significant (p > 0.05) lower levels of urine MAlb as compared to females but had significantly higher (p < 0.001) levels of urine creatinine and lower (p < 0.001) ACR compared to females. Conclusion: Urinary MAlb levels and ACR are seen to be increased in hypertensive subjects compared to normotensive subjects. ACR was significantly higher in female hypertensives than males which can be credited to the physiologically observed lower urine creatinine levels compared to males. Both Microalbuminuria and ACR can serve as specific and well-established marker of cardiovascular and renal damage in EHT.

Effect of Corticosteroids on Renal Excretion of Lithium / 영남의대학술지

Lithium salts are being used increasingly to treat patient with affective disorders, especially acute mania, or bipolar manic-depressive illness. For therapeutic effect the lithium content must be maintained at or above a particular level. Lithium poisoning due to overdosage may be seen occasionally, and its course is determined primarily by the rate of renal lithium elimination. A search is therefore indicated for procedures that could raise the lithium clearance. In a number of reports renal lithium excretion has been studied in relation to the excretion of water, sodium, potassium and hydrogen, but effects of sodium or water on the lithium excretion has not yet been clarified. Hence the present study was undertaken to investigate the effects of corticosteroid on the excretion of lithium ion. The female rat (Sprague-Dowley), weighing from 200 to 300g, was injected with 50mg/kg of lithium chloride intraperitoneally, and then injected with graded dosage of fludrocortisones and dexamethasone in each group. During the injected rats were incubated in metabolic cage, 24 hour urine of rats were collected. At 24 hours after injection, the rats were sacrificed with guillotine, the blood were collected. And then the concentrations of Na⁺, K⁺, Li⁺ of collected urine and serum were checked by Flame photometer. The results are summarized as follows 1. Fludrocortisone decreased the serum concentration of lithium and increased the urinary excretion of lithium. 2. In the group treated with low dose of dexamethasone (0.1 mg/kg), the serum concentration of lithium was decreased and high dose of dexamethasone (1 mg/kg) increased the urinary excretion of lithium. 3. Fludrocortisone increased the urinary [Na⁺]/[K⁺] in serum and decreased [Na⁺]/[K⁺] inurine, but opposite effects were occurred in dexamethasone. By above results, it may be concluded that corticosteroid increased the urinary excretion of lithium and decreased the serum concentration of lithium, but it seems to be there in no relationship between these effects of corticosteroid and of the renal Na⁺ or K⁺ transport.