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The phytosteroid ecdysterone is classified as an anabolic agent and has been included on the monitoring list of the World Anti-Doping Agency since 2020. Therefore, the consumption of food rich in ecdysterone, such as quinoa and spinach, is the focus of a lively debate. Thus, the urinary excretion of ecdysterone and its metabolites in humans was investigated following quinoa consumption alone and in combination with spinach. Eight participants (four male and four female) were included, and they ingested 368 ± 61 g cooked quinoa alone and in combination with 809 ± 115 g spinach after a washout. Post-administration urines were analyzed by LC-MS/MS. After intake of both preparations, ecdysterone and two metabolites were excreted in the urine. The maximum concentration of ecdysterone ranged from 0.44 to 5.5 µg/mL after quinoa and from 0.34 to 4.1 µg/mL after quinoa with spinach. The total urinary excreted amount as parent drug plus metabolites was 2.61 ± 1.1% following quinoa intake and 1.7 ± 0.9% in combination with spinach. Significant differences were found in the total urinary excreted amount of ecdysterone, 14-deoxy-ecdysterone, and 14-deoxy-poststerone. Only small portions of ecdysterone from quinoa and the combination with spinach were excreted in the urine, suggesting that both quinoa and spinach are poor sources of ecdysterone in terms of bioavailability.
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Chenopodium quinoa , Spinacia oleracea , Chenopodium quinoa/química , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Espectrometría de Masas en Tándem , Cromatografía LiquidaRESUMEN
Background and Objectives: Job strain is a psychological, physical, and behavioral stress that occurs at the workplace. Job strain is associated with more than double the normal risk of coronary artery disease (CAD). The main aim of this study was to determine the association between job strain and the following parameters: high-sensitivity C-reactive protein (hs-CRP), the albumin urine excretion rate (AUER), and secondary-level testing. Materials and Methods: This study was a descriptive cross-sectional study conducted on patients who underwent cardiological assessment between October 2023 and February 2024 at the Promedicanon Cardiology Center. This study comprised 210 participants, with two groups: 105 chronic coronary syndromes (CCS) patients and 105 no-CCS patients. The baseline characteristics collected were age, gender, education, rural/urban environment, traditional CAD risk factors, hs-CRP, and AUER. The secondary-level testing included an electrocardiogram (ECG), echocardiography, and enhanced contrast computed tomography (ECCT). Psychological questionnaires comprised the tertiary-level testing, including the PHQ-9 depression questionnaire, and the satisfaction with work scale (SWWS) for job strain (Likert score). Results: The baseline characteristics were all significantly different between the groups (p < 0.05) except for total cholesterol. The hs-CRP level had a mean value of 0.4837 ± 0.19082 in the CCS group; for the no-CCS group, the hs-CRP mean value was 0.2289 ± 0.11009; p-value < 0.001. The AUER had a mean value of 42.770 ± 12.8658 for the CCS group and 26.432 ± 9.7338 for the no-CCS group; p-value < 0.001. For the associations between secondary-level testing and job strain: p < 0.001 for ST depression, negative T-waves, and q-waves; p = 0.415 for atrial fibrillation (AF); p = 0.018 for wall motion studies; p = 0.005 for ECCT. The association between job strain and AF had no statistical significance. The contractility of left ventricle walls and coronary calcification score were associated with job strain, with statistical significance. The p-value was 0.013 for the relationship between depression and the ECCT; for the association between depression and CCS status, the p-value was 0.021. Depression is usually diagnosed in job strain. The association between depression, and coronary calcification, as well as depression and CCS status had statistical significance. Conclusions: Job strain increased the hs-CRP level and AUER in both the CCS and no-CCS patients. The primary and secondary prevention of CHD could also include interventions to reduce job strain.
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Biomarcadores , Proteína C-Reactiva , Estrés Laboral , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Estrés Laboral/complicaciones , Estrés Laboral/fisiopatología , Estrés Laboral/psicología , Proteína C-Reactiva/análisis , Biomarcadores/sangre , Biomarcadores/análisis , Isquemia Miocárdica/psicología , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/epidemiología , Electrocardiografía/métodos , Adulto , Anciano , Encuestas y Cuestionarios , Ecocardiografía/métodos , Factores de Riesgo , Endotelio Vascular/fisiopatologíaRESUMEN
Cimetidine at a clinical dosage decreased the renal clearance (CLr) of mirogabalin in humans by inhibition of renal secretion. Mirogabalin is a substrate of human OAT1/3, OCT2, MATE1 and/or MATE2-K. To clarify the mechanism behind the above interaction, it was investigated whether cimetidine inhibits the process of mirogabalin uptake at the basolateral side or the process of its efflux at the apical side in rat kidney in vivo.Cimetidine was administered to rats by a constant infusion to achieve an unbound plasma concentration of 7.0 µM and examine its effect on the renal disposition of [14C]metformin, [3H]p-aminohippuric acid (PAH), and [14C]mirogabalin.Cimetidine significantly induced the intrarenal accumulation of radioactivity (Kp, kidney) and decreased the renal clearance (CLr) of [14C]mirogabalin. These effects resulted in significantly decreased total clearance (CLt). Kp, kidney, and CLr of [14C]metformin, except CLt, were also affected, but no parameters of [3H]PAH were affected by cimetidine.These findings clarified that an unbound plasma concentration of cimetidine of 7.0 µM inhibited the apical efflux not the basolateral uptake of [14C]mirogabalin in rat kidney, suggesting that mirogabalin/cimetidine interaction was caused by inhibiting the apical efflux transporter, human MATE1 and/or MATE2-K, not the basolateral uptake transporter, human OCT2, in the kidney.
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Cimetidina , Metformina , Ratas , Humanos , Animales , Cimetidina/farmacología , Proteínas de Transporte de Catión Orgánico , Transportador 2 de Cátion Orgánico , Riñón , Metformina/farmacologíaRESUMEN
OBJECTIVES: Protein Z (PZ) is a γ-carboxyglutamic acid protein present in plasma that is involved in blood coagulation. Detailed analysis of urinary stones from patients with urolithiasis has revealed that PZ is often found in urinary stones composed of calcium oxalate monohydrate. In this study, we compared blood and urinary PZ concentrations between healthy individuals and patients with urolithiasis. METHODS: Plasma and urine were collected from healthy individuals and patients with urolithiasis who provided informed consent. PZ was detected as a urinary stone matrix protein in some of the patients. PZ was quantified by ELISA, creatinine was measured by the enzymatic method, and the total protein concentration was measured by the Bradford method. RESULTS: The plasma PZ level was 2.54 ± 1.02 µg/mL in healthy individuals and that in urolithiasis patients classified by stone history were from 1.16 ± 0.77 to 3.73 ± 1.09 µg/mL, which was not significantly different. The urinary excretion of PZ (PZ/creatinine) was also not different in patients with urolithiasis and in healthy individuals (from 54.1 ± 40.9 to 95.4 ± 69.4 ng/mg vs. 73.3 ± 36.0 ng/mg). A positive correlation was found between the plasma PZ level and creatinine-corrected urinary PZ concentration (r = 0.46). CONCLUSIONS: Both the plasma level and urinary excretion of PZ in urolithiasis patients were not significantly different with normal individuals. PZ detected in urinary stones as a matrix protein is thought to be incorporated into urinary stones regardless of blood and urine levels of PZ.
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Cálculos Urinarios , Urolitiasis , Humanos , Creatinina , Cálculos Urinarios/metabolismo , Proteínas Sanguíneas , CalcioRESUMEN
PURPOSE: Patients with chronic kidney disease (CKD) complicated by hypothyroidism exhibit a higher prevalence of urine protein than that in the general population. This study was aimed at investigating thyroid hormones and thyroid hormone-binding proteins excreted in urine to elucidate the urine protein-associated underlying mechanisms of hypothyroidism. METHODS: Between November 2016 and August 2018, thyroid function (serum free T3 [sFT3], free T4 [sFT4], and thyroid-stimulating hormone [sTSH]), kidney function (estimated glomerular filtration rate [eGFR]), thyroid antibodies and albumin (Alb) were evaluated in 99 Japanese CKD patients with proteinuria at our outpatient clinic. A urine examination was also performed to assess the following parameters: total T3, total T4, TSH, Alb, preAlb, thyroid-binding globulin, and protein. RESULTS: The median patient age at study recruitment was 60 years; 50 patients (50.5%) were male. The median eGFR and Alb level were 20.3 ml/min/1.73 m2 and 3.8 g/dL, respectively. 21 patients (21.2%) were diagnosed with nephrotic syndrome (NS). The median sFT3, sFT4, and sTSH levels were within normal limits. Approximately 70% of the patients had thyroid dysfunction and 51.5% had overt or subclinical hypothyroidism without predominantly antibody positive. Regarding NS and non-NS patients, age and Alb were significantly different between these groups, while sex and eGFR were not significant, but the urinary T4 and TSH levels were higher in the NS group; thus, more severe hypothyroid. CONCLUSION: We found a significant association between hypothyroidism and NS regardless of sex and antibodies. Urinary loss of thyroid hormones must be a factor influencing hypothyroidism independent of autoimmunity.
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Hipotiroidismo , Síndrome Nefrótico , Insuficiencia Renal Crónica , Humanos , Masculino , Persona de Mediana Edad , Femenino , Hipotiroidismo/complicaciones , Hormonas Tiroideas/metabolismo , Tirotropina , Síndrome Nefrótico/complicacionesRESUMEN
Diabetic nephropathy (DN) is a common complication of diabetes. DN progresses to end-stage renal disease, which has a high mortality rate. Current research is focused on identifying non-invasive potential biomarkers in the early stage of DN. We previously indicated that pyruvate kinase M2 (PKM2) is excreted in the urine of rats after cisplatin-induced acute kidney injury (AKI). However, it has not been reported whether PKM2 can be used as a biomarker to diagnose DN. Therefore, we try to compare whether the protein PKM2 can be detected in the urine samples from diabetic patients as shown in the results of DN models. In this study, high-fat diet (HFD)-induced Zucker diabetic fatty (ZDF) rats were used for DN phenotyping. After 19 weeks of receiving a HFD, the DN model's blood glucose, blood urea nitrogen, and serum creatinine levels were significantly increased; severe tubular and glomerular damages were also noted. The following protein-based biomarkers were increased in the urine of these models: kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and PKM2. PKM2 had the earliest detection rate. In the urine samples of patients, PKM2 protein was highly detected in the urine of diabetic patients but was not excreted in the urine of normal subjects. Therefore, PKM2 was selected as the new biomarker for the early diagnosis of DN. Our results reflect current knowledge on the role of PKM2 in DN.
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Diabetes Mellitus , Nefropatías Diabéticas , Ratas , Animales , Nefropatías Diabéticas/etiología , Piruvato Quinasa/metabolismo , Ratas Zucker , Lipocalina 2 , Diagnóstico Precoz , BiomarcadoresRESUMEN
BACKGROUND: Urinary metabolites of vitamin E, i.e., α- and γ-carboxyethyl hydroxychroman (α- and γ-CEHC), have gained increasing attention and have been proposed as novel biomarkers of vitamin E intake and status. However, there are insufficient data on the relationship of plasma α-tocopherol and γ-tocopherol and dietary vitamin E intake with 24 h urinary excretions of α- and γ-CEHC. OBJECTIVES: We aimed to (1) investigate the associations of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC with plasma α- and γ-tocopherol, respectively; (2) investigate the associations of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC with dietary vitamin E intake, and we hypothesize that 24 h urinary excretions of α- and γ-CEHC will better correlate with vitamin E intake than urinary α- and γ-CEHC/creatinine ratios. DESIGN: 24 h Urine and plasma samples were collected from 1519 participants (60-75 years, male: 50%) included in the Lifelines-MINUTHE Study for the assessments of urinary α- and γ-CEHC/creatinine ratios and 24 h urinary excretions of α- and γ-CEHC, and plasma α- and γ-tocopherol. Among those participants, dietary vitamin E intake data from 387 participants were available from an externally validated Flower-Food Frequency Questionnaire (FFQ). The associations of plasma α- and γ-tocopherol, dietary vitamin E intake, with urinary α- and γ-CEHC were assessed using multivariate linear regressions. RESULTS: 24 h Urinary excretion of α-CEHC (median (IQR): 0.9 (0.3-2.4) µmol) was less than that of γ-CEHC (median (IQR): 1.5 (0.5-3.5) µmol). After adjustment for covariates, we found that 24 h urinary α-CEHC excretion and urinary α-CEHC/creatinine ratio were both positively associated with plasma α-tocopherol (std.beta: 0.06, p = 0.02; std.beta: 0.06, p = 0.01, respectively). Furthermore, the sum of 24 h urinary α- and γ-CEHC excretions was positively associated with dietary vitamin E intake (std.beta: 0.08; p = 0.03), whereas there was no relation between urinary α- and γ-CEHC/creatinine ratios and vitamin E intake. No association was observed neither between plasma α- and γ-tocopherol and dietary vitamin E intake, nor between urinary γ-CEHC and plasma γ-tocopherol. CONCLUSION: Our study confirmed our hypothesis that 24 h urinary α- and γ-CEHC excretions would be a better marker for dietary vitamin E intake than urinary α- and γ-CEHC/creatinine ratios. Considering that both 24 h urinary α- and γ-CEHC excretions and α- and γ-CEHC/creatinine ratios were also associated with plasma α-tocopherol status, we suggest that 24 h urinary α- and γ-CEHC excretions could be used to assess overall vitamin E status.
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Enfermedades de Transmisión Sexual , gamma-Tocoferol , Anciano , Biomarcadores/orina , Creatinina , Humanos , Masculino , Vitamina E , alfa-TocoferolRESUMEN
1. TP0463518, a novel hypoxia-inducible factor prolyl hydroxylase inhibitor, is reportedly excreted predominantly through urinary excretion in an unchanged form in humans, with partial biliary excretion also possible. However, the clearance mechanisms remain unclear. The aim of this study was to investigate the clearance mechanisms in humans and to assess species differences in the excretion routes.2. TP0463518 was not metabolised in rat, dog, or human hepatocytes. TP0463518 is a substrate for human BCRP, OATP1B1, OATP1B3, and OAT3, suggesting that renal uptake by OAT3 is probably the predominant clearance route, with hepatic uptake by OATP1B1 and OATP1B3 contributing partially to clearance in humans.3. A species difference in excretion routes was observed. The unchanged urinary excretion rates in humans, male rats, female rats, dogs, and monkeys were 80.7%, 0.1%, 40.9%, 15.2%, and 72.6%, respectively. Urinary excretion was predominant in humans and monkeys, while only biliary excretion was observed in male rats. Uptake studies using hepatocytes showed that the hepatic uptake clearance in rats was 13.6-fold higher than that in humans. Therefore, not only reabsorption via renal tubules, but also hepatic uptake seems to be involved in the species differences in excretion routes between rats and humans.
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Prolil Hidroxilasas , Inhibidores de Prolil-Hidroxilasa , Humanos , Femenino , Masculino , Ratas , Animales , Perros , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Proteínas de Neoplasias , HipoxiaRESUMEN
Mirogabalin is a α2δ ligand as well as pregabalin. The aim of this study was to clarify whether mirogabalin is a substrate of human LAT1, which involved in absorption and disposition of pregabalin, and to investigate transporters involved in renal secretion and absorption of mirogabalin using transporter-expressing cells and fresh human kidney slices.We employed uptake assay of [3H]mirogabalin by HEK293T or HEK293 cells transiently overexpress human OAT1, OAT3, OCT2, LAT1/4F2hc, LAT2/4F2hc, PEPT1, and PEPT2 proteins. Transport assay of MDCKII cells transiently overexpress OCT2/MATE1, and OCT2/MATE2-K proteins was conducted. Contribution of transporters to renal secretion was investigated by uptake assay using human kidney slices.Uptake clearances of [3H]mirogabalin by OAT1-, OAT3-, OCT2-, PEPT1-, and PEPT2-expressing cells were higher than that by vector cells, but by LAT1/4F2hc and LAT2/4F2hc-expressing cells were not. In transport assay using OCT2/MATE1 and OCT2/MATE2-K cells, [3H]mirogabalin showed directional transport from basolateral to apical side. Contribution of OAT1, OAT3, and OCT2 was observed by uptake of [3H]mirogabalin into the kidney slices.These results indicate that mirogabalin is not a substrate of LAT1, but of PEPT1 and PEPT2 involved in absorption and of OAT1, OAT3, OCT2, MATE1 and/or MATE2-K involved in its urinary secretion.
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Proteínas de Transporte de Catión Orgánico , Humanos , Proteínas de Transporte de Catión Orgánico/metabolismo , Células HEK293 , Ligandos , Pregabalina , Transportador 2 de Cátion Orgánico/metabolismoRESUMEN
Phellodendri Chinensis Cortex (PCC) and Atractylodis Rhizoma (AR) are frequently used as herb pair to treat eczema and gout owing to their synergistic effects. Alkaloids are the major ingredients from PCC and the effect of their combination on the in vivo processing of alkaloids remains unclear. In this study, a simple and reliable UPLC-MS/MS method for simultaneous determination of six alkaloids in rat plasma was developed. This method was applied to a comparative pharmacokinetic study between PCC and PCC-AR in rats. Effect of AR on absorption of alkaloids was investigated by a single-pass intestinal perfusion study. The effect of AR on urinary excretion of alkaloids was studied. Pharmacokinetic studies showed that the values of rea under the concentration-time curve of phellodendrine, magnoflorine and palmatine were greater in the PCC-AR group than in the PCC group. The intestinal absorptive parameters absorption rate constant and effective permeability of phellodendrine and jatrorrhizine in PCC-AR groups were higher than those in the PCC group. Urinary excretion studies revealed that the excreted amount of alkaloids in the PCC-AR group was lower than that in the PCC group. The results revealed that the combination of PCC and AR improves intestinal absorption of alkaloids and reduces their urinary excretion, which enhances their systemic exposure. This study may explain the synergetic effects of PCC and AR in clinical applications.
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Alcaloides , Medicamentos Herbarios Chinos , Absorción Intestinal/efectos de los fármacos , Alcaloides/sangre , Alcaloides/farmacocinética , Alcaloides/orina , Animales , Cromatografía Liquida , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Límite de Detección , Modelos Lineales , Masculino , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Espectrometría de Masas en TándemRESUMEN
PURPOSE: The World Health Organization recommends reduction of salt intake to < 5 g/day and the use of iodized salt to prevent iodine deficiency states. A high prevalence of excess salt consumption and an inadequate iodine intake has been previously shown in an Italian pediatric population. It was appropriate, therefore, to analyse in the same population the relationship occurring between salt consumption and iodine intake. METHODS: The study population was made of 1270 children and adolescents. Estimates of salt consumption and iodine intake were obtained by measuring 24 h urinary sodium and iodine excretion. RESULTS: The iodine intake increased gradually across quartiles of salt consumption independently of sex, age and body weight (p < 0.001). Median iodine intake met the European Food Safety Authority adequacy level only in teenagers in the highest quartile of salt consumption (salt intake > 10.2 g/day). We estimated that approximately 65-73% of the total iodine intake was derived from food and 27-35% from iodized salt and that iodized salt made actually only 20% of the total salt intake. CONCLUSION: In this pediatric population, in face of an elevated average salt consumption, the use of iodized salt was still insufficient to ensure an adequate iodine intake, in particular among teenagers. In the perspective of a progressive reduction of total salt intake, the health institutions should continue to support iodoprophylaxis, in the context of the national strategies for salt reduction. In order for these policies to be successful, in addition to educational campaigns, it is needed that the prescriptions contained in the current legislation on iodoprophylaxis are made compelling through specific enforcement measures for all the involved stakeholders.
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Yodo , Cloruro de Sodio Dietético , Adolescente , Niño , Humanos , Italia/epidemiología , Estado Nutricional , Cloruro de SodioRESUMEN
BACKGROUND: In utero Cytomegalovirus (CMV) vertical transmission occurs predominantly during primary maternal infection. There are no known non-invasive methods for diagnosis of fetal infection before delivery, however some risk factors have been suggested. We aimed to evaluate the association between maternal CMV urinary excretion and congenital CMV infection. METHODS: A retrospective cohort study of all women who were diagnosed with primary CMV infection during pregnancy in a single university affiliated tertiary medical center, between 2012 and 2016. We examined congenital CMV infection and disease rates among infants born to women with and without CMV urinary excretion. RESULTS: Overall, 126 women were included, 77 in the positive urinary excretion group, and 49 in the negative urinary excretion group. There was no difference in maternal symptoms between the groups. We found no difference in congenital CMV infection and disease rates between infants born to women with and without urinary excretion of CMV (congenital infection rate 37.1% vs. 24.4%, p = 0.209, congenital disease rate of 18.2% vs. 22.4%, p = 0.648). Women with positive urinary CMV excretion had lower IgG avidity values (36.7% vs 54.6%, p = 0.007), with no additional difference in serology pattern. Compared to asymptomatic women, those with CMV related symptoms did not have significantly higher rates of urinary excretion of CMV (70% vs. 60.5%, p = 0.38) or congenital infection rates (40.7% vs. 31.2%, p = 0.48). CONCLUSION: Among infants of women with primary CMV infection in pregnancy, we did not find an association between urinary excretion of CMV and congenital CMV infection.
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Infecciones por Citomegalovirus/transmisión , Infecciones por Citomegalovirus/orina , Enfermedades del Recién Nacido/virología , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/orina , Adulto , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Israel/epidemiología , Embarazo , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
AIMS/INTRODUCTION: The relationship between urinary excretion rate of glucose (UEGL) and uric acid (UA) metabolism in adults with type 2 diabetes (T2D) remains unclear to date. This study aimed to investigate the relationships of UEGL with serum UA (SUA), urinary excretion rate of uric acid (UEUA), and renal clearance of uric acid (CLUA) in adults with T2D. We hypothesised that high UEGL increases UA excretion, which in turn leads to lower SUA. MATERIALS AND METHODS: This was a cross-sectional study of 635 inpatients with T2D recruited between 2018 and 2019. The relationships of UEGL with UEUA, CLUA, and hyperuricaemia were assessed using analysis of covariance and multivariate regression analysis. RESULTS: Patients in the higher quartile of UEGL tended to have lower SUA levels than those in the lower quartile. In contrast, patients in the higher quartile of UEGL tended to have higher CLUA (p for trend < 0.0001), and a similar trend was observed for UEUA. In adjusted multivariable linear regression model, UEGL was negatively correlated with SUA (ß = - 0.023, 95% CI - 0.034 to - 0.013, p < 0.0001). However, positive correlations of UEGL with UEUA (ß = 0.046, 95% CI 0.018-0.074, p = 0.001) and CLUA (ß = 0.063, 95% CI 0.042-0.085, p < 0.0001) were found. Furthermore, consistent significant inverse associations were observed between quartiles of UEGL and hyperuricaemia in the adjusted multivariate logistic regression model. CONCLUSIONS: A high UEGL level was positively correlated with UEUA and CLUA. Moreover, it was inversely associated with SUA level, and a consistently increased UEGL level reduced the risk of hyperuricaemia in patients with T2D.
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Diabetes Mellitus Tipo 2/metabolismo , Glucosuria/metabolismo , Ácido Úrico/sangre , Estudios Transversales , Femenino , Humanos , Hiperuricemia , Riñón/metabolismo , Riñón/fisiología , Pruebas de Función Renal , Modelos Lineales , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The metabolism, excretion, and pharmacokinetics of mirogabalin were investigated following a single oral administration of [14C]mirogabalin at 30 mg/5.55 MBq to six healthy male subjects.The mean recovery values of radioactivity in urine and faeces were 96.85 and 1.21%, respectively. The main component of radioactivity in the plasma, urine, and faeces was mirogabalin. A204-4455 (lactam form), mirogabalin N-glucuronide, and glucuronide of oxidized A204-4455 were detected as minor components in the specimens. Renal clearance of mirogabalin was higher than the glomerular filtration rate of the human kidneys, indicating renal secretion is involved in the clearance.In vitro studies revealed that UDP-glucuronosyltransferase produced two metabolites: A204-4455, formed via mirogabalin acylglucuronide, and a ring-opened form of mirogabalin N-glucuronide.Mirogabalin was absorbed almost completely, and was eliminated via urine. A part of the orally administered dose of mirogabalin was metabolized through glucuronidation at the amine and carboxylic acid moiety, which represents the primary metabolic pathway.
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Compuestos Bicíclicos con Puentes , Administración Oral , Heces , Voluntarios Sanos , Humanos , Ligandos , MasculinoRESUMEN
This study aimed to characterize the rumen bacterial diversity of beef steers differing in the efficiency of nitrogen retention (ENR). Eight castrated steers and fitted with ruminal silicone - and duodenal T-type cannulas were used in a cross-over design with three consecutive periods and three diets. During each experimental period, nitrogen balance was measured, and based on the efficiency of N utilization data, steers were split into three ENR groups: high (HNR, 56.6% ± 3.3%, n = 10), medium (MNR, 45.8% ± 2.2%, n = 6), and low (LNR, 37.7% ± 1.9%, n = 8) using the NbClust package version 2.0.4 in R. Prevotellaceae, Lactobacillaceae, Leuconostocaceae, Clostridiales_Incertae_Sedis_XIII, Lachnospiraceae, and Peptostreptococcaceae were more abundant in LNR (P < 0.05) compared to HNR or MNR. Negative correlations were found between N retention and Mogibacterium, Anaerofustis, Butyrivibrio, Coprococcus, Hespellia, Lactonifactor and Lachnospiraceae (r ≤ -0.61; P ≤ 0.05). Prevotella, Hespellia, Lactonifactor, Lachnospiraceae_other, and Anaerobiospirillum were positively correlated between urinary N excretion (r > 0.55; P < 0.01), and negative correlations were found with Elusimicrobia, Victivallis and Treponema (r < -0.41; P < 0.05). The adjustment of the rumen bacterial community differed significantly between the N use retention groups. The high N retention in beef cattle was associated with less abundant bacteria in the rumen; however, N fixation capacity and uncharacterized rumen microorganisms need to be elucidated in future studies. In contrast, lower N utilization was associated with high abundance of bacteria that promote greater urinary N excretion through ruminal protein degradation.
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Bacterias/clasificación , Bacterias/metabolismo , Bovinos/fisiología , Nitrógeno/metabolismo , Rumen/microbiología , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Biodiversidad , ADN Bacteriano , Dieta/veterinaria , Heces/química , Interacciones Microbiota-Huesped , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Orina/químicaRESUMEN
The present study was conducted with privately owned dogs and cats to investigate whether a relationship exists between the dietary AGEs and the urinary excretion of AGEs, as indication of possible effective absorption of those compounds in the intestinal tract of pet carnivores. For this purpose, data were collected from both raw fed and dry processed food (DPF) fed to dogs and cats, through spot urine sampling and questionnaires. Raw pet food (RF, low in AGE diets) was fed as a primary food source to 29 dogs and DPF to 28 dogs. Cats were categorized into 3 groups, which were RF (n = 15), DPF (n = 14) and dry and wet processed pet food (DWF, n = 25). Urinary-free carboxymethyllysine (CML), carboxyethyllysine (CEL) and lysinoalanine (LAL) were analysed using ultrahigh-performance liquid chromatography (UHPLC)-mass spectrometry, and were standardized for variable urine concentration by expressing the AGE concentrations as a ratio to urine creatinine (Ucr) concentration (µg/µmol Ucr). Urinary excretion of CML, CEL and LAL in dogs fed with DPF was 2.03, 2.14 and 3 times higher compared to dogs fed with RF (p < .005). Similar to the dogs, a significant difference in CML:Ucr, CEL:Ucr and LAL:Ucr between the three diet groups was observed in cats (p-overall < 0.005, ANOVA), in which the RF fed group excreted less AGEs than the other groups. Linear regression coefficients and SE of CML:Ucr, CEL:Ucr and LAL:Ucr showed that body weight and neuter status were significantly correlated with CML and CEL excretion, but not to LAL excretion. Our results revealed a significant correlation between dietary AGEs and urinary excretion of free CML, CEL and LAL, and also showed that endogenous formation of these AGEs occurs in both dogs and cats under physiological conditions.
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Dieta , Productos Finales de Glicación Avanzada/orina , Animales , Gatos , Cromatografía Liquida/veterinaria , Dieta/veterinaria , PerrosRESUMEN
Objective: Older adults present higher risk of functional disability detected by handgrip strength and an increased risk of poor health conditions, such as dehydration and low values of the sodium-to-potassium (Na/K) ratio. This study aimed to quantify the association of hydration status and Na/K ratio with handgrip strength, based on the urinary excretion of older adults.Methods: A cross-sectional study was conducted in 735 older adults ≥ 65 years old. Handgrip strength was measured with a Jamar Dynamometer and low values were defined according to body mass index and to sex-specific cutoff points. The hydration status was evaluated based on free water reserve. Sodium and potassium intake were evaluated after converting 24-hour urinary sodium and potassium excretion, respectively. A logistic regression model was used to estimate the probability of presenting low handgrip strength, according to risk of hypohydration and to quartiles of Na/K, stratified by sex and adjusted for potential confounders.Results: The adjusted odds ratio (OR) for presenting low handgrip strength was higher in women at risk of hypohydration, but this association was not found in men. Both women and men with the highest values of Na/K ratio presented higher adjusted OR for low handgrip strength (OR in women was 2.03; 95% confidence interval [CI]: 1.12-3.68, and in men was 2.19; 95% CI: 1.11-4.29).Conclusions: The risk of hypohydration was directly associated with low handgrip strength in older women. In older adults, higher values of urinary Na/K ratio were also directly associated with low handgrip strength.
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Fuerza de la Mano , Estado de Hidratación del Organismo , Potasio/orina , Sodio/orina , Anciano , Anciano de 80 o más Años , Estudios Transversales , Deshidratación/epidemiología , Femenino , Humanos , Masculino , Oportunidad Relativa , Factores SexualesRESUMEN
In Victoria, Australia, a statewide salt reduction partnership was launched in 2015. The aim was to measure Na intake, food sources of Na (level of processing, purchase origin) and discretionary salt use in a cross-section of Victorian adults prior to a salt reduction initiative. In 2016/2017, participants completed a 24-h urine collection (n 338) and a subsample completed a 24-h dietary recall (n 142). Participants were aged 41·2 (sd 13·9) years, and 56 % were females. Mean 24-h urinary excretion was 138 (95 % CI 127, 149) mmol/d for Na. Salt equivalent was 8·1 (95 % CI 7·4, 8·7) g/d, equating to about 8·9 (95 % CI 8·1, 9·6) g/d after 10 % adjustment for non-urinary losses. Mean 24-h intake estimated by diet recall was 118 (95 % CI 103, 133) mmol/d for Na (salt 6·9 (95 % CI 6·0, 7·8 g/d)). Leading dietary sources of Na were cereal-based mixed dishes (12 %), English muffins, flat/savoury/sweet breads (9 %), regular breads/rolls (9 %), gravies and savoury sauces (7 %) and processed meats (7 %). Over one-third (38 %) of Na consumed was derived from discretionary foods. Half of all Na consumed came from ultra-processed foods. Dietary Na derived from foods was obtained from retail stores (51 %), restaurants and fast-food/takeaway outlets (28 %) and fresh food markets (9 %). One-third (32 %) of participants reported adding salt at the table and 61 % added salt whilst cooking. This study revealed that salt intake was above recommended levels with diverse sources of intake. Results from this study suggest a multi-faceted salt reduction strategy focusing on the retail sector, and food reformulation would most likely benefit Victorians and has been used to inform the ongoing statewide salt reduction initiative.
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Dieta Hiposódica/normas , Dieta/estadística & datos numéricos , Análisis de los Alimentos/estadística & datos numéricos , Política Nutricional , Sodio en la Dieta/análisis , Adulto , Estudios Transversales , Encuestas sobre Dietas , Femenino , Humanos , Masculino , Persona de Mediana Edad , VictoriaRESUMEN
PURPOSE: The objectives of this study were (1) to estimate caffeine intake and identify the main sources of intake using a dietary questionnaire, (2) to assess 24-h urinary excretion of caffeine and its metabolites, and (3) to assess how self-reported intake estimates correlates with urinary excretion among children in Switzerland. METHODS: We conducted a cross-sectional study of children between 6 and 16 years of age in one region of Switzerland. The participants filled in a dietary questionnaire and collected a 24-h urine sample. Caffeine intake was estimated with the questionnaire. Caffeine, paraxanthine, theophylline, and theobromine excretions were measured in the urine sample. Correlations between questionnaire-based intake and urinary excretion estimates were assessed using Spearman correlation coefficients. RESULTS: Ninety-one children were included in the analysis (mean age 10.6 years; 43% female). The mean daily caffeine intake estimate derived from the diet questionnaire was 39 mg (range 0-237), corresponding, when related to body weight, to 1.2 mg/kg (range 0.0-6.3). Seven children (8%) had a caffeine intake above the upper recommended level of 3 mg/kg per day. The main sources of caffeine intake were cocoa milk (29%), chocolate (25%), soft drinks (11%), mocha yogurt (10%), tea (8%), and energy drinks (8%). The 24-h urinary excretion of caffeine was 0.3 mg (range 0.0-1.5), paraxanthine 1.4 mg (range 0.0-7.1), theophylline 0.1 mg (range 0.0-0.6), and theobromine 14.8 mg (range 0.3-59.9). The correlations between estimates of caffeine intake and the 24-h urinary excretion of caffeine was modest (ρ = 0.21, p = 0.046) and with the metabolites of caffeine were weak (ρ = 0.09-0.11, p = 0.288-0.423). CONCLUSIONS: Caffeine intake in a sample of children in a region of Switzerland was relatively low. The major sources of intake were cocoa milk, chocolate and soft drinks. Self-reported caffeine intake correlated weakly with urinary excretion of caffeine and some of its main metabolites. TRIAL REGISTRATION NUMBER: NCT02900261.
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Cafeína , Toma de Muestras de Orina , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , SuizaRESUMEN
PURPOSE: Urinary spot samples are a promising method for the biomonitoring of micronutrient intake in children. Our aim was to assess whether urinary spot samples could be used to estimate the 24-h urinary excretion of potassium, phosphate, and iodine at the population level. METHODS: A cross-sectional study of 101 children between 6 and 16 years of age was conducted. Each child collected a 24-h urine collection and three urinary spot samples (evening, overnight, and morning). Several equations were used to estimate 24-h excretion based on the urinary concentrations of each micronutrient in the three spot samples. Various equations and spot combinations were compared using several statistics and plots. RESULTS: Ninety-four children were included in the analysis (mean age: 10.5 years). The mean measured 24-h urinary excretions of potassium, phosphate, and iodine were 1.76 g, 0.61 g, and 95 µg, respectively. For potassium, the best 24-h estimates were obtained with the Mage equation and morning spot (mean bias: 0.2 g, correlation: 0.27, precision: 56%, and misclassification: 10%). For phosphate, the best 24-h estimates were obtained with the Mage equation and overnight spot (mean bias: - 0.03 g, correlation: 0.54, precision: 72%, and misclassification: 10%). For iodine, the best 24-h estimates were obtained with the Remer equation and overnight spot (mean bias: - 8 µg, correlation: 0.58, precision: 86%, misclassification: 16%). CONCLUSIONS: Urinary spot samples could be a good alternative to 24-h urine collection for the population biomonitoring of iodine and phosphate intakes in children. For potassium, spot samples were less reliable.