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1.
Int J Cancer ; 150(2): 374-386, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34569060

RESUMO

Recurrent upper tract urothelial carcinomas (UTUCs) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). Here we delineated the molecular programs underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe. We applied an integrative multiomics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative microRNA (miRNA) and messenger ribonucleic acid (mRNA) expression profiling, immunohistochemical analysis by tissue microarrays and exome and transcriptome sequencing were performed in UTUC and nontumor tissues. Urinary miRNAs of cases undergoing surgery were profiled before and after tumor resection. Ribonucleic acid (RNA) and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC-specific miRNA:mRNA networks comprising 89 miRNAs associated with 1,862 target mRNAs, involving deregulation of cell cycle, deoxyribonucleic acid (DNA) damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC-specific transcripts were confirmed at the protein level. Exome and transcriptome sequencing of UTUCs revealed AA-specific mutational signature SBS22, with 68% to 76% AA-specific, deleterious mutations propagated at the transcript level, a possible basis for neoantigen formation and immunotherapy targeting. We next identified a signature of UTUC-specific miRNAs consistently more abundant in the patients' urine prior to tumor resection, thereby defining biomarkers of tumor presence. The complex gene regulation programs of AAN-associated UTUC tumors involve regulatory miRNAs prospectively applicable to noninvasive urine-based screening of AAN patients for cancer presence and recurrence.


Assuntos
Ácidos Aristolóquicos/efeitos adversos , Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/urina , Mutação , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/induzido quimicamente , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/urina , Exoma , Seguimentos , Humanos , Prognóstico , Proteoma/análise , Proteoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/urina
2.
Nutrition ; 93: 111440, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34534944

RESUMO

Vitamin E (α-tocopherol [α-TOH]) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology of Obesity Study, we aimed to investigate the associations of 147 circulating metabolomic measures obtained through targeted nuclear magnetic resonance with serum α-TOH and its urinary enzymatic (α-CEHC) and oxidized (α-TLHQ) metabolites from 24-h urine quantified by liquid chromatography with tandem mass spectrometry. Multivariable linear regression analyses, in which multiple testing was taken into account, were performed to assess associations between metabolomic measures (determinants; standardized to mean = 0, SD = 1) and vitamin E metabolites (outcomes), adjusted for demographic factors. We analyzed 474 individuals (55% women, 45% men) with a mean (SD) age of 55.7 (6.0) y. Out of 147 metabolomic measures, 106 were associated (P < 1.34 × 10-3) with serum α-TOH (median ß [interquartile range] = 0.416 [0.383-0.466]), predominantly lipoproteins associated with higher α-TOH. The associations of metabolomic measures with urinary α-CEHC have directions similar to those with α-TOH, but effect sizes were smaller and non-significant (median ß [interquartile range] = 0.065 [0.047-0.084]). However, associations of metabolomic measures with urinary α-TLHQ were markedly different from those with both serum α-TOH and urinary α-CEHC, with negative and small-to-null relations to most very-low-density lipoproteins and amino acids. Therefore, our results highlight the differences in the lipoproteins involved in the transportation of circulating α-TOH and oxidized vitamin E metabolites. This indicates that circulating α-TOH may be representative of the enzymatic but not the antioxidative function of vitamin E.


Assuntos
Metaboloma , Vitamina E , alfa-Tocoferol , Antioxidantes , Feminino , Humanos , Lipoproteínas , Masculino , Pessoa de Meia-Idade , Oxirredução , Vitamina E/sangue , Vitamina E/urina , alfa-Tocoferol/sangue , alfa-Tocoferol/urina
3.
Ann Lab Med ; 42(2): 178-187, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635611

RESUMO

Background: Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED. Methods: This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses. Results: Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m)2/1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P=0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development (P<0.05). The T0 NephroCheck value predicted 30-day mortality (AUC, 0.68; P<0.001). Conclusions: NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or ruling-out of AKI in the ED.


Assuntos
Injúria Renal Aguda , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Inibidor Tecidual de Metaloproteinase-2 , Doença Aguda , Injúria Renal Aguda/diagnóstico , Idoso , Biomarcadores , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-2/urina , Estados Unidos
4.
Hypertension ; 79(1): 93-103, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34788057

RESUMO

Fibromuscular dysplasia (FMD), a nonatherosclerotic, noninflammatory disease of medium-sized arteries, is an underdiagnosed disease. We investigated the urinary proteome and developed a classifier for discrimination of FMD from healthy controls and other diseases. We further hypothesized that urinary proteomics biomarkers may be associated with alterations in medium-sized, but not large artery geometry and mechanics. The study included 33 patients with mostly multifocal, renal FMD who underwent in depth arterial exploration using ultra-high frequency ultrasound. The cohort was separated in a training set of 23 patients with FMD from Belgium and an independent test set of 10 patients with FMD from Italy. For each set, controls matched 2:1 were selected from the Human Urinary Proteome Database. The specificity of the classifier was tested in 700 additional controls from general population studies, patients with chronic kidney disease (n=66) and coronary artery disease (n=31). Three hundred thirty-five urinary peptides, mostly related to collagen turnover, were identified in the training cohort and combined into a classifier. When applying in the test cohort, the area under the receiver operating characteristic curve was 1.00, 100% specificity at 100% sensitivity. The classifier maintained a high specificity in additional controls (98.3%), patients with chronic kidney (90.9%) and coronary artery (96.8%) diseases. Furthermore, in patients with FMD, the proteomic score was positively associated with radial wall thickness and wall cross-sectional area. In conclusion, a proteomic score has the potential to discriminate between patients with FMD and controls. If confirmed in a wider and more diverse cohort, these findings may pave the way for a noninvasive diagnostic test of FMD.


Assuntos
Colágeno/urina , Displasia Fibromuscular/urina , Adulto , Idoso , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/urina , Feminino , Displasia Fibromuscular/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/urina , Sensibilidade e Especificidade
5.
Chem Commun (Camb) ; 58(3): 463-466, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34908034

RESUMO

Parahydrogen hyperpolarization has been shown to enhance NMR sensitivity in urine analysis by several orders of magnitude if urine samples are prepared by solid phase extraction (SPE). We present a different approach, developed for minimal sample alteration before analysis. Removing SPE from the workflow allows to retain a wider range of metabolites and paves the way towards more universal hyperpolarized NMR metabolomics of low abundance metabolites.


Assuntos
Adenosina/análogos & derivados , Complexos de Coordenação/metabolismo , Cotinina/análogos & derivados , Irídio/metabolismo , Metabolômica , Extração em Fase Sólida , Adenosina/metabolismo , Adenosina/urina , Complexos de Coordenação/urina , Cotinina/metabolismo , Cotinina/urina , Humanos , Irídio/urina , Espectroscopia de Ressonância Magnética , Conformação Molecular
6.
Dis Colon Rectum ; 65(1): 40-45, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882627

RESUMO

BACKGROUND: Approximately 5% to 10% of patients with Lynch syndrome develop urothelial carcinoma. Current screening recommendations vary and are based on expert opinion. Practices need to be evaluated for clinical effectiveness. Our program utilizes urinalysis as a screening test, followed by additional evaluation of microscopic hematuria. OBJECTIVE: This study aimed to determine the clinical utility of a urinalysis-based screening approach for urothelial cancers in patients with Lynch syndrome. DESIGN: This is a retrospective review of a prospectively maintained cohort. SETTING: Patients with Lynch syndrome were managed at a tertiary referral center. PATIENTS: All patients with a Lynch syndrome diagnosis who had a screening urinalysis done as part of our institutional screening protocol (N = 204) were included. MAIN OUTCOME MEASURES: A single-institution hereditary colorectal cancer syndrome registry was queried for patients with Lynch syndrome who had been screened for urothelial carcinomas by urinalysis. Demographics, genotype, family history of urothelial carcinoma, urinalysis results, and subsequent screenings and final diagnosis were gathered for patients between 2008 and 2017. RESULTS: Two hundred four asymptomatic patients underwent screening by urinalysis. Nineteen patients (9.3%) had microscopic hematuria and were further evaluated with urine cytology, imaging, cystoscopy, and/or Urology consultation. None of the 19 patients with microscopic hematuria had urothelial carcinoma. During the same study period, 5 of 204 (2.4%) patients with Lynch syndrome were diagnosed with urothelial cancer, and all presented with symptoms between screening intervals. LIMITATIONS: This is a retrospective study, and not all patients underwent the same secondary evaluation. CONCLUSIONS: No urothelial carcinomas were detected by screening urinalysis in our cohort of asymptomatic patients with Lynch syndrome. False-positive testing led to extensive, mostly uninformative, workups. If urothelial cancer screening is to continue, more effective screening approaches need to be identified. See Video Abstract at http://links.lww.com/DCR/B702. EVALUACIN DEL CRIBADO BASADO EN ANLISIS DE ORINA PARA CARCINOMA UROTELIAL EN PACIENTES CON SNDROME DE LYNCH: ANTECEDENTES:Aproximadamente el 5-10% de los pacientes con síndrome de Lynch desarrollan carcinoma urotelial. Las recomendaciones actuales de detección varían y se basan en la opinión de expertos. Las prácticas deben evaluarse para determinar su eficacia clínica. Nuestro programa utiliza el análisis de orina como prueba de detección, seguido de una evaluación adicional con hematuria microscópica.OBJETIVO:Determinar la utilidad clínica desde un enfoque de cribado basado en análisis de orina, para cánceres uroteliales en pacientes con síndrome de Lynch.DISEÑO:Revisión retrospectiva de una cohorte mantenida prospectivamente.ENTORNO CLINICO:Pacientes con síndrome de Lynch atendidos en un centro de referencia terciario.PACIENTES:Criterios de inclusión fueron todos los pacientes con diagnóstico de síndrome de Lynch realizándoles un análisis de orina de detección como parte de nuestro protocolo de detección institucional (N = 204).PRINCIPALES MEDIDAS DE VALORACION:Solicitando un registro de síndrome de cáncer colorrectal hereditario de una sola institución para pacientes con síndrome de Lynch previamente evaluados para carcinomas uroteliales mediante análisis de orina. Se recopilaron para los pacientes entre 2008 y 2017, datos demográficos, genotipo, antecedentes familiares de carcinoma urotelial, resultados del análisis de orina, posteriores exámenes de detección posteriores y diagnóstico final.RESULTADOS:Doscientos cuatro pacientes asintomáticos fueron sometidos a cribado mediante análisis de orina. Diecinueve pacientes (9,3%) tenían hematuria microscópica y fueron investigados más a fondo con citología de orina, imágenes, cistoscopia y / o consulta de urología. Ninguno de los 19 pacientes con hematuria microscópica tenían carcinoma urotelial. Durante el mismo período de estudio, 5 de 204 (2,4%) pacientes con síndrome de Lynch fueron diagnosticados con cáncer urotelial y todos presentaron presentando síntomas entre los intervalos de detección.LIMITACIONES:Estudio retrospectivo y no todos los pacientes sometidos a la misma evaluación secundaria.CONCLUSIONES:No se detectaron carcinomas uroteliales mediante análisis de orina de detección en nuestra cohorte de pacientes asintomáticos con síndrome de Lynch. Las pruebas de falsos positivos. Condujeron a estudios exhaustivos y en su mayoría poco informativos. Si se desea continuar con la detección del cáncer de urotelio, es necesario identificar enfoques de detección más efectivos. Consulte Video Resumen en http://links.lww.com/DCR/B702.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Urinálise/métodos , Urotélio/patologia , Adulto , Idoso , Carcinoma de Células de Transição/urina , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Eficiência Organizacional , Reações Falso-Positivas , Feminino , Hematúria/diagnóstico , Hematúria/etiologia , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Urinálise/estatística & dados numéricos , Neoplasias Urológicas/patologia
7.
J Urol ; 207(1): 144-151, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34428923

RESUMO

PURPOSE: Urinary stone disease (USD) has been associated with an increased risk of chronic kidney disease (CKD) and end-stage renal disease in Western populations. However, the metabolic disorders associated with unilateral and bilateral renal stones and the association of these types of stones with CKD and kidney tubular injury markers, such as urine N-acetyl-ß-D-glucosaminidase (NAG) and alpha-1-microglobulin (α1-MG), have not been fully examined. MATERIALS AND METHODS: We performed a cross-sectional study of 10,281 participants in rural China in 2014. All the subjects underwent renal ultrasound to detect USD; stone formers were divided into groups with unilateral or bilateral renal stones by ultrasound examinations. CKD was defined as a decreased estimated glomerular filtration rate (eGFR, <60 mL/minute/1.73 m2) and/or albuminuria (albumin-to-creatinine ratio ≥30 mg/gm). Increased urine NAG and α1-MG levels were defined as their values above the 75th percentile of the sample distribution. RESULTS: Among all the participants, 4.9% (507) had unilateral renal stones, and 0.7% (75) had bilateral renal stones. The proportion of CKD in the nonstone, unilateral and bilateral renal stone formers was 11.0%, 19.2% and 29.7%, respectively (p for trend <0.001). Individuals with bilateral renal stones had the highest proportion of metabolic components, such as elevated blood pressure and serum glucose. In multivariate analyses after adjustment for multiple confounders, bilateral renal stones were significantly associated with an increased risk of decreased eGFR (OR 3.38; 95% CI 1.05-10.90), albuminuria (OR 3.01; 95% CI 1.76-5.13), CKD (OR 3.18; 95% CI 1.88-5.36), increased urine NAG-to-creatinine ratio (OR 1.95; 95% CI 1.21-3.16) and α1-MG-to-creatinine ratio levels (OR 2.54; 95% CI 1.56-4.12) compared with the lack of stones. CONCLUSIONS: Bilateral renal stones were associated with a higher risk of CKD and higher levels of kidney tubular injury markers. Clinicians should pay attention to metabolic disorders in bilateral renal stone formers.


Assuntos
Cálculos Renais/complicações , Cálculos Renais/metabolismo , Insuficiência Renal Crônica/etiologia , Idoso , Biomarcadores/urina , Estudos Transversais , Feminino , Humanos , Cálculos Renais/patologia , Cálculos Renais/urina , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/urina
8.
Eur J Endocrinol ; 186(2): 297-308, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34914631

RESUMO

Objective: Cushing's syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing's syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation. Currently, hormone assays contribute to identify Cushing's syndrome or adrenal insufficiency. However, no biomarker directly quantifies the biological glucocorticoid action. The aim of this study was to identify such markers. Design: We evaluated whole blood DNA methylome in 94 samples obtained from patients with different glucocorticoid states (Cushing's syndrome, eucortisolism, adrenal insufficiency). We used an independent cohort of 91 samples for validation. Methods: Leukocyte DNA was obtained from whole blood samples. Methylome was determined using the Illumina methylation chip array (~850 000 CpG sites). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore methylome profiles. A Lasso-penalized regression was used to select optimal discriminating features. Results: Whole blood methylation profile was able to discriminate samples by their glucocorticoid status: glucocorticoid excess was associated with DNA hypomethylation, recovering within months after Cushing's syndrome correction. In Cushing's syndrome, an enrichment in hypomethylated CpG sites was observed in the region of FKBP5 gene locus. A methylation predictor of glucocorticoid excess was built on a training cohort and validated on two independent cohorts. Potential CpG sites associated with the risk for specific complications, such as glucocorticoid-related hypertension or osteoporosis, were identified, needing now to be confirmed on independent cohorts. Conclusions: Whole blood DNA methylome is dynamically impacted by glucocorticoids. This biomarker could contribute to better assessment of glucocorticoid action beyond hormone assays.


Assuntos
Síndrome de Cushing/genética , Metilação de DNA/genética , DNA/sangue , Epigenoma/genética , Glucocorticoides/sangue , Glucocorticoides/genética , Adolescente , Insuficiência Adrenal/sangue , Insuficiência Adrenal/genética , Adulto , Idoso , Biomarcadores/sangue , Ilhas de CpG/genética , Síndrome de Cushing/sangue , Feminino , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Hidrocortisona/urina , Leucócitos/química , Masculino , Pessoa de Meia-Idade , Saliva/química , Proteínas de Ligação a Tacrolimo/genética
9.
Nutrients ; 13(12)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34959780

RESUMO

Ketogenic diets (KDs) may be a helpful complement in the prevention of and therapy for several diseases. Apart from their non-cariogenic properties, it is still unclear how KDs affect oral parameters. The aim of this study was to investigate the influence of a KD on clinical periodontal parameters. Twenty generally healthy volunteers with an average age of 36.6 years underwent a KD for 6 weeks. Their compliance was monitored by measuring their urinary ketones daily and by keeping 7-day food records. Clinical oral parameters included plaque (PI), gingival inflammation (GI), a complete periodontal status (probing depths, bleeding on probing), and general physical and serologic parameters at baseline and after 6 weeks. The results showed a trend towards lower plaque values, but with no significant changes from baseline to the end of the study with regard to the clinical periodontal parameters. However, their body weight and BMI measurements showed a significant decrease. The regression analyses showed that the fat mass and the BMI were significantly positively correlated to periodontal inflammation, while HDL, fiber, and protein intake were negatively correlated to periodontal inflammation. The KD change did not lead to clinical changes in periodontal parameters in healthy participants under continued oral hygiene, but it did lead to a significant weight loss.


Assuntos
Índice de Placa Dentária , Dieta Cetogênica/métodos , Saúde Bucal/estatística & dados numéricos , Índice Periodontal , Adulto , Composição Corporal , Índice de Massa Corporal , Placa Dentária/prevenção & controle , Registros de Dieta , Feminino , Gengiva/patologia , Gengivite/prevenção & controle , Voluntários Saudáveis , Humanos , Cetonas/urina , Masculino , Projetos Piloto , Análise de Regressão , Perda de Peso
10.
PLoS One ; 16(12): e0261746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34941922

RESUMO

OBJECTIVE: Women living with HIV (WLWH) experience psychosocial stress related to social-structural vulnerabilities. To investigate neuroendocrine pathways linking stress and increased cardiovascular disease risk among WLWH, we evaluated associations between psychosocial stress (i.e., perceived stress, posttraumatic stress, and experiences of race- and gender-based harassment) and a composite neuroendocrine biomarker index among WLWH and women without HIV. METHODS: In 2019-2020, Women's Interagency HIV Study participants in Washington, DC completed a questionnaire and provided blood and 12-hour overnight urine samples for testing of serum dehydroepiandrosterone sulfate (DHEA-S) and urinary free cortisol, epinephrine, and norepinephrine. Psychosocial stress was measured using the Perceived Stress Scale, PTSD Checklist-Civilian Version, and Racialized Sexual Harassment Scale. Latent profile analysis was used to classify participants into low (38%), moderate (44%), and high (18%) stress groups. Composite biomarker index scores between 0-4 were assigned based on participants' number of neuroendocrine biomarkers in high-risk quartiles (≥75th percentile for cortisol, epinephrine, and norepinephrine and ≤25th percentile for DHEA-S). We evaluated associations between latent profile and composite biomarker index values using multivariable linear regression, adjusting for socio-demographic, behavioral, metabolic, and HIV-related factors. RESULTS: Among 90 women, 62% were WLWH, 53% were non-Hispanic Black, and median age was 55 years. In full multivariable models, there was no statistically significant association between psychosocial stress and composite biomarker index values among all women independent of HIV status. High (vs. low) psychosocial stress was positively associated with higher mean composite biomarker index values among all monoracial Black women (adjusted ß = 1.32; 95% CI: 0.20-2.43), Black WLWH (adjusted ß = 1.93; 95% CI: 0.02-3.83) and Black HIV-negative women (adjusted ß = 2.54; 95% CI: 0.41-4.67). CONCLUSIONS: Despite a null association in the overall sample, greater psychosocial stress was positively associated with higher neuroendocrine biomarker concentrations among Black women, highlighting a plausible mechanism by which psychosocial stress could contribute to cardiovascular disease risk.


Assuntos
Epinefrina/urina , Infecções por HIV , HIV-1 , Hidrocortisona/urina , Norepinefrina/urina , Estresse Psicológico/urina , Biomarcadores/urina , District of Columbia , Feminino , Infecções por HIV/psicologia , Infecções por HIV/urina , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Socioeconômicos
11.
Nutrients ; 13(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34959764

RESUMO

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ol (FL)s, a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FLs possibly activate sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FLs. In addition, we examined the impact of the repeated administration of 50 mg/kg FLs for 14 days on adipose tissues in mice. In BAT, FLs tended to increase the level of Ucp-1 along with significant increase of thermogenic transcriptome factors expressions, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Expression of browning markers, CD137 and transmembrane protein (TMEM) 26, in addition to PGC-1α were increased in epididymal adipose (eWAT) by FLs. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 by FLs. These results exert that FLs induce browning in adipose, and this change is possibly produced by the activation of the SNS.


Assuntos
Tecido Adiposo/metabolismo , Flavonoides/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Administração Oral , Animais , Catecolaminas/urina , Proteínas de Membrana/metabolismo , Camundongos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Termogênese/efeitos dos fármacos , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Proteína Desacopladora 1/metabolismo
12.
Nutrients ; 13(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34959951

RESUMO

Potassium supplementation has been associated with reduced urinary calcium (Ca) excretion and increased Ca balance. Dietary interventions assessing the impact of potassium on bone are lacking. In this secondary analysis of a study designed primarily to determine blood pressure effects, we assessed the effects of potassium intake from potato sources and a potassium supplement on urinary Ca, urine pH, and Ca balance. Thirty men (n = 15) and women (n = 15) with a mean ± SD age and BMI of 48.2 ± 15 years and 31.4 ± 6.1 kg/m2, respectively, were enrolled in a cross-over, randomized control feeding trial. Participants were assigned to a random order of four 16-day dietary potassium interventions including a basal diet (control) of 2300 mg/day (~60 mmol/day) of potassium, and three phases of an additional 1000 mg/day (3300 mg/day(~85 mmol/day) total) of potassium in the form of potatoes (baked, boiled, or pan-heated), French fries (FF), or a potassium (K)-gluconate supplement. Calcium intake for all diets was approximately 700-800 mg/day. Using a mixed model ANOVA there was a significantly lower urinary Ca excretion in the K-gluconate phase (96 ± 10 mg/day) compared to the control (115 ± 10 mg/day; p = 0.027) and potato (114 ± 10 mg/day; p = 0.033). In addition, there was a significant difference in urinary pH between the supplement and control phases (6.54 ± 0.16 vs. 6.08 ± 0.18; p = 0.0036). There were no significant differences in Ca retention. An increased potassium intake via K-gluconate supplementation may favorably influence urinary Ca excretion and urine pH. This trial was registered at ClinicalTrials.gov as NCT02697708.


Assuntos
Cálcio/metabolismo , Cálcio/urina , Suplementos Nutricionais , Gluconatos/administração & dosagem , Hipertensão/metabolismo , Potássio na Dieta/administração & dosagem , Solanum tuberosum , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio na Dieta/administração & dosagem , Estudos Cross-Over , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Nutrients ; 13(12)2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34959987

RESUMO

Copious fluid intake is the most essential nutritional measure in the treatment of urolithiasis, and is suggested to be a protective factor in the primary prevention of urinary stone formation. Although the intake of black tea contributes to daily fluid intake, the high oxalate content could outweigh the beneficial effect of urine dilution. The present study investigated the effect of black tea consumption on urinary risk factors for kidney stone formation. Ten healthy men received a standardized diet for a period of ten days. Subjects consumed 1.5 L/day of fruit tea (0 mg/day oxalate) during the 5-day control phase, which was replaced by 1.5 L/day of black tea (86 mg/day oxalate) during the 5-day test phase. Fractional and 24-h urines were obtained. The intake of black tea did not significantly alter 24-h urinary oxalate excretion. Urinary citrate, an important inhibitor of calcium stone formation, increased significantly, while the relative supersaturation of calcium oxalate, uric acid, and struvite remained unchanged. No significantly increased risk for kidney stone formation could be derived from the ingestion of black tea in normal subjects. Further research is needed to evaluate the impact of black tea consumption in kidney stone patients with intestinal hyperabsorption of oxalate.


Assuntos
Ingestão de Líquidos/fisiologia , Ingestão de Alimentos/fisiologia , Cálculos Renais/prevenção & controle , Chá , Adulto , Ácido Cítrico/urina , Humanos , Cálculos Renais/metabolismo , Cálculos Renais/urina , Masculino , Oxalatos/administração & dosagem , Oxalatos/análise , Oxalatos/metabolismo , Fatores de Risco , Chá/química , Fatores de Tempo , Ácido Úrico/metabolismo , Adulto Jovem
14.
Nutrients ; 13(12)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34959995

RESUMO

Dietary potassium intake is a dilemma in patients with chronic kidney disease (CKD). We investigated the association of urine potassium excretion, a surrogate for dietary potassium intake, with blood pressure variability (BPV) and cardiovascular (CV) outcomes in patients with pre-dialysis CKD. A total of 1860 participants from a cohort of pre-dialysis CKD (KNOW-CKD) patients were divided into the quartiles by spot urine potassium-to-creatinine ratio. The first quartile (26.423 ± 5.731 mmol/gCr) was defined as low urine potassium excretion. Multivariate linear regression analyses revealed an independent association of low urine potassium excretion with high BPV (adjusted ß coefficient 1.163, 95% confidence interval 0.424 to 1.901). Cox regression analyses demonstrated that, compared to high urine potassium excretion, low urine potassium excretion is associated with increased risk of CV events (adjusted hazard ratio 2.502, 95% confidence interval 1.162 to 5.387) but not with all-cause mortality. In conclusion, low urine potassium excretion is associated with high BPV and increased risk of CV events in patients with pre-dialysis CKD. The restriction of dietary potassium intake should be individualized in patients with pre-dialysis CKD.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Potássio/urina , Insuficiência Renal Crônica/urina , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Creatinina/urina , Diálise/métodos , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Potássio/administração & dosagem , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Sódio/urina
15.
J Occup Health ; 63(1): e12307, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34957641

RESUMO

OBJECTIVE: This study assessed the health risk of benzene exposure among Thai gasoline station workers through biomarker detection and experience of adverse symptoms. METHODS: Trans, trans-muconic acid (tt-MA) metabolites of benzene were analyzed from spot urine sampled among gasoline station workers after shift work using HPLC-UV. Air benzene monitoring was done with an active sampler connected to a charcoal sorbent tube, and analyzed by GC-FID. The health risk was calculated by using the biomatrix of the likelihood of benzene exposure and the severity of adverse symptoms. RESULTS: The tt-MA concentration, among 235 workers, ranged from less than 10-2159 µg/g Cr, which corresponded to the air benzene concentration range of <0.1 to 65.8 ppb. In total, 32.3% of workers had a higher than acceptable risk level and there was a significant association between gasoline station work zones and the likelihood of benzene exposure as well as the health risk of workers. The health risk levels estimated from the biomarker monitoring were consistent with the risk matrix of air benzene monitoring. CONCLUSION: This tt-MA biomarker monitoring and biomatrix of health risk assessment is suggested as useful for health surveillance of gasoline station workers exposed to benzene.


Assuntos
Poluentes Ocupacionais do Ar/análise , Benzeno/toxicidade , Gasolina/toxicidade , Exposição Ocupacional/efeitos adversos , Medição de Risco/métodos , Adolescente , Adulto , Benzeno/análise , Biomarcadores/urina , Monitoramento Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Sórbico/análogos & derivados , Ácido Sórbico/toxicidade , Tailândia , Adulto Jovem
16.
Nutrients ; 13(12)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34959880

RESUMO

In this study we aimed to assess vitamin D metabolism in patients with Cushing's disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently higher 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.


Assuntos
Colecalciferol/administração & dosagem , Hipersecreção Hipofisária de ACTH/sangue , Hipersecreção Hipofisária de ACTH/terapia , Vitamina D/sangue , Vitaminas/administração & dosagem , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/urina , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Hipersecreção Hipofisária de ACTH/urina , Albumina Sérica/efeitos dos fármacos , Resultado do Tratamento , Vitamina D/análogos & derivados , Proteína de Ligação a Vitamina D/sangue
17.
Cells ; 10(12)2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34943802

RESUMO

Nephropathic cystinosis is a rare disease caused by mutations of the CTNS gene that encodes for cystinosin, a lysosomal cystine/H+ symporter. The disease is characterized by early-onset chronic kidney failure and progressive development of extra-renal complications related to cystine accumulation in all tissues. At the cellular level, several alterations have been demonstrated, including enhanced apoptosis, altered autophagy, defective intracellular trafficking, and cell oxidation, among others. Current therapy with cysteamine only partially reverts some of these changes, highlighting the need to develop additional treatments. Among compounds that were identified in a previous drug-repositioning study, disulfiram (DSF) was selected for in vivo studies. The cystine depleting and anti-apoptotic properties of DSF were confirmed by secondary in vitro assays and after treating Ctns-/- mice with 200 mg/kg/day of DSF for 3 months. However, at this dosage, growth impairment was observed. Long-term treatment with a lower dose (100 mg/kg/day) did not inhibit growth, but failed to reduce cystine accumulation, caused premature death, and did not prevent the development of renal lesions. In addition, DSF also caused adverse effects in cystinotic zebrafish larvae. DSF toxicity was significantly more pronounced in Ctns-/- mice and zebrafish compared to wild-type animals, suggesting higher cell toxicity of DSF in cystinotic cells.


Assuntos
Cistinose/patologia , Dissulfiram/toxicidade , Nefropatias/patologia , Testes de Toxicidade , Acetilcisteína/farmacologia , Animais , Apoptose , Cistina/metabolismo , Cistinose/urina , Modelos Animais de Doenças , Dissulfetos/metabolismo , Dissulfiram/química , Embrião não Mamífero/metabolismo , Humanos , Nefropatias/urina , Larva/metabolismo , Camundongos Knockout , Peixe-Zebra/embriologia
18.
Biomolecules ; 11(12)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34944449

RESUMO

Salt-sensitive hypertension resulting from an increase in blood pressure after high dietary salt intake is associated with an increase in the production of reactive oxygen species (ROS). ROS are known to increase the activity of the epithelial sodium channel (ENaC), and therefore, they have an indirect effect on sodium retention and increasing blood pressure. Extracellular vesicles (EVs) carry various molecules including proteins, microRNAs, and lipids and play a role in intercellular communication and intracellular signaling in health and disease. We investigated changes in EV lipids, urinary electrolytes, osmolality, blood pressure, and expression of renal ENaC and its adaptor protein, MARCKS/MARCKS Like Protein 1 (MLP1) after administration of the antioxidant Tempol in salt-sensitive hypertensive 129Sv mice. Our results show Tempol infusion reduces systolic blood pressure and protein expression of the alpha subunit of ENaC and MARCKS in the kidney cortex of hypertensive 129Sv mice. Our lipidomic data show an enrichment of diacylglycerols and monoacylglycerols and reduction in ceramides, dihydroceramides, and triacylglycerols in urinary EVs from these mice after Tempol treatment. These data will provide insight into our understanding of mechanisms involving strategies aimed to inhibit ROS to alleviate salt-sensitive hypertension.


Assuntos
Antioxidantes/administração & dosagem , Óxidos N-Cíclicos/administração & dosagem , Vesículas Extracelulares/química , Hipertensão/tratamento farmacológico , Lipídeos/urina , Cloreto de Sódio na Dieta/efeitos adversos , Animais , Antioxidantes/farmacologia , Proteínas de Ligação a Calmodulina/metabolismo , Óxidos N-Cíclicos/farmacologia , Modelos Animais de Doenças , Canais Epiteliais de Sódio/metabolismo , Vesículas Extracelulares/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/urina , Bombas de Infusão , Lipidômica , Camundongos , Proteínas dos Microfilamentos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Marcadores de Spin
19.
Nutrients ; 13(12)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34960084

RESUMO

High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2-77.8) RU/mL in men, and 70.3 (56.5-89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. ß -0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01-1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01-1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population.


Assuntos
/sangue , Hipertensão/prevenção & controle , Potássio na Dieta/administração & dosagem , Potássio na Dieta/farmacologia , Potássio/urina , Adulto , Estudos de Coortes , Feminino , /metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Arch. pediatr. Urug ; 92(2): e307, dic. 2021. ilus, tab
Artigo em Espanhol | LILACS, BNUY, UY-BNMED | ID: biblio-1339135

RESUMO

Las porfirias son un grupo complejo y heterogéneo de defectos en la vía de la síntesis del hemo. La porfiria hepato eritropoyética es un subtipo muy poco frecuente y de presentación en la infancia, con compromiso cutáneo predominante. Describimos el caso clínico de una paciente de 5 años, que se presenta con lesiones cutáneas e hipertricosis, se confirma el diagnóstico por elevación de uroporfirinas en orina y secuenciación del gen UROD.


Porphyria is a complex and heterogeneous group of heme synthesis disorder. Hepato-erythropoietic porphyria is a very rare subtype that onsets in childhood, and shows predominant skin involvement. We describe the clinical case of a 5-year-old patient who showed skin lesions and hypertrichosis and whose diagnosis was confirmed due to increased uroporphyrins in urine and UROD gene sequencing


A porfiria é um grupo complexo e heterogêneo de distúrbios da síntese do grupo heme. A porfiria hepato-eritropoiética é um subtipo muito raro que se inicia na infância e mostra envolvimento predominante da pele. Descrevemos o caso clínico de uma paciente de 5 anos que apresentou lesões cutâneas e hipertricose e cujo diagnóstico foi confirmado por aumento de uroporfirinas na urina e sequenciamento do gene UROD.


Assuntos
Humanos , Feminino , Pré-Escolar , Vesícula/etiologia , Porfiria Hepatoeritropoética/complicações , Porfiria Hepatoeritropoética/genética , Porfiria Hepatoeritropoética/urina , Diabetes Mellitus Tipo 1/complicações , Hipertricose/etiologia , Uroporfirinogênio Descarboxilase/análise , Uroporfirinas/urina , Vesícula/tratamento farmacológico , Coproporfirinas/urina , Hipertricose/tratamento farmacológico
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