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2.
Ecotoxicol Environ Saf ; 203: 111044, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888613

RESUMO

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with various adverse health outcomes. Although several mechanisms have been proposed including oxidative stress and inflammatory responses, the exact mechanism is still unknown. Few studies have investigated the mechanism linking PM2.5 and blood pressure (BP). In this study, we measured urinary metabolites and BP -related renin-angiotensin-aldosterone system (RAAS) to investigate the associations between ambient PM2.5 exposure and BP in healthy C57BL/6 mice. METHODS: The C57BL/6 mice were exposed to ambient concentrated PM2.5 or filtered air (FA) for 16 weeks. Systolic BP and diastolic BP were measured by noninvasive BP system. The urine metabolites were quantified using the untargeted metabolomics approach. The expression of RAAS-related proteins angiotensin-converting enzyme (ACE)2, angiotensin (Ang) II, Ang (1-7) and aldosterone (ALD) were measured using Western blot and ELISA kits. RESULTS: The metabolomics analysis demonstrated that PM2.5 exposure induced significant changes of some metabolites in urine, including stress hormones, amino acids, fatty acids, and lipids. Furthermore, there was an elevation of BP, increase of serous Ang II and ALD, along with the decrease of ACE2 and Ang (1-7) in kidney in the PM2.5-exposed mice compared with FA-exposed mice. CONCLUSIONS: The results demonstrated that PM2.5 exposure-induced BP elevation might be associated with RAAS activation. Meanwhile, PM2.5 exposure-induced changes of stress hormone and lipid metabolism might mediate the activation of RAAS. The results suggested that the systemic stress hormone and lipid metabolism was associated with the development of hypertension.


Assuntos
Poluentes Atmosféricos/toxicidade , Angiotensina I/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Material Particulado/toxicidade , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Acetilglucosaminidase/urina , Angiotensina I/sangue , Animais , Biomarcadores/sangue , Biomarcadores/urina , Hipertensão/urina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , beta-Galactosidase/urina
3.
Medicine (Baltimore) ; 99(37): e21386, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925711

RESUMO

Serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) are standard biomarkers of contrast-induced nephropathy (CIN). However, recent studies suggest that serum neutrophil gelatinase-associated lipocalin (sNGAL) and urine neutrophil gelatinase-associated lipocalin (uNGAL) may be better predictors, particularly within 24 hours of contrast medium exposure.We conducted a prospective, observational cohort study of 107 consecutive patients diagnosed with arteriosclerosis obliterans between February 2016 and October 2018. We divided the patients into 2 groups: CIN (n = 22) and non-CIN (n = 85). We assessed the correlation between sNGAL and uNGAL concentrations and standard renal markers at baseline, 6, 24, and 48 hours post-procedure. We constructed conventional receiver operating characteristic (ROC) curves and calculated the area under the curve to assess the performance of SCr, eGFR, sNGAL, and uNGAL. We derived biomarker cutoff levels from ROC analysis to maximize sensitivity and specificity.The incidence of CIN within our cohort was 20.6%. sNGAL levels correlated significantly with SCr and eGFR at baseline, 6, 24, and 48 hours post-contrast medium exposure. Similarly, uNGAL levels correlated with SCr and eGFR at baseline, 24, and 48 hours post-exposure. sNGAL and uNGAL were significantly elevated as early as 6 hours post-catheterization in the CIN group, whereas only minor changes were observed in the non-CIN group. SCr was also significantly elevated in the CIN group, but not until 24 hours post-catheterization.Both sNGAL and uNGAL may be superior to SCr and eGFR as early biomarkers of CIN in patients with peripheral vascular disease undergoing endovascular therapy.


Assuntos
Lesão Renal Aguda/diagnóstico , Meios de Contraste/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Lipocalina-2/análise , Complicações Pós-Operatórias/diagnóstico , Lesão Renal Aguda/induzido quimicamente , Idoso , Área Sob a Curva , Arteriosclerose Obliterante/cirurgia , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/induzido quimicamente , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
4.
Medicine (Baltimore) ; 99(31): e21332, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756118

RESUMO

Biliary atresia (BA) is a devastating cholestatic disorder of infants that presents during the first several months after birth due to an idiopathic obstruction to the bile flow. Without prompt diagnosis, Kasai portoenterostomy, and deliberate follow-ups, the resulting cholestasis leads to progressive hepatic failure. Oxidative stress is an abnormal phenomenon inside cells or tissues caused by a disturbance in the reactive oxygen species (ROS). We aimed to measure perioperative ROS in BA patients.Data are presented as median (25th, 75th percentiles). We evaluated 15 BA patients (age 55 [48, 69] days) and measured ROS; serum superoxide dismutase (SOD), urinary 8-iso prostaglandin F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) preoperatively and 30 days later to compare values with serum liver function tests and histologic grades of liver cholestasis. For compared BA patients, 4 normal subjects as control group (age 55 [27, 75] days) measured ROS and serum liver function tests.In BA patients, the preoperative serum SOD was 6.1 IU/mL (4.7, 7.2), urinary 8-iso-PGF2α was 1969 pg/mg Cre (1697, 2374), and urinary 8-OHdG was 37.1 ng/mg Cre (33.1, 53.7). At the postoperative day 30, the serum SOD was 5.2 IU/mL (4.2, 6.7), urinary 8-iso-PGF2α was 1761 pg/mg Cre (1256, 3036), and urinary 8-OHdG was 42.1 ng/mg Cre (29.65, 72.64). In ROS, there were no significant differences between the 2 periods. In control group, urinary 8-iso-PGF2α was significantly lower than that in preoperative BA patient group. However, other ROS were not significant differences between control group and BA patient group. The concentration of urinary 8-iso-PGF2α was positively correlated with total bilirubin and direct bilirubin levels (preoperatively: r = 0.6921, P = .0042 and r = 0.6639, P = .007, postoperatively: r = 0.6036, P = .0172 and r = 0.6464, P = .0092, respectively). The preoperative ROS were not correlated with histologic grades of liver cholestasis. Various factors such as liver inflammation, lipid malabsorption, and tissue disorders due to jaundice might affect the antioxidant activity and elevated urinary 8-iso-PGF2α. However, at least until 30 days later, urinary 8-OHdG as oxidative DNA damage might persist after the operation whether the cholestasis improved or not.


Assuntos
Atresia Biliar/cirurgia , Espécies Reativas de Oxigênio/sangue , Atresia Biliar/sangue , Bilirrubina/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Testes de Função Hepática , Masculino , Estudos Retrospectivos
5.
Ecotoxicol Environ Saf ; 202: 110920, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800255

RESUMO

Advanced glycation end products (AGE) and the receptor for AGE (RAGE) have been found to be pivotal biomarkers to predict the risk of inflammation and oxidative stress. Limited evidence focuses on the influence of occupational exposure to polycyclic aromatic hydrocarbon (PAH) and metal fumes on AGE and RAGE in shipyard welders. Our aim was to determine the relationships among PAH, metal exposure, and inflammatory biomarkers. From September 1 to December 31, 2017, 53 welding workers (exposed group) and 29 office workers (control group) were enrolled in the study. Comprehensive workups included demographic characteristics, laboratory data, AGE, RAGE, Interleukin-6 (IL-6), tumor necrosis factor-α, PAH, and urinary metal concentrations. RAGE levels were measured by flow cytometric analysis. Urinary 1-hydroxypyrene (1-OHP) was used as a biomarker of exposure to PAH. Several metals were elevated in the personal fine particulate matter (PM2.5) samples, including Mn, Fe, V, Co, Zn, and Cu. The exposed group had significantly higher exposure to PM2.5 (p = 0.015), RAGE (p = 0.020), IL-6 (p = 0.008) than the control group. After adjusting for pertinent variables, there was still a significant and positive association between Ni level and AGE (ß = 0.101; 95% CI, 0.031-0.172). Significant relationship between Cr and Cd levels and RAGE was observed (ß = 0.173; 95% CI, 0.017-0.329; ß = 0.084; 95% CI, 0.011-0.157, respectively). Participants with elevated 1-OHP level had higher odds of high RAGE level in the model 1 (OR = 3.466, 95% CI, 1.053-11.412) and model 2 (OR = 3.454, 95% CI, 1.034-11.536). The RAGE expression of participants was significantly associated with IL-6 levels in the fully adjusted model (ß = 0.294; 95% CI, 0.083-0.732). Our findings highlighted that urinary metal levels and PAH were associated with increased AGE and RAGE formation in shipyard workers. Elevated serum RAGE might induce the production of proinflammatory cytokines and trigger ensuing inflammatory cascades.


Assuntos
Poluentes Ocupacionais do Ar/análise , Metais/análise , Exposição Ocupacional/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Poluentes Ocupacionais do Ar/toxicidade , Biomarcadores/urina , Gases/análise , Produtos Finais de Glicação Avançada/sangue , Humanos , Inflamação , Masculino , Metais/toxicidade , Estresse Oxidativo , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Fator de Necrose Tumoral alfa , Soldagem
6.
BMC Infect Dis ; 20(1): 555, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736601

RESUMO

BACKGROUND: Determine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART. METHODS: Consecutive, HIV-positive adults with a CD4 count < 100 cells/uL presenting for ART initiation were enrolled. TB diagnoses and outcomes (hospitalization, loss-to-follow and mortality) were recorded during the first year following enrolment. Baseline urine samples were retrospectively tested using the urine-LAM POC assay. Kaplan Meier survival curves were used to assess the cumulative probability of hospitalization or mortality in the first year of follow-up, according to urine-LAM status. Cox regression analyses were performed to determine independent predictors of hospitalization and mortality at three months and one year of follow-up. RESULTS: 468 patients with a median CD4 count of 59 cells/uL were enrolled. There were 140 patients (29.9%) with newly diagnosed TB in the first year of follow-up of which 79 (56.4%) were microbiologically-confirmed. A total of 18% (n = 84) required hospital admission and 12.2% (n = 57) died within a year of study entry. 38 out of 468 (8.1%) patients retrospectively tested urine-LAM positive - including 19.0% of those with microbiologically-proven TB diagnoses (n = 15/79) and 23.0% (n = 14/61) of those with clinical-only TB diagnoses; 9 of 38 (23.7%) of patients retrospectively testing LAM positive were never diagnosed with TB under routine program conditions. Among all patients (n = 468) in the first year of follow-up, a positive urine-LAM result was strongly associated with all-cause hospitalization and mortality with a corresponding adjusted hazard ratio (aHR) of 3.7 (95%CI, 1.9-7.1) and 2.6 (95%, 1.2-5.7), respectively. CONCLUSIONS: Systematic urine-LAM testing among ART-naïve HIV-positive outpatients with CD4 counts < 100 cells/uL detected TB cases that were missed under routine programme conditions and was highly predictive for subsequent hospitalization and mortality in the first year of ART.


Assuntos
Infecções por HIV/complicações , Lipopolissacarídeos/urina , Tuberculose/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Contagem de Linfócito CD4 , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Testes Imediatos , Estudos Prospectivos , Estudos Retrospectivos , África do Sul/epidemiologia , Resultado do Tratamento , Tuberculose/mortalidade , Tuberculose/terapia , Tuberculose/urina , Urinálise/métodos
7.
PLoS One ; 15(7): e0235328, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628701

RESUMO

OBJECTIVE: Current urinary tract infection (UTI) diagnostic strategies that rely on leukocyte esterase have limited accuracy. We performed an aptamer-based proteomics pilot study to identify urine protein levels that could differentiate a culture proven UTI from culture negative samples, regardless of pyuria status. METHODS: We analyzed urine from 16 children with UTIs, 8 children with culture negative pyuria and 8 children with negative urine culture and no pyuria. The urine levels of 1,310 proteins were quantified using the Somascan™ platform and normalized to urine creatinine. Machine learning with support vector machine (SVM)-based feature selection was performed to determine the combination of urine biomarkers that optimized diagnostic accuracy. RESULTS: Eight candidate urine protein biomarkers met filtering criteria. B-cell lymphoma protein, C-X-C motif chemokine 6, C-X-C motif chemokine 13, cathepsin S, heat shock 70kDA protein 1A, mitogen activated protein kinase, protein E7 HPV18 and transgelin. AUCs ranged from 0.91 to 0.95. The best prediction was achieved by the SVMs with radial basis function kernel. CONCLUSIONS: Biomarkers panel can be identified by the emerging technologies of aptamer-based proteomics and machine learning that offer the potential to increase UTI diagnostic accuracy, thereby limiting unneeded antibiotics.


Assuntos
Aptâmeros de Nucleotídeos/química , Proteômica/métodos , Máquina de Vetores de Suporte , Urinálise/métodos , Infecções Urinárias/diagnóstico , Adolescente , Biomarcadores/urina , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Infecções Urinárias/urina
8.
Rev Environ Health ; 35(3): 295-300, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32639945

RESUMO

Background People who work long hours on the road are intensively exposed to high levels of fine particulate matters (PM2.5) which may lead to oxidative stress mechanisms in the human body that cause deleterious health problems. Malondialdehyde (MDA) is the major metabolite produced during lipid peroxidation metabolism that serves as a reliable biomarker for oxidative stress in cells. Objectives To identify the association between PM2.5 exposure and other characteristics with urinary MDA levels among public transport drivers in Jakarta. Methods A cross-sectional design was implemented by involving 130 public transport drivers of nine trajectories from Kampung Melayu Terminal, Jakarta. The continuous PM2.5 data were collected in personal measurement during one round trip of driving. Weight and height measurements were obtained to calculate body mass index (BMI) and structured questionnaires were completed to identify other characteristics. MDA levels were examined from the driver's urine right after driving and evaluated using TBARS analysis. Results The average of PM2.5 exposure was 91.56 ± 20.05 µg/m3 and MDA levels were 2.23 ± 1.57 nmoL/mL. Drivers with overweight and obese BMI had significantly higher MDA levels (2.66 ± 1.65 nmoL/mL) compared to those with normal and underweight BMI status (1.97 ± 1.47 nmoL/mL). Multiple linear regression analysis demonstrated low PM2.5 exposure, normal and underweight BMI status, and a long period of working as drivers were associated with MDA levels (p<0.05). Contrary to the prior study, PM2.5 exposure was negatively associated with MDA levels due to most drivers' BMI status being normal and underweight. Conclusion Our study suggests that the drivers who were obese and overweight should lose weight to lower the risk of increased MDA levels. We also suggest the drivers to consider maintaining their vehicle's ventilation system or using personal protection equipment (PPE) to avoid high PM2.5 exposure while driving.


Assuntos
Poluentes Atmosféricos/análise , Malondialdeído/urina , Exposição Ocupacional/análise , Material Particulado/análise , Transportes , Biomarcadores/urina , Cidades , Estudos Transversais , Humanos , Indonésia , Masculino , Tamanho da Partícula
9.
PLoS One ; 15(7): e0236357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687509

RESUMO

Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50µg iv+arginine 0,5 g/Kg test, with a peak GH response <9 µg /L when BMI was <30 kg/m2 or <4 µg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder.


Assuntos
Antioxidantes/análise , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/metabolismo , Síndrome Metabólica/metabolismo , Estresse Oxidativo/fisiologia , 8-Hidroxi-2'-Desoxiguanosina/urina , Adulto , Malformação de Arnold-Chiari/sangue , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Síndrome da Sela Vazia/sangue , Síndrome da Sela Vazia/complicações , Síndrome da Sela Vazia/metabolismo , Feminino , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/etiologia , Hipopituitarismo/urina , Peroxidação de Lipídeos , Lisina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Síndrome Metabólica/urina , Pessoa de Meia-Idade , Triptofano/análogos & derivados , Triptofano/sangue , Tirosina/análogos & derivados , Tirosina/urina
10.
J Sports Med Phys Fitness ; 60(7): 1034-1039, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32597619

RESUMO

BACKGROUND: Creatine represents a natural supplement and ergogenic aid for sport performance, but there are several concerns regarding its safety for health. The present double-blind placebo-controlled study evaluated the effect of creatine monohydrate supplementation on a panel of blood and urine health indicators in resistance training practitioners. METHODS: Eighteen males performing resistance training three times per week were supplemented with 0.3 g/kg per day creatine monohydrate for 7 days and compared with matched controls supplemented with dextrosol. Blood and urine samples were collected pre- and 30 days post-supplementation to evaluate 41 biochemical parameters and renal function. RESULTS: Creatine monohydrate supplementation did not cause adverse events and, as expected, promoted an increase of the performance and body weight. No modification of red blood cells parameters, white blood cells profile, blood lipid profile, metabolic and urine markers, hepatic and renal function were observed in the supplemented group. CONCLUSIONS: Despite the expected weight increase, the creatine monohydrate supplementation is safe for health and no detrimental effects on different organs and physiological systems were observed in our cohort of volunteers.


Assuntos
Desempenho Atlético/fisiologia , Creatina/administração & dosagem , Creatina/efeitos adversos , Suplementos Nutricionais , Substâncias para Melhoria do Desempenho/administração & dosagem , Substâncias para Melhoria do Desempenho/efeitos adversos , Treinamento de Resistência , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Método Duplo-Cego , Testes Hematológicos , Humanos , Rim/fisiologia , Contagem de Leucócitos , Lipídeos/sangue , Fígado/fisiologia , Masculino , Músculo Esquelético/metabolismo , Ganho de Peso , Adulto Jovem
11.
J Sports Sci ; 38(16): 1924-1932, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32543279

RESUMO

Athlete Biological Passport (ABP) is an indirect approach, implemented by WADA, aimed at detecting blood manipulation based on abnormal changes in haematological markers. Cases report the use of hyperhydration as masking method during anti-doping urine sample collection which could potentially mask suspicious fluctuations on ABP profiles. This study investigated the hyperhydration effect on haemoglobin concentration, reticulocyte percentage and OFF-hr score (an algorithm based on haemoglobin concentration and reticulocyte percentage), with and without recombinant human erythropoietin (rHuEPO) administration. A five-week clinical study performed; Baseline and rHuEPO Phase. Water and a sports drink were used as hyperhydration agents. To examine the hyperhydration effect on the normal ABP profile per volunteer, hyperhydration was implemented at 0, 24 and 48 hours during the baseline. During the rHuEPO phase, volunteers received Epoetin beta (3000 IU) with hyperhydration to be implemented at 0, 24 and 48 hours after drug administration. Blood and urine samples were collected and analysed according to WADA guidelines. No significant effect on ABP markers was observed due to hyperhydration at any time during the study. Pre- and post-hyperhydration data were not statistically different compared to individual baseline data. In conclusion, hyperhydration does not affect the ABP haematological markers under the examined conditions.


Assuntos
Biomarcadores/sangue , Doping nos Esportes , Comportamento de Ingestão de Líquido , Hemoglobinas/análise , Contagem de Reticulócitos , Adulto , Biomarcadores/urina , Bebidas Energéticas , Eritropoetina/administração & dosagem , Humanos , Masculino , Proteínas Recombinantes/administração & dosagem , Detecção do Abuso de Substâncias/métodos , Fatores de Tempo , Água
12.
PLoS One ; 15(6): e0234934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569286

RESUMO

BACKGROUND: Studies on adriamycin mice model suggest complement system is activated and together with IgM contributes to the glomerular injury of primary focal segmental glomerulosclerosis (FSGS). We recently reported primary FSGS patients with IgM and C3 deposition showed unfavorable therapeutic responses and worse renal outcomes. Here we examined the plasma and urinary complement profile of patients with primary FSGS, aiming to investigate the complement participation in FSGS pathogenesis. METHODS: Seventy patients with biopsy-proven primary FSGS were enrolled. The plasma and urinary levels of C3a, C5a, soluble C5b-9, C4d, C1q, MBL, and Bb were determined by commercial ELISA kits. RESULTS: The levels of C3a, C5a and C5b-9 in plasma and urine of FSGS patients were significantly higher than those in normal controls. The plasma and urinary levels of C5b-9 were positively correlated with urinary protein, renal dysfunction and interstitial fibrosis. The plasma C5a levels were positively correlated with the proportion of segmental sclerotic glomeruli. The urinary levels of Bb were elevated, positively correlated with C3a and C5b-9 levels, renal dysfunction, and interstitial fibrosis. The plasma C1q level was significantly decreased, and negatively correlated with urinary protein excretion. Urinary Bb level was a risk factor for no remission (HR = 3.348, 95% CI 1.264-8.870, P = 0.015) and ESRD (HR = 2.323, 95% CI 1.222-4.418, P = 0.010). CONCLUSION: In conclusion, our results identified the systemic activation of complement in human primary FSGS, possibly via the classical and alternative pathway. The activation of complement system was partly associated with the clinical manifestations, kidney pathological damage, and renal outcomes.


Assuntos
Ativação do Complemento/imunologia , Proteínas do Sistema Complemento , Glomerulosclerose Segmentar e Focal/imunologia , Glomérulos Renais , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/urina , Feminino , Humanos , Glomérulos Renais/imunologia , Glomérulos Renais/lesões , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
PLoS One ; 15(6): e0234970, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32589682

RESUMO

The incidence of type 2 diabetes is increasing more rapidly in adolescents than in any other age group. We identified and compared metabolite signatures in obese children with type 2 diabetes (T2D), obese children without diabetes (OB), and healthy, age- and gender-matched normal weight controls (NW) by measuring 273 analytes in fasting plasma and 24-hour urine samples from 90 subjects by targeted LC-MS/MS. Diabetic subjects were within 2 years of diagnosis in an attempt to capture early-stage disease prior to declining renal function. We found 22 urine metabolites that were uniquely associated with T2D when compared to OB and NW groups. The metabolites most significantly elevated in T2D youth included members of the betaine pathway, nucleic acid metabolism, and branched-chain amino acids (BCAAs) and their catabolites. Notably, the metabolite pattern in OB and T2D groups differed between urine and plasma, suggesting that urinary BCAAs and their intermediates behaved as a more specific biomarker for T2D, while plasma BCAAs associated with the obese, insulin resistant state independent of diabetes status. Correlative analysis of metabolites in the T2D signature indicated that betaine metabolites, BCAAs, and aromatic amino acids were associated with hyperglycemia, but BCAA acylglycine derivatives and nucleic acid metabolites were linked to insulin resistance. Of major interest, we found that urine levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) were increased in diabetic youth, identifying urine SAICA-riboside as a potential biomarker for T2D.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Purinas/biossíntese , Adolescente , Aminoácidos de Cadeia Ramificada/metabolismo , Betaína/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Vias Biossintéticas , Cromatografia Líquida de Alta Pressão , Biologia Computacional , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Feminino , Humanos , Masculino , Metabolômica/métodos , Ácidos Nucleicos/metabolismo , Obesidade/sangue , Obesidade/urina , Espectrometria de Massas em Tandem , Adulto Jovem
14.
Toxicology ; 441: 152493, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32479839

RESUMO

Early diagnosis of liver injuries caused by drugs or occupational exposures is necessary to enable effective treatments and prevent liver failure. Whereas histopathology remains the gold standard for assessing hepatotoxicity in animals, plasma aminotransferase levels are the primary measures for monitoring liver dysfunction in humans. In this study, using Sprague Dawley rats, we investigated whether integrated analyses of transcriptomic and metabolomic data with genome-scale metabolic models (GSMs) could identify early indicators of injury and provide new insights into the mechanisms of hepatotoxicity. We obtained concurrent measurements of gene-expression changes in the liver and kidneys, and expression changes along with metabolic profiles in the plasma and urine, from rats 5 or 10 h after exposing them to one of two classical hepatotoxicants, acetaminophen (2 g/kg) or bromobenzene (0.4 g/kg). Global multivariate analyses revealed that gene-expression changes in the liver and metabolic profiles in the plasma and urine of toxicant-treated animals differed from those of controls, even at time points much earlier than changes detected by conventional markers of liver injury. Furthermore, clustering analysis revealed that both the gene-expression changes in the liver and the metabolic profiles in the plasma induced by the two hepatotoxicants were highly correlated, indicating commonalities in the liver toxicity response. Systematic GSM-based analyses yielded metabolites associated with the mechanisms of toxicity and identified several lipid and amino acid metabolism pathways that were activated by both toxicants and those uniquely activated by each. Our findings suggest that several metabolite alterations, which are strongly associated with the mechanisms of toxicity and occur within injury-specific pathways (e.g., of bile acid and fatty acid metabolism), could be targeted and clinically assessed for their potential as early indicators of liver damage.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/sangue , Acetaminofen/toxicidade , Animais , Biomarcadores/sangue , Biomarcadores/urina , Bromobenzenos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/urina , Perfilação da Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metabolômica , Ratos Sprague-Dawley
15.
Toxicol Lett ; 331: 235-241, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32562636

RESUMO

The study aims to investigate the influence of exposure to low concentrations of benzene on urinary biomarkers of nucleic acid oxidative damage and methylation. Benzene exposure was characterized for 93 coke production workers by measuring both airborne benzene and S-phenylmercapturic acid (SPMA) and unmodified benzene (U-B) in urine samples, collected at the end of the shift (ES) and at the next morning before shift (next BS). In the same urinary samples, biomarkers of nucleic acid oxidative damage and methylation were determined. Urinary concentrations of cotinine and creatinine were also determined to evaluate the smoking effect and to normalize urinary concentrations of analytes, respectively. The biomarkers of benzene internal dose, of oxidative damage (8-hydroxyy-7,8-dihydroguanine, 8-hydroxy-7,8-dihydroguanosine and 8-hydroxy-7,8-2'deoxyguanosine) and some of the biomarkers of nucleic acid methylation (5-Methyl-Cytosine, 1-Methyl-Guanine and 7-Methyl-Guanine) were higher in the ES than the next BS samples. Positive associations between ES 5-Methyl-Cytosine and both SPMA and U-B were found. In conclusion, occupational exposure to low levels of benzene seems to be related to urinary ES 5-Methyl-Cytosine that could be a possible biomarker to evaluate the changes of the nucleic acid methylation status.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Benzeno/toxicidade , Citosina/urina , Monitoramento Ambiental/métodos , Ácidos Nucleicos/metabolismo , Exposição Ocupacional/análise , Poluentes Ocupacionais do Ar/análise , Benzeno/análise , Biomarcadores/urina , Citosina/análogos & derivados , Humanos , Metilação , Oxirredução
16.
Ecotoxicol Environ Saf ; 200: 110741, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497990

RESUMO

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl ß-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 µg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.


Assuntos
Cálcio , Rim/efeitos dos fármacos , Triazinas/toxicidade , Triazinas/urina , Urolitíase/urina , Acetilglucosaminidase/urina , Adulto , Idoso , Teorema de Bayes , Biomarcadores/urina , Exposição Ambiental , Feminino , Humanos , Rim/fisiopatologia , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Método de Monte Carlo , Probabilidade , Urolitíase/fisiopatologia
17.
Rev. esp. patol. torac ; 32(2): 106-117, mayo 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193903

RESUMO

FUNDAMENTO Y OBJETIVOS: el cáncer de pulmón (CP) es el que provoca mayor mortalidad, especialmente por su frecuente diagnóstico tardío, con menos posibilidades de curación. En el inicio del proceso carcinogénico, previo al diagnóstico clínico, los oligoelementos (metales o metaloides), desempeñan un papel importante al activar o inhibir las reacciones enzimáticas y las metaloproteínas. El objetivo de nuestro estudio es analizar la utilidad de diversos metales como biomarcadores (BM) precoces de CP, obtenidos en muestras de suero, orina, y lavado broncoalveolar (LBA)MATERIAL Y MÉTODOS: hemos analizado las concentraciones totales, incluyendo fracciones de alto y bajo peso molecular, de 11 metales en muestras de suero, orina y LBA de pacientes CP, controles sanos (CS) y pacientes con patología respiratoria no cáncer (NCP) empleando una técnica de análisis basada en un plasma de acoplamiento inductivo-espectrometría de masas (ICP-QQQ-MS). RESULTADOS: obtuvimos una clara discriminación entre los grupos en las tres muestras analizadas. Hemos obtenido metales sobreexpresados o reducidos en el CP que podrían utilizarse como BM. La concentración de vanadio (V) y cromo (Cr) en suero es claramente mayor en pacientes con CP. Hemos demostrado que varios metales (V, Cr y cobre), relacionados con procesos metabólicos alterados en CP como estrés oxidativo y homeostasis, y/o sus relaciones podrían ser buenos BM de CP. CONCLUSIONES: diversos metales, y sus relaciones y correlaciones, en la población estudiada diferencian claramente a los pacientes con cáncer de pulmón de los CS y NCP y parecen ser buenos biomarcadores en el diagnóstico precoz del cáncer de pulmón


BACKGROUND AND OBJECTIVES: Lung cancer (LC) has the highest mortality rate, especially due to its late diagnosis, with a lower chance of recovery. At the start of the carcinogenic process, before a clinical diagnosis, trace elements (metals or metalloids) play an important role by activating or inhibiting enzymatic reactions and metalloproteins. The objective of our study is to analyze the utility of different metals as early biomarkers (BM) for LC which are obtained in serum, urine and bronchoalveolar lavage (BAL) samples. MATERIAL AND METHODS: We analyzed the total concentrations, including fractions of high and low molecular weight, of 11 metals in serum, urine and BAL samples from patients with LC, healthy controls (HC) and patients with non-cancerous respiratory pathology (NCP) using an analysis technique based on inductively coupled plasma mass spectrometry (ICP-QQQ-MS).RESULTS: We obtained a clear discrimination between groups for the three samples analyzed. We obtained overexpressed or reduced metals in LC that could be used as BM. The concentration of vanadium (V) and chromium (Cr) in serum is clearly higher in patients with LC. We have shown that several metals (V, Cr and copper) related to the altered metabolic processes in LC such as oxidative stress and homeostasis and/or their connections could be good BM for LC. CONCLUSIONS: in the population studied, several metals and their connections and correlations were clearly differentiated in the patients with lung cancer compared to the HC and NCP groups and they appear to be good biomarkers for the early diagnosis of lung cancer


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Diagnóstico Precoce , Oligoelementos/análise , Lavagem Broncoalveolar/métodos , Espectrometria de Massas/métodos , Prognóstico , Curva ROC
18.
PLoS One ; 15(5): e0232522, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365131

RESUMO

Chronic Kidney Disease of uncertain etiology (CKDu) is an endemic, disease that mostly affects young agricultural workers in the rural dry zone of Sri Lanka. This study was designed to identify specific biochemical manifestations of CKDu cases. All (119) non-dialysis definite CKDu patients in Girandurukotte and Wilgamuwa were selected. Blood and urine samples were collected and measured biochemical parameters. All analyses were performed in IBM SPSS statistics version 23 (IBM Corp, USA). The median blood pressure was normal though nearly half of the patients (45.4%) who were in the advanced stages (Stage 3b, 4 and 5) of CKDu. Patients without a history of hypertension before the diagnosis of CKDu (100%) and minimal proteinuria (26%) are similar to the previous findings. Patients without a history of diabetes before the CKDu diagnosis had high percentages of diabetes (15.7%) and pre-diabetes (59.8%) and hence indicated the possibility of uremia induced impaired glucose intolerance in the rural areas of the country. There were 62.2% patients who had low vitamin D and only a minority had evidence of bone mineral diseases. Out of liver disease markers serum glutamic pyruvic transaminases (SGPT), serum glutamic oxaloacetic transaminases (SGOT), gamma-glutamyl transferase (GGT), and Lactic acid degydrogenase (LDH) had an inverse correlation with the advancement of the disease indicating subclinical liver disease. Osmolality in serum and urine showed a discrepancy despite > 50% of CKDu patients had increased their serum osmolality. The current study supports most of the previously described manifestations of CKDu. Moreover, some specific patterns have been identified which need to be validated in a larger group.


Assuntos
Insuficiência Renal Crônica/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Sódio/sangue , Sri Lanka/epidemiologia , Adulto Jovem
19.
Crit Care Resusc ; 22(2): 142-151, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32389106

RESUMO

BACKGROUND: Frequent assessment of urine output (UO), serum creatinine (sCr) and urinary cell cycle arrest biomarkers (CCAB) may improve acute kidney injury (AKI) prediction. OBJECTIVE: To study the performance of UO, short term sCr changes and urinary CCAB to predict severe AKI. METHODS: We measured 6 hours of UO, 6-hourly sCr changes, and urinary CCABs in all critically ill patients with cardiovascular or respiratory failure or early signs of renal stress between February and October 2018. We studied the association of such measurements, and their combination, with the development of AKI Stage 2 or 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) definition at 12 hours. We evaluated predictive performance with logistic regression, area under the receiver operating characteristic (AUROC) curve, and net reclassification indices. We computed an optimal cut-off value for each biomarker. RESULTS: We assessed 622 patients and, as per the exclusion criteria, we enrolled 105 critically ill patients. After 12 hours of enrolment, AKI occurred in 32 patients (30%). UO, sCr change over 6 hours and CCABs were significantly associated with severe AKI at 12 hours, with all variables achieving an AUROC > 0.7 after adjustment. Combination of any of the two or three variables achieved an AUROC > 0.7 for subsequent severe AKI at 12 hours. The optimal predictive high specificity cut-off values were ≤ 0.4 mL/kg/h for UO, variation of +15 µmol/L over 6 hours in sCr, and ≥ 1.5 (ng/mL)2/1000 for CCABs. CONCLUSION: In this prospective study, an integrative approach using UO, short term sCr change and/or urinary CCABs showed a satisfactory performance for the prediction of severe AKI development at 12 hours.


Assuntos
Lesão Renal Aguda , Biomarcadores/urina , Pontos de Checagem do Ciclo Celular/fisiologia , Urina , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/urina , Creatinina/sangue , Estado Terminal , Taxa de Filtração Glomerular , Humanos , Unidades de Terapia Intensiva , Testes de Função Renal , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Micção
20.
Parasitol Res ; 119(7): 2227-2235, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32435898

RESUMO

Babesiosis among humans is on the rise in North America. Current diagnostic assays for the screening of babesiosis require blood collection by venipuncture, which is an invasive method. Urine on the other hand is a desirable biospecimen for biomarker analysis of Babesia microti infections because it can be collected periodically and non-invasively. Our group uses a new class of biomarker harvesting nanocage technology, which, when combined with mass spectrometry (MS), can determine the presence of parasite proteins shed in different bodily fluids of mammalian hosts, including urine. Using the hamster model of babesiosis, our nanoparticle-MS approach identified several B. microti proteins in erythrocytes, plasma, and urine samples. Surface and secreted antigens previously shown to elicit host immune responses against the parasite were particularly abundant in erythrocytes and plasma compared to other proteins. Two of these antigens, BmSA1 and BMR1_03g00947, showed different localization patterns by immunofluorescence of infected erythrocytes. Hamster urine samples from parasitemic animals harbored lower numbers of B. microti proteins compared to erythrocytes and plasma, with glycolytic enzymes, cytoskeletal components, and chaperones being the most frequently detected proteins. By applying novel nanoparticle-MS methods, a high level of analytical sensitivity can be achieved to detect multiple B. microti proteins in blood and urine. This is generally difficult to obtain with other techniques due to the masking of parasite biomarkers by the complex biomolecular matrix of bodily fluids from the host.


Assuntos
Babesia microti/isolamento & purificação , Babesiose/diagnóstico , Eritrócitos/parasitologia , Proteínas de Protozoários/metabolismo , Animais , Babesia microti/metabolismo , Babesiose/sangue , Babesiose/urina , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Cricetinae , Espectrometria de Massas , Proteômica , Proteínas de Protozoários/sangue , Proteínas de Protozoários/urina , Sensibilidade e Especificidade
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