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1.
Sci Rep ; 14(1): 18854, 2024 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143107

RESUMO

The rapid and sensitive indicator of inflammation in the human body is C-Reactive Protein (CRP). Determination of CRP level is important in medical diagnostics because, depending on that factor, it may indicate, e.g., the occurrence of inflammation of various origins, oncological, cardiovascular, bacterial or viral events. In this study, we describe an interferometric sensor able to detect the CRP level for distinguishing between no-inflammation and inflammation states. The measurement head was made of a single mode optical fiber with a microsphere structure created at the tip. Its surface has been biofunctionalized for specific CRP bonding. Standardized CRP solutions were measured in the range of 1.9 µg/L to 333 mg/L and classified in the initial phase of the study. The real samples obtained from hospitalized patients with diagnosed Urinary Tract Infection or Urosepsis were then investigated. 27 machine learning classifiers were tested for labeling the phantom samples as normal or high CRP levels. With the use of the ExtraTreesClassifier we obtained an accuracy of 95% for the validation dataset. The results of real samples classification showed up to 100% accuracy for the validation dataset using XGB classifier.


Assuntos
Proteína C-Reativa , Aprendizado de Máquina , Humanos , Proteína C-Reativa/análise , Infecções Urinárias/diagnóstico , Infecções Urinárias/urina , Interferometria/métodos , Inflamação/diagnóstico , Inflamação/urina , Sepse/diagnóstico , Sepse/urina , Técnicas Biossensoriais/métodos , Fibras Ópticas
2.
Clin Nutr ; 43(8): 1865-1871, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38964203

RESUMO

BACKGROUND: Metabolic syndrome (MetS) in adolescence is a risk factor for future cardiovascular disease. The chronic inflammation associated with MetS can be attenuated by the anti-inflammatory effect of polyphenols. We aimed to evaluate total urinary polyphenols as a biomarker of anti-inflammatory diets and their effect on MetS in adolescents. METHODS: In this retrospective analysis of a longitudinal cohort study, the relationship between total polyphenol excretion (TPE) in urine, the inflammatory potential of the diet measured through the Children's Dietary Inflammatory Index (C-DII), and the presence of metabolic syndrome was evaluated. The study population consisted of adolescents enrolled in the SI! Program for Secondary Schools trial, who had completed all the study forms and provided urine samples at baseline and at the two-year follow-up. Multivariate linear regression and multinominal logistic regression models were generated to evaluate the relationship of changes in TPE with changes in the C-DII score and changes in MetS status, respectively. An analysis of the ROC curve was performed to assess the potential of TPE as a biomarker of an anti-inflammatory diet. RESULTS: This study included 662 adolescents, 51.2% were males, and 48.8% were females, with a mean age of 12 (0.38) years at baseline. The relationship between changes in TPE and changes in the C-DII score was stratified by sex with a p-value <0.001 for the interaction. TPE and C-DII were inversely associated in males (-0.13 mg GAE/g creatinine [-0.26; -0.01] per 1-SD increase, p-value = 0.037). In addition, an increase in changes in TPE levels were associated with a reversal in MetS status in all adolescents (1.30 [1.27; 1.34] per 1-SD increase, p-value<0.001). The ROC curve showed that urinary TPE levels can predict dietary inflammatory potential with an AUC = 0.793 (0.725; 0.863) in males. CONCLUSION: Polyphenols excreted in urine are a potential biomarker of anti-inflammatory diets in males and are associated with a reversal of MetS status in adolescents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03504059, https://clinicaltrials.gov/study/NCT03504059.


Assuntos
Biomarcadores , Dieta , Síndrome Metabólica , Polifenóis , Humanos , Masculino , Feminino , Polifenóis/administração & dosagem , Polifenóis/urina , Adolescente , Biomarcadores/urina , Síndrome Metabólica/urina , Estudos Longitudinais , Estudos Retrospectivos , Dieta/métodos , Inflamação/urina , Criança , Anti-Inflamatórios/administração & dosagem
3.
Chemosphere ; 361: 141485, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38438022

RESUMO

Evidence on the association of volatile organic compounds (VOCs) with chronic bronchitis (CB) and emphysema is spare and defective. To evaluate the relationship between urinary metabolites of VOCs (mVOCs) with CB and emphysema, and to identify the potential mVOC of paramount importance, data from NHANES 2011-2014 waves were utilized. Logistic regression was conducted to estimate the independent association of mVOCs with respiratory outcomes. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen a parsimonious set of CB- and emphysema-relevant mVOCs that were used for further co-exposure analyses of weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). Mediation analysis was employed to detect the mediating role of inflammatory makers in such associations. In single exposure analytic model, nine mVOCs were individually and positively associated with CB, while four mVOCs were with emphysema. In WQS regression, positive association between LASSO selected mVOCs and CB was identified (OR = 1.82, 95% CI: 1.25 to 2.69), and N-acetyl-S-(4-hydroxy-2-butenyl)-l-cysteine (MHBMA3) weighted the highest. Results from BKMR further validated such combined association and the significance of MHBMA3. As for emphysema, significantly positive overall trend of mVOCs was only observed in BKMR model and N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) contributed most to the mixed effect. White blood cell count (WBC) and lymphocyte number (LYM) were mediators in the positive pattern of mVOCs mixture with CB, while association between mVOCs mixture and emphysema was significantly mediated by LYM and segmented neutrophils num (NEO). This study demonstrated that exposure to VOCs was associated with CB and emphysema independently and combinedly, which might be partly speculated that VOCs were linked to activated inflammations. Our findings shed novel light on VOCs related respiratory illness, and provide a new basis for the contribution of certain VOCs to the risk of CB and emphysema, which has potential public health implications.


Assuntos
Bronquite Crônica , Enfisema , Inflamação , Inquéritos Nutricionais , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/urina , Bronquite Crônica/urina , Bronquite Crônica/epidemiologia , Humanos , Enfisema/urina , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Inflamação/urina , Teorema de Bayes , Idoso , Poluentes Atmosféricos/urina , Poluentes Atmosféricos/análise , Modelos Logísticos , Exposição Ambiental/estatística & dados numéricos
4.
Physiol Rep ; 11(2): e15590, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695752

RESUMO

Diet has the potential to decrease oxidative stress and inflammation and this may be beneficial in several diseases. This study investigated the association between food quality score (FQS) with antioxidant and inflammatory properties in 171 apparently healthy young women. This cross-sectional study was conducted using a validated food frequency questionnaire to determine the dietary intake of participants. FQS was calculated by summing all the scores obtained from healthy and unhealthy food groups. The total antioxidant capacity and free radical scavenging activity of serum and urine were quantified using the ferric reducing/antioxidant power (FRAP) and α, α-diphenyl-ß-picrylhydrazyl (DPPH) methods, respectively. Malondialdehyde (MDA) was measured using the formation of thiobarbituric acid reactive substances (TBARS). White blood cell (WBC) and neutrophil counts, mean platelet volume (MPV) and red blood cell distribution width (RDW), were measured. Neutrophil: lymphocyte ratio (NLR), platelet: lymphocyte ratio (PLR), and RDW: platelet ratio (RPR) were also calculated. A high food quality (rich in fruit and vegetables, nuts, whole grain, and low intake of sweetened beverage, potato chips and fried food from outside the home) was related to lower hematological inflammatory biomarkers including WBC count, RDW, NLR, and PLR. Multivariable-adjusted odds ratios (95% CIs) demonstrated that higher FQS group (third tertile vs. first tertile) was associated with a significant lower levels of urinary FRAP (ORadj  = 0.82; 95%CI: 0.70 to 0.97), and DPPH. High food quality was associated with reduced of markers of inflammation and oxidative stress in Iranian young girl.


Assuntos
Antioxidantes , Biomarcadores , Dieta , Inflamação , Feminino , Humanos , Antioxidantes/análise , Biomarcadores/sangue , Biomarcadores/urina , Estudos Transversais , Inflamação/sangue , Inflamação/urina , Irã (Geográfico) , Linfócitos , Neutrófilos , Dieta/estatística & dados numéricos , Análise Química do Sangue , Contagem de Células Sanguíneas
5.
Front Immunol ; 12: 676105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650548

RESUMO

Background: Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA. Methods: Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation. Results: Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP. Conclusions: This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/urina , Adulto , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Proteína C-Reativa/análise , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/urina , Análise dos Mínimos Quadrados , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética
6.
J Biochem ; 170(4): 547-558, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34165535

RESUMO

Cancer development and progression is often associated with inflammation. Late diagnosis of inflammation that directly leads to the development of neoplasm-cancer is associated with a reduction in the chance of successful treatment or is associated with therapeutic difficulties. A panel of chromogenic substrates was used for the qualitative determination of the specific activity of enzymes in urine of patients with confirmed inflammatory reaction and/or epithelial neoplasms in particular tumours at various stages of development. Urine of people with excluded inflammation was used as a control group. Proteolytic activity was determined in urine samples collected from patients with epithelial neoplasms and/or inflammation. What is more, we determine human neutrophil elastase activity-related inflammation based on the examination of urine samples. We suspect that the proteolytical activity of urine samples is due to neutrophil response to inflammation, which is directly related to cancer. This is the first study to determine elastolytic activity in bladder cancer urine samples. It supports wider use of urine for inflammation screening.


Assuntos
Inflamação/urina , Elastase de Leucócito/metabolismo , Neoplasias da Bexiga Urinária/urina , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/urina , Feminino , Humanos , Inflamação/enzimologia , Inflamação/metabolismo , Elastase de Leucócito/urina , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Proteólise , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/metabolismo
7.
BMC Urol ; 21(1): 39, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740940

RESUMO

BACKGROUND: Contemporary studies have discredited the methods used to exclude urinary tract infection (UTI) when treating overactive bladder (OAB). Thus we must revisit the OAB phenotype to check that UTI has not been overlooked. AIMS: To examine the differences in urinary cytokines IL6 and lactoferrin in OAB patients compared to controls, with references to microscopy of urine and enhanced quantitative urine culture. METHODS: A blinded, prospective cohort study with normal controls using six repeated measures, achieved two-monthly, over 12 months. RESULTS: The differences between patients and controls in urine IL6 (F = 49.0, p < .001) and lactoferrin (F = 228.5, p < .001) were significant and of a magnitude to have clinical implications. These differences were for lactoferrin correlated to symptoms (9.3, p = .003); for both to pyuria (IL6 F = 66.2, p < .001, Lactoferrin F = 73.9, p < .001); and for IL6 microbial abundance (F = 5.1, p = .024). The pathological markers had been missed by urinary dipsticks and routine MSU culture. CONCLUSION: The OAB phenotype may encompass patients with UTI that is being overlooked because of the failure of standard screening methods.


Assuntos
Interleucina-6/urina , Lactoferrina/urina , Bexiga Urinária Hiperativa/urina , Idoso , Feminino , Humanos , Inflamação/etiologia , Inflamação/urina , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Bexiga Urinária Hiperativa/complicações
8.
Sci Rep ; 10(1): 21167, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33273625

RESUMO

When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X2 and P2X3 receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6-S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.


Assuntos
Trifosfato de Adenosina/metabolismo , Bactérias/metabolismo , Reflexo/fisiologia , Transdução de Sinais , Bexiga Urinária/fisiologia , Micção/fisiologia , Urotélio/fisiologia , Animais , Inflamação/patologia , Inflamação/urina , Lipopolissacarídeos , Vértebras Lombares/patologia , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Receptores Purinérgicos/metabolismo , Reflexo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Bexiga Urinária/efeitos dos fármacos , Micção/efeitos dos fármacos , Urotélio/efeitos dos fármacos
9.
Sci Rep ; 10(1): 19306, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168850

RESUMO

The objective of this study was to assess the diagnosis value of urinary inflammatory index (UII) and systemic immune-inflammation index (SII) for UTI. Nine inflammatory indexes including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, SII and six UIIs were calculated for Receiver operating characteristic curve analysis to select which one is suitable for the screening of UTIs or distinguishing the types of bacteria. UII3, which calculated from leucocyte esterase (LE), nitrite, white blood cells and bacteria, was preferentially used as an indicator for the diagnosis of UTI when the threshold was set at 0.53. UII2 was more suitable for the distinction between groups when the cutoff is set to 0.94. Appropriate urinary inflammation index calculated by rapid urinalysis of urine dipstick and urine sediment can help us to predict urinary tract infection and bacterial type, and reduce the workload and costs of urine culture.


Assuntos
Inflamação/urina , Urinálise/normas , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia , Idoso , Bacteriúria/microbiologia , Plaquetas/citologia , Hidrolases de Éster Carboxílico/metabolismo , Feminino , Humanos , Elastase de Leucócito/metabolismo , Leucócitos/metabolismo , Linfócitos/citologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Neutrófilos/citologia , Nitritos/metabolismo , Curva ROC , Kit de Reagentes para Diagnóstico/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
PLoS One ; 15(10): e0240753, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108383

RESUMO

BACKGROUND: Immune system suppression during critical care contributes to the risk of acquired bacterial infections with Pseudomonas (P.) aeruginosa. Repeated exposure to endotoxin can attenuate systemic inflammatory cytokine responses. Mechanical ventilation affects the systemic inflammatory response to various stimuli. AIM: To study the effect of pre-exposure to mechanical ventilation with and without endotoxin-induced systemic inflammation on P. aeruginosa growth and wet-to-dry weight measurements on lung tissue and plasma and bronchoalveolar lavage levels of tumor necrosis factor alpha, interleukins 6 and 10. METHODS: Two groups of pigs were exposed to mechanical ventilation for 24 hours before bacterial inoculation and six h of experimental pneumonia (total experimental time 30 h): A30h+Etx (n = 6, endotoxin 0.063 µg x kg-1 x h-1) and B30h (n = 6, saline). A third group, C6h (n = 8), started the experiment at the bacterial inoculation unexposed to endotoxin or mechanical ventilation (total experimental time 6 h). Bacterial inoculation was performed by tracheal instillation of 1x1011 colony-forming units of P. aeruginosa. Bacterial cultures and wet-to-dry weight ratio analyses were done on lung tissue samples postmortem. Separate group comparisons were done between A30h+Etx vs.B30h (Inflammation) and B30h vs. C6h (Ventilation Time) during the bacterial phase of 6 h. RESULTS: P. aeruginosa growth was highest in A30h+Etx, and lowest in C6h (Inflammation and Ventilation Time both p<0.05). Lung wet-to-dry weight ratios were highest in A30h+Etx and lowest in B30h (Inflammation p<0.01, Ventilation Time p<0.05). C6h had the highest TNF-α levels in plasma (Ventilation Time p<0.01). No differences in bronchoalveolar lavage variables between the groups were observed. CONCLUSIONS: Mechanical ventilation and systemic inflammation before the onset of pneumonia increase the growth of P. aeruginosa in lung tissue. The attenuated growth of P. aeruginosa in the non-pre-exposed animals (C6h) was associated with a higher systemic TNF-α production elicited from the bacterial challenge.


Assuntos
Endotoxemia/complicações , Pulmão/microbiologia , Pneumonia/complicações , Pneumonia/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Respiração Artificial , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Inflamação/urina , Masculino , Nitritos/urina , Norepinefrina/metabolismo , Tamanho do Órgão , Perfusão , Suínos
11.
Int Urol Nephrol ; 52(11): 2051-2057, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32524496

RESUMO

PURPOSE: To evaluate the expression of urinary biomarkers of inflammation and tissue remodeling in patients with BPH undergoing surgery and evaluate the association of biomarkers with postoperative urodynamic outcomes MATERIALS AND METHODS: We analyzed urine samples from 71 patients treated with TURP from 2011 to 2017. Urinary levels of epidermal growth factor (EGF), matrix-metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), nerve growth factor (NGF) and monocyte-chemoattractant protein-1 (MCP-1) (by commercial ELISA kit) were measured, adjusted by urinary creatinine (Cr) and analyzed according to patients clinical and urodynamic characteristics (baseline and 12-month postoperative urodynamic) RESULTS: MMP-1/Cr levels were significantly higher among subjects with higher detrusor pressure on preoprative urodynamic. MCP-1/Cr levels were significantly higher amongs subjects with preoperative DO. Preoperative levels of NGF/Cr (0.13 vs 0.08, p = 0.005) and MMP-1/Cr (0.11 vs 0.04, p = 0.021) were predictors of persistent DO 12 months after surgery. The following factors were shown to be useful for predicting the persistence of DO in the postoperative period: NGF/Cr, with an AUC of 0.77 (95% CI 0.62-0.92) (p = 0.006), and MMP-1/Cr, with an AUC of 0.72 (95% CI 0.56-0.88) (p = 0.022). CONCLUSIONS: MMP-1/Cr was associated with higher detrusor pressure and MCP-1/CR with DO. NGF/Cr and MMP-1/Cr were shown to be predictors of persistent postoperative DO.


Assuntos
Complicações Pós-Operatórias/epidemiologia , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/urina , Ressecção Transuretral da Próstata , Doenças da Bexiga Urinária/epidemiologia , Idoso , Biomarcadores/urina , Humanos , Inflamação/complicações , Inflamação/urina , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Valor Preditivo dos Testes , Hiperplasia Prostática/complicações , Hiperplasia Prostática/patologia , Resultado do Tratamento , Doenças da Bexiga Urinária/fisiopatologia , Urodinâmica
12.
J Sports Sci ; 38(18): 2080-2091, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32530734

RESUMO

Acute and adaptive changes in systemic markers of oxidatively generated nucleic acid modifications (i.e., 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo)) as well as inflammatory cytokines (i.e., C-reactive protein, interleukin-6, interleukin-10, and tumour necrosis factor alpha), a liver hormone (i.e., fibroblast growth factor 21 (FGF21)), and bone metabolism markers (sclerostin, osteocalcin, C-terminal telopeptide, and N-terminal propeptide of type 1 procollagen) were investigated following a marathon in 20 study participants. Immediate changes were observed in inflammatory cytokines, FGF21, and bone metabolism markers following the marathon. In contrast, no immediate changes in urinary excretion of 8-oxodG and 8-oxoGuo were evident. Four days after the marathon, decreased urinary excretion of 8-oxodG (-2.9 (95% CI -4.8;-1.1) nmol/24 h, P < 0.01) and 8-oxoGuo (-5.8 (95% CI -10.3;-1.3) nmol/24 h, P = 0.02) was observed. The excretion rate of 8-oxodG remained decreased 7 days after the marathon compared to baseline (-2.3 (95%CI -4.3;-0.4) nmol/24 h, P = 0.02), whereas the excretion rate of 8-oxoGuo was normalized. In conclusion marathon participation immediately induced a considerable inflammatory response, but did not increase excretion rates of oxidatively generated nucleic acid modifications. In fact, a delayed decrease in oxidatively generated nucleic acid modifications was observed suggesting adaptive antioxidative effects following exercise. ABBREVIATIONS: 8-oxodG: 8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxoGuo: 8-oxo-7,8-dihydroguanosine; CI: confidence interval; CTX: C-terminal telopeptide of type 1 collagen; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunosorbent assay; FGF21: Fibroblast growth factor 21; h: hour; hsCRP: high sensitivity C-reactive protein; IL: interleukin; IQR: interquartile range; MS: mass spectrometry: P1NP: N-terminal propeptide of type 1 procollagen; TNFα: tumour necrosis factor alpha; UPLC: ultra-performance liquid chromatography.


Assuntos
Inflamação/sangue , Inflamação/urina , Estresse Oxidativo , Resistência Física/fisiologia , Corrida/fisiologia , 8-Hidroxi-2'-Desoxiguanosina/urina , Biomarcadores/sangue , Biomarcadores/urina , Remodelação Óssea , Creatinina/urina , Citocinas/sangue , Humanos , Masculino , Fatores de Tempo , Adulto Jovem
13.
J Crohns Colitis ; 14(8): 1090-1102, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32119090

RESUMO

BACKGROUND AND AIMS: Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease. METHODS: Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. RESULTS: Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease. CONCLUSIONS: This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.


Assuntos
Adalimumab , Ácidos e Sais Biliares/análise , Doença de Crohn , Cisteína/análise , Histidina/análise , Inflamação , Infliximab , Metabolismo dos Lipídeos/efeitos dos fármacos , RNA Ribossômico 16S/análise , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Biomarcadores Farmacológicos/análise , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Doença de Crohn/imunologia , Fezes , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/urina , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Londres , Estudos Longitudinais , Masculino , Metabolômica/métodos , Valor Preditivo dos Testes , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversos
14.
Methods Mol Biol ; 2138: 207-216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219750

RESUMO

Nicotinamide adenine dinucleotide (NAD+) and its related metabolites (NADome) are important endogenous analytes that are thought to play important roles in cellular metabolism, inflammation, oxidative stress, cancer, neurodegeneration, and aging in mammals. However, these analytes are unstable during the collection of biological fluids, which is a major limiting factor for their quantitation. Herein, we describe a highly robust and quantitative method using liquid chromatography coupled to tandem mass spectrometry to quantify the NADome in whole blood, plasma, mononuclear cells, platelets, cerebrospinal fluid (CSF), and urine. This methodology represents a "gold standard" of measure for understanding biological pathways and developing targeted pharmacological interventions to modulate NAD+ biosynthesis and NAD-dependent mediators in health and disease.


Assuntos
Envelhecimento/metabolismo , Biomarcadores/metabolismo , Cromatografia Líquida/métodos , Envelhecimento Saudável/metabolismo , NAD/metabolismo , Espectrometria de Massas em Tandem/métodos , Envelhecimento/sangue , Envelhecimento/urina , Biomarcadores/sangue , Biomarcadores/urina , Plaquetas/metabolismo , Células Cultivadas , Líquido Cefalorraquidiano/metabolismo , Estudos de Avaliação como Assunto , Envelhecimento Saudável/sangue , Envelhecimento Saudável/urina , Humanos , Inflamação/sangue , Inflamação/metabolismo , Inflamação/urina , Leucócitos Mononucleares/metabolismo , NAD/sangue , NAD/urina , Estresse Oxidativo/fisiologia , Urina/química
15.
Cancer Epidemiol Biomarkers Prev ; 29(4): 871-879, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32051195

RESUMO

BACKGROUND: We examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers. METHODS: Secondary analysis was conducted on two cross-sectional samples of adult, daily smokers from Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (<0.26) in the nationally representative PATH Study was used to distinguish slow from normal/fast nicotine metabolizers. NMR was modeled continuously in secondary analysis. RESULTS: Compared with slow metabolizers, normal/fast metabolizers had greater cigarettes per day and higher levels of total nicotine equivalents, tobacco-specific nitrosamines, volatile organic componds, and polycyclic aromatic hydrocarbons. A novel finding was higher levels of inflammatory biomarkers among normal/fast metabolizers versus slow metabolizers. With NMR modeled as a continuous measure, the associations between NMR and biomarkers of inflammation were not significant. CONCLUSIONS: The results are suggestive that normal/fast nicotine metabolizers may be at increased risk for tobacco-related disease due to being heavier smokers, having higher exposure to numerous toxicants and carcinogens, and having higher levels of inflammation when compared with slow metabolizers. IMPACT: This is the first documentation that NMR is not only associated with smoking exposure but also biomarkers of biological effects that are integral in the development of tobacco-related disease. Results provide support for NMR as a biomarker for understanding a smoker's exposure and potential risk for tobacco-related disease.


Assuntos
Fumar Cigarros/sangue , Cotinina/análogos & derivados , Nicotina/sangue , Tabagismo/diagnóstico , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Fumar Cigarros/imunologia , Fumar Cigarros/metabolismo , Fumar Cigarros/urina , Cotinina/sangue , Cotinina/metabolismo , Cotinina/urina , Estudos Transversais , Conjuntos de Dados como Assunto , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/urina , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nicotina/metabolismo , Nicotina/urina , Ensaios Clínicos Controlados Aleatórios como Assunto , Autorrelato/estatística & dados numéricos , Índice de Gravidade de Doença , Fumantes/estatística & dados numéricos , Tabagismo/sangue , Tabagismo/imunologia , Tabagismo/urina , Estados Unidos
16.
Int Urol Nephrol ; 52(4): 603-610, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31832877

RESUMO

PURPOSE: To investigate the urinary levels of TGF-ß1, VEGF, and MCP-1 as potential biomarkers of latent inflammation and fibrosis in the kidney before and 6 months after correction of vesicoureteral reflux (VUR) in children. METHODS: A total of 88 patients (mean age 26 months) with VUR were divided into three groups: group A-patients with grades II-III VUR, conservative treatment; group B-patients with grades III-V VUR, endoscopic correction of VUR; group C-patients with grades III-V VUR, ureteral reimplantation after failed endoscopic correction. Control group included 20 healthy children. Biomarker levels were measured by ELISA. 99mTc-DMSA scintigraphy and renal histology were performed if possible. RESULTS: At admission, TGF-ß1 was close to control in all study groups, VEGF increased with severity of the disease, and MCP-1 increased in group C. Six months after correction of VUR, despite clinical and laboratory improvement, TGF-ß1 and MCP-1 increased while VEGF decreased compared to the admission values in all groups; no amelioration of renal scarring was detected either by 99mTc-DMSA scintigraphy or renal histology. CONCLUSION: The results support our hypothesis that successful correction of VUR is not sufficient to stop or reduce the latent inflammatory and fibrotic processes that have already started in the kidney regardless of the reflux grade and treatment option. Measuring the urinary levels of TGF-ß1, VEGF, and MCP-1 may aid in the development of non-invasive, pathophysiologically relevant approach to diagnosis and monitoring of kidney injury and fibrosis in children with VUR.


Assuntos
Quimiocina CCL2/urina , Inflamação/urina , Rim/patologia , Fator de Crescimento Transformador beta1/urina , Fator A de Crescimento do Endotélio Vascular/urina , Refluxo Vesicoureteral/complicações , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Tratamento Conservador , Endoscopia , Feminino , Fibrose , Seguimentos , Humanos , Lactente , Inflamação/etiologia , Rim/diagnóstico por imagem , Masculino , Cintilografia , Refluxo Vesicoureteral/patologia , Refluxo Vesicoureteral/terapia
17.
Urologiia ; (5): 98-104, 2019 Dec.
Artigo em Russo | MEDLINE | ID: mdl-31808640

RESUMO

AIM: To identify predictors of perioperative complications in children with obstructive uropathy. MATERIALS AND METHODS: A total of 178 patients with obstructive uropathy were divided into 3 groups. In Group 1 there were 108 children with hydronephrosis, while Group 2 included 47 children with ureterohydronephrosis and Group 3 consisted of 23 children with bladder outlet obstruction according to the results of clinical, laboratory, microbiological, X-ray and pathologic study. The evaluation of the urine level of pro- (IL-8) and anti-inflammatory (IL-10) cytokines was performed at two timepoints, prior to treatment (1 point) and on the 3-5th day after the surgery (2 point) using "Vector - Best" (Russia, Novosibirsk) (IL-8), "Bender Medsystems" (Austria) (IL-10) on the enzyme immunoassay analyzer Stat Fax 2010 (USA). RESULTS: The active phase of chronic pyelonephritis was shown in Groups 1, 2 and 3 in 38%, 36% and 100% of cases, respectively. Microbiological examination of urine allowed to identify a causative agent in 85% and 89% of biopsy specimens from the ureteropelvic and ureterovesical junction, respectively. In all groups, Escherichia coli was a main pathogen (40%). In 25% of patients of Groups 1 and 2, isolated pathogens in biopsy specimen and urine were different. According to the evaluation of cytokines in the urine, during the active phase of chronic pyelonephritis there was an increase in the level of IL8 (p<0.0001) at points 1 and 2 in all patients. In the latent phase of inflammation, there was an increase in the concentration of IL-8 (p<0.04) and IL-10 (p<0.002) at point 2 in Groups 1 and 2. Using the ratio of IL-8 and IL-10, an index of inflammation activity (IIA) was suggested, whose values were increased in all Groups at point 1 and 2. Based on the regression analysis of the changes in IIA level, a model for predicting perioperative complications and an algorithm for personalized patient management were developed. CONCLUSION: Cytokines are indicators of latent inflammation in children with OU and may be predictors of perioperative complications.


Assuntos
Citocinas/urina , Hidronefrose , Inflamação/urina , Interleucina-10/urina , Interleucina-8/urina , Pielonefrite , Obstrução do Colo da Bexiga Urinária , Criança , Humanos , Assistência Perioperatória , Federação Russa
18.
Horm Mol Biol Clin Investig ; 40(1)2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31693494

RESUMO

Background Metabolic syndrome (MetS) is an important contributor to both type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Although MetS affects one third of American adults, its pathogenesis remains to be elucidated. Tyramine, a derivative of tyrosine, has been shown to act as a catecholamine releasing agent in the human body. The aim of this study is to investigate the role of tyramine as an early biomarker for nascent MetS without the confounding of T2DM, ASCVD or smoking. Patients and methods This was an exploratory study of 28 patients with nascent MetS and 20 matched controls carried out in 2018. Metabolites were evaluated from patient's frozen early morning urine samples and were correlated with biomarkers of inflammation and adipokines. They were assayed by the National Institutes of Health (NIH) Western Metabolomics Center using liquid chromatography/mass spectrometry (LC/MS) and standardized to urinary creatinine. All patients had normal hepatic and renal function. Results Tyramine concentrations were significantly reduced in patients with MetS compared to controls, p = 0.0009. In addition, tyramine was significantly inversely correlated with multiple biomarkers of inflammation and cardiometabolic risk factors such as RBP4, monocyte TLR-4 abundance and P38MAPKinase activity, body mass index (BMI) and blood pressure (BP) (both systolic and diastolic). Conclusion In conclusion, low levels of tyramine could contribute to the proinflammatorty state of MetS.


Assuntos
Inflamação/urina , Síndrome Metabólica/urina , Tiramina/urina , Adulto , Idoso , Biomarcadores/metabolismo , Biomarcadores/urina , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/metabolismo , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/metabolismo , Metabolômica , Pessoa de Meia-Idade , Tiramina/metabolismo
19.
PLoS One ; 14(10): e0223703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31613925

RESUMO

Activin A, a member of the transforming growth factor-beta superfamily, is a critical modulator of inflammation and plays a key role in controlling the cytokine cascade that drives the inflammatory response. However, the role of activin A in inflammatory kidney diseases remains unknown. To address this issue, we examined here whether activin A can be detected in the kidney and/or urine from patients with antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV). Fifty-one patients who had been diagnosed with AAV and were treated in our department between November 2011 to March 2018 were included in this study. Forty-one patients had renal complications (renal AAV). Serum and urinary activin A levels were measured by enzyme-linked immunosorbent assay. Correlation of urinary activin A concentration with clinical parameters was analyzed. Urinary activin A was undetectable in healthy volunteers. In contrast, urinary activin A concentration was significantly increased in patients with renal AAV but not in those with non-renal AAV. Urinary activin A concentration decreased rapidly after immunosuppressive treatment. There was a significant correlation of urinary activin A level with urinary protein, L-FABP, and NAG. Histologic evaluation revealed that urinary activin A levels were significantly higher in patients with cellular crescentic glomeruli than in those lacking this damage. In situ hybridization demonstrated that the mRNA encoding the activin A ßA subunit was undetectable in normal kidneys but accumulated in the proximal tubules and crescentic glomeruli of the kidneys of patients with renal AAV. Immunostaining showed that activin A protein also was present in the proximal tubules, crescentic glomeruli, and macrophages infiltrating into the interstitium in the kidneys of patients with renal AAV. These data suggested that urinary activin A concentration reflects renal inflammation and tubular damage in AAV and may be a useful biomarker for monitoring renal AAV.


Assuntos
Ativinas/urina , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , Inflamação/urina , Túbulos Renais/patologia , Ativinas/genética , Ativinas/metabolismo , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Biomarcadores/urina , Biópsia , Feminino , Humanos , Inflamação/complicações , Subunidades beta de Inibinas/genética , Subunidades beta de Inibinas/metabolismo , Túbulos Renais/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Investig Clin Urol ; 60(5): 343-350, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501796

RESUMO

Purpose: To investigate whether measurement of urinary calprotectin can serve as a biomarker in the diagnosis of primary bladder cancer and to confirm its diagnostic role in determining high grade and stage disease. Materials and Methods: Urinary calprotectin was measured in spot urine samples from patients with primary bladder cancer and control subjects. To confirm levels in urine, tissue samples were also obtained from bladder tumor and healthy trigone of bladder by transurethral resection in both groups. Finally, calprotectin levels in tissue and urine of the patients and control subjects were compared and their diagnostic potential was investigated in high grade and stage bladder cancers. Results: Of 82 participants, 52 were patients with bladder cancer and 30 were control subjects. The two groups were comparable in terms of age, smoking status, and comorbidities. Tissue and urinary calprotectin levels were significantly higher in the bladder cancer group. In subgroup analyses, urinary calprotectin levels were significantly higher in patients with high-grade, muscle-invasive tumors. After receiver operating characteristic analyses, the sensitivity and specificity of urinary calprotectin was 100% and 96.7%, respectively, in the diagnosis of primary bladder cancer. High grade and stage bladder cancers were detected with sensitivity and specificity of 70% and 74.2%, and 80% and 84.8%, respectively. Conclusions: Urinary calprotectin may be a valuable parameter in the diagnosis of primary bladder cancer with high sensitivity and specificity. Furthermore, it may be useful in the prediction of high grade and stage disease. However, more investigations are needed.


Assuntos
Complexo Antígeno L1 Leucocitário/análise , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/urina , Complexo Antígeno L1 Leucocitário/biossíntese , Complexo Antígeno L1 Leucocitário/urina , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/metabolismo
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