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Sci Rep ; 10(1): 15218, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939046


Repeated intravesical injections of autologous platelet-rich plasma (PRP) have been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a paucity of objective evidence of the effectiveness of this therapy. In this study, we investigated the changes in urinary markers after PRP treatment. Forty patients with IC/BPS who were refractory to conventional therapy received four injections of PRP at monthly intervals; 10 mL PRP solution with 2.5 times the peripheral blood platelet concentration was used. Urine levels of thirteen functional proteins, growth factors, and cytokines were assessed at baseline and at the 4th PRP injection. The clinical parameters included visual analog scale (VAS) pain score, daily urinary frequency, nocturia episodes, functional bladder capacity, and global response assessment (GRA). The GRA and symptom score significantly decreased post-treatment. In patients with GRA ≥ 2, the success rates at 1 month and at 3 months after the 4th PRP injection were 70.6% and 76.7%, respectively. The VAS pain score, frequency, and nocturia showed a significant decrease (all p < 0.05). Urinary levels of nerve growth factor, matrix metalloproteinase-13, and vascular endothelial growth factor significantly decreased post-treatment (p = 0.043, p = 0.02, and p = 0.000, respectively); platelet-derived growth factor-AB showed a significant increase (p = 0.004) at the 4th PRP treatment compared with baseline. In this study, repeated intravesical PRP injections provided significant symptom improvement in IC/BPS patients with concomitant changes in the related biomarker levels.Trial registration: NCT03104361; IRB: TCGH 105-48-A.

Biomarcadores/urina , Cistite Intersticial/terapia , Plasma Rico em Plaquetas , Administração Intravesical , Idoso , Cistite Intersticial/urina , Feminino , Humanos , Masculino , Metaloproteinase 13 da Matriz/urina , Pessoa de Meia-Idade , Fator de Crescimento Neural/urina , Fator de Crescimento Derivado de Plaquetas/urina , Estudos Prospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/urina , Escala Visual Analógica
J Neurosurg Pediatr ; 18(4): 396-407, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27314542


OBJECTIVE The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing JPAs from other CNS diseases, including other brain tumors. Preliminary screening of an array of tumors implicated proteases (including matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinase [TIMPs]) as well as growth factors (including basic fibroblast growth factor [bFGF]) as candidate biomarkers. These data led the authors to hypothesize that tissue inhibitor of metalloproteinase 3 (TIMP3) and bFGF would represent high-probability candidates as JPA-specific biomarkers. METHODS Urine was collected from 107 patients, which included children with JPA (n = 21), medulloblastoma (n = 17), glioblastoma (n = 9), arteriovenous malformations (n = 25), moyamoya (n = 14), and age- and sex-matched controls (n = 21). Biomarker levels were quantified with enzyme-linked immunosorbent assay, tumor tissue expression was confirmed with immunohistochemical analysis, and longitudinal biomarker expression was correlated with imaging. Results were subjected to univariate and multivariate statistical analyses. RESULTS Using optimal urinary cutoff values of bFGF > 1.0 pg/µg and TIMP3 > 3.5 pg/µg, multiplexing bFGF and TIMP3 predicts JPA presence with 98% accuracy. Multiplexing bFGF and MMP13 distinguishes JPA from other brain tumor subtypes with up to 98% accuracy. Urinary biomarker expression correlated with both tumor immunohistochemistry and in vitro tumor levels. Urinary bFGF and TIMP3 decrease following successful tumor treatment and correlate with changes in tumor size. CONCLUSIONS This study identifies 2 urinary biomarkers-bFGF and TIMP3-that successfully detect one of the most common pediatric brain tumors with high accuracy. These data highlight potential benefits of urinary biomarkers and support their utility as diagnostic tools in the treatment of children with JPA.

Astrocitoma/urina , Neoplasias Encefálicas/urina , Fator 2 de Crescimento de Fibroblastos/urina , Inibidor Tecidual de Metaloproteinase-3/urina , Malformações Arteriovenosas/urina , Biomarcadores Tumorais/urina , Linhagem Celular Tumoral , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Metaloproteinase 13 da Matriz/urina , Meduloblastoma/urina , Doença de Moyamoya/urina , Análise Multivariada
Mol Cell Biochem ; 388(1-2): 95-111, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24281856


Diabetic nephropathy (DN) is a microvascular complication associated with diabetes causing slow deterioration of kidneys leading to end-stage renal disease. Timely intervention and diagnosis are crucial in order to ameliorate and halt the progression of DN. Current diagnosis of DN consists of urine assays for detection of microalbuminuria, which have inadequate specificity and sensitivity. Hence, there arises a need to discover stage-specific biomarkers which can aid in the early detection of DN and also in identifying the mechanisms underlying pathogenesis of DN. Therefore the present study was undertaken to identify the differentially expressed proteins in the urine and to examine the pattern of proteomic changes occurring in the rat kidneys during the course of progression of streptozotocin-induced model of DN in rats. Two-dimensional gel electrophoresis coupled to MALDI-TOF mass spectrometry was employed to identify the differentially expressed proteins under diabetic conditions. Among the identified proteins Calgranulin A and Calgranulin B appeared in the urinary proteome at the fourth week of induction of diabetes while we recorded a time-dependent decrease in the expression of major urinary protein (alpha 2u globulin) in the urine as well as kidneys of diabetic rats. Parallel monitoring of targeted proteomic changes in the renal proteome revealed an increase in histone H2B phosphorylation at serine14 along with a gradual decrease in Bcl-2 and MMP-13 expression during the course of progression and development of streptozotocin-induced DN.

Biomarcadores/urina , Nefropatias Diabéticas/urina , Rim/patologia , Proteoma/análise , alfa-Globulinas/urina , Animais , Nitrogênio da Ureia Sanguínea , Caderinas/urina , Calgranulina A/biossíntese , Calgranulina B/urina , Colágeno/urina , Creatinina/sangue , Diabetes Mellitus Experimental/urina , Eletroforese em Gel Bidimensional , Fibronectinas/urina , Masculino , Metaloproteinase 13 da Matriz/urina , Proteínas Tirosina Quinases/urina , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Estreptozocina
Injury ; 43(3): 274-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21689817


Whilst the majority of fractures heal normally, it is estimated that ∼10% of fractures exhibit some level of delayed or impaired healing. Although radiography is the primary diagnostic tool to assess the progression of fracture healing, radiographic features only qualitatively correlate with tissue level increases in mineral content and do not quantitatively measure underlying biological processes that are associated with the progression of healing. Specific metaloproteinases have been shown to be essential to processes of both angiogenesis and mineralised cartilage resorption and bone remodelling at different phases of fracture healing. The aim of this study was to determine the potential of using a simple urine based assay of the activity of two MMPs as a means of assessing the biological progression of fracture healing through the endochondral phase of healing. Using a standard mid-diaphyseal murine model of femoral fracture, MMP9 and MMP13 proteins and enzymatic activity levels were quantified in the urine of mice across the time-course of fracture healing and compared to the mRNA and protein expression profiles in the calluses. Both urinary MMP9 and MMP13 protein and enzymatic activity levels, assessed by Western blot, zymogram and specific MMP fluorometric substrate assays, corresponded to mRNA expression and immunohistologic assays of the proteins within callus tissues. These studies suggest that urinary levels of MMP9 and MMP13 may have potential as metabolic markers to monitor the progression of fracture healing.

Remodelação Óssea , Fraturas do Fêmur/urina , Consolidação da Fratura , Metaloproteinase 13 da Matriz/urina , Metaloproteinase 9 da Matriz/urina , RNA Mensageiro/urina , Animais , Biomarcadores/urina , Western Blotting , Fraturas do Fêmur/fisiopatologia , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos , Valor Preditivo dos Testes