RESUMO
Background: Prolidase is a manganese (Mn)-dependent cytosolic exopeptidase that degrades imidodipeptides with C-terminal proline or hydroxyproline. Prolidase recycling from imidodipeptides plays a critical role in collagen resynthesis and extracellular matrix (ECM) remodelling. Following an increase in gonadotropins, ovarian and follicular collagen undergo substantial degradation. Abnormal ovarian ECM composition is associated with polycystic ovary syndrome (PCOS). This study aimed to examine prolidase activity in the serum and follicular fluid (FF) of women undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment, comparing those with PCOS to those with normal ovarian function.Methods: This prospective study enrolled 50 participants, of whom 44 were included. PCOS diagnosis followed the Rotterdam consensus criteria, with 20 patients constituting the study group. The control group comprised 24 individuals with mild-to-moderate male infertility. Prolidase enzyme activity in serum and FF was measured using the Chinard reagent via spectrophotometric analysis and compared between the groups.Results: Serum and FF prolidase levels were significantly lower in patients with PCOS (p < 0.05). A direct correlation was observed between serum and FF prolidase levels (p < 0.05). Although blastocyst quality scoring (BQS) significantly decreased in PCOS patients, no statistical difference was observed in the clinical pregnancy rate between the groups (p < 0.05) (p > 0.05). A negative correlation existed between serum prolidase levels and total antral follicle (AF) count (p < 0.05). Conversely, both serum and FF prolidase levels positively correlated with BQS (r = 0.574)(p < 0.05) (r = 0.650)(p < 0.05).Conclusions: Patients with PCOS showed lower serum and FF prolidase levels, indicating abnormal degradation of ovarian and follicular collagen, potentially causing anovulation.
Polycystic ovary syndrome (PCOS), the most prevalent endocrinopathy among reproductive-aged women, affects approximately 315% of this demographic. Long-term disorders such as cardiovascular disease, type 2 diabetes mellitus, obesity, and infertility are commonly associated with PCOS, with approximately 70% of affected women experiencing infertility. Although the aetiology of PCOS remains unclear, complex multigenic disorders and environmental factors such as abnormal ovarian extracellular matrix composition, disruption of the inflammatory pathway, and lifestyle factors have been found to be related.This study addresses the aetiology of PCOS, focusing on the close association between abnormal ovarian extracellular matrix composition and the syndrome, as seen in previous reports. Prolidase is a manganese-dependent cytosolic exopeptidase that degrades imidodipeptides using the C-terminal proline or hydroxyproline. Proline recycling from imidodipeptides by prolidase plays a critical role in the resynthesis of collagen and remodelling of the extracellular matrix. Our aim was to evaluate prolidase activity in the serum and follicular fluid of women diagnosed with PCOS. Our findings revealed a direct correlation between serum and follicular fluid prolidase levels, both of which were diminished in women with PCOS. Furthermore, a negative correlation was observed between serum prolidase levels and total antral follicle count indicating a potential link between prolidase activity and ovarian follicle development. In contrast, both serum and follicular fluid prolidase levels were positively correlated with blastocyst quality. In conclusion, PCOS patients showed lower serum and follicular fluid prolidase levels, indicating abnormal degradation of ovarian and follicular collagen, and potentially causing anovulation. Future studies measuring manganese levels in larger numbers of participants are required.
Assuntos
Dipeptidases , Líquido Folicular , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/enzimologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Feminino , Adulto , Dipeptidases/sangue , Dipeptidases/metabolismo , Estudos Prospectivos , Líquido Folicular/metabolismo , Infertilidade Feminina/etiologia , Infertilidade Feminina/sangue , Fertilização in vitro , Gravidez , Injeções de Esperma Intracitoplásmicas , Estudos de Casos e ControlesRESUMO
BACKGROUND: Currently utilized serum tumor markers and fecal immunochemical tests do not have sufficient diagnostic power for colorectal cancer (CRC) due to their low sensitivities. To establish non-invasive urinary protein biomarkers for early CRC diagnosis, we performed stepwise analyses employing urine samples from CRCs and healthy controls (HCs). METHODS: Among 474 urine samples, 363 age- and sex-matched participants (188 HCs, 175 stage 0-III CRCs) were randomly divided into discovery (16 HCs, 16 CRCs), training (110 HCs, 110 CRCs), and validation (62 HCs, 49 CRCs) cohorts. RESULTS: Of the 23 urinary protein candidates comprehensively identified from mass spectrometry in the discovery cohort, urinary levels of dipeptidase 1 (uDPEP1) and Trefoil factor1 (uTFF1) were the two most significant diagnostic biomarkers for CRC in both training and validation cohorts using enzyme-linked immunosorbent assays. A urinary biomarker panel comprising uDPEP1 and uTFF1 significantly distinguished CRCs from HCs, showing area under the curves of 0.825-0.956 for stage 0-III CRC and 0.792-0.852 for stage 0/I CRC. uDPEP1 and uTFF1 also significantly distinguished colorectal adenoma (CRA) patients from HCs, with uDPEP1 and uTFF1 increasing significantly in the order of HCs, CRA patients, and CRC patients. Moreover, expression levels of DPEP1 and TFF1 were also significantly higher in the serum and tumor tissues of CRC, compared to HCs and normal tissues, respectively. CONCLUSIONS: This study established a promising and non-invasive urinary protein biomarker panel, which enables the early detection of CRC with high sensitivity.
Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Dipeptidases , Detecção Precoce de Câncer , Fator Trefoil-1 , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/urina , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/sangue , Masculino , Detecção Precoce de Câncer/métodos , Feminino , Fator Trefoil-1/urina , Pessoa de Meia-Idade , Idoso , Dipeptidases/urina , Dipeptidases/sangue , Estudos de Casos e Controles , Estadiamento de Neoplasias , Ensaio de Imunoadsorção Enzimática , Adulto , Sensibilidade e Especificidade , Adenoma/diagnóstico , Adenoma/urina , Proteínas Ligadas por GPIRESUMO
Pseudoexfoliation syndrome (PEX) represents an age-related systemic disease that is characterized by the accumulation of extracellular matrix material in ocular tissues and visceral organs. Abnormal matrix remodeling is thought to be one of the important factors in the etiopathogenesis of the disease. Prolidase represents an enzyme, which takes a significant part in collagen biosynthesis and remodeling of the extracellular matrix. The purpose of the current research was to assess the prolidase enzyme activity in the aqueous and serum samples of subjects with PEX. The study population consisted of 66 subjects, involving 33 subjects with age-related cataract among patients with PEX and 33 subjects with age-related cataract without PEX. The prolidase activity measurement was performed using the modified Chinard's method. Significantly increased aqueous prolidase activity was detected in the group with PEX (p < 0.01). Despite about a three times higher increase in the serum prolidase activity of the group with PEX in comparison with the control group, the two groups did not differ statistically significantly (p > 0.05). The high prolidase enzyme activity in the aqueous samples of subjects with PEX suggests that the collagen cycle and the remodeling of the extracellular matrix are accelerated. These results can be a guide for understanding the formation mechanisms of PEX.
Assuntos
Humor Aquoso/enzimologia , Catarata/sangue , Dipeptidases/sangue , Síndrome de Exfoliação/sangue , Idoso , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Microscopia com Lâmpada de Fenda , Espectrofotometria , Acuidade Visual/fisiologiaRESUMO
To improve the power of mediation in high-throughput studies, here we introduce High-throughput mediation analysis (Hitman), which accounts for direction of mediation and applies empirical Bayesian linear modeling. We apply Hitman in a retrospective, exploratory analysis of the SLIMM-T2D clinical trial in which participants with type 2 diabetes were randomized to Roux-en-Y gastric bypass (RYGB) or nonsurgical diabetes/weight management, and fasting plasma proteome and metabolome were assayed up to 3 years. RYGB caused greater improvement in HbA1c, which was mediated by growth hormone receptor (GHR). GHR's mediation is more significant than clinical mediators, including BMI. GHR decreases at 3 months postoperatively alongside increased insulin-like growth factor binding proteins IGFBP1/BP2; plasma GH increased at 1 year. Experimental validation indicates (1) hepatic GHR expression decreases in post-bariatric rats; (2) GHR knockdown in primary hepatocytes decreases gluconeogenic gene expression and glucose production. Thus, RYGB may induce resistance to diabetogenic effects of GH signaling.Trial Registration: Clinicaltrials.gov NCT01073020.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Derivação Gástrica , Fígado/metabolismo , Metaboloma , Obesidade/sangue , Proteoma , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Proteínas de Transporte/sangue , Proteínas de Transporte/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/cirurgia , Dipeptidases/sangue , Dipeptidases/genética , Jejum/fisiologia , Regulação da Expressão Gênica , Hemoglobinas Glicadas/genética , Hemoglobinas Glicadas/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/genética , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fígado/patologia , Obesidade/genética , Obesidade/patologia , Obesidade/cirurgia , Cultura Primária de Células , Ratos , Estudos RetrospectivosRESUMO
INTRODUCTION: Carnosine is a naturally occurring dipeptide abundant in the skeletal and cardiac muscle and brain, which has been shown to improve glucose metabolism and cardiovascular risk. This study showed that carnosine supplementation had positive changes on plasma lipidome. Here, this study aimed to establish the relationship of muscle carnosine and serum carnosinase-1 with cardiometabolic risk factors and the lipidome. METHODS AND RESULTS: This study profiles >450 lipid species in 65 overweight/obese nondiabetic individuals. Intensive metabolic testing is conducted using direct gold-standard measures of adiposity, insulin sensitivity and secretion, as well as measurement of serum inflammatory cytokines and adipokines. Muscle carnosine is negatively associated with 2-h glucose concentrations, whereas serum carnosinase-1 levels are negatively associated with insulin sensitivity and positively with IL-18. O-PLS and machine learning analyses reveal a strong association of muscle carnosine with ether lipids, particularly arachidonic acid-containing plasmalogens. Carnosinase-1 levels are positively associated with total phosphatidylethanolamines, but negatively with lysoalkylphosphatidylcholines, trihexosylceramides, and gangliosides. In particular, alkylphosphatidylethanolamine species containing arachidonic acid are positively associated with carnosinase-1. CONCLUSION: These associations reinforce the role of muscle carnosine and serum carnosinase-1 in the interplay among low-grade chronic inflammation, glucose homeostasis, and insulin sensitivity.
Assuntos
Carnosina/fisiologia , Dipeptidases/fisiologia , Lipídeos/sangue , Plasmalogênios/fisiologia , Adulto , Carnosina/análise , Dipeptidases/sangue , Feminino , Glucose/metabolismo , Humanos , Resistência à Insulina , Interleucina-18/sangue , Masculino , Músculo Esquelético/química , Obesidade/metabolismo , Sobrepeso/metabolismo , Adulto JovemRESUMO
Diabetic nephropathy (DN) is one of the major complications of diabetes and contributes significantly towards end-stage renal disease. Previous studies have identified the gene encoding carnosinase (CN-1) as a predisposing factor for DN. Despite this fact, the relationship of the level of serum CN-1 and the progression of DN remains uninvestigated. Thus, the proposed study focused on clarifying the relationship among serum CN-1, indicators of renal function and tissue injury, and the progression of DN. A total of 14 patients with minimal changes disease (MCD) and 37 patients with DN were enrolled in the study. Additionally, 20 healthy volunteers were recruited as control. Further, DN patients were classified according to urinary albumin excretion rate into two groups: DN with microalbuminuria (n = 11) and DN with macroalbuminuria (n = 26). Clinical indicators including urinary protein components, serum carnosine concentration, serum CN-1 concentration and activity, and renal biopsy tissue injury indexes were included for analyzation. The serum CN-1 concentration and activity were observed to be the highest, but the serum carnosine concentration was the lowest in DN macroalbuminuria group. Moreover, within DN group, the concentration of serum CN-1 was positively correlated with uric acid (UA, r = 0.376, p = 0.026) and serum creatinine (SCr, r = 0.399, p = 0.018) and negatively correlated with serum albumin (Alb, r = - 0.348, p = 0.041) and estimated glomerular filtration rate (eGRF, r = - 0.432, p = 0.010). Furthermore, the concentration of serum CN-1 was discovered to be positively correlated with indicators including 24-h urinary protein-creatinine ratio (24 h-U-PRO/CRE, r = 0.528, p = 0.001), urinary albumin-to-creatinine ratio (Alb/CRE, r = 0.671, p = 0.000), urinary transferrin (TRF, r = 0.658, p = 0.000), retinol-binding protein (RBP, r = 0.523, p = 0.001), N-acetyl-glycosaminidase (NAG, r = 0.381, p = 0.024), immunoglobulin G (IgG, r = 0.522, p = 0.001), cystatin C (Cys-C, r = 0.539, p = 0.001), beta-2-microglobulin (ß2-MG, r = 0.437, p = 0.009), and alpha-1-macroglobulin (α1-MG, r = 0.480, p = 0.004). Besides, in DN with macroalbuminuria group, serum CN-1 also showed a positive correlation with indicators of fibrosis, oxidative stress, and renal tubular injury. Taken together, our data suggested that the level of CN-1 was increased as clinical DN progressed. Thus, the level of serum CN-1 might be an important character during the occurrence and progression of DN. Our study will contribute significantly to future studies focused on dissecting the underlying mechanism of DN.
Assuntos
Nefropatias Diabéticas/enzimologia , Dipeptidases/sangue , Adulto , Biomarcadores , Estudos de Casos e Controles , Creatinina/sangue , Cistatina C/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/lesões , Rim/fisiopatologia , Falência Renal Crônica/sangue , Falência Renal Crônica/enzimologia , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
An increasing number of studies have focussed on the neurobiology of schizophrenia (SCH), contributing to a better understanding of this disorder. Prolidase is a metalloprotease found in various tissues, which has been associated with the concentrations of proline, a neurotransmitter, in the brain. There is evidence to suggest that elevated proline levels play a role in SCH. The aim of the present study was to compare plasma proline levels in patients with drug-naive first-episode psychosis (FEP) and in those with SCH. Patients diagnosed with FEP (n = 26) and SCH (n = 26) were recruited for this study, in addition to healthy control volunteers (n = 26). Plasma prolidase levels were found to be elevated in the SCH group compared to drug-naive FEP and healthy control groups. This finding indicates that prolidase levels are higher in SCH patients, while levels in patients with drug-naive FEP are similar to those of healthy control. Follow-up studies are needed to provide a better understanding of prolidase in the etiopathogenesis of SCH.
Assuntos
Dipeptidases , Transtornos Psicóticos , Esquizofrenia , Estudos de Casos e Controles , Dipeptidases/sangue , Humanos , Transtornos Psicóticos/sangue , Transtornos Psicóticos/diagnóstico , Esquizofrenia/sangue , Esquizofrenia/diagnósticoRESUMO
AIM AND OBJECTIVE: Sleep bruxism is a complicated disease, and its cause remains controversial. If the etiology of bruxism is resolved, the treatment can be adjusted to the prevailing aetiological factor. Thus, the aim of this study was to evaluate the oxidative stress level and serum prolidase activity in patients with sleep bruxism. MATERIALS AND METHODS: Seventy healthy subjects and 51 patients with sleep bruxism were included in this study, and blood samples from all patients were collected. Serum samples were analyzed for total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and prolidase activity. RESULTS: The prolidase, TOS, and OSI levels were significantly higher in patients with bruxism than in the healthy controls (p = 0.001, p = 0.001, p = 0.001, respectively). The TAS level was significantly lower in bruxism patients than in healthy controls (p = 0.003). CONCLUSION: The increased TOS, OSI, and prolidase levels and decreased TAS levels could be assumed to result in oxidative injury in patients with sleep bruxism. However, the study could not determine whether oxidative imbalance and increased serum prolidase levels could be a cause or a result of bruxism.
Assuntos
Dipeptidases/metabolismo , Bruxismo do Sono/metabolismo , Adulto , Dipeptidases/sangue , Feminino , Humanos , Masculino , Estresse Oxidativo , Bruxismo do Sono/sangueRESUMO
OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is a highly prevalent breathing disorder in sleep. The aim of this study was to evaluate the relationship between OSAS and prolidase activity, the oxidative stress index (OSI), total antioxidative capacity (TAC), total oxidative capacity (TOC) and the carotid intima media thickness (CIMT). METHOD: : After night polysomnography, 74 people were diagnosed with OSAS and simple snoring. Plasma prolidase activities, TAC and TOC were measured in blood samples taken in the morning after the sleep study. The patients' bilateral common carotid arteries were scanned. RESULTS: In total, 56 patients were in OSAS group [13 subjects 23.2% mild, 19 subjects 33.9% moderate, 24 subjects 42.8% severe] and 18 in simple snoring control group. The mean Prolidase, TOC, TAC and OSI levels were 744.7 ± 156.8, 59.2 ± 19.2, 2.12 ± 0.41, 3.12 ± 1.03, in the mild OSAS group, 761.6 ± 114.4, 57.9 ± 18.3, 2.03 ± 0.37, 3.15 ± 0.8, in the moderate OSAS group, 754.08 ± 133.9, 51.15 ± 12.1, 1.97 ± 0.27, 2.8 ± 0.82, in the severe OSAS group, and 711.9 ± 139, 52.3 ± 15.1, 1.83 ± 0.32, 3.06 ± 0.92 in the control group, respectively. Mean CIMT measurements were 0.71(±0,13) in the OSAS group and 0.76(±0.07) in the control group. CONCLUSION: There was no difference between the control and OSAS groups in terms of the parameters studied. Further studies should be undertaken in order to clarify the relation.
Assuntos
Antioxidantes/metabolismo , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/fisiopatologia , Espessura Intima-Media Carotídea , Dipeptidases/sangue , Estresse Oxidativo/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Sono/fisiologia , Ronco/fisiopatologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnóstico , Ronco/diagnósticoRESUMO
INTRODUCTION: Familial Mediterranean Fever (FMF) is an autoinflammatory disease. Prolidase is a specific imidodipeptidase that plays a role in collagen degradation, and an important role in inflammation and wound healing. Hypoxia-inducible factor-1α (HIF-1) is an important protein in the regulation of immunological response, hemostasis, vascularization. The aim of the study was to compare serum prolidase and HIF-1α levels in patients with FMF in attack-free period and healthy control group. METHODS: Between August 2017 and December 2017, sixty patients diagnosed with FMF according to the criteria of the Tel-hashomer and admitted to Sivas Cumhuriyet University Medical Faculty, Internal Medicine Rheumatology Department and sixty healthy volunteers were enrolled in the study. RESULTS: Median serum prolidase levels were 72.1 (25.1-114.9) ng/ml in FMF group and 30.7 (21.3-86.2) ng/mL in healthy control (HC) group (p = 0.018). ROC analysis showed that the sensitivity was 65% and the specificity was 68.3% at serum prolidase levels 54.03 ng/mL (p < 0.05). The median serum levels of HIF-1α in the FMF group was 482.0 (292.0-3967.0) pg/mL and 632.0 (362.0-927.0) pg/mL in the HC group (p > 0.05). There was no significant correlation between laboratory findings, sex, age, and prolidase (p > 0.05). CONCLUSION: Serum prolidase enzyme levels in FMF patients with attack-free period were significantly higher than in the HC group. However, the role of prolidase and HIF1-α in the FMF disease needs to be clarified with more extensive and comprehensive studies.
Assuntos
Dipeptidases/sangue , Febre Familiar do Mediterrâneo/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Febre Familiar do Mediterrâneo/enzimologia , Febre Familiar do Mediterrâneo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pirina/genética , Curva ROC , Índice de Gravidade de Doença , Adulto JovemRESUMO
PURPOSE: We aimed to investigate the predictive power of plasma prolidase activity and oxidative-stress parameters for distinguishing in patients with various causes of non-traumatic abdominal pain who presented to the emergency department. METHODS: This study enrolled 100 consecutive adult patients and 100 age- and sex-matched healthy controls. The patients were divided into surgically treated patients (STP); medically treated patients (MTP) and nonspecific abdominal pain (NSAP) patients. As predictors of early oxidative changes, the plasma prolidase activity, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were assessed using a novel automated method. RESULTS: No significant difference was observed between the patients and the controls with respect to age or sex (pâ¯=â¯0.837 and 0.188, respectively). The plasma TOS, OSI value, and prolidase activity were significantly higher in the patients with abdominal pain than in the controls (pâ¯<â¯0.001, pâ¯=â¯0.001, and pâ¯<â¯0.001, respectively); however, there was no significant difference in the TAS (pâ¯=â¯0.211). The mean plasma TOS, OSI value, and prolidase activity differed significantly among the three groups (pâ¯<â¯0.001, pâ¯=â¯0.001, and pâ¯<â¯0.001, respectively). The STP had the highest TOS and prolidase activity. However, there was no significant difference in the mean plasma TAS in either group of patients (pâ¯=â¯0.419). CONCLUSION: The plasma prolidase activity and TOS level, as biomarkers of oxidative stress, enable discrimination of patients with NSAP from those with surgical abdominal pain that requires emergent surgical treatment.
Assuntos
Abdome Agudo/sangue , Dipeptidases/sangue , Estresse Oxidativo , Abdome Agudo/enzimologia , Abdome Agudo/etiologia , Adolescente , Adulto , Idoso , Antioxidantes/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxidantes/sangue , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Recurrent aphthous stomatitis is a common disease characterized by single or multiple, self-healing, well-circumscribed, periodic ulcers occurring in the oral cavity. Although the relationship between recurrent aphthous stomatitis and oxidative stress has been extensively reviewed in the past, its relationship with prolidase enzyme levels has not been previously investigated. AIM: The aim of this study is to investigate plasma antioxidant status and prolidase enzyme levels in patients with recurrent aphthous stomatitis. METHODS: The serum total oxidant status, total antioxidant status, oxidative stress index, prolidase and paraoxonase levels of 34 recurrent aphthous stomatitis patients (mean age 35.1) and 34 healthy controls (mean age 37.7) were compared in this study. RESULTS: Total oxidant status was significantly higher in the recurrent aphthous stomatitis group (P < 0.005). The mean total oxidant status value was 5.19 mmol/L in the recurrent aphthous stomatitis group, while it was 2.90 mmol/L in the control group. Oxidative stress index was significantly higher in the recurrent aphthous stomatitis group (P = 0.016*). The mean oxidative stress index level was 0.28 AU in the recurrent aphthous stomatitis group, while it was 0.18 AU in the control group. When control and patient groups were compared, there was no significant difference between groups with regard to the total antioxidant status (P = 0.343). The total antioxidant status levels were 1.09 and 1.14 mmol/L in control and patient groups, respectively. There was no statistically significant difference between PON1 levels of recurrent aphthous stomatitis and control groups (P = 0.218). Mean PON1 levels were 326 U/L in the recurrent aphthous stomatitis group and 381 U/L in the control group. Prolidase levels were not significantly different between recurrent aphthous stomatitis and control groups (P = 0.955). The mean prolidase level was 219.79 U/L in the recurrent aphthous stomatitis group and 219.26 U/L in the control group. LIMITATIONS: The limitation of this study is the small size of both patient and control groups and exclusion of pediatric patients., Similar studies performed in pediatric patient populations with a comparison to adults may be useful in providing meaningful results. CONCLUSIONS: We detected that the total oxidant status and oxidative stress index was higher in patients with recurrent aphthous stomatitis as compared to healthy controls. We could not demonstrate a significant difference in total antioxidant status, PON1 and prolidase values.
Assuntos
Dipeptidases/sangue , Estresse Oxidativo/fisiologia , Estomatite Aftosa/sangue , Adulto , Arildialquilfosfatase/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Oxidantes/sangue , Estudos ProspectivosRESUMO
Background/aim: Changes in collagen metabolism and fibroblastic activity may play a role in the pathogenesis of brucellosis. The prolidase enzyme plays an important role in collagen synthesis. We aimed to investigate the association of prolidase levels with brucellosis. Materials and methods: Serum prolidase levels in 20 patients newly diagnosed with brucellosis were compared with levels in 30 healthy control subjects. Patients with brucellosis were reassessed 3 months later for prolidase, other laboratory measurements, and response to treatment. Results: The levels of serum prolidase were significantly higher in brucellosis patients compared with those of healthy controls. Prolidase, sedimentation, and C-reactive protein levels were significantly lower after antibrucellosistreatment than before treatment. Conclusion: The current study is the first to demonstrate significantly increased serum prolidase levels in patients with brucellosis compared with healthy controls. Prolidase levels also significantly decreased with antibrucellosis treatment. This finding provides a new experimental basis to understand the pathogenesis of brucellosis in relation to collagen metabolism. The increase in serum prolidase levels might be related to several factors such as tissue destruction, increased fibroblastic activity, and granuloma formation, all of which are involved in the natural history of brucellosis.
Assuntos
Brucelose/sangue , Brucelose/etiologia , Dipeptidases/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Tissue fibrosis increases in the structure of the atrial tissue of atrial fibrillation patients. Prolidase enzyme regulates collagen synthesis. There may be an association between electrocardiography (ECG) findings and prolidase activity. OBJECTIVE: This study investigated the association between atrial conduction time and prolidase activity, a collagen synthesis enzyme, and P-wave dispersion (PWD) in patients with Paroxysmal Atrial Fibrillation (PAF). METHODS: Exclusion criteria included the age of <18 years, heart failure, diabetes, hypertension, hyperlipidemia, malignancy, cerebrovascular disease, chronic respiratory distress, osteoporosis, rheumatoid arthritis, renal disease, cirrhosis, and other types of arrhythmia. Patients diagnosed with PAF within 48 hours were considered to have a definite diagnosis. PWD was calculated using a 12-lead ECG, and inter- and intraatrial electromechanical delay (EMD) was assessed using tissue Doppler imaging and conventional echocardiography. Serum prolidase levels were measured in both groups. RESULTS: A total of 43 patients with PAF (20 female, 23 male; mean age, 46.8 ± 5.7 years) and 42 healthy volunteers (21 female, 21 male; mean age, 43.9 ± 5.1 years) were included in the study. Inter- and intraatrial EMD, PWD, minimum P-wave (Pmin), and maximum P-wave (Pmax) measurements were significantly higher (39.7 ± 2.7, 35.7 ± 2.3, p < 0.001; 13.2 ± 2.6, 8.5 ± 1.9, p < 0.001; 47.1 ± 11, 24.1 ± 7.1, p < 0.001; 69.8 ± 8.8, 66.7 ± 10.2, p < 0.130; 114.8 ± 13, 93.6 ± 8.6, p < 0.001, respectively) and serum prolidase levels were significantly lower in patients with PAF compared to healthy controls (3.96 ± 1.2, 8.5 ± 3.56, p < 0.001). In patients with PAF, correlation analysis showed a negative correlation between prolidase levels and intra- and interatrial EMD, PWD, and Pmax (r = -0.41, p < 0.05; r = -0.54, p < 0.05; r = -0.62, p < 0.05; r = -0.49, p < 0.05, respectively). Interatrial EMD showed a significant positive correlation with intraatrial EMD, Pmax, and PWD in patients with PAF (r = 0.90, p < 0.05; r = 0.574, p < 0.05; r = 0.43, p < 0.05, respectively). Additionally, the level of high-sensitivity C-reactive protein (hs-CRP) was significantly higher in patients with PAF (6.6 ± 8, 1.8 ± 1.6, p < 0.001). CONCLUSION: The decreased plasma prolidase activity in patients with PAF may explain the irregularity of the collagen metabolism of different extracellular components and may indicate the onset of atrial remodeling. Changes in PWD, interatrial EMD, and serum prolidase level may predict PAF before diagnosis.
Assuntos
Fibrilação Atrial/metabolismo , Dipeptidases/metabolismo , Adulto , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Dipeptidases/sangue , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
Various psychological, genetic, and biochemical factors are thought to be involved in the aetiology of pediatric bipolar disorder (PBD). However, few studies have evaluated the biochemical basis of PBD. The level of peripheral blood mononuclear cells and serum prolidase activity were determined in PBD and matched healthy comparison subjects. Blood from 38 (age range: 14-17) PBD-type I and 37 age- and gender-matched healthy comparison subjects was analyzed for numbers of neutrophils, lymphocytes, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and serum prolidase activity. The prolidase activity and monocyte count were significantly higher in PBD than the control group. There were no significant differences in numbers of neutrophils, lymphocytes, LMR and NLR between the patient and control groups. These results suggest that the immune system and prolidase activity may be activated in PBD. There is a clinical benefit from the early detection of PBD using serum prolidase activity levels and monocyte counts. Especially, prolidase activity may be a trait marker for diagnosing PBD. However, further studies are needed to verify these findings.
Assuntos
Transtorno Bipolar/sangue , Dipeptidases/sangue , Monócitos , Adolescente , Biomarcadores/sangue , Feminino , Humanos , Contagem de Leucócitos , MasculinoRESUMO
BACKGROUND: Alopecia areata (AA) is a disease characterized by the hair loss sharply limited in any part of the body, especially on the scalp, in circular or oval areas. The purpose of this study is to search the serum paraoxonase 1 (PON1), arylesterase and oxidative status with serum prolidase activities in people with AA. METHODS: The study included 60 AA and 50 healthy control subjects. In both groups, serum PON1, prolidase, arylesterase activities, total oxidative status (TOS) and total antioxidant capacity (TAS) levels and oxidative stress index (OSI) were calculated. RESULTS: TOS, OSI levels and prolidase activity in patients with AA were found to be significantly higher compared to the control group (p = 0.02, p = 0.004, p < 0.001, respectively), whereas PON1 and arylesterase activities were significantly lower (p < 0.001, p = 0.005, respectively). There was no difference in serum TAS levels between the two groups. CONCLUSION: This comprehensive work shows that the role of oxidative stress is very important in the pathogenesis of AA. In this study, we believe that we clarified the pathogenesis of oxidative stress for AA patients by investigating the TAS, TOS, OSI levels, PON1, arylesterase and prolidase enzyme activity parameters.
Assuntos
Alopecia em Áreas/sangue , Arildialquilfosfatase/sangue , Hidrolases de Éster Carboxílico/sangue , Dipeptidases/sangue , Adulto , Feminino , Humanos , Masculino , Estresse Oxidativo , Adulto JovemRESUMO
Carnosinase 1 (CN1) has been postulated to be a susceptibility factor for developing diabetic nephropathy (DN). Although its major substrate, carnosine, is beneficial in rodent models of DN, translation of these findings to humans has been hampered by high CN1 activity in human serum resulting in rapid degradation of carnosine. To overcome this hurdle, we screened a protease-directed small-molecule library for inhibitors of human recombinant CN1. We identified SAN9812 as a potent and highly selective inhibitor of CN1 activity with a Ki of 11 nM. It also inhibited CN1 activity in human serum and serum of transgenic mice-overexpressing human CN1. Subcutaneous administration of 30 mg/kg SAN9812 led to a sustained reduction in circulating CN1 activity in human CN1 transgenic (TG) mice. Simultaneous administration of carnosine and SAN9812 increased carnosine levels in plasma and kidney by up to 100-fold compared to treatment-naïve CN1-overexpressing mice. To our knowledge, this is the first study reporting on a potent and selective CN1 inhibitor with in vivo activity. SAN9812, also called carnostatine, may be used to increase renal carnosine concentration as a potential therapeutic modality for renal diseases linked to glycoxidative conditions.
Assuntos
Carnosina/administração & dosagem , Dipeptidases/antagonistas & inibidores , Descoberta de Drogas , Imidazóis/farmacologia , Propionatos/farmacologia , Inibidores de Proteases/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Adulto , Animais , Carnosina/sangue , Dipeptidases/sangue , Dipeptidases/genética , Feminino , Expressão Gênica , Humanos , Imidazóis/química , Injeções Subcutâneas , Cinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Propionatos/química , Inibidores de Proteases/química , Ligação Proteica , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética , Bibliotecas de Moléculas Pequenas/química , TransgenesRESUMO
BACKGROUND: Carnosinase-1 (CN-1) can be detected in 24 h urine of healthy individuals and patients with type 2 diabetes (T2DM). We aimed to assess whether urinary CN-1 is also reliably measured in spot urine and investigated its association with renal function and the albumin/creatinine ratio (ACR). We also assessed associations between the CNDP1 (CTG) n genotype and CN-1 concentrations in serum and urine. METHODS: Patients with T2DM (n = 85) and nondiabetic patients with chronic kidney disease (CKD) (n = 26) stratified by albuminuria (ACR ≤ 300 mg/g or ACR > 300 mg/g) recruited from the nephrology clinic and healthy subjects (n = 24) were studied. RESULTS: Urinary CN-1 was more frequently detected and displayed higher concentrations in patients with ACR > 300 mg/g as compared to those with ACR ≤ 300 mg/g irrespective of the baseline disease (T2DM: 554 ng/ml [IQR 212-934 ng/ml] vs. 31 ng/ml [IQR 31-63 ng/ml] (p < 0.0001) and nondiabetic CKD: 197 ng/ml [IQR 112-739] vs. 31 ng/ml [IQR 31-226 ng/ml] (p = 0.015)). A positive correlation between urinary CN-1 and ACR was found (r = 0.68, p < 0.0001). Multivariate linear regression analysis revealed that ACR and serum CN-1 concentrations but not eGFR or the CNDP1 genotype are independent predictors of urinary CN-1, explaining 47% of variation of urinary CN-1 concentrations (R 2 = 0.47, p < 0.0001). CONCLUSION: These results confirm and extend previous findings on urinary CN-1 concentrations, suggesting that assessment of CN-1 in spot urine is as reliable as in 24 h urine and may indicate that urinary CN-1 in macroalbuminuric patients is primarily serum-derived and not locally produced.
Assuntos
Albuminúria/urina , Nefropatias Diabéticas/metabolismo , Dipeptidases/genética , Dipeptidases/urina , Insuficiência Renal Crônica/metabolismo , Idoso , Creatinina/sangue , Diabetes Mellitus Tipo 2/metabolismo , Dipeptidases/sangue , Feminino , Genótipo , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Albumina Sérica/análiseRESUMO
AIM: Assessment of plasma prolidase levels in polycystic ovary syndrome (PCOS). PATIENTS & METHODS: PCOS patients were screened according to Rotterdam Criterion and prolidase levels were measured. RESULTS: A total of 170 patients and 160 controls were recruited for the study and it was found that prolidase levels were significantly higher in PCOS group (991.10 ± 39.52) than control (621.89 ± 23.94). Furthermore it has been found that prolidase levels increase with the number of cysts in ovaries. CONCLUSION: Significant difference between prolidase levels in PCOS and control shows that it may be used as a diagnostic marker for disease. In addition to this, there is a positive correlation found between prolidase levels and number of cysts, hence may be used as a prognostic marker to monitor disease status.