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The molecular events leading to nephrolithiasis are extremely complex. Previous studies demonstrated that calcium and transforming growth factor-ß1 (TGF-ß1) may participate in the pathogenesis of stone formation, but the explicit mechanism has not been defined. Using a self-created genetic hypercalciuric stone-forming (GHS) rat model, we observed that the increased level of serous/uric TGF-ß1 and elevated intracellular calcium in primary renal tubular epithelial cells (PRECs) was associated with nephrolithiasis progression in vivo. In the setting of high calcium plus high TGF-ß1 in vitro, PRECs showed great potential epithelial to mesenchymal transition (EMT) progression and osteochondral differentiation properties, representing the multifarious increased mesenchymal and osteochondral phenotypes (Zeb1, Snail1, Col2A1, OPN, Sox9, Runx2) and decreased epithelial phenotypes (E-cadherin, CK19) bythe detection of mRNAs and corresponding proteins. Moreover, TGF-ß-dependent Wnt11 knockdown and L-type Ca2+ channel blocker could greatly reverse EMT progression and osteochondral differentiation in PRECs. TGF-ß1 alone could effectively promote EMT, but it had no effect on osteochondral differentiation in NRK cells (Rat kidney epithelial cell line). Stimulation with Ca2+ alone did not accelerate differentiation of NRK. Co-incubation of extracellular Ca2+ and TGF-ß1 synergistically promotes EMT and osteochondral differentiation in NRK control cells. Our data supplied a novel view that the pathogenesis of calcium stone development may be associated with synergic effects of TGF-ß1 and Ca2+, which promote EMT and osteochondral differentiation via Wnt11 and the L-type calcium channel.
Assuntos
Diferenciação Celular , Condrócitos/patologia , Transição Epitelial-Mesenquimal , Nefrolitíase/metabolismo , Nefrolitíase/patologia , Transdução de Sinais , Proteínas Wnt/metabolismo , Animais , Biomarcadores/metabolismo , Western Blotting , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/metabolismo , Diferenciação Celular/efeitos dos fármacos , Separação Celular , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Imunofluorescência , Técnicas de Silenciamento de Genes , Espaço Intracelular/metabolismo , Túbulos Renais/patologia , Nefrolitíase/sangue , Nifedipino/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/urinaRESUMO
Objective: Ureteral lesions caused by impacted ureteral stones are likely to result in postoperative ureteral stricture. On this basis, the study aimed to investigate if dual-energy spectral computed tomography can predict ureteral hardening caused by impacted stones and to explore the relationship between different types of ureteral lesions and the risk of ureteral stricture. Methods: This prospective study collected data of 93 patients with impacted stones from hospital automation system during January 2018 to October 2019. They underwent an abdominal scan on a dual-energy spectral computed tomography. During surgery, the operator used ureteroscopy to identify ureteral lesions, which were classified into four categories: edema, polyps, pallor, and hardening. Seven months later, 90 patients were reviewed for the degree of hydronephrosis. Results: Endoscopic observations revealed 38 (41%) cases of ureteral edema, 20 (22%) cases of polyps, 13 (14%) cases of pallor, and 22 (24%) cases of hardening. There were significant differences in hydronephrosis, the period of impaction, the calcium concentration of the ureter, and the slope of the spectral Hounsfield unit curve between the four groups. After that, we evaluated the factors associated with ureteral hardening and found that the calcium concentration of the ureter and hydronephrosis remained independent predictors of ureteral hardening. Receiver operating characteristic curve analysis showed that 5.3 mg/cm³ calcium concentration of the ureter is an optimal cut-off value to predict ureteral hardening. The result of follow-up showed that 80 patients had complete remission of hydronephrosis, with a complete remission rate of 61.9% (13/21) in the hardening group and 97.1% (67/69) in the non-hardening group (p<0.001). Conclusion: Calcium concentration of the ureter is an independent predictor of ureteral hardening. Patients with ureteral hardening have more severe hydronephrosis after ureteroscopic lithotripsy. When the calcium concentration of the ureter is less than 5.3 mg/cm³, ureteral lesions should be actively treated.
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This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico por imagem , Biópsia , Nomogramas , Estudos RetrospectivosRESUMO
OBJECTIVE: To report the incidence, risk factors, and outcomes of subcapsular renal haematoma (SRH) after ureteroscopic lithotripsy (URSL) using holmium:yttrium-aluminum-garnet (Ho:YAG) laser to treat ureteric stones. PATIENTS AND METHODS: Prospective data from 2848 URSLs performed between January 2003 and September 2010 were retrospectively analysed. In all 11 patients were identified as having a SRH after URSL if they had persistent severe ipsilateral flank pain or a palpable mass within a day of surgery, or presented with radiographic evidence of a SRH. Risk factors for the development and course of the SRH were reported. RESULTS: Of the 2848 consecutive patients treated with URSL using Ho:YAG laser, 11 (0.4%) developed a SRH after surgery. Patients who developed a SRH had larger stones (1.4 vs 0.9 cm, P < 0.001), more severe ipsilateral hydronephrosis (P < 0.001), longer operation duration (41 vs 33 min, P < 0.001), and higher perfusion pressure of hydraulic irrigation (176.8 vs 170.2 mmHg, P < 0.001) than patients who did not develop a SRH. Patient age, sex, body mass index, presence of diabetes mellitus, history of urolithiasis and hypertension, presence of multiple stones, stone location and flow rate of hydraulic irrigation were not statistically different in patients who did or did not develop a SRH. Most patients were managed conservatively, with no further intervention or with a flank drain, until the SRH resolved. Overall, in three patients the SRH resolved with no further intervention, six patients were treated with a drain only, and two patients had open surgery within a day of presenting with SRH. CONCLUSIONS: The rate of development of SRH after URSL is very low. Most patients who present with a SRH after URSL, can be treated conservatively with no intervention or with a drain only.
Assuntos
Hematoma/etiologia , Nefropatias/etiologia , Lasers de Estado Sólido/efeitos adversos , Litotripsia a Laser/efeitos adversos , Ureterolitíase/terapia , Ureteroscopia/efeitos adversos , Adulto , Idoso , China/epidemiologia , Feminino , Hematoma/diagnóstico , Hematoma/epidemiologia , Humanos , Incidência , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Lasers de Estado Sólido/uso terapêutico , Litotripsia a Laser/instrumentação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cálculos Ureterais/terapia , Urografia , Adulto JovemRESUMO
Purpose: This study aimed to compare the detection rate of prostate cancer (PCa) between targeted biopsy and systematic biopsy. Patients and Methods: A total of 671 patients who underwent both targeted biopsy and systematic biopsy were included in this study. The stratified analysis was conducted based on Prostate Imaging Reporting and Data System (PIRADS) scores, region of interest load (ROI-load). Results: There was no statistical difference in the detection rate of PCa patients between systematic biopsy and targeted biopsy (44.41% vs 45.6%, P>0.05), while the detection rate of targeted biopsy in clinically significant PCa (csPCa) patients was slightly higher than that of systematic biopsy (40.83% vs 38.15%, P=0.033). Stratified analysis indicated that targeted biopsy was more advantageous in csPCa patients with PIRADS score ≥ 4 and ROI-load > 5%. The comparison of diagnostic sensitivity of systematic biopsy and targeted biopsy demonstrated that targeted biopsy was more sensitive than systematic biopsy to diagnose PCa (Z=2.110, P=0.035) at ROI-load ≤ 5%. In addition, ROI-load may be a better targeted biopsy indicator than ROI diameter for the diagnosis of PCa (Z=2.168, P=0.030). Conclusion: MRI/US fusion targeted biopsy may be more suitable for PCa detection than systematic biopsy in patients with low ROI-load.
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UNLABELLED: What's known on the subject? and What does the study add? Experimental data have shown that VDR overexpression in the duodenum and kidney cortex is a biological characteristic of genetic hypercalciuric stone-forming rats (GHS rat), and a link between idiopathic calcium stone formation and the microstatellite marker D12S339 (near the VDR locus) has been proven in humans. Our study shows that VDR can positively regulate the mRNA and protein expression of TRPV5, calbindin-D28k and PMCA1b in NRK cell lines. VDR knockdown results in a decrease in intracellular Ca²âº concentration in NRK cell lines. The effect of the elevated VDR level in the kidney on hypercalciuria and the underlying mechanisms need to be further addressed. OBJECTIVE: ⢠To determine the effects of vitamin D receptor (VDR) on hypercalciuria and the mechanisms underlying such effects. MATERIALS AND METHODS: ⢠The adenovirus vector-delivered microRNA targeting rat VDR was constructed. We infected the normal rat kidney epithelial cell line NRK (Cellbank, China) with the adenovirus and then collected the cells at 0, 48, 72, 96, 120 h after infection. The mRNA and protein levels of VDR and VDR-dependent epithelial Ca2+ transport proteins were detected using real-time polymerase chain reaction and Western blot assays, respectively. ⢠Fluorescent Ca²âº indicator Fluo-4 NW (Fluo-4 NW calcium assay kit, Molecular Probes, Invitrogen, USA) and laser scanning confocal microscope (Olympus, FV500-IX71, Japan) were used to detect the cytosolic free Ca²âº concentration at different time points after infection. RESULTS: ⢠The mRNA and protein level of VDR, transient receptor potential vanilloid receptor subtype 5 (TRPV5), calbindin-D28k and plasma membrane Ca²âº-ATPase (PMCA1b) in infected NRK cells was significantly lower at 72 and 96 h after infection than that in control cells. ⢠There was no significant difference between the two groups in the mRNA and protein level of TRPV6 and the Naâº/Ca²âº-exchanger (NCX1). ⢠Furthermore, VDR knockdown results in a decrease in intracellular Ca²âº concentration ([Ca²âº]i) in NRK cell lines. CONCLUSIONS: ⢠Our study shows that VDR can positively regulate the mRNA and protein expression of TRPV5, calbindin-D28k and PMCA1b, but not of TRPV6 or NCX1, in NRK cell lines. VDR knockdown results in a decrease in [Ca²âº]i in NRK cell lines. ⢠The effect of the elevated VDR level in the kidney on hypercalciuria and the mechanisms underlying need to be further addressed.
Assuntos
Cálcio/metabolismo , Regulação da Expressão Gênica , Marcação de Genes/métodos , MicroRNAs/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , Receptores de Calcitriol/genética , Urotélio/metabolismo , Adenoviridae/genética , Animais , Western Blotting , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Hipercapnia/genética , Hipercapnia/metabolismo , Líquido Intracelular/metabolismo , Córtex Renal/metabolismo , Córtex Renal/patologia , Microscopia Confocal , ATPases Transportadoras de Cálcio da Membrana Plasmática/biossíntese , RNA Viral/genética , Ratos , Receptores de Calcitriol/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Urotélio/patologiaRESUMO
BACKGROUND: Traditional surgical methods have high complication rate and large injury in the resection of adult polycystic kidney. We investigated the effect of retroperitoneal laparoscopic resection of adult polycystic kidney assisted by arterial embolization. METHODS: The data of adult polycystic kidney patients who underwent laparoscopic surgery assisted by arterial embolization from November 2015 to November 2018 in our hospital were retrospectively analyzed, and the data of patients who underwent open surgery during the same period were collected. The basic data, surgical conditions, postoperative recover situation, and complications of the two groups were compared. RESULTS: There was no significant difference in the basic situation between the laparoscopic operation group and open operation (control) group. The bleeding volume, hospitalization time, and the length of incision in the laparoscopic operation group were significantly better than those in the open operation (control) group, but the operation time was significantly longer than that in the open operation group. There was no significant difference in drainage tube extraction time, bed rest time and blood transfusion rate between the two groups. There was no significant difference in the complication rate between the two groups. CONCLUSIONS: Arterial interventional embolization-assisted retroperitoneal laparoscopy is an effective method for the resection of polycystic kidney.
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The expression of calcium epithelium TRPV5, alcium binding protein Calbindin-D28k and Na(+)/Ca(2+) exchanger NCX1 was detected in renal distal convoluted tubule, and their effects on urine calcium reabsorption and the possible pathogenic mechanism in idiopathic hypercalciuria (IH) were investigated. Genetic hypercalciuric stone-forming (GHS) rats were chosen as animal models to study urine calcium reabsorption and IH. The cognate female and male rats that had maximal urine calcium were matched to breed next generation. Twelve GHS rats and 12 normal control (NC) SD rats were selected. Western blot and real time quantitative PCR were used to detect the protein and gene expression of TRPV5, Calbindin-D28k and NCX1 respectively. The expression levels of TRPV5 protein and mRNA in GHS rats were significantly lower than in NC rats (P<0.05). Western blot revealed that the expression levels of Calbindin-D28k in GHS rats and NC rats were 0.49+/-0.02 and 0.20+/-0.01 respectively, with the difference being significant between them (P<0.05). By using real time quantitative PCR, it was found that there was no significant difference in Calbindin-28k mRNA expression levels between GHS rats and NC rats (P>0.05). There was no significant difference in the NCX1 expression between GHS rats and NC rats (P>0.05). It was suggested that TRPV5 and Calbindin-D28k might play an important role in urine calcium reabsorption and IH, but they differently contributed to the pathogenesis: The down-regulation of TRPV5 decreases urine calcium reabsorption, directly leading to loss of the urine calcium and resulting in hypercalciuria, and the increased Calbindin-D28k expression could relieve, neutralize and decrease intracellular Ca(2+) concentration to maintain calcium balance. NCX1 is not the key protein in urine calcium reabsorption.
Assuntos
Canais de Cálcio/metabolismo , Hipercalciúria/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Calbindina 1 , Calbindinas , Canais de Cálcio/genética , Feminino , Túbulos Renais Distais/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína G de Ligação ao Cálcio S100/genética , Trocador de Sódio e Cálcio/genética , Canais de Cátion TRPV/genéticaRESUMO
OBJECTIVE: To explore the role of CD4+CD25+ regulatory T cells in the pathogenesis of chronic abacterial prostatitis/chronic pelvic pain syndrome (CAP/CPPS). METHODS: Peripheral blood samples were collected from 45 CAP/CPPS patients and 18 healthy age-matched male persons. Peripheral blood mononuclear cells (PBMCs) were isolated. The percentages of CD4+CD25+ and CD4+CD25high regulatory T cells were detected by flow cytometry. PCR was used to examine the mRNA expression of Foxp3, a transcription factor expressed in the CD4+CD25+ cells. ELISA was used to examine the plasma level of tumor growth factor (TGF)-beta1. RESULTS: There were no significant differences in the percentages of peripheral blood CD4+CD25+ and CD4+CD25highT cells between the CAP/CPPS patients and normal control group (both P>0.05). The Foxp3 mRNA in the PBMCs of the CAP/CPPS IIIA and CAP/CPPS IIIB patients were (0.69+/-0.23) and (0.44+/-0.18) respectively, both significantly lower than that of the control group [(1.37+/-0.19), P<0.05]. The serum TGF-beta1 levels of the CAP/CPPS IIIA and CAP/CPPS IIIB patients were (18.09+/-10.45) pg/ml and (14.06+/-6.22) pg/ml respectively, both significantly lower than that of the control group [(27.01+/-13.29) pg/ml, both P<0.05]. CONCLUSION: Not the number of peripheral blood CD4+CD25+ regulatory T cells, but its defective function participates in the pathogenesis of CAP/CPPS. The Foxp3 gene and TGF-beta1 play important roles in the process of pathogenesis of CAP/CPPS too.
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Dor Pélvica/imunologia , Prostatite/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Linfócitos T CD4-Positivos/metabolismo , Doença Crônica , Citometria de Fluxo , Fatores de Transcrição Forkhead/genética , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Dor Pélvica/sangue , Prostatite/sangue , Fator de Crescimento Transformador beta/sangueRESUMO
OBJECTIVE: To study the expression level of calbindin-D28k, a kind of calcium binding protein, in the kidneys of genetic hypercalciuric stone-forming (GHS) rats and to investigate its role in idiopathic hypercalciuria (IH). METHODS: Kidneys were taken out from 16 GHS rats and 6 normal control (NC) rats. Western blotting and real time quantitative PCR were used to detect the protein and mRNA expression levels of calbindin-D28k respectively. RESULTS: Western blotting showed that the A value of calbindin-D28k of the GHS rats was 0.49 +/- 0.02, significantly higher than that of the NC rats (0.20 +/- 0.01, P < 0.05). The 2(-(delta delta CT)) value of mRNA of calbindin-D28k of the GHS rats was 1.21, remarkably higher than that of the NC rats [with the of 2(-(delta delta CT)) value of 1.0]. There was not significant difference in the delta CT value between the two groups (P > 0.05). CONCLUSION: The up-regulation of calbindin-D28k in the GHS rats is possibly caused by hyperexpression of VDR and hypercalcinuria, and plays an important role in urine calcium reabsorption; however, it is not the key protein that results in IH.
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Hipercalciúria/genética , Rim/metabolismo , Proteína G de Ligação ao Cálcio S100/genética , Cálculos Urinários/genética , Animais , Western Blotting , Calbindina 1 , Calbindinas , Feminino , Expressão Gênica , Hipercalciúria/metabolismo , Hipercalciúria/patologia , Rim/patologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína G de Ligação ao Cálcio S100/biossíntese , Cálculos Urinários/metabolismo , Cálculos Urinários/patologiaRESUMO
OBJECTIVE: To address whether hypercalciuria can stimulate calcium oxalate (CaOx) crystal deposition in kidney through osteopontin (OPN). MATERIALS AND METHODS: Rat tubular epithelial NRK cells were exposed to calcium. The cell viability, the cellular malondialdehyde content as a marker of reactive oxygen species (ROS), and the release of lactate dehydrogenase as markers of injury were detected. The production and gene expression of OPN were also examined. CaOx crystal attachment to cells was accomplished by measuring the calcium concentration of the cell lysates with atomic absorption analysis. RESULTS: Exposure to calcium produced signs of cell injury and ROS-induced lipid peroxidation. The messenger ribonucleic acid expression and production of OPN increased significantly. OPN knockdown can significantly decrease the amount of CaOx crystal attachment to NRK cells. CONCLUSION: In response to exposure to high concentration of calcium, renal tubular epithelial NRK cells increase the production of OPN, which may have a promoting role in CaOx crystal adhesion to NRK cells by calcium stimulation.
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Oxalato de Cálcio/metabolismo , Cálcio/metabolismo , Regulação da Expressão Gênica , Hipercalciúria/genética , Túbulos Renais/metabolismo , Osteopontina/genética , RNA/genética , Animais , Western Blotting , Células Cultivadas , Cristalização , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Hipercalciúria/metabolismo , Hipercalciúria/patologia , Túbulos Renais/patologia , Osteopontina/biossíntese , Reação em Cadeia da Polimerase , RatosRESUMO
OBJECTIVES: To investigate the prognostic factors associated with the treatment efficacy of minimally invasive percutaneous nephrolithotomy (MPCNL) and develop a preoperative logistic regression model for predicting the stone-free rate after the initial procedure. METHODS: We retrospectively analyzed the records of 865 patients who had undergone MPCNL in our department from January 2006 to September 2009. Patient age, sex, body mass index, degree of hydronephrosis, and stone side, number, size, and location were the investigated variables. According to the treatment outcome, the patients were divided into 2 groups, those who became stone free and those who did not. Student's t test, chi-square test, and multiple logistic regression analysis were performed to determine the statistically significant variables and to develop a predictive mathematical model. RESULTS: The stone-free rate after primary MPCNL was 80.1% (693 of 865). On univariate analysis, the stone number, size, and location and degree of hydronephrosis were identified as significant factors between the 2 groups. On multivariate analysis, they were also independent predictors of the surgical outcome. Next, a logistic regression model was developed using these variables to estimate the stone-free rate after MPCNL. CONCLUSIONS: The results of our study have demonstrated that an increased stone number and size, location in a calix, staghorn calculus, and moderate to severe hydronephrosis were associated with decreased stone-free rates after MPCNL. We have developed a mathematical model for predicting the stone-free rate that will be helpful for patient counseling and surgeon decision-making regarding the management of upper urinary tract calculi.
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Cálculos Renais/cirurgia , Nefrostomia Percutânea , Cálculos Ureterais/cirurgia , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nefrostomia Percutânea/métodos , Prognóstico , Análise de Regressão , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To address the molecular mechanisms that the vitamin D receptor (VDR) in the kidney might contribute to decreased renal calcium reabsorption in idiopathic hypercalciuria using genetic hypercalciuric stone-forming (GHS) rats. METHODS: We silenced the VDR gene in the GHS and normal control (NC) rat kidney in vivo using adenovirus vector-delivered microRNA targeting VDR through renal venous transduction. On days 3-21 after injection with adenovirus, the expression levels of the VDR, calcium-sensing receptor, and epithelial calcium transporters in the kidney were detected. The urine calcium and serum calcium, phosphorus, 1,25(OH)(2)D(3), and parathyroid hormone levels were measured. RESULTS: The basal expression levels in the kidney tissues of VDR, calbindin-D(28k), and calcium-sensing receptor were significantly greater in the GHS rats than in the NC rats, and the basal expression levels of transient receptor potential vanilloid receptor subtype 5, transient receptor potential vanilloid receptor subtype 6, calbindin-D(9k), and plasma membrane calcium-adenosine triphosphatase were significantly lower in the GHS rats than in the NC rats. VDR knockdown in the kidney caused significant increase in renal transient receptor potential vanilloid receptor subtype 5, sodium/calcium exchanger, and calbindin-D(9k) expression levels in the GHS rats. The GHS rats excreted significantly more urine calcium after VDR knockdown. The serum calcium, phosphorus, parathyroid hormone, and 1,25(OH)(2)D(3) levels were not altered during the study period in the GHS and NC rats. CONCLUSION: Our findings suggest that VDR knockdown in the kidney can upregulate the expression of transient receptor potential vanilloid receptor subtype 5 in GHS rats. However, VDR depletion results in an increase in urine calcium excretion. The role of VDR in the hypercalciuric formation needs to be elucidated further.
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Cálcio/metabolismo , Rim/metabolismo , RNA Mensageiro/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Análise de Variância , Animais , Calbindinas , Calcitriol/sangue , Canais de Cálcio/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Epitélio/metabolismo , Regulação da Expressão Gênica , Inativação Gênica , Hipercalciúria/genética , Rim/enzimologia , Masculino , Modelos Animais , Hormônio Paratireóideo/sangue , Fósforo/sangue , Ratos , Ratos Sprague-Dawley , Proteína G de Ligação ao Cálcio S100/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Canais de Cátion TRPV/metabolismoRESUMO
OBJECTIVES: We developed minimal incision-assisted retroperitoneoscopic surgery (MARP) in an attempt to pursue optimized patient-related benefits. We evaluated the clinical value of MARP for upper urinary tract diseases compared with pure retroperitoneoscopic surgery (PRPS). PATIENTS AND METHODS: Between January 2003 and September 2008, PRPS and MARP were carried out in 338 and 85 patients, respectively. The upper urinary tract surgical procedures were defined as simple and complex procedures. We defined our experience from January 2003 to December 2005 as our early stage of PRPS learning curve. Our experience from January 2006 to September 2008 was defined as our late stage of PRPS learning curve. Patients' perioperative details were compared. RESULTS: MARP was associated with shorter operative time for each complex procedure and with less frequent conversion to open surgery (2.4% vs. 11.3%, p = 0.023). A significantly greater proportion of MARP patients underwent complex procedures (81.2% vs. 49.1%, p < 0.001), and a significantly greater proportion of MARP were carried out at the early stage of PRPS learning curve (62.4% vs. 44.1%, p = 0.003). Estimated blood loss, hospital stay, the amount of analgesic use (diclofenac sodium suppository), and intraoperative and postoperative complications were comparable. CONCLUSIONS: MARP maintains the patient-related benefits of PRPS while allowing surgeons to perform more complex cases of upper urinary tract diseases and shortening the relevant operative time. It can be useful for cases in which the specimen is going to be extracted intact, when starting out learning retroperitoneoscopy, or when unable to progress the case using laparoscopic techniques.
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Espaço Retroperitoneal/cirurgia , Sistema Urinário/cirurgia , Doenças Urológicas/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Humanos , Aprendizagem , Assistência Perioperatória , Procedimentos Cirúrgicos Urológicos/educaçãoRESUMO
PURPOSE: We compared the efficacy and safety of percutaneous nephrolithotomy (PCNL) with different intracorporeal lithotriptors for proximal ureteral stones in patients with severe hydronephrosis. PATIENTS AND METHODS: We retrospectively analyzed the records of 192 patients with proximal ureteral calculi and severe hydronephrosis who underwent PCNL between February 2003 and December 2007. Calculi were fragmented with a pneumatic lithotriptor in 44 patients (group 1), Swiss Lithoclast Master in 54 (group 2), low-power holmium:yttrium-aluminum-garnet (YAG) laser in 56 (group 3) and high-power holmium:YAG laser in 38 (group 4). Patients were assessed about 12 months postoperatively with intravenous urography and ultrasonography for late complications. Stone size, operative time, stone-free rate, and follow-up were analyzed in each group. RESULTS: Mean stone size for different groups were 16.2 +/- 2.8 mm, 16.6 +/- 2.1 mm, 16.0 +/- 2.7 mm, and 16.4 +/- 1.1 mm, respectively. Average operative time for different groups were 118 +/- 17 minutes, 81 +/- 10 minutes, 85 +/- 14 minutes, 110 +/- 16 minutes, respectively. Group 2 and group 3 showed superior outcomes of shorter operative time (P = 0.000). The overall stone-free rate was 86.5%. As stratified by lithotriptors, the stone-free rate was 81.8% in group 1, 92.9% in group 2, 88.9% in group 3, and 78.9% in group 4 (P = 0.190). No significant difference was found among the groups in terms of blood loss and postoperative hospital stay. Repeated PCNL or shockwave lithotripsy was necessary as an auxiliary procedure in 26 patients. The overall complication rate was 18.2%; most complications were minor and insignificant. During the follow-up, ureteral stricture developed in 10 patients and new renal stones developed in 4 patients. CONCLUSIONS: PCNL combined with Swiss Lithoclast Master or low-power holmium:YAG laser is the preferred endourologic modality for the management of proximal ureteral calculi in patients with severe hydronephrosis.
Assuntos
Hidronefrose/complicações , Litotripsia/instrumentação , Nefrostomia Percutânea , Cálculos Ureterais/complicações , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Cálculos Ureterais/patologia , Adulto JovemRESUMO
OBJECTIVES: To identify the characteristics of circulating CD4(+)CD25(high) regulatory T cells in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We sought to discover the possible mechanism underlying induction of CP/CPPS by autoimmune factors. METHODS: A total of 69 men with CP/CPPS and 25 age-matched, asymptomatic controls underwent quantification of peripheral blood CD4(+)CD25(high) regulatory T cells, using flow cytometry, followed by measurement of interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGFbeta1) in serum, and forkhead box P3 (FOXP3) mRNA level in peripheral blood mononuclear cells, using enzyme-linked immunosorbent assay and real-time quantitative reverse transcriptase-polymerase chain reaction, respectively. RESULTS: The FOXP3 gene mRNA level in CP/CPPS patients was significantly lower than that in controls. Serum TNF-alpha level increased but the TGFbeta1 level decreased in CP/CPPS patients. No change was observed in the levels of IL-6 and IL-10. However, there was normal frequency of CD4(+)CD25(high) T cells in CP/CPPS patients. No differences were observed in expression of FOXP3 and serum cytokines and population of CD4(+)CD25(high) T cells between CP/CPPS IIIA and IIIB patients. In addition, statistically significant correlation was only found between serum IL-6 production and national institutes of health-chronic prostatitis symptom index total score of CP/CPPS patients. The frequency of CD4(+)CD25(high) T cells and FOXP3 expression level did not correlate with age, duration, and total national institutes of health-chronic prostatitis symptom index score of CP/CPPS patients. CONCLUSIONS: FOXP3 and serum cytokines, such as TNF-alpha and TGFbeta1, might be important for the pathogenesis of CP/CPPS and possibly affect the suppressive function of CD4(+)CD25(high) regulatory T cells. This influence may result in the onset of CP/CPPS, but its assessment requires further study.
Assuntos
Linfócitos T CD4-Positivos , Subunidade alfa de Receptor de Interleucina-2 , Prostatite/sangue , Prostatite/imunologia , Linfócitos T Reguladores , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Adulto JovemRESUMO
PURPOSE: We investigated ureteral lesions associated with impacted stones and compared the long-term outcomes after ureteroscopic lithotripsy (URSL) with a holmium laser with open ureterolithotomy, resection of concurrent pathologic ureter, and ureteroureterostomy (OUU) for patients with impacted ureteral stone. PATIENTS AND METHODS: Between January 2004 and December 2007, 86 patients with impacted ureteral stones were treated with URSL (61) or OUU (25) because of tortuous ureter or failed access to stones. The stone size, location, impaction, ureteral lesions, and long-term outcomes were recorded. RESULTS: Mean stone size for the URSL group and the OUU group was 11.8 +/- 2.6 mm and 15.3 +/- 4.2 mm, respectively (P = 0.078). The impaction duration was 8.5 +/- 1.1 months for the URSL group and 17.2 +/- 3.8 months for the OUU group (P < 0.001). Endoscopic observation revealed two types of ureteral lesions that were defined as villous or polypoid protrusion (type 1) and edematous hemispheric lesions (type 2). Stone-free rates for the URSL group and the OUU group were 91.8% and 100%, respectively (P = 0.140). URSL was associated with a higher incidence of stricture (26.2% v 4.0%; P = 0.019) and worse recovery of hydronephrosis (P < 0.001). Stricture occurred more frequently in patients with type II lesions in the URSL group (P = 0.022). Stone recurrence for the URSL group and the OUU group were 13.1% and 4%, respectively (P = 0.210). CONCLUSIONS: Chronically impacted stones are frequently associated with ureteral polyp or stricture lesions. Our results reveal that combined removal of stones with resection of the pathologic ureter may achieve better long-term outcomes for patients with impacted stones with stricture lesions.
Assuntos
Constrição Patológica/complicações , Constrição Patológica/patologia , Cálculos Ureterais/patologia , Cálculos Ureterais/cirurgia , Adulto , Idoso , Demografia , Feminino , Humanos , Litotripsia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Cálculos Ureterais/complicações , Ureteroscopia/efeitos adversosRESUMO
Summary: The expression of calcium epithelium TRPV5, alcium binding protein Calbindin-D28k and Na+/Ca2+ exchanger NCX1 was detected in renal distal convoluted tubule, and their effects on urine calcium reabsorption and the possible pathogenic mechanism in idiopathic hypercalciuria (IH) were investigated. Genetic hypercalciuric stone-forming (GHS) rats were chosen as animal models to study urine calcium reabsorption and IH. The cognate female and male rats that had maximal urine calcium were matched to breed next generation. Twelve GHS rats and 12 normal control (NC) SD rats were selected. Western blot and real time quantitative PCR were used to detect the protein and gene expression of TRPV5, Calbindin-D28k and NCX1 respectively. The expression levels of TRPV5 protein and mRNA in GHS rats were significantly lower than in NC rats (P<0.05). Western blot revealed that the expression levels of Caibindin-D28k in GHS rats and NC rats were 0.49±0.02 and 0.20±0.01 respectively, with the difference being significant between them (P<0.05). By using real time quantitative PCR, it was found that there was no significant difference in Calbindin-28k mRNA expression levels between GHS rats and NC rats (P0.05). There was no significant difference in the NCX1 expression between GHS rats and NC rats (P0.05). It was suggested that TRPV5 and Caibindin-D28k might play an important role in urine calcium reabsorption and IH, but they differently contributed to the pathogenesis: The down-regulation of TRPV5 decreases urine calcium reabsorption, directly leading to loss of the urine calcium and resulting in hypercalciuria, and the increased Calbindin-D28k expression could relieve, neutralize and decrease intracellular Ca2+ concentration to maintain calcium balance. NCX1 is not the key protein in urine calcium reabsorption.