RESUMEN

Primary testicular carcinoid tumours (TCT) are very rare, and a large tumour size and the presence of carcinoid syndrome predict a malignant course. Histologically, it is difficult to differentiate between benign and malignant TCTs. We report a case of a primary pure TCT with an unusual presentation in a 23- year-old man, who had an asymptomatic, enlarged scrotum on the right side for 7 years. On gross examination, the tumour was 9.6 cm in diameter. The Ki-67 labelling index was 19.8%. High inguinal orchidectomy was performed, and 30 months after surgery the patient remains asymptomatic.

Asunto(s)

Tumor Carcinoide/cirugía , Orquiectomía/métodos , Neoplasias Testiculares/cirugía , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patología , Humanos , Masculino , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Adulto Joven

RESUMEN

UNLABELLED: Abstract Purpose: To evaluate the efficacy of endoscopic combined intrarenal surgery (ECIRS) using retrograde flexible ureteroscopy and miniature percutaneous nephrolithotomy (PNL) for the treatment of patients with staghorn calculi in the prone split-leg position. PATIENTS AND METHODS: We retrospectively reviewed the records of 42 patients with staghorn calculi (45.8±3.2 mm) who underwent ECIRS using retrograde flexible ureteroscopy and miniature PNL in the prone split-leg position for the treatment of staghorn calculi in our center between December 2010 and August 2013. A flexible ureteroscope with a laser fiber was inserted through a ureteral access sheath, and lithoclast lithotripsy was performed through a mini-percutaneous tract. Both procedures were performed simultaneously by two urologists. Surgical parameters, including surgical time, stone-free (SF) rates, modified Clavien complication grades, and risk factors for residual stones, were analyzed. RESULTS: Fifteen patients (35.7%) had complete staghorn calculi. Among the 42 staghorn calculi treated, 23 had 0 to 5 stone branches, 14 had 6 to 10 stone branches, and 5 had ≥11 stone branches. All procedures were performed successfully using a single lithotripsy tract with the patient in the prone split-leg position. The mean surgical time was 143.2±9.2 minutes. The initial SF rate was 71.4%, and the final SF rate was 83.3% after further treatment. One patient required a blood transfusion (2.4%), but no patient experienced a ≥3 Clavien grade complication. Risk factors for residual stones were stone size, stone surface area, complete staghorn calculi, and the number of stone branches. CONCLUSIONS: ECIRS for staghorn calculi in the prone split-leg position is a safe, efficient, and versatile method for the effective management of staghorn calculi without the creation of multiple percutaneous tracts.

Asunto(s)

Cálculos Renales/cirugía , Nefrostomía Percutánea/métodos , Ureteroscopía/métodos , Endoscopía/métodos , Femenino , Humanos , Litotripsia por Láser/métodos , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente/métodos , Posición Prona , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

PURPOSE: We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation. MATERIALS AND METHODS: Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. RESULTS: The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells. CONCLUSIONS: Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types.

Asunto(s)

Adipocitos/metabolismo , Oxalato de Calcio/metabolismo , Citocinas/metabolismo , Cálculos Renales/metabolismo , Túbulos Renales/metabolismo , Macrófagos/metabolismo , Síndrome Metabólico/metabolismo , Células 3T3-L1 , Adipocitos/patología , Animales , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Cálculos Renales/patología , Túbulos Renales/patología , Macrófagos/patología , Síndrome Metabólico/patología , Ratones

RESUMEN

BACKGROUND: Residents (n=157) of Kamisu City, Ibaraki, Japan, were orally exposed to diphenylarsinic acid (DPAA) via the ingestion of contaminated underground water. Subsequently, a clinical syndrome associated with a variety of cerebellar and brainstem symptoms, was observed in 20 of the 30 residents who consumed high concentrations of DPAA in the contaminated well water. While the clinical symptoms of DPAA were defined, the toxicokinetics of DPAA remained unclear. METHODS: In order to investigate the underlying toxicokinetics of DPAA, we collected serum and cerebrospinal fluid (CSF) samples from 5 patients with DPAA intoxication, and attempted to estimate the half-life of serum DPAA and the CSF/serum ratio of DPAA. RESULTS: DPAA, and its derivatives, such as phenylmethylarsinic acid (PMAA) and phenylarsinic acid (PAA), were detected in serum from residents exposed to DPAA. Serum DPAA was observed for >200 days after the last ingestion of contaminated water. The half-life of serum DPAA was 22.5 days in children and 39.4 days in youths and adults, which was nearly double that observed in children. DPAA was found in CSF, and the CSF/serum ratios of DPAA in 2 patients were 3.0% and 3.7%, respectively, suggesting that this toxicant is able to cross the blood-brain barrier. CONCLUSION: An established animal model of DPAA intoxication was examined regarding the toxicokinetics, distribution and direct DPAA accumulation in the cerebrum. On the basis of existing animal data, and the present results arising from human subjects, the development of new therapies for DPAA intoxication should be enhanced, such as accelerated DPAA excretion.

Asunto(s)

Arsenicales/sangre , Arsenicales/líquido cefalorraquídeo , Adolescente , Adulto , Intoxicación por Arsénico/sangre , Intoxicación por Arsénico/líquido cefalorraquídeo , Arsenicales/farmacocinética , Barrera Hematoencefálica/metabolismo , Niño , Femenino , Semivida , Humanos , Lactante , Masculino

RESUMEN

We established an experimental co-culture system for renal tubular cells and adipocytes to investigate kidney stone formation mechanisms under metabolic syndrome (MetS) conditions and examined the interaction between these cells morphologically and genetically. M-1s and 3T3-L1s were cultured individually (control, CON), with 24-h culture media from each cell type added to the other cell type (replacement, RP) in 2-layer co-culture dishes for 24 h (transwell, TW). M-1s were then exposed to calcium oxalate monohydrate (COM) crystals, and attached (14)C-labeled COM crystals were quantified. Expression of kidney stone- and adipocyte-related genes was analyzed. The radioactivity of adherent COM crystals significantly increased in TW and was relatively higher in RP compared to CON. M-1s demonstrated significant upregulation of adiponectin (Adipoq) in RP and secreted phosphoprotein 1 (Spp1) in TW compared to CON before COM crystal exposure, and significant downregulation of Spp1 in TW and upregulation of tumor necrosis factor (Tnf), interleukin 6 (Il-6), and chemokine (C-C motif) ligand 2 (Ccl2) compared to CON after COM crystal exposure. 3T3-L1s showed significant upregulation of Spp1, Adipoq, Tnf-α, and Ccl2 compared to CON. Enzyme-linked immunosorbent assays of co-culture medium revealed significantly increased TNF-α in TW. Our results highlight the potential for paracrine interactions between renal tubular cells and adipocytes and suggest that MetS conditions may lead to kidney stone formation.

Asunto(s)

Adipocitos/citología , Adipocitos/metabolismo , Cálculos Renales/metabolismo , Túbulos Renales/citología , Túbulos Renales/metabolismo , Síndrome Metabólico/metabolismo , Células 3T3-L1 , Adiponectina/genética , Animales , Oxalato de Calcio/química , Oxalato de Calcio/metabolismo , Comunicación Celular , Línea Celular , Técnicas de Cocultivo , Cristalización , Células Epiteliales/citología , Células Epiteliales/metabolismo , Expresión Génica , Cálculos Renales/etiología , Cálculos Renales/patología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/patología , Ratones , Modelos Biológicos , Osteopontina/genética , Osteopontina/metabolismo , Comunicación Paracrina , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

PURPOSE: The purpose of this study was to evaluate the efficacy of retroperitoneal laparoscopic ureterolithotomy for the management of large proximal ureteric stones and the impact of this treatment on postoperative renal function. METHODS: The data of 12 patients (7 men and 5 women; mean age, 68.5 ± 8.9 years) with large pyeloureteral junction (2 cases) and upper ureteral (10 cases) stones (25.3 ± 7.4 mm) that had undergone retroperitoneal laparoscopic ureterolithotomy were reviewed. Renal function was analyzed by the estimated glomerular filtration rate (eGFR) and renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) before and 3 months after surgery. RESULTS: The mean operative time was 129.5 ± 21.4 minutes, with a mean blood loss of 64.4 ± 78.2 mL. The mean duration of hospital stay after surgery was 6.4 ± 2.7 days, and the mean duration of stenting was 7.2 ± 1.7 weeks. A stone clearance rate of 100% was achieved, and no patient developed ureteric stricture. 99mTc-MAG3 scintigraphy showed that laparoscopic removal of calculi did not affect renal function, but did improve ureteral occlusion. CONCLUSIONS: Retroperitoneal laparoscopic ureterolithotomy is a safe and effective treatment option for reducing ureteral obstruction in select patients with large proximal ureteric stones.

RESUMEN

Renal tubular cell injury induced by oxalate plays an important role in kidney stone formation. Water containing oxygen nano-bubbles (nanometer-sized bubbles generated from oxygen micro-bubbles; ONB) has anti-inflammatory effects. Therefore, we investigated the inhibitory effects of ONB water on kidney stone formation in ethylene glycol (EG)-treated rats. We divided 60 rats, aged 4 weeks, into 5 groups: control, the water-fed group; 100 % ONB, the 100 % ONB water-fed group; EG, the EG treated water-fed group; EG + 50 % ONB and EG + 100 % ONB, water containing EG and 50 % or 100 % ONB, respectively. Renal calcium oxalate (CaOx) deposition, urinary excretion of N-acetyl-ß-D-glucosaminidase (NAG), and renal expression of inflammation-related proteins, oxidative stress biomarkers, and the crystal-binding molecule hyaluronic acid were compared among the 5 groups. In the control and 100 % ONB groups, no renal CaOx deposits were detected. In the EG + 50 % ONB and EG + 100 % ONB groups, ONB water significantly decreased renal CaOx deposits, urinary NAG excretion, and renal monocyte chemoattractant protein-1, osteopontin, and hyaluronic acid expression and increased renal superoxide dismutase-1 expression compared with the EG group. ONB water substantially affected kidney stone formation in the rat kidney by reducing renal tubular cell injury. ONB water is a potential prophylactic agent for kidney stones.

Asunto(s)

Oxalato de Calcio/metabolismo , Cálculos Renales/metabolismo , Cálculos Renales/prevención & control , Oxígeno/administración & dosificación , Agua/química , Animales , Quimiocina CCL2/genética , Glicol de Etileno/toxicidad , Expresión Génica/efectos de los fármacos , Cálculos Renales/patología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/lesiones , Túbulos Renales/metabolismo , Masculino , Nefrolitiasis/metabolismo , Nefrolitiasis/patología , Nefrolitiasis/prevención & control , Osteopontina/genética , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/genética , Superóxido Dismutasa-1

RESUMEN

OBJECTIVE: Recently, we reported that alpha 1A-adrenoceptor (AR) is the main participant in phenylephrine-induced human ureteral contraction. We therefore decided to carry out a prospective randomized study to evaluate the effects of silodosin, a selective alpha 1A AR antagonist, as a medical expulsive therapy (MET) for distal ureteral stones. METHODS: A total of 112 male patients, who were referred to our department for the management of symptomatic unilateral distal ureteral calculi of less than 10 mm, were randomly divided into two groups: group A (56 patients) who were instructed to drink 2 L of water daily and group B (56 patients) who received the same instruction and were also given silodosin (8 mg/daily) for a maximum of 4 weeks. Expulsion rate, expulsion time and need for analgesics were examined. RESULTS: The expulsion rate was 55.3 % (56 patients) for group A and 72.7 % (55 patients) for group B (P = 0.106). The expulsion rate for <5 mm was 92.9 % (28 patients) for group A and 69.2 % (26 patients) for group B (P = 0.053). The expulsion rate for ≥ 5 mm was 17.9 % (28 patients) for group A and 75.9 % (29 patients) for group B (P = 0.001). The expulsion time was 13.40 ± 5.90 and 9.29 ± 5.91 days, respectively (P = 0.012). Analgesics were required 1.5 ± 3.1 and 0.3 ± 0.9 times, respectively (P = 0.382). Stone size in expulsion cases was 3.64 ± 1.25 and 5.23 ± 2.32 mm, respectively (P = 0.003). CONCLUSIONS: Stone size has been identified as an important predictive factor for stone expulsion. Therefore, it is important that administration of silodosin can facilitate expulsion of 1.5 mm or larger distal ureteral stones, as compared to control. We believe that silodosin might have potential as a MET for distal ureteral stones.

Asunto(s)

Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Indoles/administración & dosificación , Cálculos Ureterales/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Cálculos Ureterales/diagnóstico por imagen

RESUMEN

Renal tubular cell injury induced by oxidative stress via mitochondrial collapse is thought to be the initial process of renal calcium crystallization. Mitochondrial collapse is generally caused by mitochondrial permeability transition pore (mPTP) opening, which can be blocked by cyclosporine A (CsA). Definitive evidence for the involvement of mPTP opening in the initial process of renal calcium crystallization, however, is lacking. In this study, we examined the physiological role of mPTP opening in renal calcium crystallization in vitro and in vivo. In the in vitro study, cultured renal tubular cells were exposed to calcium oxalate monohydrate (COM) crystals and treated with CsA (2 µM). COM crystals induced depolarization of the mitochondrial membrane potential and generated oxidative stress as evaluated by Cu-Zn SOD and 4-HNE. Furthermore, the expression of cytochrome c and cleaved caspase 3 was increased and these effects were prevented by CsA. In the in vivo study, Sprague-Dawley rats were administered 1% ethylene glycol (EG) to generate a rat kidney stone model and then treated with CsA (2.5, 5.0, and 10.0 mg/kg/day) for 14 days. EG administration induced renal calcium crystallization, which was prevented by CsA. Mitochondrial collapse was demonstrated by transmission electron microscopy, and oxidative stress was evaluated by measuring Cu-Zn SOD, MDA, and 8-OHdG generated by EG administration, all of which were prevented by CsA. Collectively, our results provide compelling evidence for a role of mPTP opening and its associated mitochondrial collapse, oxidative stress, and activation of the apoptotic pathway in the initial process of renal calcium crystallization.

Asunto(s)

Oxalato de Calcio/metabolismo , Calcio/química , Calcio/metabolismo , Riñón/metabolismo , Riñón/patología , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Animales , Western Blotting , Células Cultivadas , Cristalización , Ciclosporina/farmacología , Técnicas para Inmunoenzimas , Inmunosupresores/farmacología , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Poro de Transición de la Permeabilidad Mitocondrial , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley

RESUMEN

In 2002, speedy elimination of ureterolithiasis in the lower part of ureter was first reported with the alpha 1 blocker. Thereafter, there are a lot of reports including meta-analysis about tamsulosin. In 2011 EAU Guidelines on Urolithiasis, it is the most important to establish effective MET (medical expulsive therapy) to facilitate spontaneous stone passage. Alpha 1 blockers are the preferred agents for MET. As a basic evidence for MET, we reported that alpha 1a and 1d AR subtype mRNA was highly expressed in the human ureter and that alpha 1A AR is the main participant in the human ureteral contraction. It is published newly in Japanese Guidelines on Urolithiasis revised edition to schedule to be published soon.

Asunto(s)

Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Sulfonamidas/uso terapéutico , Cálculos Urinarios/tratamiento farmacológico , Medicina Basada en la Evidencia , Humanos , Indoles/farmacología , Indoles/uso terapéutico , Metaanálisis como Asunto , Piperazinas/farmacología , Piperazinas/uso terapéutico , Guías de Práctica Clínica como Asunto , ARN Mensajero , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/metabolismo , Tamsulosina , Uréter/metabolismo

RESUMEN

Recently, we reported that α1A adrenoceptor (AR) is the main participant in phenylephrine-induced human ureteral contraction. We therefore decided to carry out a prospective randomized study to evaluate the effects of silodosin, a selective α1A AR antagonist, as a medical expulsive therapy for ureteral stones. A total of 187 male patients, who were referred to our department for the management of symptomatic unilateral ureteral calculi of less than 10 mm, were randomly divided into two groups: group A (92 patients), who were instructed to drink 2 L of water daily, and group B (95 patients), who received the same instruction and were also given silodosin (8 mg/daily) for a maximum of 8 weeks. Expulsion rate, mean expulsion time and need for analgesics were examined. Overall, the mean expulsion time was 15.19 ± 7.14 days for group A and 10.27 ± 8.35 days for group B (P = 0.0058). In cases involving distal ureteral stones, the mean expulsion time was 13.40 ± 5.90 and 9.29 ± 5.91 days, respectively (P = 0.012). For stones of 1-5 mm in diameter, the mean expulsion time was 14.28 ± 6.35 and 9.56 ± 8.45 days, respectively (P = 0.017). For stones of 6-9 mm in diameter, the stone expulsion rate was 30.4% and 52.2% (P = 0.036), and the mean expulsion time was 21.00 ± 9.9 and 11.33 ± 8.31 days, respectively (P = 0.038). Herein, we report the first on silodosin in the management of ureteral lithiasis. Our findings suggest that silodosin might have potential as a medical expulsive therapy for ureteral stones.

Asunto(s)

Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Indoles/uso terapéutico , Cálculos Ureterales/tratamiento farmacológico , Adulto , Anciano , Analgésicos/uso terapéutico , Ingestión de Líquidos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento

RESUMEN

We studied the effects of cholesterol load on urinary stone in rats receiving a standard diet or a high fat diet. Sixty male rats were randomized to two groups and were fed either a standard diet (SD group) or a high fat diet (HFD group) for 8 weeks. Then the two groups were further divided into four groups. SD group, HFD group, SD + EG group (with standard diet + ethylene glycol administration for two weeks), and HFD + EG group (with high fat diet + ethylene glycol administration). The starting date of EG administration was considered to be week 0. Twenty-four-hour urine samples were collected in week 0, week 1, and week 2, and oxalate excretion and citrate excretion were measured by capillary electrophoresis analyzer The excretion of phosphorus, magnesium, and creatinine for 24 hours was measured using an automated analyzer Serum sodium, potassium, chloride, calcium, phosphate, magnesium, creatinine, total cholesterol, triglyceride, HDL-cholesterol and glucose were determined using an automated analyzer The kidney tissues were obtained to perform hematoxyline-eosine staining and Pizzolato's staining to detect oxalate-containing crystals. The average body weight in HFD groups and HFD + EG group in week 0 was significantly higher than that of SD group and SD + EG group. The calcium oxalate crystal deposition was not observed in all groups in week 0. HFD + EG group in week 1 had sporadically calcium oxalate crystal deposition in renal distal tubular cells and tubular lumens. In week 2, the number of crystal deposition in HFD + EG group was increased remarkably. The crystals were slightly observed in SD + EG group in week 2. The excretion of urinary calcium and phosphate in HFD group and HFD + EG group was significantly higher than that of the SD group and SD + EG group in week 0. The amount of urinary citrate excretion in the SD group and SD + EG group showed a significantly higher value compared with that of the HFD group and HFD + EG group in week 0. The level of serum total cholesterol in the HFD group and HFD + EG group was higher compared to that in the SD group and SD + EG group. The serum triglyceride level was not significantly different in the four groups in week 0. Interestingly, the level of triglyceride of EG administration groups (SD + EG and HFD + EG group) was significantly higher than that in EG no-administration groups (SD group and HFD group) in week 1 and week 2. The serum glucose level in the HFD group and HFD + EG group was significantly higher than that in the SD group and SD + EG group in week 0. In week 2, the glucose level of EG administration groups (HDF + EG group and SD + EG group) was significantly lower than that of EG no-administration groups (HFD group and SD group). In conclusion, this result suggested that long-term loading of cholesterol could increase renal calcium stone formation.

Asunto(s)

Colesterol/metabolismo , Cálculos Renales/etiología , Riñón/metabolismo , Animales , Cristalización , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo

RESUMEN

Osteopontin (OPN) has been described to play a nonredundant role in the formation of renal crystals. This biological activity of OPN may be attributed to its characteristic structure, which includes 2 calcium binding sites, Arg-Gly-Asp (RGD) sequences. To test this hypothesis, we evaluated wild-type mice (WT group), OPN-knockout mice (KO group), and two types of transgenic mice : (1) one type carrying a transgene in which the sequences coding for the 2 calcium-binding sites of the OPN were deleted (CaX group) and (2) the other type carrying a transgene in which the sequence that codes for the RGD sequence of the OPN was modified to one that codes for Arg-Gly-Glu (RGE ; RGE group). Changes occurring after intraperitoneal injection of glyoxylate for 9 d were analyzed. The amount of crystals deposited was the greatest in mice of the WT group and the least in those of the KO group. The number of crystal deposits in mice of the RGE and KO groups was approximately the same. Microscopic observations revealed that the crystal nuclei in mice in the CaX group were stratified and exhibited a disordered pattern ; this pattern was dissimilar to that observed in the mice in the WT and RGE groups, wherein the crystal nuclei exhibited a rosette petal-like radial pattern. The results indicate the possibility that each domain contributes to the mechanism by which OPN stimulates crystal formation.

Asunto(s)

Osteopontina/genética , Animales , Glioxilatos/análisis , Ratones , Ratones Noqueados , Osteopontina/fisiología , Transgenes , Urolitiasis/etiología

RESUMEN

Mice have a strong ability to eliminate renal calcium oxalate crystals, and our previous examination indicated a susceptibility in which monocyte-macrophage interaction could participate in the phenomenon. To clarify the macrophage-related factors playing roles in the prevention of crystal formation in mouse kidneys, morphologic and expression studies based on microarray pathway analysis were performed. Eight-week-old male C57BL/6N mice were administered 80 mg/kg of glyoxylate by daily intraabdominal injection for 15 days, and the kidneys were extracted every 3 days for DNA microarray analysis. Based on the raw data of microarray analysis, pathway analyses of inflammatory response demonstrated macrophage activation through the increased expression of chemokine (C-X-C) ligand 1, fibronectin 1, and major histocompatability (MHC) class II. Association analysis of related gene expression values by quantitative reverse transcription polymerase chain reaction (RT-PCR) indicated the high association of chemokine (C-C) ligand 2, CD44, colony-stimulating factor 1, fibronectin 1, matrix gla protein, secreted phosphoprotein 1, and transforming growth factor ß1 (TGF-ß1) with the amount of both renal crystals and F4/80, a macrophage marker. Immunohistochemically, interstitial macrophages increased during the experimental course, and CD44 and MHC class II were upregulated around crystal-formation sites. Ultrastructural observation of renal macrophages by transmission electron microscopy indicated interstitial macrophage migration with the phagocytosis of crystals. In conclusion, increased expression of inflammation-related genes of renal tubular cells induced by crystal formation and deposition could induce monocyte-macrophage migration and phagocytosis via the interaction of CD44 with osteopontin and fibronectin. Such crystal-removing ability of macrophages through phagocytosis and digestion might become a new target for the prevention of stone formation.

Asunto(s)

Oxalato de Calcio/metabolismo , Movimiento Celular , Inflamación/genética , Cálculos Renales/genética , Riñón/patología , Macrófagos/patología , Fagocitosis , Animales , Regulación de la Expresión Génica , Estudios de Asociación Genética , Glioxilatos , Inflamación/complicaciones , Riñón/metabolismo , Riñón/ultraestructura , Cálculos Renales/complicaciones , Cálculos Renales/patología , Macrófagos/metabolismo , Macrófagos/ultraestructura , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/metabolismo , Monocitos/patología , Análisis de Secuencia por Matrices de Oligonucleótidos

RESUMEN

Osteopontin (OPN) has been described as playing a nonredundant role in renal crystal formation. Here we investigated the effects of impaired domains of OPN, namely, the Arg-Gly-Asp (RGD) sequence and two calcium-binding sites on crystal formation. We used wild-type mice (WT group), OPN knockout mice (KO group), and OPN knockout mice carrying either a transgene in which the RGD sequence had been modified to Arg-Gly-Glu (RGE group) or whose two calcium-binding sites had been deleted (CaX group). Following intraperitoneal injection of glyoxylate for 9 days, the changes occurring in three parameters of crystal formation--localization, number, and microstructure--were analyzed. In the WT group, crystal deposits increased gradually at the renal corticomedullary junction in an orderly fashion, whereas those in the KO group were observed sporadically in the renal cortex. In both the CaX and RGE groups, deposits were localized near the corticomedullary junction. Crystal deposition was greatest in the WT group and least in the KO group. The number of deposits in the RGE group was nearly equal to that in the KO group. Microscopic observations revealed that the crystal nuclei in the CaX group were stratified and occurred in a disordered pattern; this pattern was dissimilar to that in the WT group, in which a rosette petal-like radial pattern was observed. In the RGE group, the nuclei exhibited a radial pattern similar to that in the WT group. The results indicated the possibility that each domain contributes to the mechanism by which OPN stimulates crystal formation.

Asunto(s)

Oxalato de Calcio/metabolismo , Cálculos Renales/etiología , Osteopontina/química , Osteopontina/metabolismo , Secuencia de Aminoácidos , Animales , Cruzamiento , Inmunohistoquímica , Riñón/metabolismo , Riñón/patología , Cálculos Renales/metabolismo , Cálculos Renales/patología , Cálculos Renales/orina , Ratones , Ratones Noqueados , Microscopía Electrónica de Rastreo , Datos de Secuencia Molecular , Osteopontina/deficiencia , Estructura Terciaria de Proteína , Transporte de Proteínas , Relación Estructura-Actividad

RESUMEN

OBJECTIVES: To clarify the role of renal tubular cell (RTC) injury and oxidative stress in the early stage of renal calcium oxalate crystal formation in a mouse model. METHODS: Daily intra-abdominal injections of glyoxylate (1.35 mmol/kg/day) into 8-week-old mice were carried out over 6 days. Kidneys were extracted before and at 6, 12 and 24 h and 3 and 6 days after glyoxylate injection. Crystal formation was detected using Pizzolato staining and polarized light optical microscopy. Immunohistochemical staining and western blotting of superoxide dismutase, and 4-hydroxynonenal and malondialdehyde were carried out in order to observe oxidative stress and lipid peroxidation, respectively. RTC microstructural damage and crystal nuclei formation were observed using transmission electron microscopy. To ameliorate RTC injury, mice were treated with green tea 1 week before and 1 week after glyoxylate administration. The number of crystals and RTC damage were observed and comparisons were made between glyoxylate-treated mice with and without green tea administration. RESULTS: Oxidative stress and lipid peroxidation were observed after 6 h. Crystal nuclei containing collapsed mitochondria and fallen microvilli appeared in the renal distal tubular lumen after 24 h. Crystals occupying the tubular lumen were detected on day 3. The number of crystals in mice receiving green tea was significantly lower than in those receiving glyoxylate alone. CONCLUSIONS: RTC injury, especially mitochondrial damage, and oxidative stress induce the early stage of calcium oxalate crystal formation in mice.

Asunto(s)

Oxalato de Calcio , Células Epiteliales/patología , Túbulos Renales/metabolismo , Túbulos Renales/patología , Estrés Oxidativo , Animales , Cristalización , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión

RESUMEN

OBJECTIVE: Osteoporosis is associated with the pathogenesis and risk of urolithiasis, which is higher among postmenopausal women (as opposed to premenopausal). Bisphosphonates potently inhibit bone resorption, and are used in the management of bone disease. We investigated the ability of a bisphosphonate to prevent calcium stone formation. METHODS: We studied 12 postmenopausal women (63.8 +/- 7.3 years) who were not receiving osteoporosis therapy, and had stones comprised of calcium phosphate (CaP; n = 3), calcium oxalate (CaOx; n = 3) and CaP + CaOx (n = 6). We measured bone mineral density (BMD), serum and urinary values in 24-hour urine specimens before and 3 months after the oral administration of 5 mg/day of alendronate (ALN). The indexes of the ionic activity product of calcium oxalate, AP(CaOx), and of calcium phosphate, AP(CaP), were estimated using the Tiselius method. RESULTS: ALN significantly reduced the AP(CaP) index (1.53 +/- 1.37 to 0.89 +/- 0.81, p <0.05). Urinary calcium, oxalate, phosphate and the AP(CaOx) index did not significantly change. BMD improved in 11 of the 12 patients. Urinary stones did not develop in any of the patients during the course of the study. CONCLUSION: The results suggested that ALN not only improves BMD and osteoporosis, but also reduces the risk of calcium phosphate stone formation in postmenopausal women.

Asunto(s)

Alendronato/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Fosfatos de Calcio , Osteoporosis/complicaciones , Posmenopausia , Cálculos Urinarios/etiología , Cálculos Urinarios/prevención & control , Fosfatos de Calcio/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis/metabolismo , Factores de Riesgo , Cálculos Urinarios/metabolismo

RESUMEN

PURPOSE: This study was performed to characterize the α1-adrenoceptor subtypes in mouse ureters as regards gene expressions and contractile functions. METHODS: The mRNAs for these subtypes were quantified by the real-time quantitative reverse transcription polymerase chain reaction. In a functional study, α1-adrenoceptor antagonists were evaluated against the noradrenaline-induced contraction in mouse isolated ureteral preparations. RESULTS: In mouse ureter, the relative mRNA expression levels for α1a-, α1b- and α1d-adrenoceptors were 74.5, 14.3 and 11.2%, respectively. Adrenaline and noradrenaline each produced a concentration-dependent phasic contraction (pD 2 values, 5.73±0.05 and 5.69±0.06, respectively). Prazosin (non-selective α1-adrenoceptor antagonist), silodosin (selective α1A-adrenoceptor antagonist), and BMY-7378 (selective α1D-adrenoceptor antagonist) all shifted the concentration­response curve for noradrenaline to the right, the rank order of potencies (apparent pA 2 values) being silodosin (9.32±0.11)>prazosin (8.55±0.10)>BMY-7378 (6.06±0.15). The α1A-adrenoceptor antagonist silodosin was thus much more effective than the α1D-adrenoceptor antagonist BYM-7378. CONCLUSIONS: Our results demonstrate that in mouse ureters: the mRNA for the α1A-adrenoceptor was more prevalent than those for the α1B- and α1D-adrenoceptors, and that among these subtypes, the α1A-adrenoceptor plays the major role in noradrenaline-induced contraction.

Asunto(s)

Contracción Muscular/fisiología , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/fisiología , Uréter/fisiología , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Animales , Epinefrina/farmacología , Expresión Génica/fisiología , Indoles/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Contracción Muscular/efectos de los fármacos , Norepinefrina/farmacología , Piperazinas/farmacología , Prazosina/farmacología , ARN Mensajero/metabolismo , Uréter/efectos de los fármacos

RESUMEN

We determined the applicability of the running single-knotted suture with Lapra-Ty clips to locking the vesicourethra at the 6 o'clock position for teaching anastomosis during laparoscopic radical prostatectomy to trainee surgeons. Fifty consecutive patients underwent laparoscopic radical prostatectomy for prostate cancer conducted by five surgeons with no experience of this procedure. Twenty (group 1) and 30 (group 2) of the patients underwent vesicourethral anastomosis using the single-knot running technique without or with Lapra-Ty clips. Surgical data, duration of surgical anastomosis, extravasation rate, time until healing and catheter removal, and occurrence of anastomotic structures were evaluated. The duration of surgical anastomosis was significantly greater without than with the Lapra-Ty clips (56 +/- 13 min versus 45 +/- 10 min, P < 0.01). The extravasation rate on postoperative cystography was significantly higher without than with the Lapra-Ty clips (30.0% versus 10.0%, P < 0.05). Leakage occurred on the 6 o'clock side of the anastomosis in all of these patients and urinary retention occurred in one patient (5.0%) in group 1. The single-knot method with Lapra-Ty clips in vesicourethral anastomosis during laparoscopic radical prostatectomy is useful, safe, and efficient, especially for surgeons learning the technique.

Asunto(s)

Laparoscopía , Prostatectomía/educación , Técnicas de Sutura/instrumentación , Suturas , Uretra/cirugía , Vejiga Urinaria/cirugía , Adulto , Anciano , Anastomosis Quirúrgica/educación , Anastomosis Quirúrgica/instrumentación , Estudios de Factibilidad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/cirugía , Técnicas de Sutura/educación , Resultado del Tratamiento

RESUMEN

We previously established a mouse kidney stone formation model and showed that mice have a higher tolerance to stone formation than rats. Furthermore, we showed that the generated calcium oxalate crystal deposits could be eliminated after several days. This study investigated the transcriptome of stone formation and elimination in the mouse kidney based on gene selection using a microarray technique. Eight-week-old male C57BL/6N mice were administered 80 mg/kg glyoxylate for 15 days, and kidney calcium oxalate crystal depositions had increased by day 6; thereafter, depositions decreased gradually and had almost disappeared by day 15. On microarray analysis, mRNA expression in the crystal-formed kidneys showed the significant expression of 18,064 genes. Thirty-one, 21, and 25 genes showed at least a 2-fold increased expression during the experimental course (days 3-15), stone formation phase-specific (days 3-6), and stone elimination phase-specific (days 9-15) stages, respectively. Among these genes, those related to chemotaxis and monocyte/macrophage activation were identified. Gene ontology analysis to identify overexpressed genes highlighted categories related to inflammation, immune reactions and the complement activation pathway. Quantitative PCR of 17 previously reported stone-related genes with a significant expression on microarray analysis showed significantly increased chemokines, stone matrix proteins, and their receptors; the significant decrease of several types of transporters and superoxide dismutase; and the persistently high expression of Tamm-Horsfall protein throughout the experiment. In conclusion, inflammation and immune reactivity through macrophage migration are involved in stone formation and elimination in mouse kidneys.

Asunto(s)

Oxalato de Calcio/metabolismo , Estudio de Asociación del Genoma Completo , Cálculos Renales/genética , Macrófagos/metabolismo , Animales , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Análisis de Secuencia por Matrices de Oligonucleótidos