RESUMEN
Acute loss of kidney function is a critical internal stressor. Arginine vasopressin (AVP) present in the parvocellular division of the paraventricular nucleus (PVN) plays a key role in the regulation of stress responses. However, hypothalamic AVP dynamics during acute kidney dysfunction remain unclear. In this study, we investigated the effects of bilateral nephrectomy on AVP, using a transgenic rat line that expressed the AVP-enhanced green fluorescent protein (eGFP). The eGFP fluorescent intensities in the PVN were dramatically increased after bilateral nephrectomy. The mRNA levels of eGFP, AVP, and corticotrophin-releasing hormone in the PVN were dramatically increased after bilateral nephrectomy. Bilateral nephrectomy also increased the levels of Fos-like immunoreactive cells in brainstem neurons. These results indicate that bilateral nephrectomy upregulates the AVP-eGFP synthesis. Further studies are needed to identify the neural and/or humoral factors that activate AVP synthesis and regulate neuronal circuits during acute kidney dysfunction.
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Lesión Renal Aguda/metabolismo , Arginina Vasopresina/metabolismo , Hipotálamo/metabolismo , Riñón/metabolismo , Animales , Hormona Liberadora de Corticotropina/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas TransgénicasRESUMEN
BACKGROUND: Obesity is a risk factor for the development of chronic kidney disease (CKD). However, it remains to be fully examined whether fatness is more useful in predicting incident CKD. We aimed this study to determine the association of body fat, body mass index and waist circumference (WC) with subsequent changes in estimated glomerular filtration rate (eGFR) and incident CKD in young- to middle-aged working men. METHODS: We analyzed data from annual health check-up in male workers aged from 20 to 60 years with basal eGFR of 60-90 mL/min/1.73 m2. Cut-off values of parameters and odds ratio (OR) for the incident CKD were calculated by receiver operator characteristics analysis andχ2 test, respectively. We also tested trends of changes in eGFR according to changes in WC in each age decade. RESULTS: There were 8,015 men participants. During the 5-year follow-up, 11.0% of the participants (N = 878) had developed to incident CKD. When basal WC was greater than 80.0 cm, which was decided by Youden's Index, there was a significantly higher risk of incident CKD [OR 1.57 (95% confident interval 1.35-1.84)]. Changes in WC over 5 years were significantly related to eGFR decline in young men (< 40 years old) with normal blood pressures and normoglycemia. CONCLUSIONS: These findings suggest that WC > 80.0 cm is a risk factor for incident CKD and strongly associated with a decline in eGFR in the young- to middle-aged working healthy men.
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Adiposidad , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Adulto , Envejecimiento , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Valores de Referencia , Estudios Retrospectivos , Factores de Riesgo , Circunferencia de la Cintura , Adulto JovenRESUMEN
Furosemide, which is used worldwide as a diuretic agent, inhibits sodium reabsorption in the Henle's loop, resulting in diuresis and natriuresis. Arginine vasopressin (AVP) is synthesized in the supraoptic nucleus (SON), paraventricular nucleus (PVN), and suprachiasmatic nucleus (SCN) of the hypothalamus. The synthesis AVP in the magnocellular neurons of SON and PVN physiologically regulated by plasma osmolality and blood volume and contributed water homeostasis by increasing water reabsorption in the collecting duct. Central AVP dynamics after peripheral administration of furosemide remain unclear. Here, we studied the effects of intraperitoneal (i.p.) administration of furosemide (20 mg/kg) on hypothalamic AVP by using transgenic rats expressing AVP-enhanced green fluorescent protein (eGFP) under the AVP promoter. The i.p. administration of furosemide did not affect plasma osmolality in the present study; however, eGFP in the SON and magnocellular divisions of the PVN (mPVN) were significantly increased after furosemide administration compared to the control. Immunohistochemical analysis revealed Fos-like immunoreactivity (IR) in eGFP-positive neurons in the SON and mPVN 90 min after i.p. administration of furosemide, and AVP heteronuclear (hn) RNA and eGFP mRNA levels were significantly increased. These furosemide-induced changes were not observed in the suprachiasmatic AVP neurons. Furthermore, furosemide induced a remarkable increase in Fos-IR in the organum vasculosum laminae terminals (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), locus coeruleus (LC), nucleus of the solitary tract (NTS), and rostral ventrolateral medulla (RVLM) after i.p. administration of furosemide. In conclusion, we were able to visualize and quantitatively evaluate AVP-eGFP synthesis and neuronal activations after peripheral administration of furosemide, using the AVP-eGFP transgenic rats. The results of this study may provide new insights into the elucidation of physiological mechanisms underlying body fluid homeostasis induced by furosemide. This article is protected by copyright. All rights reserved.
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BACKGROUND: It remains to be fully clarified whether there is a relationship between uncontrolled dyslipidemia and decline in estimated glomerular filtration rate (eGFR) in the general population. Therefore, this study's aim was to test the association of dyslipidemia with changes in eGFR in apparently healthy working men. METHODS: We retrospectively examined the annual medical check-up list of 14,510 male workers aged 20-60 years with eGFR ≥ 60 mL/min/1.73 m2 at baseline, and then evaluated the association of the changes in the check-up parameters with a decline in eGFR during the 5-year observation period. RESULTS: Mean age and eGFR were 38.5 years and 82.3 mL/min/1.73 m2 at baseline, respectively. Evaluated low-density lipoprotein cholesterol (LDL-C) (≥140 mg/dL) was a strong indicator of CKD development in participants (basal eGFR 60-90 mL/min/1.73 m2) without hypertension [odds ratio (95% confidence interval): 1.46 (1.12-1.90)] or diabetes mellitus (DM) [1.49 (1.23-1.82)]. When LDL-C normalized under 140 mg/dL during follow-up, the decline in eGFR was smaller in non-hypertensive participants [-5.9 (-14.4 to -0.9) vs -13.4 (-18.4 to -4.5) mL/min/1.73 m2, p < 0.05]. There was an inverse correlation between change of LDL-C and decline in eGFR (p for trend <0.001). CONCLUSION: Increased LDL-C levels are associated with the development of incident CKD and eGFR decline in young to middle-aged working men without hypertension and/or DM.
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LDL-Colesterol/sangre , Tasa de Filtración Glomerular , Adulto , Dislipidemias/sangre , Dislipidemias/complicaciones , Humanos , Japón , Masculino , Persona de Mediana Edad , Salud Laboral , Valores de Referencia , Insuficiencia Renal Crónica/sangre , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
We investigated the effects of bicarbonate/lactate-buffered peritoneal dialysis fluid (B/L-PDF) and lactate-buffered PDF (L-PDF) on cell viability and apoptosis, focusing on monocarboxylate transporters (MCTs). MCT-1 transports lactate into cells. Cell viability and apoptosis of human peritoneal mesothelial cells (HPMCs) were examined by water-soluble tetrazolium salt-1 and TUNEL assays, respectively. The relative number of viable HPMCs was significantly decreased by L-PDF at 48 h (8.8 ± 0.4%) compared with cells cultured in M199, but not by B/L-PDF (66.7 ± 1.1%). Apoptosis was markedly induced by L-PDF at 48 h (69.3 ± 16.2%), but not by B/L-PDF (2.6 ± 0.3%). Knockdown of MCT-1 by small interfering RNA (siRNA) attenuated the L-PDF-induced reduction of viable cells and increased apoptosis compared with control siRNA, but MCT-4 knockdown had no effect. B/L-PDF had lesser effects on cell viability and apoptosis of HPMCs compared with L-PDF. These results suggest that B/L-PDF biocompatibility occurs by avoiding the induction of apoptosis in HPMCs.
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Bicarbonatos/metabolismo , Soluciones para Diálisis/metabolismo , Ácido Láctico/metabolismo , Transportadores de Ácidos Monocarboxílicos/fisiología , Diálisis Peritoneal , Simportadores/fisiología , Apoptosis , Supervivencia Celular , Células Cultivadas , Humanos , Concentración de Iones de Hidrógeno , Transportadores de Ácidos Monocarboxílicos/genética , Simportadores/genéticaRESUMEN
This correct the article DOI: 10.14670/HH-11-756.
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BACKGROUND: Continuous exposure to peritoneal dialysis fluids (PDFs) is associated with pathological responses such as persistent micro-inflammation, which leads to ultrafiltration failure. Pentraxin-3 (PTX3), a multifunctional soluble pattern recognition receptor, is produced at sites of inflammation by a wide range of cell types. This study investigates the in vivo expression of PTX3 in the peritoneal membrane of a rat continuous peritoneal dialysis (PD) model, as well as the effect of high glucose on the in vitro expression of PTX3. METHODS: The expression of PTX3 was analyzed using RT-PCR, real-time PCR, immunohistochemistry and western blotting in a PD rat model receiving saline or conventional PDF containing 3.86% glucose for 8 weeks. The effects of high glucose on the expression of PTX3 were examined in cultured rat peritoneal mesothelial cells (RPMCs), mouse macrophage-like cells, and mouse fibroblasts. RESULTS: In a rat model of PD, eight-week instillation of the conventional PDF produced increased submesothelial thickening, followed by substantially enhanced PTX3 protein levels in the submesothelial layer of peritoneal membrane. PTX3 was detected in peritoneal mesothelial cells, macrophages and fibroblasts in the thickened submesothelial area. Glucose was found to induce PTX3 protein expression in RPMCs as well as macrophage-like cells and fibroblasts. CONCLUSION: Continuous exposure to conventional PDF induces PTX3 expression in the peritoneal membrane of rats. High glucose may be involved in the mechanism of PDF-induced local micro-inflammation in the peritoneum.
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Proteína C-Reactiva/biosíntesis , Soluciones para Diálisis/química , Glucosa/administración & dosificación , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/métodos , Componente Amiloide P Sérico/biosíntesis , Animales , Western Blotting , Modelos Animales de Enfermedad , Inmunohistoquímica , Inflamación/etiología , Peritoneo/metabolismo , Reacción en Cadena de la Polimerasa , Ratas , Ratas WistarRESUMEN
Fibrosis occurs in systemic tissues other than the brain and finally induces dysfunction of the fibrotic organ. Kidney fibrosis is related to scarring after acute kidney injury and the progression of chronic kidney disease. Kidney function decreases with the progression of kidney fibrosis. As fibrotic tissue cannot return to its original status, advanced kidney fibrosis requires the administration of dialysis or kidney transplantation. Thus, elucidation the mechanism of kidney fibrosis is an important research theme. The proliferation and activation of (myo) fibroblasts and the excessive production of an extracellular matrix are common mechanisms in fibrosis in many organs, but it seems that kidney fibrosis has specific pathways. Tubular epithelial, mesangial cells, and erythropoietin producing cells, which exist only in the kidney, participate in forming kidney fibrosis. This review highlights an understanding of the cells and their underlying mechanisms, which are specific to kidney fibrosis process: transforming growth factor-ß (TGF-ß), epithelial-mesenchymal transition, wingless/int-1 (WNT) signaling, renal anemia, and uremia. Finally, we describe potential therapies that focus on the mechanisms of kidney fibrosis: anti-TGF-ß antibody and mammalian target of rapamycin (mTOR).
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Enfermedades Renales/genética , Enfermedades Renales/terapia , Riñón/patología , Terapia Molecular Dirigida , Factor de Crecimiento Transformador beta , Vía de Señalización Wnt , Animales , Anticuerpos Monoclonales/uso terapéutico , Transición Epitelial-Mesenquimal/genética , Fibrosis , Humanos , Inflamación/complicaciones , Enfermedades Renales/etiología , Enfermedades Renales/patología , Proteínas Serina-Treonina Quinasas/uso terapéutico , Serina-Treonina Quinasas TOR/uso terapéutico , Factor de Crecimiento Transformador beta/inmunología , Factor de Crecimiento Transformador beta/fisiología , Uremia/complicaciones , Vía de Señalización Wnt/genética , Vía de Señalización Wnt/fisiologíaRESUMEN
BACKGROUND: In addition to corticosteroids and inhibition of the renin-angiotensin-aldosterone system, tonsillectomy with steroid pulse therapy (TSP) may have a beneficial impact on the clinical course of IgA nephropathy (IgAN). However, there is still much uncertainty regarding the indications for therapy, treatment protocol, and therapeutic options for IgAN. METHODS: In this multicenter retrospective cohort study, we enrolled 284 patients with biopsy-proven IgAN who received TSP or corticosteroid therapy or conservative therapy. The effects of TSP on clinical remission (CR) were evaluated after a median follow-up period of 4.1 years in relation to histological classifications. RESULTS: Among the 284 participants, 161 patients received TSP. During the observation time, 141 patients (49.6%) achieved CR, with a median time to remission of 397 days. In multivariate Cox regression analyses, TSP had an impact on achieving CR in only the group with histological grade 3 defined as glomerulosclerosis, crescent formation or adhesion to Bowman's capsule in 10-30% of all biopsied glomeruli, or mild cellular infiltration in the interstitium (hazard ratio (HR) 4.29, 95% confidence interval (95%CI) 1.88-11.19, P < 0.001). TSP independently contributed to a higher incidence of CR, particularly in the patient group showing evident mesangial hypercellularity (HR 2.54, 95%CI 1.38-5.08, P = 0.002). CONCLUSIONS: TSP may have a beneficial effect on the clinical course in IgAN patients with mild to moderate glomerular and interstitial lesions, particularly with distinct mesangial cell proliferation.
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Glomerulonefritis por IGA/terapia , Glomérulos Renales/efectos de los fármacos , Esteroides/administración & dosificación , Tonsilectomía , Adulto , Biopsia , Distribución de Chi-Cuadrado , Terapia Combinada , Femenino , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/inmunología , Humanos , Japón , Estimación de Kaplan-Meier , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Quimioterapia por Pulso , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Medical intervention for patients with IgA nephropathy and mild proteinuria (<1.0 g/day) is controversial, and the effectiveness of tonsillectomy plus steroid pulse therapy (TSP) for such patients remains obscure. METHODS: Among 323 patients in our multicenter cohort study, 79 who had mild proteinuria (0.4-1.0 g/day) at diagnosis were eligible to participate in this study. We compared the clinicopathological findings at diagnosis, a decline in renal function defined as a 50 or 100% increase in serum creatinine (sCr) and clinical remission (CR) defined as the disappearance of hematuria and proteinuria (<0.3 g/day) among groups given TSP (n = 46), steroid therapy (ST) (n = 9), and non-ST (n = 24). Factors contributing to CR were also evaluated using multivariate analysis. RESULTS: Background factors at diagnosis including age, ratio (%) of patients with hypertension, sCr, proteinuria, and histological severity did not significantly differ among the groups. Only two patients each in the TSP (4.3%) and non-ST (8.3%) groups achieved a 50% increase in sCr during a mean follow-up period of 4.7 years. At the final observation, 71.7, 44.4, and 41.7% of patients in the TSP, ST, and non-ST groups, respectively, achieved CR (p = 0.032). Cox proportional hazards models revealed that TSP led to CR more effectively than non-TSP by a factor of about threefold (hazard ratio, 2.74; p = 0.008). CONCLUSION: TSP therapy has potential for inducing CR in patients with IgAN and mild proteinuria (<1.0 g/day).
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Glomerulonefritis por IGA/terapia , Proteinuria/terapia , Esteroides/administración & dosificación , Tonsilectomía , Adolescente , Adulto , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Terapia Combinada , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/fisiopatología , Hematuria/prevención & control , Humanos , Japón , Estimación de Kaplan-Meier , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Proteinuria/diagnóstico , Proteinuria/inmunología , Proteinuria/fisiopatología , Quimioterapia por Pulso , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: Patient socialization and preservation of socioeconomic status are important patient-centred outcomes for those who start dialysis, and retention of employment is a key enabler. This study examined the influence of dialysis inception and modality upon these outcomes in a contemporary Japanese cohort. METHODS: We conducted a survey of prevalent chronic dialysis patients from 5 dialysis centres in Japan. All patients who had been on peritoneal dialysis (PD) since dialysis inception were recruited, and matched with a sample of those on in-centre haemodialysis (ICHD). We assessed patients' current social functioning (Short Form 36 Health Survey), and evaluated changes to patient employment status, annual income, and general health condition from the pre-dialysis period to the current time. RESULTS: A total of 179 patients were studied (102 PD and 77 ICHD). There were no differences in social functioning by modality. Among them, 113 were employed in the pre-dialysis period with no difference by modality. Of these, 22% became unemployed after dialysis inception, with a corresponding decline in average working hours and annual income. The odds of unemployment after dialysis inception were 5.02 fold higher in those on ICHD compared to those on PD, after adjustment for covariates. There were no changes for those who were already unemployed in the pre-dialysis period. CONCLUSIONS: Employment status is significantly hampered by dialysis inception, although PD was associated with superior retention of employment and greater income compared to ICHD. This supports a positive role for PD in preservation of socioeconomic status and potentially other patient-centred outcomes.
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Diálisis Peritoneal , Evaluación de Procesos, Atención de Salud , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Conducta Social , Socialización , Factores Socioeconómicos , Anciano , Femenino , Encuestas de Atención de la Salud , Estado de Salud , Humanos , Renta , Japón , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/economía , Diálisis Peritoneal/psicología , Evaluación de Procesos, Atención de Salud/economía , Diálisis Renal/efectos adversos , Diálisis Renal/economía , Diálisis Renal/psicología , Insuficiencia Renal Crónica/economía , Insuficiencia Renal Crónica/psicología , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento , DesempleoRESUMEN
Previous studies have suggested that the deterioration of renal function increases the risk of major adverse clinical events not only in culprit lesions but also in non-culprit lesions (NCLs) after percutaneous coronary intervention (PCI). This study evaluated serial coronary plaque change of NCL in patients with different stages of chronic kidney disease (CKD) using intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS). In 113 patients (113 NCLs) underwent both IVUS-guided PCI and follow-up IVUS, volumetric IVUS analyses were performed at proximal reference NCLs in de novo target vessels post PCI and at 8-month follow-up. NCLs were divided into 4 groups based on baseline CKD stage: CKD-1, n = 18; CKD-2, n = 42; CKD-3, n = 29; and CKD4-5, n = 24. We compared serial changes of plaque burden and composition among groups under statin treatment. Plaque progression occurred in CKD-3 (+4.6 mm(3), p < 0.001) and CKD4-5 (+9.8 mm(3), p < 0.001) despite anti-atherosclerotic treatment, whereas plaque regression occurred in CKD-1 (-5.4 mm(3), p = 0.002) and CKD-2 (-3.2 mm(3), p = 0.001) mainly due to initiate statin treatment after PCI. Plaque volume change was correlated with eGFR (p < 0.0001). Multivariate analysis showed CKD stage 3-5 was an independent predictor of plaque progression. Regarding IB-IVUS analyses, lipid plaque increased in CKD-3 (+4.6 mm(3), p < 0.001) and CKD4-5 (+5.4 mm(3), p < 0.001), but decreased in CKD-2 (-2.7 mm(3), p < 0.05). Fibrotic plaque also increased in CKD4-5 (+3.4 mm(3), p < 0.001). Moderate to advanced CKD was associated with coronary plaque progression characterized by greater lipid and fibrotic plaque volumes in NCL under statin treatment after culprit PCI.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/diagnóstico por imagen , Intervención Coronaria Percutánea , Placa Aterosclerótica , Insuficiencia Renal Crónica/complicaciones , Ultrasonografía Intervencional , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Enfermedad de la Arteria Coronaria/metabolismo , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/metabolismo , Femenino , Fibrosis , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Interpretación de Imagen Asistida por Computador , Modelos Lineales , Lípidos/análisis , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Insuficiencia Renal Crónica/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Dispersión de Radiación , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Uromodulin-associated kidney disease (UAKD) is an autosomal dominant disease caused by a mutation in the uromodulin (UMOD) gene, leading to end-stage renal disease. We herein report the case of a family with UAKD caused by a novel mutation (C135G) in the UMOD gene. A 31-year-old woman had a low estimated glomerular filtration rate (59.7 mL/min per 1.73 m(2)). Her father, grandfather and paternal aunt had received maintenance hemodialysis therapy since their 40's. This case underscores the importance of performing genetic testing in young patients even in cases involving only moderate abnormalities in the kidney function.
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Enfermedades Renales/diagnóstico , Enfermedades Renales/metabolismo , Mutación , Uromodulina/metabolismo , Adulto , Pueblo Asiatico , Análisis Mutacional de ADN , Femenino , Humanos , Enfermedades Renales/genética , Linaje , Uromodulina/genéticaRESUMEN
Nitric oxide (NO) is synthesized by three distinct NO synthases (neuronal, inducible, and endothelial NOSs), all of which are expressed in almost all tissues and organs in humans. The regulatory roles of NOSs in vivo have been investigated in pharmacological studies with non-selective NOS inhibitors. However, the specificity of the inhibitors continues to be an issue of debate, and the authentic significance of NOSs is still poorly understood. To address this issue, we generated mice in which all three NOS genes are completely disrupted. The triple NOSs null mice exhibited cardiovascular abnormalities, including hypertension, arteriosclerosis, myocardial infarction, cardiac hypertrophy, diastolic heart failure, and reduced EDHF responses, with a shorter survival. The triple NOSs null mice also displayed metabolic abnormalities, including metabolic syndrome and high-fat diet-induced severe dyslipidemia. Furthermore, the triple NOSs null mice showed renal abnormalities (nephrogenic diabetes insipidus and pathological renal remodeling), lung abnormalities (accelerated pulmonary fibrosis), and bone abnormalities (increased bone mineral density and bone turnover). These results provide evidence that NOSs play pivotal roles in the pathogenesis of a wide variety of disorders. This review summarizes the latest knowledge on the significance of NOSs in vivo, based on lessons learned from experiments with our triple mutant model.
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Huesos/enzimología , Enfermedades Cardiovasculares/enzimología , Enfermedades Metabólicas/enzimología , Óxido Nítrico Sintasa/metabolismo , Fibrosis Pulmonar/enzimología , Insuficiencia Renal Crónica/enzimología , Animales , Modelos Animales de Enfermedad , Humanos , Enfermedades Metabólicas/genética , Ratones , Ratones Noqueados , Óxido Nítrico Sintasa/genética , Fibrosis Pulmonar/genética , Insuficiencia Renal Crónica/genéticaRESUMEN
OBJECTIVE: The aim of this study was to clarify the clinical characteristics and predictors of silent LN (SLN), a type of LN in SLE without abnormal urinalysis or renal impairment. METHODS: Of 182 patients who underwent renal biopsy, 48 did not present with abnormal urinalysis or renal impairment at the time of biopsy. The patients with LN (SLN group, n = 36) and those without LN (non-LN group, n = 12) were compared with respect to their baseline characteristics. Bivariate analysis comprised Fisher's exact test and the Mann-Whitney test, whereas multivariate analysis employed binomial logistic regression analysis. RESULTS: LN was histopathologically identified in 36 of 48 patients. According to the International Society of Nephrology/Renal Pathology Society classification, 72% of the SLN patients were classified as having class I/II, with a further 17% having class III/IV. Bivariate analyses indicated that platelet count, serum albumin, complement components (C3 and C4), complement haemolytic activity (CH50), anti-Sm antibody titre and anti-ribonucleoprotein antibody titre were significantly different between groups. Multivariate analysis indicated that CH50 and C3 titres were significantly lower in the SLN group, whereas anti-Sm antibody titre was significantly higher. The cut-off titre, calculated based on the receiver operating characteristic curve for CH50, was 33 U/ml, with a sensitivity and specificity of 89% and 83%, respectively. The cut-off titre for anti-Sm antibodies was 9 U/ml, with a sensitivity and specificity of 74% and 83%, respectively. CONCLUSION: Low titres of CH50 and C3 and a high titre of anti-Sm antibody were identified as predictors of SLN.
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Anticuerpos Antiidiotipos/sangre , Proteínas del Sistema Complemento/metabolismo , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/orina , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/etiología , Proteínas Nucleares snRNP/inmunología , Adulto , Biomarcadores/sangre , Biopsia , Complemento C3/metabolismo , Complemento C4/metabolismo , Ensayo de Actividad Hemolítica de Complemento , Femenino , Humanos , Riñón/patología , Riñón/fisiopatología , Lupus Eritematoso Sistémico/fisiopatología , Nefritis Lúpica/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de Regresión , Sensibilidad y Especificidad , UrinálisisRESUMEN
BACKGROUND: Active fixation pacing leads with silicon cylinder tips have been used for their safety and flexibility. Measurement of baseline sensing/pacing characteristics before fixation of helix helps to identify the optimal pacing site, but we encountered difficulties in making these measurements despite multiple attempts with the model LPA 1200M lead. To identify the cause and overcome this complication, we compared 4 different retractable active fixation lead models, which enabled baseline sensing/pacing measurements before extension of helix. METHODSâANDâRESULTS: We immersed 4 different lead tips and rings in a 0.18% saline solution, and measured the lead impedance before and after flushing of air bubble visible inside the lead tip. Before evacuation of the air bubble, the impedance of the model LPA 1200M lead was >4,000 Ω in 8 out of 10 measurements, although that of the other leads was within the measurable range. After evacuation of the air bubble, the lead impedance returned to within the measurable range. There was no prominent change in the impedance of the metal cylinder tip lead. CONCLUSIONS: Air bubbles may interfere with the measurement of baseline sensing/pacing characteristics before active fixation of pacing leads with cylindrical silicon tips. In the case of high impedance beyond the measurable range before extension of helix, the measurement should be repeated after fixation into the myocardium before suspecting lead dysfunction.
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Artefactos , Estimulación Cardíaca Artificial/métodos , Electrodos Implantados , Marcapaso Artificial , Síndrome del Seno Enfermo/terapia , Aire , Diseño de Equipo , Humanos , Masculino , Persona de Mediana Edad , Síndrome del Seno Enfermo/fisiopatologíaRESUMEN
We investigated the effect of subtotal nephrectomy on the incidence of acute myocardial infarction (AMI) in mice deficient in all three nitric oxide synthases (NOSs). Two-thirds nephrectomy (NX) was performed on male triple NOSs(-/-) mice. The 2/3NX caused sudden cardiac death due to AMI in the triple NOSs(-/-) mice as early as 4months after the surgery. The 2/3NX triple NOSs(-/-) mice exhibited electrocardiographic ST-segment elevation, reduced heart rate variability, echocardiographic regional wall motion abnormality, and accelerated coronary arteriosclerotic lesion formation. Cardiovascular risk factors (hypertension, hypercholesterolemia, and hyperglycemia), an increased number of circulating bone marrow-derived vascular smooth muscle cell (VSMC) progenitor cells (a pro-arteriosclerotic factor), and cardiac up-regulation of stromal cell-derived factor (SDF)-1α (a chemotactic factor of the progenitor cells) were noted in the 2/3NX triple NOSs(-/-) mice and were associated with significant increases in plasma angiotensin II levels (a marker of renin-angiotensin system activation) and urinary 8-isoprostane levels (a marker of oxidative stress). Importantly, combined treatment with a clinical dosage of an angiotensin II type 1 receptor blocker, irbesartan, and a calcium channel antagonist, amlodipine, markedly prevented coronary arteriosclerotic lesion formation and the incidence of AMI and improved the prognosis of those mice, along with ameliorating all those pro-arteriosclerotic parameters. The 2/3NX triple NOSs(-/-) mouse is a new experimentally useful model of AMI. Renin-angiotensin system activation, oxidative stress, cardiovascular risk factors, and SDF-1α-induced recruitment of bone marrow-derived VSMC progenitor cells appear to be involved in the pathogenesis of AMI in this model.
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Infarto del Miocardio/enzimología , Óxido Nítrico Sintasa/genética , Animales , Modelos Animales de Enfermedad , Masculino , Ratones Noqueados , Infarto del Miocardio/genética , Nefrectomía , Óxido Nítrico Sintasa/metabolismo , Estrés OxidativoRESUMEN
WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN). We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR) and WNT10A expression using kidney biopsies from 20 patients with AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR than WNT10A-negative patients. However, changes in kidney function were not related to the level of expression of other WNT family members. Furthermore, there was positive correlation between WNT10A and α-SMA expression. We next investigated the involvement of WNT10A in kidney fibrosis processes using COS1 cells, a kidney fibroblast cell line. WNT10A overexpression increased the level of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A overexpression renders cells resistant to apoptosis induced by hydrogen peroxide and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate with kidney dysfunction in AIN.
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Fibroblastos/patología , Riñón/patología , Nefritis Intersticial/genética , Nefritis Intersticial/patología , Proteínas Wnt/genética , Actinas/análisis , Actinas/genética , Enfermedad Aguda , Anciano , Apoptosis , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Fibrosis , Regulación de la Expresión Génica , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Masculino , Nefritis Intersticial/fisiopatología , Estrés Oxidativo , Proteínas Wnt/análisis , Proteínas Wnt/metabolismoRESUMEN
BACKGROUND: Unnecessary ventricular pacing in sinus node disease (SND) must be avoided. To test the hypothesis that in SND, with or without 1st degree atrioventricular (AV) block, cumulative percent ventricular pacing (cum%VP) can be limited by low right atrial septal (LRAS) instead of right atrial appendage (RAA) pacing. METHODS: We studied 102 dual-chamber pacemaker recipients with SND. The PQ interval on 12-lead electrocardiogram and the atrial paced to ventricular sensed interval (Ap-Vs) during LRAS and RAA pacing were measured and compared at implantation, 3 months and 1 year of follow-up. Group 1 included 62 patients with baseline PQ interval <200 milliseconds during LRAS (n = 28) versus RAA (n = 34) pacing. Group 2 included 40 patients with baseline PQ ≥200 milliseconds during LRAS (n = 20) versus RAA (n = 20) pacing. cum%VP were measured at 3 months and 1 year. RESULTS: The characteristics and AV conduction properties were similar and the Ap-Vs interval was significantly shorter in the LRAS than in the RAA pacing group up to 1 year (193 ± 32 milliseconds vs. 220 ± 27 milliseconds in Group 1; P = 0.003, 222 ± 41 milliseconds vs. 281 ± 30 milliseconds in Group 2; P < 0.001). While cumulative percent atrial pacing was consistently similar, cum%VP was significantly smaller during LRAS than RAA pacing (1 ± 1% vs. 8 ± 18% in Group 1; P = 0.03, 7 ± 10% vs. 48 ± 38% in Group 2; P < 0.001). Similar observations were made with or without left atrial (LA) enlargement. CONCLUSION: Compared with RAA, LRAS pacing showed shorter AV interval in SND patients with or without 1st degree AV block and LA enlargement. This beneficial effect persisted through 1-year follow-up, and decreased cum%VP significantly.