RESUMEN
Bimetallic nanostructured core-shell structures are commonly used as catalysts in a wide variety of reactions. We surmised that the addition of an additional metal would potentially allow catalytic tailoring with the possibility of an increase in activity. Here a tri-metallic catalytic structure, consisting of clustered catalytic Pt on the surface of a Pd shell supported on a rod shaped Au core was fabricated. The significance of the additional metallic component is shown by comparative electrochemically active surface area (ECSA) analysis results for the trimetallic Aurod-Pdshell-Ptcluster, bimetallic Aurod-Ptcluster and monometallic JM-Pt (used as a reference), which have respective ECSA values (cm(2)/mgPt) of 1883.0, 1371.7 and 879. The potential utility of the trimetallic catalysts was shown in a hydrogen peroxide sensing protocol, which showed the catalyst to have a sensitivity of 604 ìA/mMcm(2) within a linear range of 0.0013-6.191 mM.
RESUMEN
We have developed a new finite element (FE) model of human right ear, including the accurate geometry of middle ear ossicles, external ear canal, tympanic cavity, and mastoid cavity. The FE model would be suitable to study the dynamic behaviors of pathological middle ear conditions, including changes of stapedial ligament stiffness, tensor tympani ligament (TTL), and tympanic membrane (TM) stiffness and thickness. Increasing stiffness of stapedial ligament has substantial effect on stapes footplate movement, especially at low frequencies, but less effect on umbo movement. Softer TTL will result in increasing umbo and stapes footplate displacement, especially at low frequencies (f<1000Hz). When the TTL was detached, the vibration amplitude of umbo increased by 6dB at 600Hz and two peaks (300 and 600Hz) were found in the vibration amplitude of stapes footplate. Increasing the stiffness of tensor tympani resulted in a slightly decreased umbo amplitude at very low frequencies (f<500Hz) and significantly decreased displacement up to 12dB at middle frequencies (1000Hz
Asunto(s)
Oído Medio/fisiología , Modelos Biológicos , Sonido , Membrana Timpánica/fisiología , Simulación por Computador , Oído Medio/anatomía & histología , Análisis de Elementos Finitos , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Programas Informáticos , Hueso Temporal/anatomía & histología , Hueso Temporal/fisiología , Membrana Timpánica/anatomía & histología , VibraciónRESUMEN
The oral adsorbent AST-120 has been widely used in Japan to delay the initiation of dialysis therapy in patients with chronic renal failure. This study evaluated the long-term effects of AST-120 in patients with chronic renal failure who had not previously undergone dialysis. One hundred out-patients were prospectively enrolled and prescribed 6 g/day oral AST-120 for >or= 1 year. The clinical effectiveness of AST-120 was evaluated by comparing changes in the slope of the reciprocal serum creatinine-time plot (1/sCr slope) before and after AST-120 administration. The 1/sCr slope improved significantly after >or= 1 year of AST-120 treatment and greatest improvement was observed in patients with the longest AST-120 administration period (> 30 months). The results suggest that long-term treatment with AST-120 may be beneficial for chronic renal failure patients in the pre-dialysis stage.
Asunto(s)
Carbono/administración & dosificación , Carbono/metabolismo , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/metabolismo , Óxidos/administración & dosificación , Óxidos/metabolismo , Administración Oral , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Carbono/uso terapéutico , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxidos/uso terapéutico , Diálisis Renal , Factores de TiempoRESUMEN
AIMS: In this study, dose-response of the serum potassium-lowering effect of a calcium polystyrene sulfonate (PS) preparation was investigated. Changes in the serum potassium level were also examined with or without application of a RAAS inhibitor, which is said to increase the serum potassium level. SUBJECTS AND METHODS: 23 patients diagnosed to have hyperkalemia associated with chronic renal failure were enrolled in this study. The study drug, a PS-Ca jelly preparation (Argamate jelly), was started at a daily dose of 1 preparation (5 g as PS-Ca), and the dose was increased by 1 preparation every month to finally reach 3 preparations per day. Blood samples were collected once a month and serum levels of creatinine and electrolytes were measured. RESULTS: PS-Ca jelly decreased serum potassium levels in a dose-dependent manner. Decreases were 0.67 mEq/l at 5 g of PS-Ca/day, 1.06 mEq/l at 10 g/d, and 1.33 mEq/l at 15 g/d. Irrespective of the use of the RAAS inhibitor, serum potassium levels decreased significantly in a dose-dependent manner. Furthermore, no major change in serum creatinine levels occurred in subjects in which the RAAS inhibitor was used, although in subjects in which the RAAS inhibitor was not used, serum creatinine level tended to gradually increase. CONCLUSION: Serum potassium levels were reduced in a dose-dependent manner by administration of 5-15 g/d of PS-Ca, and it appeared that together with control of serum potassium levels, renal function should be maintained by continuous administration of RAAS inhibitor.
Asunto(s)
Hiperpotasemia/tratamiento farmacológico , Poliestirenos/uso terapéutico , Sistema Renina-Angiotensina/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Formas de Dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hiperpotasemia/sangre , Masculino , Persona de Mediana Edad , Potasio/sangreAsunto(s)
Hiperlipidemias/genética , Receptores de Lipopolisacáridos/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Diálisis Renal , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaAsunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Captopril/uso terapéutico , Diabetes Mellitus Experimental/fisiopatología , Hipertensión/tratamiento farmacológico , Glomérulos Renales/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Glomérulos Renales/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKYRESUMEN
To investigate the changes of renal type IV collagen turnover in diabetic nephropathy, urinary type IV collagen was measured by a highly sensitive one-step sandwich enzyme immunoassay (EIA). Urinary samples were obtained from 698 diabetic patients and 191 healthy adults. Among the patients, 264 had urinary albumin levels of less than 29 mg/g.creatine (Cr) (Stage I: normoalbuminuric stage), 169 had microalbuminuria from 30 to 299 mg/g.Cr (Stage II: microalbuminuric stage), 84 patients had macroalbuminuria of more than 300 mg/g.Cr and serum Cr of less than 1.1 mg/dl (Stage IIIA: macroalbuminuric stage without renal dysfunction), 97 had macroalbuminuria of more than 300 mg/g.Cr and serum Cr of more than 1.2 mg/dl (Stage IIIB: macroalbuminuric stage with renal dysfunction), and 84 had renal failure (Stage IV). The levels of urinary type IV collagen in Stages II, IIIA, IIIB, and IV were significantly higher than those in Stage I (P < 0.0001). The level of urinary type IV collagen in Stage I (5.00 +/- 0.23 microg/g.Cr; mean +/- SE) was also higher than that in normal adults (3.44 +/- 0.11 microg/g.Cr; mean +/- SE). These levels increased gradually due to progression of the clinical stage of diabetic nephropathy. It appears that the levels of urinary type IV collagen can be a useful marker for detecting renal injuries in diabetes according to our Asian multicenter trials.
Asunto(s)
Colágeno/orina , Nefropatías Diabéticas/orina , Anciano , Albuminuria/orina , Glucemia/análisis , Índice de Masa Corporal , Creatinina/orina , Diabetes Mellitus Tipo 1/orina , Diabetes Mellitus Tipo 2/orina , Femenino , Hemoglobina Glucada/análisis , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
We determined the clinical and immunopathological effects of dilazep hydrochloride (dilazep) on IgA nephropathy of ddY mice. Group I (early-treatment group, n = 10) was orally treated with 300 mg/kg body weight of this drug from 12 weeks of age until 60 weeks of age, and group II (late-treatment group, n = 10) was also treated with the same dosage of this drug from 20 weeks of age until 60 weeks of age. Group III (control group, n = 10) received drinking water. On immunofluorescence, distribution and intensity of IgA and C3 depositions in glomeruli of group I and group II animals were significantly decreased as compared with those in group III. The expression of fibronectin, laminin, or type IV collagen in glomeruli was basically similar in the three groups treated with or without dilazep. On light microscopy, the expansion of glomerular mesangial areas and the average number of intraglomerular cells were markedly decreased as compared with those in group III. The levels of urinary protein excretion in groups I and II were significantly lower than those in group III (p < 0.01 and p < 0.05). These findings suggest that treatment with dilazep might improve the clinical and immunopathological findings in IgA nephropathy of ddY mice.
Asunto(s)
Dilazep/farmacología , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/patología , Vasodilatadores/farmacología , Animales , Colágeno/análisis , Femenino , Fibronectinas/análisis , Técnica del Anticuerpo Fluorescente , Mesangio Glomerular/química , Mesangio Glomerular/patología , Laminina/análisis , Ratones , Proteinuria/tratamiento farmacológico , Proteinuria/patologíaRESUMEN
1. The effects of 11 week treatments with the new hydroxy3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on renal intrinsic anti-oxidant enzyme (AOE) activities and renal function were evaluated in streptozotocin (STZ)-induced diabetic rats. 2. Renal intrinsic AOE activities, creatinine clearance and urinary albumin excretion were examined in STZ-induced diabetic rats. The levels of total cholesterol (TC), triglyceride (TG) and phospholipid (PL) were also examined. 3. In general, renal AOE activities and function were lower in diabetic rats than in non-diabetic Sprague-Dawley rats. 4. Decreases in TC, TG and PL levels and urinary albumin excretion by the HMG-CoA reductase inhibitor fluvastatin improved renal function and produced a non-uniform alteration in renal AOE; only glutathione peroxidase (GSH-Px) activity increased significantly with fluvastatin treatment. 5. It appears that the improvement in renal function and albuminuria may be related to increases in GSH-Px activity, but there was no correlation between changes in renal function and changes in the activity of Mn-superoxide dismutase or catalase.
Asunto(s)
Catalasa/metabolismo , Diabetes Mellitus Experimental/enzimología , Ácidos Grasos Monoinsaturados/farmacología , Glutatión Peroxidasa/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Indoles/farmacología , Riñón/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Creatinina/orina , Fluvastatina , Riñón/enzimología , Pruebas de Función Renal , Masculino , Fosfolípidos/sangre , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Triglicéridos/sangreRESUMEN
We investigated the renal protective effect of nifedipine (2-nitrophenyl derivative BAY a 1040) in streptozotocin (STZ)-induced spontaneously hypertensive rats (SHRs, 8 weeks of age). Diabetic SHRs were treated with 40 mg/kg/day of nifedipine or efonidipine as controls for 16 weeks. Dosage of nifedipine or efonidipine was chosen after preliminary studies demonstrated that it showed moderate antihypertensive action (more than a 20% decrease in systemic blood pressure after treatment). In the diabetic SHR, the excretion of urinary albumin was increased and reached 4.41 +/- 0.08 mg/day at 24 weeks. The levels of urinary albumin in the diabetic SHR after treatment with nifedipine were significantly less than those in the diabetic SHR at 24 weeks (p < 0.01). Levels of the ratio of creatinine clearance to body weight were significantly decreased in the diabetic SHR after treatment with nifedipine. In light microscopy, the ratio of glomerular tufts to Bowman's areas was significantly decreased compared with those in the diabetic SHRs (p < 0.05). These findings suggest that nifedipine inhibits the development of albuminuria and glomerular enlargement in STZ-induced diabetic SHRs. There was no significant difference in the changes in antihypertensive or antialbuminuric effects between nifedipine and efonidipine. Thus, nifedipine, as well as efonidipine, may become a useful antihypertensive drug with a renal protective effect.
Asunto(s)
Albuminuria/prevención & control , Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/prevención & control , Nifedipino/farmacología , Nitrofenoles , Vasodilatadores/farmacología , Animales , Antihipertensivos/farmacología , Creatinina/farmacocinética , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/metabolismo , Dihidropiridinas/farmacología , Riñón/efectos de los fármacos , Masculino , Compuestos Organofosforados/farmacología , Ratas , Ratas Endogámicas SHR , Factores de TiempoRESUMEN
The purpose of the present study was to evaluate the correlations among expression of intercellular adhesion molecule 1 (ICAM-1) in glomeruli, levels of soluble ICAM-1 (sICAM-1) in sera, and renal injuries in patients with IgA nephropathy. The levels of sICAM-1 in sera from 27 patients with IgA nephropathy and 7 healthy controls were measured by the human soluble ICAM-1 immunoassay. The expression of ICAM-1 in glomeruli was detected by indirect immunofluorescence. We observed marked expression of ICAM-1 in glomerular capillary walls and mesangial areas in patients with advanced-stage, but not in those with mild IgA nephropathy. Since the histopathological changes in the advanced stage of this disease were characterized by diffuse mesangial cell proliferation and tubulointerstitial injury, the expression of ICAM-1 in the glomeruli may be of value in evaluating the degree of renal lesions in patients with IgA nephropathy. However, there was no significant change in the levels of serum sICAM-1 among mild-stage and advanced-stage patients and healthy controls. It appears that the measurement of serum sICAM-1 is not useful in evaluating the degree of renal injuries in patients with IgA nephropathy.
Asunto(s)
Glomerulonefritis por IGA/diagnóstico , Molécula 1 de Adhesión Intercelular/metabolismo , Glomérulos Renales/patología , Estudios de Casos y Controles , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Glomérulos Renales/metabolismoRESUMEN
Using a sandwich ELISA, we studied 48 patients with IgA nephropathy and 10 patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (non-IgA PGN) to determine if levels of serum soluble Fas (s-Fas) might reflect the disease activity. The levels of serum s-Fas in patients with the advanced stage of IgA nephropathy were significantly higher than those in patients with the mild stage of the disease, in non-IgA PGN or in healthy controls. The results showed that advanced stage IgA nephropathy patients who showed heavy proteinuria and the presence of urinary casts revealed high levels of serum s-Fas. It was thus suggested that the measurement of serum s-Fas is useful in evaluating the degree of renal injury in patients with IgA nephropathy.
Asunto(s)
Glomerulonefritis por IGA/sangre , Receptor fas/sangre , Adolescente , Adulto , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/patología , Glomerulonefritis Membranoproliferativa/sangre , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/patología , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Receptor fas/inmunologíaRESUMEN
Immunopathological studies were performed to determine whether the glomerular injuries in ddY mice, a model for IgA nephropathy (Berger's disease), are influenced by treatment with mizoribine, a new immunosuppressive agent. The ddY mice were treated with a low (0.05 mg/ml) or a high (0.1 mg/ml) dose of mizoribine for 35 weeks. Flow cytometry analysis showed that there was a marked decrease in the number of B cells and IgA-bearing B cells. In immunofluorescence, the deposition of IgA in the glomerular mesangial areas and capillary walls of the high-dose mizoribine-treated ddY mice was markedly decreased as compared with that of control ddY mice receiving drinking water. The glomerular mesangial expansion in the high-dose mizoribine-treated ddY mice was milder than that found in the control ddY mice. In 45-week-old ddY mice, the average number of intraglomerular cells in the high-dose and low-dose mizoribine-treated ddY mice was slightly lower than that in drinking water treated ddY mice. The levels of urinary protein excretion in the high-dose mizoribine-treated ddY mice were also lower than those in the low-dose mizoribine-treated or drinking water treated ddY mice. It appears that treatment of mizoribine might influence the proliferation of B cells, especially IgA-bearing B cells, and improve the glomerular IgA deposition and glomerular expansion in early-stage IgA nephropathy of ddY mice.
Asunto(s)
Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis/tratamiento farmacológico , Inmunosupresores/farmacología , Ribonucleósidos/uso terapéutico , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Modelos Animales de Enfermedad , Citometría de Flujo , Mesangio Glomerular/patología , Inmunoglobulina A/inmunología , Inmunohistoquímica , Ratones , Ratones Endogámicos , ProteinuriaRESUMEN
1. We investigated the renal protective effect of efonidipine hydrochloride (efonidipine, NZ-105) in STZ-induced spontaneously hypertensive rats (SHRs, 8 weeks of age). Diabetic SHRs were treated with 15 mg/kg/day of efonidipine for 12 weeks. 2. The dosage of efonidipine was chosen after preliminary studies demonstrated that it showed mild antihypertensive action (within 20% decrease of systemic blood pressure). 3. In the diabetic SHRs, the excretion of urinary albumin was increased (1.78 +/- 0.09 mg/day) at 4 weeks and reached 4.41 +/- 0.12 mg/day at 12 weeks. The levels of urinary albumin in the diabetic SHRs after treatment with efonidipine were significantly less than those in the diabetic SHRs at 8 and 12 weeks (P < 0.01). 4. Levels of creatinine clearance were decreased in the diabetic SHRs after treatment with efonidipine. 5. In light microscopy, the ratio of glomerular tuft to Bowman's areas was significantly decreased compared with those in the diabetic SHRs (P < 0.05). 6. These findings suggest that efonidipine inhibits the development of albuminuria and glomerular enlargement in the streptozotocin-induced diabetic SHRs and may become a useful antihypertensive drug with a renal protective effect.
Asunto(s)
Albuminuria/tratamiento farmacológico , Antihipertensivos/uso terapéutico , Dihidropiridinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Riñón/efectos de los fármacos , Nitrofenoles , Compuestos Organofosforados/uso terapéutico , Albuminuria/complicaciones , Animales , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Hipertensión/complicaciones , Riñón/patología , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , EstreptozocinaRESUMEN
The reactive oxygen species has been proposed as a key mediator of the progression of renal injury associated with essential hypertension. Among the defense systems operating against the reactive oxygen species, superoxide dismutase, glutathione peroxidase, and catalase are the most important antioxidant enzymes (AOEs). In the present study, systolic blood pressure, renal function (creatinine clearance, urinary albumin, and N-acetyl-beta D-glucosaminidase excretion), renal intrinsic AOE activities, and renal histopathology were determined in stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats. The effects of a 20-week treatment using three antihypertensive drug regimens--captopril, a sulfhydryl-containing angiotensin-converting enzyme inhibitor; temocapril, a potent, non-sulfhydryl-containing angiotensin-converting enzyme inhibitor prodrug; and a conventional triple drug combination that includes a vasodilator (hydralazine, hydrochlorothiazide and reserpine)--on renal function, renal tissue, AOE activities, and renal histopathologic abnormalities were evaluated in stroke-prone spontaneously hypertensive rats. Renal function and AOE activities were lower in the stroke-prone spontaneously hypertensive rats than in the Wistar Kyoto rats. Normalization of systolic blood pressure using the antihypertensive drugs improved renal function and produced a nonuniform alteration in renal AOEs; only glutathione peroxidase activity increased significantly with the use of all three drug regimens. The mild renal histopathologic abnormality in stroke-prone spontaneously hypertensive rats was not altered by drug treatment. The improvement in renal function may be related to an increase in glutathione peroxidase activity, but no correlation was seen between renal function changes and alteration in activities of superoxide dismutase or catalase.
Asunto(s)
Antihipertensivos/farmacología , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Hipertensión/fisiopatología , Riñón/fisiopatología , Superóxido Dismutasa/metabolismo , Acetilglucosaminidasa/orina , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Captopril/farmacología , Quimioterapia Combinada , Hidralazina/farmacología , Hidroclorotiazida/farmacología , Hipertensión/tratamiento farmacológico , Hipertensión/enzimología , Riñón/efectos de los fármacos , Riñón/enzimología , Riñón/patología , Pruebas de Función Renal , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Reserpina/farmacologíaRESUMEN
Effects of benidipine hydrochloride or triple therapy (hydralazine, reserpine, and hydrochlorothiazide) on renal cortical and medullary intrinsic antioxidant enzyme (AOE) activity were evaluated in stroke-prone spontaneously hypertensive rats (SHR-SP) as an animal model for human essential hypertension with cerebral stroke. This study showed a significant decrease of renal intrinsic glutathione peroxidase (GSH-Px) activity in untreated SHR-SP. Renal GSH-Px activity in untreated SHR-SP was significantly lower than that in Wister Kyoto rats (WKY) as a normotensive reference strain. GSH-Px activity in SHR-SP was significantly improved after benidipine hydrochloride therapy. Levels of urinary albumin excretion or creatinine clearance (Ccr) in SHR-SP were also improved after the therapy. Glomerular sclerosis index was slightly improved in SHR-SP treated with benidipine hydrochloride according to light microscopic analysis. It appears that hypertension may influence the renal intrinsic GSH-Px activity, albuminuria, and Ccr in SHR-SP. Thus it is indicated that control of blood pressure may improve the GSH-Px activity in SHR-SP.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Trastornos Cerebrovasculares/enzimología , Dihidropiridinas/farmacología , Hipertensión/enzimología , Riñón/enzimología , Oxidorreductasas/metabolismo , Animales , Antioxidantes/metabolismo , Presión Sanguínea/efectos de los fármacos , Catalasa/metabolismo , Trastornos Cerebrovasculares/tratamiento farmacológico , Creatina/metabolismo , Quimioterapia Combinada , Glutatión Peroxidasa/metabolismo , Hidralazina/farmacología , Hidroclorotiazida/farmacología , Hipertensión/tratamiento farmacológico , Riñón/efectos de los fármacos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Reserpina/farmacología , Superóxido Dismutasa/metabolismoRESUMEN
The activities of glomerular intrinsic antioxidant enzymes (AOEs) were measured in a diabetic spontaneously hypertensive rat (SHR) model. The effects of antihypertensive drugs, i.e. captopril or triple therapy (hydralazine, reserpine, and hydrochlorothiazide), on glomerular intrinsic AOE activities in this model were evaluated. The effects of blood glucose control on the AOE activities were also determined. The aim of the present study was to determine whether activities of glomerular intrinsic AOEs might correlate with disease activity in diabetic SHR. This study showed a decrease of glomerular intrinsic AOE, i.e. Cu/Zn-SOD and Mn-SOD (SOD = superoxide dismutase), glutathione peroxidase, and catalase, activities in diabetic SHR. Glomerular Cu/Zn-SOD or Mn-SOD, glutathione peroxidase, and catalase activities in nondiabetic SHR were slightly lower than those in nondiabetic WKY rats. These activities in diabetic SHR were significantly improved after captopril or triple therapy or blood glucose control. The levels of urinary albumin excretion, creatinine clearance, and glomerular tuft areas in diabetic SHR were also improved after the therapy. It appears that hypertension and hyperglycemia may influence the glomerular intrinsic AOE activities, albuminuria, creatinine clearance, and glomerular tuft areas in diabetic SHR. Thus, it is indicated that control of blood pressure or blood glucose is a very important factor for preventing renal injuries in the diabetic SHR model.
Asunto(s)
Antihipertensivos/uso terapéutico , Antioxidantes/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Animales , Captopril/uso terapéutico , Catalasa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/prevención & control , Quimioterapia Combinada , Glutatión Peroxidasa/metabolismo , Hidralazina/administración & dosificación , Hidroclorotiazida/administración & dosificación , Hipertensión/metabolismo , Glomérulos Renales/enzimología , Glomérulos Renales/patología , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Reserpina/administración & dosificación , Superóxido Dismutasa/metabolismoRESUMEN
The aim of this study was to determine if treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (AIIRA) might decrease urinary albumin excretion and prevent glomerular enlargement and glomerulosclerosis in subtotal (5/6) nephrectomized rats. Morphometric image analysis of glomeruli was also performed in the subtotal nephrectomized rats. The nephrectomized rats were treated with ACEI (enalapril 100 mg/l), AIIRA (L-158,809 10 mg/l) or TRX (reserpine 5 mg/ l, hydralazine 80 mg/l, and hydrochlorothiazide 25 mg/l) and euthanized at 16 weeks after renal ablation. Treatments were started at 2 weeks (early treatment: Group I) or 8 weeks (later treatment: Group II) after the ablation. ACEI and AIIRA treatments were equally and significantly effective in limiting albuminuria and progression of glomerular sclerosis. TRX was also as effective in decreasing urinary albumin excretion and preserving the renal function as ACEI or AIIRA in Group I. The improvement of albuminuria, glomerular enlargement and sclerosis after these treatments in Group II was significantly less than that in Group I. It appears that the early treatment with angiotensin converting enzyme inhibitor, angiotensin II receptor antagonist or reserpine, hydralazine and hydrochlorothiazide (TRX) may prevent glomerular injury in human patients with renal hypertension.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Glomerulonefritis/tratamiento farmacológico , Glomérulos Renales/efectos de los fármacos , Riñón/efectos de los fármacos , Albuminuria/tratamiento farmacológico , Animales , Presión Sanguínea/efectos de los fármacos , Creatinina/metabolismo , Enalapril/farmacología , Glomerulonefritis/patología , Hidralazina/farmacología , Hidroclorotiazida/farmacología , Imidazoles/farmacología , Glomérulos Renales/patología , Masculino , Nefrectomía , Ratas , Ratas Sprague-Dawley , Reserpina/farmacología , Tetrazoles/farmacologíaRESUMEN
The purpose of this study was to determine the antioxidant enzyme activities in renal tissues of early stage ddY mice, an animal model for primary IgA nephropathy. Eight- and 40-week-old ddY female mice and normal healthy Balb/c female mice were used in this study. The levels of Cu/Zn-SOD, Mn-SOD, and GSH-PX activities in the renal cortex were significantly higher in 40-week-old ddY mice than in Balb/c control mice of the same age; no change of catalase activity was observed. There were no significant differences in the levels of Cu/Zn-SOD, Mn-SOD, GSH-PX, and catalase activities between the ddY mice and Balb/c mice at 8 weeks of age. Urinary protein was slightly higher in 40-week-old ddY mice. IgA or C3 was deposited at low levels in the glomerular mesangial areas of 8-week-old ddY mice. Marked depositions of IgA and C3 extended from the glomerular mesangial areas to the capillary walls of 40-week-old ddY mice. Expansion of glomerular mesangial matrices and mild mesangial cell proliferation was observed in 40-week-old ddY mice. Antioxidant enzyme activities in the renal cortex were already increased in the early stage IgA nephropathy in 40-week-old ddY mice. These findings suggest that measurements of antioxidant enzyme activities in the renal cortex of 40-week-old ddY mice was useful for evaluation of the pathogenesis of renal involvement in the early stage of IgA nephropathy.