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1.
Sci Rep ; 13(1): 17276, 2023 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-37828038

RESUMEN

Megalin/LRP2 is a major receptor supporting apical endocytosis in kidney proximal tubular cells. We have previously reported that kidney-specific perinatal ablation of the megalin gene in cystinotic mice, a model of nephropathic cystinosis, essentially blocks renal cystine accumulation and partially preserves kidney tissue integrity. Here, we examined whether inhibition of the megalin pathway in adult cystinotic mice by dietary supplementation (5x-fold vs control regular diet) with the dibasic amino-acids (dAAs), lysine or arginine, both of which are used to treat patients with other rare metabolic disorders, could also decrease renal cystine accumulation and protect cystinotic kidneys. Using surface plasmon resonance, we first showed that both dAAs compete for protein ligand binding to immobilized megalin in a concentration-dependent manner, with identical inhibition curves by L- and D-stereoisomers. In cystinotic mice, 2-month diets with 5x-L-lysine and 5x-L-arginine were overall well tolerated, while 5x-D-lysine induced strong polyuria but no weight loss. All diets induced a marked increase of dAA urinary excretion, most prominent under 5x-D-lysine, without sign of kidney insufficiency. Renal cystine accumulation was slowed down approx. twofold by L-dAAs, and totally suppressed by D-lysine. We conclude that prolonged dietary manipulation of the megalin pathway in kidneys is feasible, tolerable and can be effective in vivo.


Asunto(s)
Cistina , Cistinosis , Adulto , Humanos , Animales , Ratones , Cistina/metabolismo , Cistinosis/metabolismo , Lisina , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad , Riñón/metabolismo , Suplementos Dietéticos
2.
Gut ; 58(4): 582-4, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19299387

RESUMEN

The use of polytetrafluoroethylene (PTFE)-covered prostheses improves trans-jugular intrahepatic porto-systemic shunt (TIPS) patency and decreases the incidence of clinical relapses and re-interventions. Therefore, the improvement provided by covered stents might expand the currently accepted recommendations for TIPS use. Stent-related occlusion of the hepatic vein with consequent ischaemia of the corresponding liver parenchyma emerges as a novel complication reported in at least 5% of patients implanted with coated stents. However, this complication was reported to be mild, without signs or symptoms of liver failure, and self-limiting. We report a case of segmental liver ischaemia following PTFE-covered stent placement resulting in a marked impairment in liver function in a patient with hepatitis C virus cirrhosis implanted because of refractory oesophageal bleeding, thus expanding the severity range of this new procedural complication. Moreover, we discuss the possible involvement of additional pathogenetic mechanisms other than out-flow obstruction in the onset of coated-stent induced congestive liver ischaemia.


Asunto(s)
Stents Liberadores de Fármacos/efectos adversos , Isquemia/etiología , Fallo Hepático/etiología , Hígado/irrigación sanguínea , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Humanos , Isquemia/diagnóstico , Fallo Hepático/diagnóstico , Masculino , Persona de Mediana Edad , Politetrafluoroetileno , Derivación Portosistémica Intrahepática Transyugular/instrumentación , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler
3.
Gastroenterol Clin Biol ; 32(6 Suppl 1): 80-7, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18973850

RESUMEN

The measure of disease progression in chronic liver disease represents a key challenge in any of the different stages of evolution. Indeed, a correct and reliable measure of the stage of the disease has relevant implications for assessing the effectiveness of the current therapeutic regimens and for predicting the occurrence of complication. Accordingly, a current major effort is directed at evaluating methodologies characterized by no or low invasiveness to be employed as clinical discriminators in patients populations potentially requiring invasive assessment. This appears particularly relevant in patients with compensated cirrhosis, where the only reference standard is the measurement of portal pressure by hepatic venous pressure gradient (HVPG). In this particular context, transient elastography (TE) appears to be promising and needs to be further investigated, possibly in combination with other non-invasive methodologies such as serum markers algorithms and/or imaging techniques. On the other hand, the application of non-invasive methods for monitoring the response to vasoactive treatment for the reduction of portal pressure and the prevention of related complications seems at the moment not realistic.


Asunto(s)
Hipertensión Portal/diagnóstico , Hipertensión Portal/etiología , Cirrosis Hepática/complicaciones , Humanos
4.
Eur J Clin Invest ; 37(6): 509-15, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17537159

RESUMEN

BACKGROUND: Chronic liver diseases are frequently complicated by portal hypertension, an important component of which is the increased intrahepatic vascular resistance, in part related to endothelial dysfunction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is an established mediator and marker of endothelial dysfunction. We therefore investigated the possible implication of ADMA in chronic liver diseases-induced portal hypertension. MATERIALS AND METHODS: We studied 39 consecutive patients with compensated hepatitis C virus (HCV) related chronic liver diseases. All patients underwent hepatic venous pressure gradient (HVPG) measurement, and simultaneous blood sampling from the hepatic vein and the pulmonary artery, for ADMA and nitrite/nitrate (NOx) plasma level determinations. RESULTS: A positive correlation between HVPG and ADMA concentrations in hepatic veins (ADMA-h) was found (r = 0.77, P < 0.0001). Moreover, a negative correlation between HVPG and NOx concentrations in the hepatic veins (NO-h) (r = -0.50, P = 0.005), and between ADMA-h and NO-h was observed (r = -0.40, P = 0.02). ADMA concentrations in pulmonary artery (ADMA-p) (0.55 +/- 0.13 micromol L(-1)) were significantly higher than in hepatic veins (0.47 +/- 0.09 micromol L(-1)) (P < 0.0001). CONCLUSIONS: These results suggest that ADMA may play a pathophysiological role in portal hypertension by contributing to the relative intrahepatic NO deficiency typical of endothelial dysfunction.


Asunto(s)
Arginina/análogos & derivados , Hepatitis C Crónica/complicaciones , Hipertensión Portal/etiología , Cirrosis Hepática/fisiopatología , Adulto , Anciano , Arginina/fisiología , Estudios de Casos y Controles , Femenino , Hepatitis C Crónica/fisiopatología , Humanos , Hipertensión Portal/fisiopatología , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Presión Portal/fisiología
6.
Int J Immunopathol Pharmacol ; 17(3 Suppl): 21-4, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-16857102

RESUMEN

Cyclic GMP phosphodiesterase (cGMP PDE) plays an important role in pulp tissues. High levels of cGMP PDE are found in dental pulp cells. In the present study cGMP PDE activity was analyzed in normal healthy human dental pulps, in reversible pulpitis and in irreversible pulpitis. Enzymatic cGMP PDE control values for normal healthy pulps were 4.74+/-0.32 nmol/mg of proteins. In reversible pulpitis the cGMP PDE activity increased almost 3 times. In irreversible pulpitis specimens the values increased 4.5 times compared with the normal healthy pulps activity. The differences between the groups (control vs. reversible pulpitis and vs. irreversible pulpitis) were statistically significant. These results point to a role of cGMP PDE in the initial pulp response after injury.


Asunto(s)
3',5'-GMP Cíclico Fosfodiesterasas/metabolismo , Pulpa Dental/enzimología , Pulpitis/enzimología , Cromatografía Líquida de Alta Presión , Humanos
7.
Heart ; 89(8): e23, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12860889

RESUMEN

A 35 year old man with a history of transient ischaemic attack and atrial septal aneurysm underwent percutaneous closure of a patent foramen ovale (PFO) with a transcatheter device. After the procedure the patient developed effort angina not present previously. Transoesophageal echocardiography confirmed the absence of residual shunt but showed an abnormal linear image running behind the aortic root. Magnetic resonance imaging detected an anomalous origin of the circumflex coronary artery from the right coronary sinus. The anomalous artery was located between the aortic root and the PFO closing device, causing coronary insufficiency. This report describes a rare complication of transcatheter PFO closure.


Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Defectos del Tabique Interatrial/complicaciones , Isquemia Miocárdica/etiología , Adulto , Oclusión con Balón/métodos , Anomalías de los Vasos Coronarios/complicaciones , Aneurisma Cardíaco/terapia , Defectos del Tabique Interatrial/terapia , Humanos , Ataque Isquémico Transitorio/etiología , Masculino
8.
J Comput Assist Tomogr ; 24(6): 878-83, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11105704

RESUMEN

OBJECTIVE: To evaluate the role of hepatic arterial phase (HAP) spiral computed tomography (CT), as compared with iodized oil (Lipiodol ultrafluid [LUF]) CT for revealing nodular hepatocellular carcinomas (HCC). METHODS: Twenty-four cirrhotic patients underwent two-phase HCT examination: HAP 25 seconds and portal phase 70 seconds after injection of 1.5 mL/Kg contrast medium. All patients also underwent hepatic angiography and intraarterial infusion of iodized oil; LUF CT was performed 3-4 weeks after infusion. HCT images were compared with LUF CT images for detection of hepatic nodules. RESULTS: We found no significant difference between the sensitivity of HAP CT and LUF CT for nodules >10 mm, while HAP CT was more sensitive than LUF CT in revealing nodules <10 mm (47 vs. 27, p < 0.001). CONCLUSIONS: HCT should be considered as the first method for the detection of HCC, whereas LUF CT should be used only for therapy.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste , Aceite Yodado , Yohexol/análogos & derivados , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Angiografía de Substracción Digital , Distribución de Chi-Cuadrado , Medios de Contraste/administración & dosificación , Femenino , Estudios de Seguimiento , Arteria Hepática , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Infusiones Intraarteriales , Aceite Yodado/administración & dosificación , Cirrosis Hepática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Vena Porta , Sensibilidad y Especificidad
9.
J Lab Clin Med ; 134(4): 386-91, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10521085

RESUMEN

Animal experiments have shown an increase in prepro-endothelin-1 (prepro-ET-1) mRNA expression in the clipped kidney but none in the aortic and mesenteric arteries in 2-kidney, 1-clip Goldblatt hypertensive rats. The present study was aimed at investigating whether plasma and renal endothelin-1 (ET-1) systems are differently activated in patients with renovascular hypertension (RH). The plasma concentration and urinary excretion of ET-1 were measured in 5 patients with RH (before and after successful renal angioplasty), in 7 patients with essential hypertension (EH), and in 8 normotensive control subjects. Immediately before renal angioplasty, plasma samples for ET-1 and plasma renin activity (PRA) measurements were withdrawn from the aorta and both renal veins. Unlike the PRA, the plasma ET-1 concentration did not significantly differ between the involved and the uninvolved sides. The urinary ET-1 excretion level (Fig 1) was markedly increased in patients with RH (30+/-4 ng/g urinary creatinine (UC) vs. 2.5+/-0.2 ng/g UC and 2.6+/-0.5 ng/g UC in control subjects and patients with EH, respectively; P<.001), whereas the plasma ET-1 concentration was normal (0.8+/-0.2 pg/mL vs. 0.65+/-0.3 pg/mL and 0.8+/-0.2 pg/mL in control subjects and EH, respectively, not significant). Renal angioplasty was followed in all patients by normalization of blood pressure and PRA. One week after angioplasty, urinary ET-1 decreased to one fourth of baseline (8.04+/-5.23 ng/g UC, P<.001 vs. values before angioplasty and P<.04 vs. control subjects) and normalized 1 month thereafter (3.13+/-1.62 ng/g UC, not significant vs. control subjects), whereas plasma ET-1 remained steady. The present findings clearly indicate that in patients with RH, urinary ET-1 excretion is increased, whereas plasma ET-1 concentration remains normal. Successful percutaneous transluminal renal angioplasty induced a notable reduction in ET-1 urinary excretion, whereas it did not affect ET-1 plasma concentration.


Asunto(s)
Endotelina-1/sangre , Endotelina-1/orina , Hipertensión Renal/sangre , Hipertensión Renal/orina , Anciano , Aldosterona/sangre , Angioplastia , Arteriosclerosis/cirugía , Presión Sanguínea , Ecocardiografía , Femenino , Humanos , Hipertensión Renal/cirugía , Masculino , Persona de Mediana Edad , Función Ventricular Izquierda
10.
Cardiologia ; 44(2): 203-6, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10208060

RESUMEN

Left-sided partial anomalous pulmonary venous return (PAPVR) with an intact atrial septum is a rare cardiovascular anomaly. This report deals with the case of a 22-year-old woman who was referred to our Institution because of resting palpitation and exertional dyspnea. Two-dimensional echocardiography revealed right heart volume overload and a dilated coronary sinus. A left-sided PAPVR draining into a persistent left superior vena cava which, in turn, entered a dilated coronary sinus, was correctly detected by magnetic resonance imaging. Diagnosis was confirmed by cardiac catheterization. The literature on this subject is reviewed.


Asunto(s)
Venas Pulmonares/anomalías , Vena Cava Superior/anomalías , Adulto , Angiografía , Femenino , Tabiques Cardíacos , Humanos , Imagen por Resonancia Magnética , Arteria Pulmonar/diagnóstico por imagen
11.
J Nephrol ; 11(6): 325-9, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-10048499

RESUMEN

We have reviewed thirty-three cases of accelerated hypertension associated with chronic total renal artery occlusion. During the process of progressive narrowing of the arterial lumen until complete occlusion, an exceptionally elevated blood pressure occurs when a critical reduction of renal blood flow is attained. Then the patient presents one or more of the following clinical manifestations: III-IV grade KWB retinal changes, hypertensive encephalopathy including convulsive attacks, stroke, heart failure, renal insufficiency. We have called this clinical event 'hypertensive vascular crisis'. Mostly in older patients an actual or anamnestic vascular crisis makes a diagnosis of chronic total renal artery occlusion highly probable.


Asunto(s)
Hipertensión Renovascular/etiología , Obstrucción de la Arteria Renal/complicaciones , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Hipertensión Renovascular/fisiopatología , Masculino , Persona de Mediana Edad
12.
Am Heart J ; 133(2): 221-9, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9023169

RESUMEN

Two-dimensional (2D) echocardiographic and angiographic measurements of ventricular volumes are limited by geometric assumptions concerning cavity shape. We compared in vitro the accuracy of a three-dimensional (3D) echocardiographic system suitable for transthoracic imaging to magnetic resonance imaging (MRI) in the measurement of left and right ventricular volumes. Ventricular cast volumes from 14 excised formalin-fixed sheep hearts filled with an agarose solution were compared with data derived from 3D echocardiography and MRI. Left and right ventricular volumes from 3D echocardiographic reconstructions agreed well with actual volumes without significant underestimation or overestimation. MRI progressively underestimated left ventricular volumes as these increased and systematically underestimated right ventricular volumes. Our echocardiographic system designed for 3D transthoracic imaging combines excellent measurements of left and right ventricular volumes and the computed reconstruction of tomographic slices with the full spatial resolution of the original 2D images. Thus in this in vitro model, 3D echocardiography exhibited greater accuracy than MRI.


Asunto(s)
Ecocardiografía Tridimensional/métodos , Imagen por Resonancia Magnética , Animales , Volumen Cardíaco , Ecocardiografía Tridimensional/instrumentación , Ecocardiografía Tridimensional/estadística & datos numéricos , Estudios de Evaluación como Asunto , Ventrículos Cardíacos/diagnóstico por imagen , Técnicas In Vitro , Modelos Lineales , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/estadística & datos numéricos , Variaciones Dependientes del Observador , Ovinos , Procesamiento de Señales Asistido por Computador/instrumentación , Estadísticas no Paramétricas , Tórax , Transductores
13.
Am Heart J ; 123(5): 1252-60, 1992 May.
Artículo en Inglés | MEDLINE | ID: mdl-1575142

RESUMEN

To evaluate the ability of cine magnetic resonance imaging (cine MRI) in the assessment of mitral stenosis (MS), we studied 20 patients (14 women and 6 men, mean age 60.6 +/- 8.5 years) with rheumatic mitral valve stenosis by using an 0.5 T magnet. Cine MRI showed several signs of MS. Mitral leaflet thickening, reduced diastolic opening, and abnormal valve motion toward the left ventricular outflow tract were all common features. MS was also characterized by an abnormal diastolic transmitral signal from blood. Both left atrial and left ventricular dimensions were similar to those obtained at two-dimensional echocardiography (2-DE) (r = 0.89 and r = 0.86, respectively; p less than 0.001). A significant relationship was also found between the maximum mitral leaflet separation measured by cine MRI in diastole and the mitral valve area as calculated using the pressure half-time method and continuous wave Doppler (r = 0.81; p less than 0.001). These data indicate the improved ability of MRI to detect and assess MS and also suggest that this technique may contribute to the noninvasive assessment of MS.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Estenosis de la Válvula Mitral/diagnóstico , Anciano , Ecocardiografía , Estudios de Evaluación como Asunto , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Estenosis de la Válvula Mitral/diagnóstico por imagen
14.
J Mal Vasc ; 11(2): 178-84, 1986.
Artículo en Francés | MEDLINE | ID: mdl-2941510

RESUMEN

Results of treatment of a personal series of 12 patients developing a thrombus in branches of prostheses after aorto-iliac surgery are presented. A therapeutic procedure used over the last two years consists of initial local and regional thrombolysis to remove the acute obstruction, followed by surgery at the level chosen, and if necessary to correct a faulty technique or progression of the atherosclerosis. Good results were obtained even for thrombosis originating after the conventional 8-10 day postoperative period, insofar as the thrombus that develops in a graft may differ from one forming in an artery. This aspect requires further studies, which will also provide greater clarification of the etiopathogenicity.


Asunto(s)
Prótesis Vascular/efectos adversos , Fibrinolíticos/administración & dosificación , Trombosis/etiología , Angiografía , Aorta Abdominal/cirugía , Femenino , Arteria Femoral/cirugía , Heparina/administración & dosificación , Humanos , Infusiones Parenterales , Pierna/irrigación sanguínea , Masculino , Persona de Mediana Edad , Tereftalatos Polietilenos , Arteria Poplítea/cirugía , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Factores de Tiempo , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación
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