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Arritmias Cardíacas/diagnóstico , Astenia/etiología , Electrocardiografía , Hiperpotasemia/diagnóstico , Anciano de 80 o más Años , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Arritmias Cardíacas/inducido químicamente , Diagnóstico Diferencial , Diuréticos Conservadores de Potasio/efectos adversos , Diuréticos Conservadores de Potasio/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Hiperpotasemia/inducido químicamente , Diálisis Renal , Insuficiencia Renal/tratamiento farmacológicoRESUMEN
The nitric oxide (NO) signaling pathway is a major nonadrenergic-noncholinergic transmitter mechanism in the enteric nervous system. Our aim was to localize the enzymes in question, i.e., neuronal nitric oxide synthase (nNOS), soluble guanylate cyclase (sGC), and cGMP-dependent kinase type I (cGK-I) in rat small intestine by indirect immunofluorescence. nNOS staining was found in neurons of the myenteric plexus and in varicose nerve fibers mainly in the circular muscle layer. The cells positive for neurokinin-1 (NK-1) receptor and c-kit (interstitial cells of Cajal, ICC) in the deep muscular plexus (DMP) did not show nNOS reactivity, but nNOS-positive nerve fibers were directly adjacent to them. sGC was found in flattened cells surrounding myenteric ganglia (periganglionic cells, PGC), in ICC of the DMP, faintly in smooth muscle cells (SMC), and in cells perivascularly scattered throughout the circular muscle layer. cGK-I immunoreactivity was found abundantly in PGC (which presumably are ICC), in ICC of DMP, in SMC of the innermost circular and longitudinal muscle layers, but less intensively in the outer circular layer. Weak cGK-I staining occurred in nerve cells within the myenteric and submucosal plexus. Conclusively the key enzymes of the NO signaling pathway are differentially distributed: Occurrence of nNOS exclusively in neurons and the presence of sGC and cGK-I predominantly in ICC suggest a sequence of neuronal NO release, activation of ICC, and consecutive smooth muscle relaxation. ICC of the DMP seem to be the primary targets for neurally released NO.
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Sistema Nervioso Entérico/citología , Sistema Nervioso Entérico/enzimología , Intestino Delgado/inervación , Óxido Nítrico/metabolismo , Transducción de Señal/fisiología , Animales , Proteínas Quinasas Dependientes de GMP Cíclico/análisis , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Guanilato Ciclasa , Inmunohistoquímica , Masculino , Músculo Liso/inervación , Óxido Nítrico Sintasa/análisis , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo I , Proteínas Proto-Oncogénicas c-kit/análisis , Ratas , Ratas Wistar , Receptores Citoplasmáticos y Nucleares/análisis , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Neuroquinina-1/análisis , Guanilil Ciclasa SolubleRESUMEN
OBJECTIVE: To investigate whether the adenosine-antagonist theophylline reduces the incidence of contrast-induced nephropathy (CIN). DESIGN AND SETTING: Prospective, comparison to series of patients at similar risk of CIN in a university hospital medical ICU. PATIENTS: 78 ICU patients with at least one risk factor for CIN undergoing 150 consecutive contrast examinations. INTERVENTIONS: Administration of 200 mg theophylline/70 kg BW intravenously 30 min before that of 100 ml or more low-osmolarity contrast medium (CM). MEASUREMENTS AND RESULTS: Concentrations of serum creatinine and blood urea nitrogen (BUN), urine volume, fluid balance, and the incidence of CIN [increase in creatinine > or =20.5 mg/dl (= 44.2 micromol/l) within 48 h] were monitored for 48 h. Despite the large number of risk factors (6.8 per patient) including a high dose of CM (169.4 ml), impaired renal function (51%), diabetes (38%), aminoglycosides (61%), vancomycin (53%), catecholamines (52%), creatinine concentrations were not increased 24 h (1.40+/-0.92 mg/dl) or 48 h (1.38+/-0.88 mg/dl) after CM [1.47+/-1.0 mg/dl (= 130+/-88 micromol/l)] vs. baseline. The fluid balance was not different before (+3 ml/h) and after CM (-9 ml/h). The urine volume slightly increased after CM and theophylline (184 ml/h vs. 164 ml/h). Only three patients (2%) developed CIN. The incidence was significantly lower than that of 14% (78/565) in the control series with patients at comparable risk of CIN (p < 0.0001). CONCLUSIONS: Using a theophylline prophylaxis the incidence of CIN in patients with increased risk of CIN is as low as 2%.
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Adenosina/antagonistas & inhibidores , Medios de Contraste/efectos adversos , Enfermedades Renales/inducido químicamente , Inhibidores de Fosfodiesterasa/uso terapéutico , Teofilina/uso terapéutico , Anciano , Femenino , Alemania/epidemiología , Humanos , Incidencia , Unidades de Cuidados Intensivos , Enfermedades Renales/prevención & control , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Alcoholic hepatitis is a disease associated with profound alterations of the hepatocytic intermediate filament cytoskeleton. Similar cytoskeletal alterations can be induced in mice with prolonged feeding of the fungistatic drug griseofulvin. Murine hepatocytic intermediate filaments are composed of equimolar amounts of keratin polypeptides A (type II) and D (type I). Griseofulvin intoxication of mice leads to diminution, derangement and even loss of the cytoplasmic keratin meshwork and formation of keratin-containing cytoplasmic inclusions, termed Mallory bodies. To study protein alterations leading to disturbance of keratin filament architecture, soluble keratin polypeptides and keratin filaments were purified from griseofulvin-damaged and control mouse livers. In griseofulvin-damaged livers, more acidic isoforms occurred in soluble keratin D, whereas the corresponding filaments had a polypeptide composition similar to that in controls. In vivo [32P]orthophosphate incorporation revealed that the shift of isoelectric forms toward more acidic spots was due to hyperphosphorylation of keratin D. The nature of the kinase(s) involved has yet to be elucidated. In addition, rapid proteolysis only of soluble keratin A was detected in vitro, and there is evidence for increased proteolysis in griseofulvin damage in vivo. The enzyme involved has features of a calpain-type protease. Posttranslational modifications play a substantial role in the disturbance of keratin intermediate filament homeostasis in vivo.
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Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Griseofulvina/farmacología , Queratinas/metabolismo , Hígado/efectos de los fármacos , Procesamiento Proteico-Postraduccional , Animales , Endopeptidasas/metabolismo , Filamentos Intermedios/metabolismo , Membranas Intracelulares/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos , Péptido Hidrolasas/metabolismo , Péptidos/metabolismo , Fosforilación , Polímeros/metabolismo , SolubilidadRESUMEN
The GZ100 series comprises a panel of monoclonal antibodies which seem to be specific for human trophoblast antigens (with the exception of GZ111, which reacts with a number of other tissues). The GZ antibodies show different reaction patterns with different trophoblast cell types. As a panel the GZ antibodies recognize all trophoblast populations (Table 2). Thus these antibodies provide a means to distinguish between trophoblast cells and maternal cells. GZ112 might be used to sort out HLA-class I positive trophoblast cells of the basal plate without blocking the HLA antigenic determinant, since GZ112 is not an anti HLA-class I antibody. At present the antigens detected by the GZ antibodies seem to be proteins, most of them with molecular weights between 50 kD and 80 kD. The function of these antigens is unclear and will be studied in future.