RESUMEN

Cytokinesis is the final step of cell division. Increasing evidence suggests failure of cytokinesis might contribute to the development of cancer. Here, we demonstrate that the serologically defined colon cancer antigen-3 (SDCCAG3) forms a complex with PTPN13, a protein tyrosine phosphatase known to be involved in the regulation of cytokinesis, carcinogenesis and tumor aggressiveness. We show that SDCCAG3 is a novel endosomal protein, primarily localized at the early/recycling endosomal compartment. SDCCAG3 undergoes dynamic localization during cell division with strong accumulation at the midbody during cytokinesis. Overexpression as well as downregulation correlates with the generation of multinucleate cells. Furthermore, we show interaction of SDCCAG3 with the Arf GTPase activating protein GIT1 (G protein-coupled receptor kinase interactor-1). Overexpression of an ArfGAP-negative version of GIT1 also results in an increased number of multinucleate cells suggesting regulation of Arf-mediated vesicular trafficking or signaling via SDCCAG3. Finally, we demonstrate that SDCCAG3 expression levels are elevated in colon cancers. In summary, we have established SDCCAG3 as a novel endosomal protein, which is involved in the regulation of cytokinesis.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antígenos de Neoplasias/metabolismo , Proteínas de Ciclo Celular/metabolismo , Citocinesis/fisiología , Proteínas de Neoplasias/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 13/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Adenocarcinoma/química , Animales , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/fisiología , Sitios de Unión , Proteínas de Ciclo Celular/genética , Línea Celular , Neoplasias del Colon/química , Endosomas/química , Regulación Neoplásica de la Expresión Génica , Células Gigantes/patología , Humanos , Péptidos y Proteínas de Señalización Intracelular , Ratones , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Mapeo de Interacción de Proteínas , Estructura Terciaria de Proteína , ARN Interferente Pequeño/farmacología , Proteínas Recombinantes de Fusión/metabolismo , Vesículas Transportadoras/fisiología , Técnicas del Sistema de Dos Híbridos , Proteínas de Transporte Vesicular/fisiología

RESUMEN

Cholesterol-independent, pleiotropic actions of HMG-CoA reductase inhibitors (statins) lead to anti-inflammatory and antioxidant actions by as yet unidentified mechanisms. This study explores the role of heme oxygenase-1 (HO-1) as target and potential mediator of rosuvastatin. In cultured human endothelial cells (ECV 304), rosuvastatin increased HO-1 mRNA and protein levels in a concentration-dependent fashion. HO-1 induction by rosuvastatin remained unaffected by mevalonate and N-nitro-L-arginine-methylester, showing that isoprenoid- and NO-dependent pathways were not involved. Pretreatment of endothelial cells with rosuvastatin reduced NADPH-dependent production of oxygen radicals. The HO-1 metabolite bilirubin, when added exogenously to the cells, virtually abolished NADPH-dependent oxidative stress. Rosuvastatin-induced inhibition of free radical formation was rescued in the presence of the HO inhibitor, tin protoporphyrin-IX. Our results demonstrate that HO-1 is a target site and antioxidant mediator of rosuvastatin in endothelial cells. This novel pathway may contribute to and partially explain the pleiotropic antiatherogenic actions of rosuvastatin.

Asunto(s)

Antioxidantes/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Fluorobencenos/farmacología , Pirimidinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sulfonamidas/farmacología , Línea Celular , Relación Dosis-Respuesta a Droga , Hemo Oxigenasa (Desciclizante) , Hemo-Oxigenasa 1 , Humanos , Proteínas de la Membrana , Rosuvastatina Cálcica , Regulación hacia Arriba/efectos de los fármacos

RESUMEN

Brain-derived neurotrophic factor (BDNF) acutely modulates the efficacy of central glutamatergic synapses via activation of the receptor tyrosine kinase TrkB. On a longer time scale, recent evidence suggests an additional role of TrkB signaling in the formation of excitatory synaptic connections. Here, we have overexpressed full-length TrkB receptors (fl-TrkB) in hippocampal neurons, to investigate the contribution of BDNF signaling to the maturation of glutamatergic synapses. Using patch clamp recordings, we show a three-fold reduction in glutamatergic excitatory autaptic and synaptic current amplitudes in neurons overexpressing fl-TrkB, and application of saturating concentrations of BDNF and NT-4/5 completely reverses this effect. Compatible with these overexpression data, in untransfected neurons, scavenging of endogenous BDNF and NT-4/5 by TrkB-IgGs reduces excitatory autaptic current (EAC) amplitudes. By overexpression of truncated TrkB receptors (TrkB.T1, TrkB.T2) and a chimeric receptor containing only the intracellular domain of fl-TrkB, we show that intra- and extracellular domains of fl-TrkB are necessary to observe the EAC reduction. Labeling of presynaptic terminals with FM 4-64 revealed, that the reduced EAC amplitudes in fl-TrkB overexpressing neurons are accompanied by a two-fold reduction in synapse number. These results suggest, that ligand-independent signaling through fl-TrkB receptors can decrease glutamatergic synaptic strength, if sufficient amounts of BDNF or NT-4/5 are not available.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo/metabolismo , Regulación hacia Abajo/fisiología , Ácido Glutámico/metabolismo , Hipocampo/crecimiento & desarrollo , Neuronas/metabolismo , Receptor trkB/metabolismo , Sinapsis/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , Animales Recién Nacidos , Factor Neurotrófico Derivado del Encéfalo/farmacología , Células Cultivadas , Dendritas/metabolismo , Dendritas/ultraestructura , Regulación hacia Abajo/efectos de los fármacos , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/genética , Colorantes Fluorescentes , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/fisiología , Hipocampo/citología , Hipocampo/metabolismo , Factores de Crecimiento Nervioso/farmacología , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Neuronas/citología , Neuronas/efectos de los fármacos , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/metabolismo , Estructura Terciaria de Proteína/efectos de los fármacos , Estructura Terciaria de Proteína/genética , Compuestos de Piridinio , Compuestos de Amonio Cuaternario , Ratas , Receptor trkB/antagonistas & inhibidores , Receptor trkB/genética , Receptores AMPA/efectos de los fármacos , Receptores AMPA/metabolismo , Proteínas Recombinantes de Fusión/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Sinapsis/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética

RESUMEN

Semaphorins are a family of secreted and membrane-associated proteins involved in growth cone guidance during development. Here, we describe the interaction of Semaphorin4F (Sema4F) with the post-synaptic density protein SAP90/PSD-95. Using the yeast two-hybrid system and coprecipitation assays we were able to show an interaction between the extreme C-terminus of Sema4F and the PDZ domains of SAP90/PSD-95. Heterologous coexpression of a chimeric EphrinB1/Semaphorin4F protein with SAP90/PSD-95 in COS cells leads to translocation of SAP90/PSD-95 from the cytosol to the membrane. Deletion analysis shows that this translocation activity of Sema4F is completely dependent on the presence of the last three C-terminal amino acids. In addition, Sema4F immunoreactivity is present in synaptosome fractions and enriched in post-synaptic density fractions. Consistently, in cultured hippocampal neurons, we demonstrate punctate colocalization of Sema4F and SAP90/PSD-95 in dendrites, furthermore we found colocalization of Sema4F with synapsin1 suggesting a synaptic localization. Our data implicate a new functional context for semaphorins at glutamatergic synapses.

Asunto(s)

Proteínas de la Membrana/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Secuencia de Aminoácidos , Animales , Células COS , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Fraccionamiento Celular , Células Cultivadas , Efrina-B1 , Hipocampo/citología , Humanos , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Microscopía Fluorescente , Datos de Secuencia Molecular , Factores de Crecimiento Nervioso/genética , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/genética , Estructura Terciaria de Proteína , Ratas , Ratas Wistar , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Asociadas a SAP90-PSD95 , Alineación de Secuencia , Transfección , Técnicas del Sistema de Dos Híbridos

RESUMEN

Protein tyrosine phosphatase-basophil like (PTP-BL) is a large non-transmembrane protein tyrosine phosphatase implicated in the modulation of the cytoskeleton. Here we describe a novel interaction of PTP-BL with the protein kinase C-related kinase 2 (PRK2), a serine/threonine kinase regulated by the G-protein rho. This interaction is mediated by the PSD-95, Drosophila discs large, zonula occludens (PDZ)3 domain of PTP-BL and the extreme C-terminus of PRK2 as shown by yeast two-hybrid assays and coimmunoprecipitation experiments from transfected HeLa cells. In particular, we demonstrate that a conserved C-terminal cysteine of PRK2 is indispensable for the interaction with PTP-BL. In HeLa cells we demonstrate colocalization of both proteins in lamellipodia like structures. Interaction of PTP-BL with the rho effector kinase PRK2 gives further evidence for a possible function of PTP-BL in the regulation of the actin cytoskeleton.

Asunto(s)

Proteína Quinasa C/metabolismo , Proteínas Tirosina Fosfatasas/química , Proteínas Tirosina Fosfatasas/metabolismo , Actinas/metabolismo , Secuencias de Aminoácidos , Animales , Basófilos/química , Secuencia Conservada , Cisteína/química , Citoesqueleto/metabolismo , ADN Complementario/metabolismo , Biblioteca de Genes , Células HeLa , Humanos , Plásmidos/metabolismo , Pruebas de Precipitina , Unión Proteica , Estructura Terciaria de Proteína , Proteína Tirosina Fosfatasa no Receptora Tipo 13 , Proteínas Tirosina Fosfatasas/biosíntesis , Ratas , Transfección , Técnicas del Sistema de Dos Híbridos

RESUMEN

Mutations of the tumor suppressor protein APC (Adenomatous Polyposis Coli) are linked to familiar and sporadic human colon cancer. Here we describe a novel interaction between the APC protein and the protein tyrosine phosphatase PTP-BL carrying five PDZ protein-protein interaction domains. Exclusively, the second PDZ domain (PDZ2) of PTP-BL is binding to the extreme C-terminus of the APC protein, as determined by yeast two-hybrid studies. Using surface plasmon resonance analysis we established a dissociation constant (K(D)) of 8.1 x 10(-9) M. We find that a naturally occurring splice insertion of five amino acids (PDZ2b) abolishes its binding affinity to the APC protein. The in vivo interaction between PTP-BL and the APC protein was shown by coprecipitation experiments in transfected COS cells. Furthermore, in cultured epithelial Madine Carnine Kidney cells the subcellular colocalization was demonstrated for the nucleus and also for the tips of cellular extensions. The interaction of the APC protein with a protein tyrosine phosphatase may indirectly modulate the steady state levels of tyrosine phosphorylations of associated proteins, such as beta-catenin playing a major role in the regulation of cell division, migration and cell adhesion.

Asunto(s)

Proteínas del Citoesqueleto/metabolismo , Proteínas Tirosina Fosfatasas/genética , Proteínas Tirosina Fosfatasas/metabolismo , Transactivadores , Proteína de la Poliposis Adenomatosa del Colon , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Células COS , Línea Celular , Proteínas del Citoesqueleto/genética , Perros , Células Epiteliales/metabolismo , Humanos , Ratones , Datos de Secuencia Molecular , Pruebas de Precipitina , ARN Mensajero , Resonancia por Plasmón de Superficie , Transfección , Técnicas del Sistema de Dos Híbridos , beta Catenina

RESUMEN

BACKGROUND: Bile flow into the pancreatic duct has been proposed as the cause of acute biliary pancreatitis. However, the pancreatic toxicity of choledochal bile from patients with acute gallstone pancreatitis has not been studied. METHODS: Bile was collected endoscopically from the common bile ducts of 21 patients with acute gallstone pancreatitis within 72 hours after the onset of disease. The bile samples were instilled into the pancreatic duct of rabbits, and light microscopic examination of the pancreas morphology was performed to assess the toxicity of human bile. Microbiologic quantitative analysis of the aerobic and anaerobic bacterial bile flora was performed. RESULTS: Bile of six patients with acute gallstone pancreatitis (29%) induced interstitial inflammation in the rabbit pancreas. Choledochal bile of these patients harbored more than 10(4) CFU/mL bacteria (Proteus vulgaris, n = 1; Klebsiella pneumoniae, n = 1; Escherichia coli, n = 2; enterococci, n = 2). After sterilization, the bile samples did not induce acute pancreatitis. In 15 patients (71%), bile did not cause acute pancreatitis in the rabbit pancreas. These choledochal secretions were sterile or contained less than 10(4) CFU/mL. CONCLUSIONS: Reflux of infected bile may be a potential cause of acute pancreatitis in the minority of patients with bacterobilia. In most patients with gallstone pancreatitis, bile is neither infected nor harmful to the pancreas, and its flow into the gland is unlikely to be the cause of inflammation.

Asunto(s)

Bilis/fisiología , Colangiopancreatografia Retrógrada Endoscópica , Colelitiasis/fisiopatología , Pancreatitis/fisiopatología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Animales , Bilis/microbiología , Colelitiasis/diagnóstico por imagen , Colelitiasis/patología , Conducto Colédoco/diagnóstico por imagen , Conducto Colédoco/patología , Conducto Colédoco/fisiopatología , Técnicas de Cultivo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas/diagnóstico por imagen , Páncreas/patología , Páncreas/fisiopatología , Pancreatitis/diagnóstico por imagen , Pancreatitis/patología , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/patología , Pancreatitis Aguda Necrotizante/fisiopatología , Conejos

RESUMEN

Pex14p is a central component of the peroxisomal protein import machinery, which has been suggested to provide the point of convergence for PTS1- and PTS2-dependent protein import in yeast cells. Here we describe the identification of a human peroxisome-associated protein (HsPex14p) which shows significant similarity to the yeast Pex14p. HsPex14p is a carbonate-resistant peroxisomal membrane protein with its C terminus exposed to the cytosol. The N terminus of the protein is not accessible to exogenously added antibodies or protease and thus might protrude into the peroxisomal lumen. HsPex14p overexpression leads to the decoration of tubular structures and mislocalization of peroxisomal catalase to the cytosol. HsPex14p binds the cytosolic receptor for the peroxisomal targeting signal 1 (PTS1), a result consistent with a function as a membrane receptor in peroxisomal protein import. Homo-oligomerization of HsPex14p or interaction of the protein with the PTS2-receptor or HsPex13p was not observed. This distinguishes the human Pex14p from its counterpart in yeast cells and thus supports recent data suggesting that not all aspects of peroxisomal protein import are conserved between yeasts and humans. The role of HsPex14p in mammalian peroxisome biogenesis makes HsPEX14 a candidate PBD gene for being responsible for an unrecognized complementation group of human peroxisome biogenesis disorders.

Asunto(s)

Proteínas Portadoras , Proteínas Fúngicas/química , Proteínas de la Membrana/química , Proteínas Represoras , Secuencia de Aminoácidos , Secuencia de Bases , ADN Complementario , Expresión Génica , Humanos , Proteínas de Transporte de Membrana , Microcuerpos/metabolismo , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Peroxinas , Receptor de la Señal 1 de Direccionamiento al Peroxisoma , Receptores Citoplasmáticos y Nucleares/metabolismo , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae

RESUMEN

The regulation of the density of innervation and the promotion of survival of neurons are the original effects depending on neurotrophins. Here we analyse such effects evoked by trkB tyrosine kinase in transfected PC12 cells and transfected sympathetic neurons. In order to exclude the previously described modulation of trk kinase activity by the extracellular activation of the low-affinity p75 neurotrophin receptor, we applied a chimeric receptor approach: The extracellular domain of colony-stimulating factor-1 (CSF-1) receptor was fused to the transmembrane and cytoplasmic domain of the trkB tyrosine kinase receptor, allowing its selective activation by the heterologous ligand. Protein expression and CSF-1-induced tyrosine phosphorylation of the chimeric receptor protein was demonstrated in transfected COS cells. After stable transfection into nerve growth factor (NGF)-responsive PC12 cells, CSF-1 mediated the K252a-sensitive induction of fiber outgrowth. Furthermore, we were able to show by heterologous expression of the chimeric receptor, that activation of trkB tyrosine kinase activity is sufficient to promote survival of neurotrophin deprived sympathetic neurons.

Asunto(s)

Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptor de Factor Estimulante de Colonias de Macrófagos/genética , Receptor de Factor Estimulante de Colonias de Macrófagos/metabolismo , Receptores de Factor de Crecimiento Nervioso/genética , Receptores de Factor de Crecimiento Nervioso/metabolismo , Fibras Adrenérgicas/efectos de los fármacos , Fibras Adrenérgicas/metabolismo , Animales , Células COS , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Embrión de Pollo , Chlorocebus aethiops , Expresión Génica , Ligandos , Factor Estimulante de Colonias de Macrófagos/farmacología , Factores de Crecimiento Nervioso/farmacología , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Células PC12 , Fosforilación , Ratas , Receptor de Factor Neurotrófico Ciliar , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Transducción de Señal , Transfección , Tirosina/metabolismo

RESUMEN

A cDNA clone encoding a novel truncated form of the chicken TrkB receptor has been isolated and sequenced. Compared to two previously reported forms from mouse and rat, this clone contains an 141-bp insert (47 amino acids) in the cytoplasmic region.

Asunto(s)

Proteínas Tirosina Quinasas Receptoras/biosíntesis , Receptores de Factor de Crecimiento Nervioso/biosíntesis , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Pollos , Clonación Molecular , Secuencia Conservada , ADN Complementario/análisis , ADN Complementario/biosíntesis , Ratones , Datos de Secuencia Molecular , Ratas , Proteínas Tirosina Quinasas Receptoras/genética , Receptor trkB , Receptores de Factor de Crecimiento Nervioso/genética , Homología de Secuencia de Aminoácido

RESUMEN

A dose reduction of vancomycin to 1000 mg once a week usually is recommended for haemodialysis patients. Our modified dosing schedule consists of a loading dose of 1000 mg and a maintenance dose of 500 mg administered 3 times a week after haemodialysis. Different vancomycin regimens were retrospectively evaluated by therapeutic drug monitoring and bayesian parameter estimates in 39 dialysis patients. The mean (+/- SD) trough level in 7 patients receiving only the conventional dosage regimen was significantly lower than in 17 patients strictly treated by the modified schedule (7 +/- 4 versus 17 +/- 8 mg/L; p = 0.001). The corresponding peaks were low in both groups and no different (23 +/- 10 versus 27 +/- 12 mg/L). The one week average vancomycin clearance was significantly lower in the conventional dosage group compared to the modified dosage group (6 +/- 3 versus 10 +/- 3 ml/min; p = 0.001). High-flux dialysers were not used in the conventional dosage group but for 30 percent of the procedures in the modified dosage group, where the vancomycin one week average elimination half-life was 66 hours (+/- 18) and the volume of distribution 50 litres (+/- 5). As compared to the bayesian programme, NONMEM calculated comparable pharmacokinetic parameters but could be applied only in 5 cases with a sufficient number of concentration measurements. Ototoxicity occurred in 1 patient, whereas vancomycin treatment was judged as ineffective against infection in 5 of the 39 patients. Their troughs were below 15 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Diálisis Renal , Vancomicina/farmacocinética , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/terapia , Anciano , Teorema de Bayes , Femenino , Humanos , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vancomicina/administración & dosificación

RESUMEN

The distribution and elimination of various drugs depend on kidney function. This dependence is published either as a linear regression equation or as the discrete extreme values for normal kidney function and anuria. A meta-analysis of the published pharmacokinetic data is required to build up a knowledge-based computer system for dosage adjustment in renal failure. A sample comparison of 4 statistical methods for meta-analysis was performed by applying them to 13 publications about the aminoglycoside netilmicin. Parametric meta-analytical methods I and II are based on regression equations alone (Z-transformation, maximum likelihood) and yield unreliable data, especially with regard to extreme values for anuria. The parametric meta-analytical method III is based on means of extreme values (standard 2-stage approach) and does not permit a decision as to whether linear interpolation of a parameter (e.g. volume of distribution) can be used for all degrees of renal insufficiency. In contrast, the nonparametric median (meta-analytical method IV) is based on the extreme values calculated from regression equations and empirical extreme values combined into 1 group of data on normal kidney function and another on anuria. For netilmicin, the meta-analytical median with the 95% confidence interval (95% CI) yields a significant increase in the dominant elimination half-life from 2h (95% CI 1.9h, 2.6h) in patients with normal kidney function to 45h (95% CI 41h, 301h) in those with anuria (p = 0.001). For a normal bodyweight of 65kg, the volume of distribution also increases significantly from 13L (95% CI 9L, 15L) to 20L (95% CI 14L, 21L) in patients with anuria (p = 0.04). Thus, drug dosage adjustment according to therapeutic peak and trough concentrations requires knowledge of the distribution and elimination parameters, since they can both be independently altered in renal failure. We conclude that the most robust meta-analysis of these alterations is achieved with the nonparametric median of extreme values.

Asunto(s)

Riñón/metabolismo , Netilmicina/farmacocinética , Creatinina/metabolismo , Semivida , Humanos , Riñón/efectos de los fármacos , Metaanálisis como Asunto , Análisis de Regresión

RESUMEN

Intravenous regional anesthesia (IVRA) may be used as a diagnostic method in patients suffering from chronic pain in the forearm or hand to differentiate the origin of pain within the anesthetic area from that above. For this purpose it needs to be proven that all nerve fibers are blocked and that conduction blockade induced by IVRA takes place within the nerve trunks. Therefore the transmission of impulses in a nerve trunk to the central nervous system has been studied. Diagnostic intravenous regional anesthesia (5 mg/kg mepivacaine 1%) of the arm was performed in eight patients for 30 min. Short-latency somatosensory evoked potentials (SSEPs) induced by median nerve stimulation at the wrist were recorded from the scalp at 5-min intervals before, during, and after IVRA. In five patients, sensory nerve action potentials (SNAPs) of the median nerve, at the elbow and axilla, and SSEPs at spinous processus C-7 were recorded simultaneously. During IVRA the function of the nerve fibers which are assumed to mediate pain was tested by the patient's sensation following median nerve stimulation at an intensity which evoked pain before IVRA. During IVRA, peak latencies of the scalp recorded SSEPs (N20) increased progressively and interpeak amplitudes (N20/P25) decreased. After 20 min, SSEPs could no longer be recorded, and median nerve stimulation no longer evoked any sensation at all. After deflation of the cuff, both peak latency (N20) and interpeak amplitude (N20/P25) of SSEPs recovered. The changes in latency and amplitude of SSEPs from the scalp as well as SNAPs and SSEPs from the neck were similar. Because SSEPs, SNAPs, and the pain sensation following median nerve stimulation disappeared during IVRA, it may be concluded that the thick and thin myelinated nerve fibers of the median nerve have been blocked. For diagnostic use, IVRA is superior to peripheral nerve blockade, which has been shown previously to not abolish SSEPs.

Asunto(s)

Nervio Mediano , Bloqueo Nervioso , Dolor/diagnóstico , Adulto , Anestesia de Conducción , Anestesia Intravenosa , Electrofisiología , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Masculino , Mepivacaína , Persona de Mediana Edad

RESUMEN

The basic law in nephropharmacology states that pharmacokinetic parameters depend linearly on renal function. Few exceptions to linear dependence have been reported, e.g. substances with saturable tubular reabsorption or secretion. A further example is cyclosporin, which was found to be eliminated according to log-concave nonlinear kinetics in 3 patients with hepatotoxicity after kidney transplantation. The nonlinear cyclosporin kinetics were computer-fitted to the integrated forms of the 1-exp function and the Michaelis-Menten equation by nonlinear regression analysis. The same maximal velocity (Vmax = 23 ng ml-1 h-1) and Michaelis constant (Km = 686 ng ml-1) were calculated for cyclosporin when applying either the 1-exp function or the Michaelis-Menten equation. The nonlinear elimination of cyclosporin, however, was described even more closely by the 1-exp function than by the Michaelis-Menten equation.

Asunto(s)

Enfermedades Renales/metabolismo , Riñón/fisiología , Farmacocinética , Humanos

Asunto(s)

Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina/administración & dosificación , Tromboflebitis/prevención & control , Administración Tópica , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ratas

RESUMEN

In 87 patients a new computerized EEG monitor was used in clinical anesthesia. Following aperiodic analysis, the Lifescan shows the computerized EEG in a striking color visualization allowing recognition of changes in the course of the EEG and of interhemispheric differences. The computerized EEG can be read after a brief training period. The changes caused by different clinical situations are visualized in detail. Different changes were observed with the anesthetics used. During induction with thiopentone a sudden increase in activity was obvious. During a lighter level of anesthesia with thiopentone beta activity was easily recognizable. During induction with high-dose fentanyl frequency was slowed over a long period and activity was increased. The monitor shows the changes in the lower frequency range in detail. A bimodal pattern occurred with a higher dosage of enflurane. During lightening of anesthesia with enflurane a typical pattern indicated return to consciousness. When nitrous oxide was administered during anesthesia with halothane, and to a lesser degree during anesthesia with enflurane or isoflurane, remarkable slowing and decrease in activity occurred. The monitor allowed detailed recognition of the different patterns obtained with the various anesthetics. In some cases it was possible to say what dosage of the anesthetic used had been given or what depth of anesthesia had been achieved. The effect of combined anesthesia, however, was difficult to judge. In carotid artery surgery a quick unilateral decrease in activity and slowing of frequency indicated cerebral ischemia and quickly disappeared after insertion of a shunt. This change was particularly obvious with the new monitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Anestesiología/instrumentación , Anestésicos/farmacología , Electroencefalografía/efectos de los fármacos , Monitoreo Intraoperatorio/instrumentación , Adolescente , Adulto , Anciano , Niño , Preescolar , Electroencefalografía/instrumentación , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad

RESUMEN

Short-latency somatosensory evoked potentials (SSEPs) in response to median nerve stimulation were recorded from the neck and the scalp before and during diagnostic high spinal anesthesia (touch T3, pinprick C8) in six patients with chronic pain. The central conduction time--the time difference between the neck-recorded N13 and the scalp-recorded N20--and the amplitudes of the SSEPs did not change in a statistically significant way during high spinal anesthesia. However, latencies of the neck-recorded N13 and the scalp-recorded N20 and P25 increased slightly. This may have been due to a local anesthetic effect on those spinal roots of the median nerve in which segmental pinprick analgesia occurred. Because high spinal anesthesia did not depress central nervous function, as measured by central conduction time, and SSEP amplitudes, it is concluded that scalp-recorded SSEPs during high spinal anesthesia measure the effects of local anesthetics in the cerebrospinal fluid on neuronal pathways outside the brain.

Asunto(s)

Anestesia Raquidea , Sistema Nervioso Central/fisiología , Potenciales Evocados Somatosensoriales , Adulto , Anciano , Femenino , Humanos , Masculino , Nervio Mediano/fisiología , Persona de Mediana Edad , Conducción Nerviosa

RESUMEN

During the last years the non-surgical drainage of the bile ducts developed to an efficient treatment method and is a real enrichment in the concept of treatment of the malignant obstruction of the bile ducts. In no more radically operable carcinomas in the area of the bile ducts, the pancreas or the porta of the liver it is to be preferred to a palliative drainage operation. In case the drainage of the bile ducts shall not be used therapeutically (through-drainage), an inner drainage in form of an endoprosthesis should always be preferred. As a procedure of the 1st choice the endoscopic retrograde technique is recommended, as procedure of 2nd choice the percutaneous transhepatic technique. Benign basic diseases are more infrequently the reason for the insert of a bile duct drainage. The main indications are general inoperability in non-extractable calculi in the common bile duct. In our own cases patients could be followed up up to 3.5 years. No complications were observed. The occlusion of prostheses does apparently not play a role.

Asunto(s)

Ampolla Hepatopancreática , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Colestasis Extrahepática/terapia , Neoplasias del Conducto Colédoco/terapia , Neoplasias Pancreáticas/terapia , Stents , Drenaje/instrumentación , Estudios de Seguimiento , Humanos

RESUMEN

The carcinoma of the papilla occupies a special position among the periampullary carcinomas by its favourable prognosis. Responsible for this are the early appearance of symptoms due to the close neighbourhood to the common bile duct and the restriction of the metastasation to the first stage of lymphatic nodes in the majority of cases. Symptoms are jaundice, epigastric pain and decrease of weight. In the carcinoma of the papilla the duodenoscopy with biopsy and ERCP is the method of choice. The reliability of the biopsy is larger, when it is performed after an endoscopic sphincterotomy. For the delimitation of the carcinoma of the papilla against other causes can further be used the hypotensive duodenography, the abdominal computerd tomography, the sonography and the PTC. A curative treatment is possible only surgically. On account of the better long-term results the partial duodenopancreatectomy is to be preferred to the local exstirpation of the papilla. Endoscopic drainages of the biliary tract carried out preoperatively may reduce the lethality of operations. A palliative drainage of the biliary tract on the endoscopic or percutaneous transhepatic way as well as the endoscopic sphincterotomy may improve the patients' quality of life and prolong the survival time, when there are non-resectable tumours or a general inoperability.

Asunto(s)

Ampolla Hepatopancreática , Colestasis Extrahepática/terapia , Neoplasias del Conducto Colédoco/terapia , Drenaje/instrumentación , Endoscopios , Ampolla Hepatopancreática/patología , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Colestasis Extrahepática/diagnóstico , Neoplasias del Conducto Colédoco/diagnóstico , Humanos

RESUMEN

According to current knowledge biliary (gallstone-associated) acute pancreatitis is induced by transient obstruction of the papilla by migrating gall stones. It seems, therefore, rational to remove the occluding stone as early as possible by endoscopic papillotomy (EPT). Uncontrolled studies have shown that patients with acute pancreatitis are not more endangered by EPT than those without pancreatitis and that the intervention seems to beneficially influence the course of the pancreatic disease. Early endoscopy (within 48 h), however, revealed incarcerated papillary stones only in 10% but common bile ducts free of stones in 24%. There seems to be only a small subgroup with acute biliary pancreatitis who might benefit from early EPT. This subgroup should be characterized more precisely. Early EPT indiscriminately performed in any kind of acute pancreatitis has little rational ground and is, up to now, not justified.

Asunto(s)

Ampolla Hepatopancreática , Colelitiasis/complicaciones , Cálculos Biliares/complicaciones , Pancreatitis/etiología , Enfermedad Aguda , Ampolla Hepatopancreática/cirugía , Colelitiasis/cirugía , Endoscopía , Cálculos Biliares/cirugía , Humanos