RESUMEN
Even people which have never smoked can develop lung cancer. In this population a mutation in the exons 19-21 of the Epidermal Growth Factor Receptor (EGFR) can be detected. For this patient group targeted therapies with EGFR tyrosinkinase inhibitors are available. In this case report we describe a 37 year old non-smoker who developed a non-small cell lung cancer. Following therapy with Erlotinib a partial response could be achieved.
Asunto(s)
Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Nódulos Pulmonares Múltiples/complicaciones , Nódulos Pulmonares Múltiples/tratamiento farmacológico , Derrame Pericárdico/etiología , Derrame Pericárdico/prevención & control , Quinazolinas/uso terapéutico , Adulto , Clorhidrato de Erlotinib , Hemorragia/diagnóstico , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Nódulos Pulmonares Múltiples/diagnóstico , Derrame Pericárdico/diagnóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Fumar , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: The Na(+)/H(+) exchange (NHE) inhibitor cariporide is known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic Ca(2+) overload. Leukocyte activation and infiltration also mediates I/R injury but whether cariporide reduces I/R injury by affecting leukocyte activation is unknown. We studied the effect of cariporide on thrombin and I/R induced leukocyte activation and infiltration models and examined P-selectin expression as a potential mechanism for any identified effects. EXPERIMENTAL APPROACH: An in vivo rat mesenteric microcirculation microscopy model was used with stimulation by thrombin (0.5 micro ml(-1)) superfusion or ischaemia (by haemorrhagic shock for 60 min) and reperfusion (90 min). KEY RESULTS: Treatment with cariporide (10 mg kg(-1) i.v.) significantly reduced leukocyte rolling, adhesion and extravasation after thrombin exposure. Similarly, cariporide reduced leukocyte rolling (54+/-6.2 to 2.4+/-1.0 cells min(-1), P<0.01), adherence (6.3+/-1.9 to 1.2+/-0.4 cells 100 microm(-1), P<0.01) and extravasation (9.1+/-2.1 to 2.4+/-1.1 cells per 20 x 100 microm perivascular space, P<0.05), following haemorrhagic shock induced systemic ischaemia and reperfusion. The cell adhesion molecule P-selectin showed a profound decrease in endothelial expression following cariporide administration in both thrombin and I/R stimulated groups (35.4+/-3.2 vs 14.2+/-4.1% P-selectin positive cells per tissue section, P<0.01). CONCLUSIONS AND IMPLICATIONS: The NHE inhibitor cariporide is known to limit reperfusion injury by controlling Ca(2+) overload but these data are novel evidence for a vasculoprotective effect of NHE inhibition at all levels of leukocyte activation, an effect which is likely to be mediated at least in part by a reduction of P-selectin expression.
Asunto(s)
Guanidinas/farmacología , Inflamación/fisiopatología , Selectina-P/efectos de los fármacos , Intercambiadores de Sodio-Hidrógeno/antagonistas & inhibidores , Sulfonas/farmacología , Animales , Calcio/metabolismo , Adhesión Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Rodamiento de Leucocito/efectos de los fármacos , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Masculino , Mesenterio/irrigación sanguínea , Microcirculación/metabolismo , Microscopía , Selectina-P/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/fisiopatologíaRESUMEN
The purpose of the study is to investigate the direct effect of bradykinin (BK), a potent vasoactive nonapeptide, on glucagon secretion from the perfused rat pancreas. BK (0.1, 1, and 10 micromol/L) increased glucagon secretion in a concentration-dependent manner. HOE 140, a BK2 receptor antagonist (0.01, 0.1, and 1 nmol/L), prevented the stimulatory effect of BK on glucagon secretion in a concentration-dependent manner. In contrast, des-Arg9,Leu8-BK, a BK1 receptor antagonist (1 nmol/L), failed to antagonize the effect of BK. Thus, BK stimulates glucagon secretion from the perfused rat pancreas by activating BK2 receptors, but not BK1 receptors.
Asunto(s)
Bradiquinina/farmacología , Glucagón/metabolismo , Páncreas/efectos de los fármacos , Receptores de Bradiquinina/fisiología , Animales , Bradiquinina/análogos & derivados , Masculino , Páncreas/metabolismo , Perfusión , Ratas , Ratas Sprague-Dawley , Receptor de Bradiquinina B2RESUMEN
The Medical Devices Act (Medizinproduktegesetz = MPG) took effect in Germany on 01. 01. 1995, and replaced (with the exception of diagnostic laboratory devices) the previously binding MedGV with a transition period ending on 13. 06. 1998. The new German act is the implementation of the EC directive on active implantable medical devices (90/385/EWG) and the directive on medical devices (93/42/EWG). The EC directive 93/42/EWG on medical devices permits the manufacturer of a medical device to chose the conformity assessment procedure. All medical devices are subject to conformity assessment procedures, and are awarded the EC mark through Appendix II, III, VII or VIII. All these appendices contain information about the need for carrying out assessment and the obligation to provide a written description of the risk analysis for a medical device. Risk analysis is a common method that verifiably ensures that the basic requirements of EC Directive 93/42/EWG on medical devices are met by the product. It is obvious that risk analysis is of central importance to the legal measures for ensuring appropriate device safety. The present paper presents and assesses various methods of risk analysis.
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Tornillos Óseos , Análisis de Falla de Equipo/estadística & datos numéricos , Fracturas del Cuello Femoral/cirugía , Humanos , Medición de RiesgoRESUMEN
Human T-cell lymphotropic virus type 1 Tax1 induces the activation and nuclear localization of the cellular transcription factor, NF-kappa B. Treatment of cells with calphostin C, a protein kinase C (PKC) inhibitor, blocked induction of NF-kappa B DNA binding activity in human T-cell lymphotropic virus type 1-transformed C81 cells and Tax1-stimulated murine pre-B cells, suggesting that PKC was an important intermediate in the NF-kappa B induction pathway. We further demonstrate that Tax1 associates with, and activates, PKC. PKC was coimmunoprecipitated with anti- Tax1 sera from Tax1-expressing MT4 extracts and Jurkat extracts in the presence of exogenous Tax1 protein. In addition, the glutathione-S-transferase-Tax1 protein bound specifically to the alpha, delta, and eta PKC isoenzymes synthesized in rabbit reticulocyte lysates. The addition of Tax1 to in vitro kinase reaction mixtures leads to the phosphorylation of Tax1 and an 18-fold increase in the autophosphorylation of PKC. Transfection of Jurkat cells with wild-type Tax1 stimulated membrane translocation of PKC. In contrast, Tax1 mutant M22, which fails to stimulate NF-kappa B-dependent transcription, failed to stimulate membrane translocation of PKC. Tax1 did not directly increase PKC phosphorylation of I kappa B alpha. Our results are consistent with a model in which Tax1 interacts with PKC and stimulates membrane translocation and triggering of the PKC pathway. Subsequent steps in the PKC cascade likely stimulate phosphorylation of I kappa B alpha.
Asunto(s)
Productos del Gen tax/fisiología , Virus Linfotrópico T Tipo 1 Humano/fisiología , FN-kappa B/biosíntesis , Proteína Quinasa C/metabolismo , Factores de Transcripción , Animales , Secuencia de Bases , Línea Celular , Membrana Celular/enzimología , ADN Viral , Inhibidores Enzimáticos/farmacología , Productos del Gen tax/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Datos de Secuencia Molecular , Naftalenos/farmacología , Fosforilación , Unión Proteica , Biosíntesis de Proteínas , Proteína Quinasa C/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/metabolismo , Factor de Transcripción ReIB , TransfecciónRESUMEN
BACKGROUND: Increased production of reactive oxygen species (ROS) and lipid peroxidation may contribute to vascular complications in diabetes. to test whether DNA is also oxidatively damaged in diabetes, we measured 8-hydroxydeoxyguanosine (8-OHdG), an indicator of oxidative damage of DNA, in mononuclear cells. METHODS: For this laboratory-based study, 12 patients with insulin-dependent diabetes mellitus (IDDM) and 15 patients with non-insulin-dependent diabetes mellitus (NIDDM) were matched by age with ten healthy volunteers each. DNA was extracted from mononuclear cells from whole blood. 8-OHdG was assayed by high-pressure liquid chromatography, and ROS were assayed by chemiluminescence. FINDINGS: IDDM and NIDDM patients had significantly higher median concentrations (p , 0.001, U test) of 8-OHdG in their mononuclear cells than their corresponding controls (in fmol/micrograms DNA): 128.2 (interquartile range 96.0-223.2) and 95.2 (64.0-133.5) vs 28.2 (21.7-43.4) and 21.9 (18.0-24.4), respectively. ROS generation by mononuclear cells was also significantly greater (p < 0.01) in diabetic patients than in their controls (in mV): 238.0 (107.0-243.0) and 101.3 (66.0-134.0) vs 69.5 (49.8-91.9) and 56.0 (38.8-62.5), respectively. INTERPRETATION: IDDM and NIDDM patients showed greater oxidative damage to DNA, with increased generation of ROS, than controls. Such changes might contribute to accelerated aging and atherogenesis in diabetes and to the microangiopathic complications of the disease.
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Daño del ADN , Desoxiguanosina/análogos & derivados , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Anciano , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , ADN/química , Desoxiguanosina/análisis , Angiopatías Diabéticas/etiología , Humanos , Leucocitos Mononucleares/química , Leucocitos Mononucleares/metabolismo , Peroxidación de Lípido , Mediciones Luminiscentes , Persona de Mediana EdadRESUMEN
By DNA-DNA hybridization, we classified 26 human strains, 4 dog and cat strains, and 4 hamster strains putatively identified as Helicobacter cinaedi as well as 2 human strains and 2 animal strains of Helicobacter fennelliae. All but one human strain belonged to the same hybridization group as the type strain of H. cinaedi. The animal strains also appeared to belong to this hybridization group. Both human strains of H. fennelliae were shown to be H. fennelliae by DNA-DNA hybridization, but both animal strains were less than 15% related to the type strain. All strains were also characterized by plasmid profiles and ribotyping. Plasmids were found in 23% of the human strains, 100% of the hamster strains, and 33% of the dog and cat strains. Human strains were essentially identical by ribotyping, but were clearly differentiated from the hamster and dog and cat strains. Some strains may be difficult to culture on primary isolation; we found that our strains grew well on anaerobic CDC agar, brucella agar, and tryptic soy agar II. Our H. cinaedi and H. fennelliae strains differed from those previously described because some were resistant to cephalothin: some H. cinaedi strains were also resistant to nalidixic acid. All isolates were also characterized by antimicrobial susceptibility testing. We found that human strains of H. cinaedi were more resistant to clindamycin and erythromycin than were animal isolates; 19% of the human strains were resistant to ciprofloxacin. Therefore, we recommend that antimicrobial susceptibility results be obtained before initiating therapy for H. cinaedi and H. fennelliae infections.
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Técnicas de Tipificación Bacteriana , Helicobacter/clasificación , Animales , Gatos , Cricetinae , Sondas de ADN , ADN Bacteriano , ADN Ribosómico , Perros , Genotipo , Helicobacter/genética , Helicobacter/crecimiento & desarrollo , Helicobacter/metabolismo , Infecciones por Helicobacter/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Fenotipo , Plásmidos , Especificidad de la EspecieAsunto(s)
Derechos Civiles/legislación & jurisprudencia , Internamiento Obligatorio del Enfermo Mental/legislación & jurisprudencia , Servicios de Urgencia Psiquiátrica/legislación & jurisprudencia , Francia , Humanos , Admisión del Paciente/legislación & jurisprudencia , Defensa del Paciente/legislación & jurisprudenciaRESUMEN
The in vitro response of myofibroblasts to prostaglandins F2alpha (a vasoconstrictor) and E2 (a vasodilator) were evaluated in specimens obtained from the Dupuytren's nodules of 12 patients. Fibroblasts from four control samples of palmar fascia were similarly tested. This study demonstrated the ability of prostaglandin F2alpha to induce significant contraction of myofibroblasts. Prostaglandin E2 was noted to cause significant relaxation of myofibroblasts. The contractile/relaxation responses of control fibroblasts to these prostaglandins were minimal.
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Contractura de Dupuytren/fisiopatología , Músculos/efectos de los fármacos , Prostaglandinas E/farmacología , Prostaglandinas F/farmacología , Células Cultivadas , Dinoprost , Dinoprostona , Contractura de Dupuytren/patología , Fibroblastos/efectos de los fármacos , Fibroblastos/ultraestructura , Humanos , Contracción Muscular/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Músculos/ultraestructura , SiliconasRESUMEN
The investigations were carried out in 30 patients with primary hyperlipidaemia (hypercholesterolaemia, hypertriglyceridaemia and mixed form). The serum total cholesterol and triglycerides, and in the erythrocytes the levels of AMP, ADP, ATP, ATP complex with Fe, MP, HDP and DGP were determined. Twenty blood donors served as a control group. The obtained results showed a statistically highly significant rise in ADP concentration in all investigated subgroups of hyperlipidaemic subjects, and a non-significant quantitative shift of other determined phosphate compounds.