Empiema pleural recidivante por Staphylococcus aureus tratado con instilaciones de vancomicina a través de un catéter pleural tunelizado / Recidivant pleural empyema from staphylococcus aureus treated with instilations of vancomycin through an indwelling pleural catheter

Los catéteres pleurales tunelizados (indwelling pleural catheter, IPC) tienen su indicación principal en el alivio sintomático de derrames pleurales malignos. No obstante, han sido empleados también en el tratamiento sintomático de derrames pleurales benignos de diferentes etiologías. Presentamos un caso de un empiema pleural recidivante por Staphylococcus aureus en un paciente pluripatológico, que fue tratado con instilaciones intrapleurales de antibióticos a través de un IPC

Indwelling pleural catheter (IPC) is mainly indicated in the treatment of symptomatic and malignant pleural effusions. Nevertheless it have also been used in treatment of benign pleural effusions of different etiologies. We present a case of recidivant pleural empyema from Staphylococcus aureus in a pluripathologic patient, who was treated with intrapleural instilations of antibiotics through an IPC

Two death pathways induced by sorafenib in myeloma cells: puma-mediated apoptosis and necroptosis

Purpose. Sorafenib is a multikinase inhibitor that targets the MAPK pathway and is currently used for the treatment of hepatocellular and renal carcinoma. Recently, it has been shown that sorafenib is also cytotoxic to multiple myeloma (MM) cells. Here, we have further analyzed the mechanism of sorafenib-induced death in MM cells. Methods. Cell death induced by sorafenib in MM cell lines and in plasma cells from MM patients was evaluated by analysis of gene expression by RT-MLPA and quantitative PCR, protein levels and functionality by Western blot and flow cytometry and gene silencing with siRNA. Results. Cell death was characterized by phosphatidylserine exposure, ΔΨm loss, cytochrome c release and caspase activation, hallmarks of apoptosis. DL50 at 24 h ranged from 6 to 10 µM. Ex vivo treatment with 20 µM sorafenib induced apoptosis in around 80 % myeloma cells from six multiple myeloma patients. Sorafenib induced caspase-dependent degradation of Bcl-xL and Mcl-1 proteins, destabilizing the mitochondria and speeding up the development of apoptosis. Sorafenib treatment increased levels of Puma at mRNA and protein level and gene silencing with siRNA confirmed a relevant role for Puma in the induction of apoptosis. Co-treatment with the pan-caspase inhibitor Z-VAD-fmk prevented cell death to a variable degree depending on the cell line. In RPMI 8226 cells, Z-VAD-fmk prevented most of sorafenib-induced death. However, death in MM.1S was only prevented by co-incubation with both Z-VAD-fmk and the RIP1K inhibitor necrostatin-1, indicating that under conditions of inefficient caspase activation, sorafenib induces death by necroptosis. Conclusion. Our results demonstrate a key role for Puma in the triggering of sorafenib-induced apoptosis and that this drug can also induce death by necroptosis in multiple myeloma cells (AU)

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Two death pathways induced by sorafenib in myeloma cells: Puma-mediated apoptosis and necroptosis.

PURPOSE: Sorafenib is a multikinase inhibitor that targets the MAPK pathway and is currently used for the treatment of hepatocellular and renal carcinoma. Recently, it has been shown that sorafenib is also cytotoxic to multiple myeloma (MM) cells. Here, we have further analyzed the mechanism of sorafenib-induced death in MM cells. METHODS: Cell death induced by sorafenib in MM cell lines and in plasma cells from MM patients was evaluated by analysis of gene expression by RT-MLPA and quantitative PCR, protein levels and functionality by Western blot and flow cytometry and gene silencing with siRNA. RESULTS: Cell death was characterized by phosphatidylserine exposure, ΔΨm loss, cytochrome c release and caspase activation, hallmarks of apoptosis. DL50 at 24 h ranged from 6 to 10 µM. Ex vivo treatment with 20 µM sorafenib induced apoptosis in around 80 % myeloma cells from six multiple myeloma patients. Sorafenib induced caspase-dependent degradation of Bcl-xL and Mcl-1 proteins, destabilizing the mitochondria and speeding up the development of apoptosis. Sorafenib treatment increased levels of Puma at mRNA and protein level and gene silencing with siRNA confirmed a relevant role for Puma in the induction of apoptosis. Co-treatment with the pan-caspase inhibitor Z-VAD-fmk prevented cell death to a variable degree depending on the cell line. In RPMI 8226 cells, Z-VAD-fmk prevented most of sorafenib-induced death. However, death in MM.1S was only prevented by co-incubation with both Z-VAD-fmk and the RIP1K inhibitor necrostatin-1, indicating that under conditions of inefficient caspase activation, sorafenib induces death by necroptosis. CONCLUSION: Our results demonstrate a key role for Puma in the triggering of sorafenib-induced apoptosis and that this drug can also induce death by necroptosis in multiple myeloma cells.

Generation of rabbit antibodies against death ligands by cDNA immunization.

Specificity problems, especially in immunoblot analysis, have been shown for several commercial antibodies raised against the death ligand Fas ligand (FasL) using conventional protein and/or peptide immunizations. In this work, we have optimized the development of rabbit antisera and isolated pAb against the death ligands FasL, Apo2 ligand/TRAIL and Apo3 ligand/TWEAK by cDNA intramuscular immunization. This alternative approach has generated specific pAb in all three cases, which are useful for immunoblot purposes. The present data suggest that for the production of antibodies against certain glycosylated membrane proteins, cDNA immunization could be the method of choice.

Characterization of the lipolytic pathways that mediate free fatty acid release during Fas/CD95-induced apoptosis.

We have undertaken a study to characterize the lipolytic pathway responsible for the generation of free fatty acids (FFA) during Fas/CD95-induced apoptosis in Jurkat cells. It was initially shown that the cellular lipid fraction that suffered the major quantitative decrease during Fas-induced apoptosis was that of phosphatidylcholine (PC). In addition, the secretion of palmitic acid-derived FFA was largely prevented by D609, an inhibitor of PC-specific phospholipase C (PC-PLC) and also by the diacylglycerol lipase (DAGL) inhibitor RHC-80267, suggesting that the secretion of these FFA during Fas-induced apoptosis is mediated by the generation of DAG by a PC-PLC activity and, sequentially, by a 1-DAGL activity which generates the FFA from its sn-1 position. The endocannabinoid 2-arachidonoyl glycerol (2-AG) should be generated as a sub-product of this pathway, but it did not accumulate inside the cells nor was secreted into the supernatant. Interestingly, the complete inhibition of free AA secretion during Fas-induced apoptosis was only achieved by using the AA trifluoromethylketone, which not only inhibits all types of phospholipase-A(2) (PLA(2)) activities, but also the described lytic activities on 2-AG. Using a combination of RHC-80267 and the iPLA(2)-specific inhibitor bromoenol lactone, it was shown that the DAGL pathway also cooperates with iPLA(2) in the generation of free arachidonate.

[Effectiveness of an intervention to provide information to patients with hypertension as short text messages and reminders sent to their mobile phone (HTA-Alert)]. / Eficacia de una intervención informativa a hipertensos mediante mensajes de alerta en el teléfono móvil (HTA-ALERT).

OBJECTIVE: To analyze the effect of an intervention to provide information with mobile phone text messages to patients with hypertension on compliance with therapy for hypertension. DESIGN: Comparative, controlled, multicenter, randomized cluster study. SETTING: 26 primary care health centers in Spain. PARTICIPANTS: 26 researchers were randomized to a control group or an intervention group (52 patients each, for a total of 104 patients). All patients were receiving monotherapy for uncontrolled hypertension. INTERVENTION: Patients in the control group received their physician's usual interventions. Patients in the intervention group received messages and reminders sent to their mobile phones 2 days per week during 4 months. MAIN OUTCOME MEASURES: Tablets were counted and blood pressure was measured at the start of the study and 1, 3, and 6 months later. The percentage of compliers, mean percentage of compliance and degree of control of hypertension were compared. The reduction in absolute and relative risk was calculated, as was the number of individuals needed to treat to avoid noncompliance. RESULTS: The results were evaluated for a total of 67 individuals (34 in the intervention group and 33 in the control group). The rate of compliance was 85.1% (CI, 74.9%-95.3%) overall, 85.7% (CI, 70.5%-100.9%) in the control group and 84.4% in the intervention group (CI, 70.7%-95.3%) (P=NS). Mean percentage compliance was 90.2%+/-16.3% overall, 88.1%+/-20.8% in the control group and 91.9%+/-11.6% in the intervention group (P=NS). The percentage of patients whose hypertension was controlled at the end of the study was 51.5% (CI, 34.4%-68.6%) in the control group and 64.7% (CI, 48.6%-80.8%) in the intervention group (P=NS). CONCLUSIONS: The telephone messaging intervention with alerts and reminders sent to mobile phones did not improve compliance with therapy in patients with hypertension.

Farnesyltransferase inhibitor BMS-214662 induces apoptosis in B-cell chronic lymphocytic leukemia cells.

B-cell chronic lymphocytic leukemia (B-CLL) cells develop resistance to nucleoside analogs over time. This chemoresistance may be caused by selection for B-CLL cells with defects in the particular apoptosis pathway triggered by these drugs. Therefore, anticancer agents that induce apoptosis through alternative pathways might be useful in treating chemoresistant B-CLL. Farnesyltransferase inhibitors (FTIs) are a class of synthetic drugs with definite molecular targets, which have demonstrated cytotoxicity against leukemic cell lines. We have studied the ex vivo effect of the FTI BMS-214662 on cells from 18 patients with B-CLL. Low concentrations (<1 microM) of BMS-214662 prevented farnesylation of the chaperone marker HDJ-2 and had no effect on Akt activation. BMS-214662 induced apoptosis in B-CLL cells from all patients studied, including those showing resistance to cladribine and fludarabine ex vivo and in vivo. Treatment with BMS-214662 induced loss of mitochondrial membrane potential (DeltaPsi(m)), phosphatidylserine exposure, proapoptotic conformational changes of Bax and Bak, reduction in Mcl-1 levels and activation of caspases 9 and 3. The general caspase inhibitor Z-VAD-fmk did not prevent BMS-214662-induced cell death. These results indicate that BMS-214662 may be a useful drug for treating B-CLL and, in particular, an alternative for the therapy of purine analog-resistant or relapsed B-CLL.

Intrauterine growth retardation: study of placental apoptosis.

We studied the rate of apoptosis in the placental tissue of pregnancies complicated with intrauterine growth retardation (IUGR) and compared it with the results obtained in normal placentas. Our results clearly demonstrate a strongly increased rate of apoptosis in placentas of children born with IUGR, suggesting severe placental dysfunction. The significance of these findings needs further study.

Eficacia de una intervención informativa a hipertensos mediante mensajes de alerta en el teléfono móvil (HTA-ALERT) / Effectiveness of an intervention to provide information to patients with hypertension as short text messages and reminders sent to their mobile phones (HTA-ALERT)

Objetivo. Analizar la eficacia, en el cumplimiento terapéutico de la hipertensión arterial, de una intervención informativa mediante mensajes de alerta al teléfono móvil de hipertensos. Diseño. Estudio comparativo, controlado, aleatorizado por grupos y multicéntrico. Emplazamiento. Veintiséis consultas de atención primaria de España. Participantes. Veintiséis investigadores aleatorizados a 2 grupos, que incluyeron a 104 hipertensos no controlados en monoterapia. Los investigadores se aleatorizaron al grupo control (GC) y al grupo de intervención (GI), compuestos ambos por 52 pacientes. Intervención. Los pacientes GC recibieron la intervención habitual de su médico, y los pacientes GI recibieron mensajes de alerta al teléfono móvil 2 días a la semana durante 4 meses. Mediciones principales. Se realizaron el recuento de comprimidos y la determinación de la presión arterial al inicio y a los 1, 3 y 6 meses. Se compararon los porcentajes de cumplidores, el porcentaje medio de cumplimiento y el grado de control de la hipertensión arterial. Se calculó la reducción del riesgo absoluto y relativo, así como el número de individuos en los que es necesario intervenir para evitar un incumplimiento. Resultados. Fueron evaluables 67 individuos (34 individuos en GI y 33 en GC). Tuvieron un buen cumplimiento terapéutico el 85,1 por ciento (intervalo de confianza [IC], 74,9-95,3) en el GC, el 85,7 por ciento (IC, 70,5-100,9), y el 84,4 por ciento en el GI (IC, 70,7-95,3) (p = NS). El porcentaje medio ñ desviación estándar de cumplimiento fue de 90,2 ñ 16,3 globalmente (GC, 88,1 ñ 20,8; GI, 91,9 ñ 11,6; p = NS). El porcentaje de controlados al final fue del 51,5 por ciento (IC, 34,4-68,6) en el GC y del 64,7 por ciento (IC, 48,6-80,8) en el GI (p = NS).Conclusiones. La intervención mediante mensajes de alerta al teléfono móvil de hipertensos no ha mejorado el cumplimiento terapéutico (AU)

Resultados de la primera encuesta sobre patrones de uso e interés por las nuevas tecnologías de los pacientes atendidos en Unidades de Hipertensión Arterial en España / Results of the first patient survey from Spanish arterial hypertension units regarding use patterns and interest in new technologies

El objetivo de este trabajo fue evaluar la accesibilidad a Internet y el interés por las nuevas tecnologías de los pacientes hipertensos asistidos en las Unidades de Hipertensión Arterial (HTA) españolas. Se contactó con 75 Unidades de Hipertensión de todo el territorio nacional para solicitar su colaboración. La recogida de datos se realizó mediante una encuesta de 15 preguntas facilitada por el personal de enfermería, o el propio médico, previamente instruidos. Las encuestas se cumplimentaron entre el 19 de noviembre y el 21 de diciembre de 2001.Se recogieron un total de 2.367 encuestas procedentes de más del 50 por ciento de las Unidades de HTA contactadas. El uso de Internet en el colectivo de pacientes hipertensos analizado no difiere de forma sustancial del uso de Internet en la población general. Se observa un elevado interés por el uso de nuevas tecnologías como una nueva herramienta en el control de la hipertensión por parte de los pacientes. Este interés se demuestra en que un 56 por ciento de los pacientes visitaría una página web dedicada a pacientes hipertensos, un 50 por ciento de los pacientes consultaría con su médico a través de Internet (si bien únicamente el 29 por ciento de los encuestados ha utilizado alguna vez Internet) y un 43,5 por ciento de los pacientes estaría dispuesto a recibir mensajes de salud en su teléfono móvil. En los pacientes hipertensos con edades comprendidas entre los 30 y los 60 años el uso de Internet se cifra en torno al 45 por ciento. Considerando que es en los pacientes más jóvenes donde la implantación de medidas sanitarias produce un mayor beneficio, parece indicado desarrollar programas informativos y formativos a través de Internet y las nuevas tecnologías. Por tanto, cabe afirmar que existe una demanda de nuevas herramientas tecnológicas por parte del colectivo de pacientes hipertensos (AU)

Role of caspases and apoptosis-inducing factor (AIF) in cladribine-induced apoptosis of B cell chronic lymphocytic leukemia.

We have evaluated the role of caspases and the mitochondrial apoptosis inducing-factor (AIF) in apoptosis induced by cladribine (2CdA), in vitro, in cells from patients of B-CLL and in peripheral blood lymphocytes from normal donors. In sensitive B-CLL cells, apoptosis was characterized by cell shrinking, loss of mitochondrial membrane potential (DeltaPsi(m)), phosphatidylserine exposure, activation of caspases 3, 7, 8 and 9, reduction of Mcl-1 levels, translocation of AIF from mitochondria to nucleus and chromatin condensation. No significant variations in the levels of Bcl-2, Bax and Bak proteins were noticed upon treatment with 2CdA. Co-treatment of cells with the pan-caspase inhibitor Z-VAD-fmk attenuated some morphological and biochemical characteristics of apoptosis and delayed 2CdA-induced DeltaPsi(m) loss, but did not prevent cell death. Z-VAD-fmk did not prevent 2CdA-induced AIF translocation but in this case apoptotic cells displayed only peripheral chromatin condensation, characteristic of AIF action. Reduced or negligible caspase 3 expression did not prevent 2CdA toxicity in cells from four patients. Cells from three patients that responded poorly to 2CdA lacked expression of caspases 9 or 3. Cells from another patient resistant to 2CdA expressed caspases 3, 7, 8 and 9 but they were not activated by treatment. These results indicate that execution of apoptosis is carried out independently by AIF and caspases, which are responsible for the development of apoptotic phenotype in response to 2CdA. Although caspases can also collaborate in DeltaPsi(m) loss, proapoptotic proteins from the Bcl-2 superfamily may be the key inducers of DeltaPsi(m) loss and apoptosis in B-CLL cells sensitive to 2CdA.

Increased mucosal tumour necrosis factor alpha production in Crohn's disease can be downregulated ex vivo by probiotic bacteria.

BACKGROUND AND AIMS: Tumour necrosis factor alpha (TNF-alpha) plays a key role in the pathogenesis of intestinal inflammation in Crohn's disease. The effect of bacteria on TNF-alpha release by intestinal mucosa was investigated. METHODS: Ileal specimens were obtained at surgery from 10 patients with Crohn's disease (ileal stricture) and five disease controls undergoing right hemicolectomy (caecal cancer). Mucosal explants from each specimen were cultured for 24 hours with either non-pathogenic Escherichia coli, Lactobacillus casei DN-114001, L bulgaricus LB10, or L crispatus (each study contained blank wells with no bacteria). Tissue and bacterial viability was confirmed by lactate dehydrogenase (LDH) release and culture. Concentrations of TNF-alpha were measured in supernatants and the phenotype of the intestinal lymphocytes was analysed by flow cytometry. RESULTS: Coculture of mucosa with bacteria did not modify LDH release. Release of TNF-alpha by inflamed Crohn's disease mucosa was significantly reduced by coculture with L casei or L bulgaricus; changes induced by L crispatus or E coli were not significant. The effect of L casei and L bulgaricus was not prevented by protease inhibitors. Coculture with L casei and L bulgaricus reduced the number of CD4 cells as well as TNF-alpha expression among intraepithelial lymphocytes from Crohn's disease mucosa. None of the bacteria induced changes in non-inflamed mucosa. CONCLUSIONS: Probiotics interact with immunocompetent cells using the mucosal interface and modulate locally the production of proinflammatory cytokines.

Differential secretion of Fas ligand- or APO2 ligand/TNF-related apoptosis-inducing ligand-carrying microvesicles during activation-induced death of human T cells.

Preformed Fas ligand (FasL) and APO2 ligand (APO2L)/TNF-related apoptosis-inducing ligand (TRAIL) are stored in the cytoplasm of the human Jurkat T cell line and of normal human T cell blasts. The rapid release of these molecules in their bioactive form is involved in activation-induced cell death. In this study, we show by confocal microscopy that FasL and APO2L/TRAIL are mainly localized in lysosomal-like compartments in these cells. We show also by immunoelectron microscopy that FasL and APO2L/TRAIL are stored inside cytoplasmic compartments approximately 500 nm in diameter, with characteristics of multivesicular bodies. Most of these compartments share FasL and APO2L/TRAIL, although exclusive APO2L/TRAIL labeling can be also observed in separate compartments. Upon PHA activation, the mobilization of these compartments toward the plasma membrane is evident, resulting in the secretion of the internal microvesicles loaded with FasL and APO2L/TRAIL. In the case of activation with anti-CD59 mAb, the secretion of microvesicles labeled preferentially with APO2L/TRAIL predominates. These data provide the basis of a new and efficient mechanism for the rapid induction of autocrine or paracrine cell death during immune regulation and could modify the interpretation of the role of FasL and APO2L/TRAIL as effector mechanisms in physiological and pathological situations.

Cladribine induces apoptosis in human leukaemia cells by caspase-dependent and -independent pathways acting on mitochondria.

We have studied the role of caspases and mitochondria in apoptosis induced by 2-chloro-2'-deoxyadenosine (cladribine) in several human leukaemic cell lines. Cladribine treatment induced mitochondrial transmembrane potential (DeltaPsi(m)) loss, phosphatidylserine exposure, caspase activation and development of typical apoptotic morphology in JM1 (pre-B), Jurkat (T) and U937 (promonocytic) cells. Western-blot analysis of cell extracts revealed the activation of at least caspases 3, 6, 8 and 9. Co-treatment with Z-VAD-fmk (benzyloxy-carbonyl-Val-Ala-Asp-fluoromethylketone), a general caspase inhibitor, significantly prevented cladribine-induced death in JM1 and Jurkat cells for the first approximately 40 h, but not for longer times. Z-VAD-fmk also partly prevented some morphological and biochemical features of apoptosis in U937 cells, but not cell death. Co-incubation with selective caspase inhibitors Ac-DEVD-CHO (N-acetyl-Asp-Glu-Val-Asp-aldehyde), Ac-LEHD-CHO (N-acetyl-Leu-Glu-His-Asp-aldehyde) or Z-IETD-fmk (benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone), inhibition of protein synthesis with cycloheximide or cell-cycle arrest with aphidicolin did not prevent cell death. Overexpression of Bcl-2, but not CrmA, efficiently prevented death in Jurkat cells. In all cell lines, death was always preceded by Delta Psi(m) loss and accompanied by the translocation of the protein apoptosis-inducing factor (AIF) from mitochondria to the nucleus. These results suggest that caspases are differentially involved in induction and execution of apoptosis depending on the leukaemic cell lineage. In any case, Delta Psi(m) loss marked the point of no return in apoptosis and may be caused by two different pathways, one caspase-dependent and the other caspase-independent. Execution of apoptosis was always performed after Delta Psi(m) loss by a caspase-9-triggered caspase cascade and the action of AIF.

A role of the mitochondrial apoptosis-inducing factor in granulysin-induced apoptosis.

Granulysin is a cytolytic molecule released by CTL via granule-mediated exocytosis. In a previous study we showed that granulysin induced apoptosis using both caspase- and ceramide-dependent and -independent pathways. In the present study we further characterize the biochemical mechanism for granulysin-induced apoptosis of tumor cells. Granulysin-induced death is significantly inhibited by Bcl-2 overexpression and is associated with a rapid (1-5 h) loss of mitochondrial membrane potential, which is not mediated by ceramide generation and is not inhibited by the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Ceramide generation induced by granulysin is a slow event, only observable at longer incubation times (12 h). Apoptosis induced by exogenous natural (C(18)) ceramide is truly associated with mitochondrial membrane potential loss, but contrary to granulysin, this event is inhibited by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Ceramide-induced apoptosis is also completely prevented by Bcl-2 overexpression. The nuclear morphology of cells dying after granulysin treatment in the presence of caspase inhibitors suggested the involvement of mitochondrial apoptosis-inducing factor (AIF) in granulysin-induced cell death. We demonstrate using confocal microscopy that AIF is translocated from mitochondria to the nucleus during granulysin-induced apoptosis. The majority of Bcl-2 transfectants are protected from granulysin-induced cell death, mitochondrial membrane potential loss, and AIF translocation, while a small percentage are not protected. In this small percentage the typical nuclear apoptotic morphology is delayed, being of the AIF type at 5 h time, while at longer times (12 h) the normal apoptotic morphology is predominant. These and previous results support a key role for the mitochondrial pathway of apoptosis, and especially for AIF, during granulysin-induced tumoral cell death.

[Patient assessment of the long-term benefits of surgery in inflammatory bowel disease]. / Valoración por el paciente de los beneficios a largo plazo de la cirugía de la enfermedad inflamatoria intestinal.

UNLABELLED: The objective of surgical treatment in ulcerative colitis (UC) and Crohn's disease (CD) differs. Surgery in UC is more aggressive and potentially curative whereas in CD it is more conservative and palliative. OBJECTIVE: To assess the opinion of patients with inflammatory bowel disease who underwent surgery in the distant past about the results and timing of surgery. MATERIAL AND METHODS: A total of 50 surgical patients (36 with CD and 14 with UC) who had undergone an intestinal surgical procedure at least one year before. The clinical characteristics of patients and details of surgery procedures were recorded. Also, a personal interview was conducted. Patients were asked about their current clinical status, surgical consequences and their opinion about the appropriate timing of surgery. RESULTS: Surgery for UC was total proctocolectomy in 85% of patients and it was on an emergency basis in 43% of them. Surgery for UC was partial intestinal or colonic resection, and it was on an emergency basis in 22% of them. Postsurgical complications were more common in UC than CD patients (50% versus 20%; p < 0.05). In CD surgery, recurrence of disease occurred in 78% of patients within a 2.6 years interval. Among UC and CD patients, 71% and 50%, respectively, reported that their presurgical expectatives had been fulfilled (p = 0.17). CONCLUSIONS: Surgery for UC is associated with an appreciable rate of complications; however, most patients had their expectatives fulfilled with surgery as long-term symptoms were controlled. As for CD, the patient's satisfaction degree was lower than or UC.

Valoración por el paciente de los beneficios a largo plazo de la cirugía de la enfermedad inflamatoria intestinal / Patient assessment of the long-term benefits of surgery in inflammatory bowel disease

El control de la hipertensión arterial mediante monoterapia farmacológica en Atención Primaria La intención del tratamiento quirúrgico es diferente en la colitis ulcerosa (CU) y en la enfermedad de Crohn (EC). En la CU es más agresiva y curativa, mientras que en la EC es más conservadora.Objetivo. Valorar la opinión que el paciente intervenido por enfermedad inflamatoria intestinal tiene de la cirugía a largo plazo y sobre el momento adecuado para su realización.Material y métodos. Se han estudiado 50 pacientes (36 con EC y 14 con CU) intervenidos al menos un año antes. Se evaluaron las características clínicas y quirúrgicas de los pacientes. Se realizó una entrevista personal y se les preguntó sobre su estado clínico actual, las secuelas posteriores a la cirugía y su opinión sobre la idoneidad del momento de la intervención.Resultados. La cirugía de la CU consistió en colectomía total en el 85 por ciento de los pacientes, siendo urgente en el 43 por ciento de ellos. En la EC la intervención consistió en resección intestinal o colónica parcial, practicándose de forma urgente en el 22 por ciento de los casos. La aparición de complicaciones postoperatorias fue más frecuente en la CU que en la EC (50 por ciento frente a 20 por ciento; p < 0,05). En la EC la recurrencia postquirúrgica fue del 78 por ciento en un seguimiento medio de 2,6 años. El 71 por ciento de pacientes con CU y el 50 por ciento con EC (p = 0,17) vieron cumplidas sus expectativas preoperatorias.Conclusiones. La cirugía de la CU tiene una apreciable tasa de complicaciones, pese a lo cual satisface la expectativa de la mayoría de los pacientes al controlar la enfermedad a largo plazo.En la EC el cumplimiento de las expectativas fue inferior al de la CU (AU)

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Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells.

Doxorubicin induces caspase-3 activation and apoptosis in Jurkat cells but inhibition of this enzyme did not prevent cell death, suggesting that another caspase(s) is critically implicated. Western blot analysis of cell extracts indicated that caspases 2, 3, 4, 6, 7, 8, 9, and 10 were activated by doxorubicin. Cotreatment of cells with the caspase inhibitors Ac-DEVD-CHO, Z-VDVAD-fmk, Z-IETD-fmk, and Z-LEHD-fmk alone or in combination, or overexpression of CrmA, prevented many morphological features of apoptosis but not loss of mitochondrial membrane potential (delta(psi)m), phospatidilserine exposure, and cell death. Western blot analysis of cells treated with doxorubicin in the presence of inhibitors allowed elucidation of the sequential order of caspase activation. Z-IETD-fmk or Z-LEHD-fmk, which inhibit caspase-9 activity, blocked the activation of all caspases studied, lamin B degradation, and the development of apoptotic morphology, but not cell death. All morphological and biochemical features of apoptosis, as well as cell death, were prevented by cotreatment of cells with the general caspase inhibitor Z-VAD-fmk or by overexpression of Bcl-2. Doxorubicin cytotoxicity was also blocked by the protein synthesis inhibitor cycloheximide. Delayed addition of Z-VAD-fmk after doxorubicin treatment, but prior to the appearance of cells displaying a low delta(psi)m, prevented cell death. These results, taken together, suggest that the key mediator of doxorubicin-induced apoptosis in Jurkat cells may be an inducible, Z-VAD-sensitive caspase (caspase-X), which would cause delta(psi)m loss, release of apoptogenic factors from mitochondria, and cell death.

An ORF from Bacillus licheniformis encodes a putative DNA repressor.

The complete sequence of a reading frame adjacent to the endo-beta-1,3-1,4-D-glucanase gene from Bacillus licheniformis is reported. It encodes a putative 171 amino acid residues protein with either, low significant sequence similarity in data banks or the corresponding orthologue in the recently sequenced Bacillus subtilis genome. Computer analyses predict a canonical Helix-Turn-Helix motif characteristic of bacterial repressors/DNA binding proteins. A maxicells assay shows that the encoded polypeptide is expressed. A DNA-protein binding, assay performed by gel electrophoresis shows that the expressed protein specifically binds to Bacillus licheniformis DNA.

Tyrosine phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase correlates with high proliferation rates in sublines derived from the Jurkat leukemia.

A prominent tyrosine phosphorylated protein of 85 kDa (p85) was detected in highly proliferative sublines derived from the Jurkat T cell leukemia. We undertook a study to characterize the identity of this protein and its possible role in the hyperproliferative phenotypes observed. Using immunoblot and immunoprecipitation techniques, this protein was characterized as the p85 regulatory subunit of phosphatidylinositol 3-kinase. Cell proliferation and p85 tyrosine phosphorylation was not affected by tyrphostin AG-490, an inhibitor of Jak kinases, wortmannin or LY294002, inhibitors of the activity of the catalytic phosphatidylinositol 3-kinase subunit. Herbimycin-A and PPI, inhibitors of src-like protein tyrosine kinases, and genistein, a general tyrosine kinase inhibitor, inhibited p85 tyrosine phosphorylation and induced cell death in the sublines. PD98059, an inhibitor of Mek, inhibited cell growth of the sublines, but not that of the parental cells. It was concluded that tyrosine phosphorylation of p85 is associated with highly proliferative tumoral phenotypes, at least in T cell leukemias, independent of the phosphatidylinositol 3-kinase activity of the catalytic subunit.