Sos1 disruption impairs cellular proliferation and viability through an increase in mitochondrial oxidative stress in primary MEFs.

Using a 4-hydroxytamoxifen (4OHT)-inducible, conditional Sos1-null mutation, we analyzed wild-type (WT), single Sos1-KO, Sos2-KO and double Sos1/2 KO primary mouse embryonic fibroblasts (MEF) with an aim at evaluating the functional specificity or redundancy of the Sos1 and Sos2 alleles at the cellular level. The 4OHT-induced Sos1-KO and Sos1/2-DKO MEFs exhibited distinct flat morphology, enlarged cell perimeter and altered cytoskeletal organization that were not observed in the WT and Sos2-KO counterparts. The Sos1-KO and Sos1/2-DKO MEFs also displayed significant accumulation, in comparison with WT and Sos2-KO MEFs, of cytoplasmic vesicular bodies identified as autophagosomes containing degraded mitochondria by means of electron microscopy and specific markers. Cellular proliferation and migration were impaired in Sos1-KO and Sos1/2-DKO MEFs in comparison with WT and Sos2-KO MEFs, whereas cell adhesion was only impaired upon depletion of both Sos isoforms. RasGTP formation was practically absent in Sos1/2-DKO MEFs as compared with the other genotypes and extracellular signal-regulated kinase phosphorylation showed only significant reduction after combined Sos1/2 depletion. Consistent with a mitophagic phenotype, in vivo labeling with specific fluorophores uncovered increased levels of oxidative stress (elevated intracellular reactive oxygen species and mitochondrial superoxide and loss of mitochondrial membrane potential) in the Sos1-KO and the Sos1/2-DKO cells as compared with Sos2-KO and WT MEFs. Interestingly, treatment of the MEF cultures with antioxidants corrected the altered phenotypes of Sos1-KO and Sos1/2-DKO MEFs by restoring their altered perimeter size and proliferative rate to levels similar to those of WT and Sos2-KO MEFs. Our data uncover a direct mechanistic link between Sos1 and control of intracellular oxidative stress, and demonstrate functional prevalence of Sos1 over Sos2 with regards to cellular proliferation and viability.

Relación entre la actividad arginasa y el tiempo de conservación de los concentrados de hematíes / Relationship between arginase activity and the storage time of packed red blood cells

Objetivos. Dada la creciente evidencia a favor de una relación entre el tiempo de conservación de los concentrados de hematíes y las complicaciones postransfusionales, nos planteamos analizar la relación existente entre los niveles de enzima arginasa, parámetros bioquímicos y de hemólisis, con el tiempo de conservación de concentrados de hematíes transfundidos. Material y métodos. Diseñamos un estudio prospectivo que incluyó 24 unidades de concentrado de hematíes, que habían sido transfundidos consecutivamente a pacientes de nuestro hospital. Luego de registrar el tiempo de conservación de cada bolsa, se extrajeron 15ml de sangre para determinar la actividad arginasa, los datos bioquímicos y de hemólisis. Se realizó un análisis univariante de todos los parámetros registrados y se incluyeron aquellos que resultaron significativos en un modelo de regresión múltiple (p<0,05). Resultados. El tiempo promedio de conservación fue de 18,6±6,1 días (rango: 6-31 días), con un hematocrito de 59,8%±0,05%, una hemoglobina 20,3±1,8g/dl, un pH de 6,5±0,1 y una actividad arginasa de 140,1±124,0 mU/ml. Se observó una relación lineal en el análisis univariante entre el tiempo de conservación y el pH (p=0,001), el HCO3act (p=0,001), el índice hemolítico (p=0,035) y la SpO2 (p=0,01). Una vez ajustados las variables de confusión procedentes del modelo univariante, se observó una relación lineal entre la actividad arginasa y el tiempo de conservación (p=0,031). Conclusiones. Nuestro trabajo muestra una relación lineal directamente proporcional entre el tiempo de conservación de los concentrados de hematíes y la actividad arginasa presente en los mismos. Sugerimos que estos hallazgos podrían estar relacionados con la elevada incidencia de complicaciones tras la transfusión que puede ser directamente proporcional a su tiempo de conservación(AU)

Objectives. Given the increasing evidence regarding a relationship between packed red blood cells storage time and post-transfusion complications, we decided to determine the relationship between the arginase enzyme levels, biochemical parameters and haemolysis, with the storage time of transfused packed red blood cells. Material and methods. We designed a prospective study that included 24 units of packed cells that had been consecutively transfused to patients of our hospital. After recording the storage time of each bag, 15ml of blood was removed to determine arginase activity, biochemical parameters and haemolysis. A univariate analysis was performed on all the recorded parameters, and included those that were significant in the multiple regression model (P<.05). Results. The mean storage time was 18.6±6.1 days (range: 6-31 days), with a haematocrit of 59.8%±0.05%, a haemoglobin of 20.3±1.8g/dl, a pH of 6.5±0.1, and an arginase activity of 140.1±124.0mU/ml. A linear relationship was observed in the univariate analysis between the storage time and the pH (P=.001), the actualHCO3 (P=.001), the haemolysis index (P=.035) and the SpO2 (P=.01). Once adjusted for the confounding variables of the univariate model, a linear relationship was observed between the arginase activity and the storage time (P=.031). Conclusions. Our study shows a directly proportional linear relationship between the storage time of packed red blood cells and their arginase activity. We suggest that these findings could be associated with the high incidence of complications after transfusion that may be directly proportional to their storage time(AU)

[Relationship between arginase activity and the storage time of packed red blood cells]. / Relación entre la actividad arginasa y el tiempo de conservación de los concentrados de hematíes.

OBJECTIVES: Given the increasing evidence regarding a relationship between packed red blood cells storage time and post-transfusion complications, we decided to determine the relationship between the arginase enzyme levels, biochemical parameters and haemolysis, with the storage time of transfused packed red blood cells. MATERIAL AND METHODS: We designed a prospective study that included 24 units of packed cells that had been consecutively transfused to patients of our hospital. After recording the storage time of each bag, 15 ml of blood was removed to determine arginase activity, biochemical parameters and haemolysis. A univariate analysis was performed on all the recorded parameters, and included those that were significant in the multiple regression model (P<.05). RESULTS: The mean storage time was 18.6±6.1 days (range: 6-31 days), with a haematocrit of 59.8%±0.05%, a haemoglobin of 20.3±1.8 g/dl, a pH of 6.5±0.1, and an arginase activity of 140.1±124.0 mU/ml. A linear relationship was observed in the univariate analysis between the storage time and the pH (P=.001), the actual HCO(3) (P=.001), the haemolysis index (P=.035) and the SpO(2) (P=.01). Once adjusted for the confounding variables of the univariate model, a linear relationship was observed between the arginase activity and the storage time (P=.031). CONCLUSIONS: Our study shows a directly proportional linear relationship between the storage time of packed red blood cells and their arginase activity. We suggest that these findings could be associated with the high incidence of complications after transfusion that may be directly proportional to their storage time.

[Renal synchronous tumor: association of renal adenocarcinoma and transitional tumor of renal pelvis, in the same kidney, an exceptional discovery]. / Tumor sincrónico renal: asociación de adenocarcinoma renal y tumor transicional de pelvis renal, en el mismo riñón, un hallazgo excepcional.

The renal cell tumour supposes 1% of the adult's tumors, while the transitional carcinoma has an incidence of 7%. The simultaneous appearance of a carcinoma of renal cells, and a transitional tumour of pelvis in the same kidney, they suppose an exceptional fact not existing but of 30 cases published in the world, presenting an approximate incidence of 0.14% of the pathology renal tumoral. We present a new case of this unusual association that supposes the 4 case indexed in the literature in Spanish.

Tumor sincrónico renal: asociación de adenocarcinoma renal y tumor transicional de pelvis renal, en el mismo riñón, un hallazgo excepcional / Renal synchronous tumor: association of renal adenocarcinoma and transitional tumor of renal pelvis, in the same kidney, an exceptional discovery

El tumor de células renales supone el 1% de los tumores del adulto, mientras que el carcinoma transicional tiene una incidencia del 7%. La aparición simultánea de un carcinoma de células renales, y un tumor transicional de pelvis en el mismo riñón, suponen un hecho excepcional no existiendo más de 30 casos publicados en el mundo, presentando una incidencia aproximada del 0,14% de la patología tumoral renal. Presentamos un nuevo caso de esta inusual asociación que supone el 4caso referenciado en la literatura en español (AU)

The renal cell tumour supposes 1% of the adult’s tumors, while the transitional carcinoma has an incidence of 7%. The simultaneous appearance of a carcinoma of renal cells, and a transitional tumour of pelvis in the same kidney, they suppose an exceptional fact not existing but of 30 cases published in the world, presenting an approximate incidence of 0.14% of the pathology renal tumoral. We present a new case of this unusual association that supposes the 4 case indexed in the literature in Spanish (AU)

Self-expanding metallic ureteral stents for treatment of ureteral stenosis after kidney transplantation.

The incidence of post-renal transplantation ureteral stenosis ranges from 2%-12%. Because the role of self-expanding ureteral metallic stents for its treatment has been scarcely reported, the aim of this study was to evaluate the efficacy of Nitinol stents. Eleven ureteral stenoses in patients with chronic graft dysfunction (8 cases) or high surgical risk (3 cases) were treated by antegrade percutaneous implantation of Nitinol stents through a nephrostomy tract. The mean follow-up period was 48 +/- 7 months (range, 3-85 months). The patency rate at the moment of return to dialysis, death, or last check-up was 73% (8/11). Three patients (27%) developed stent occlusion. Two patients were treated using a trans-stent double-J catheter and 1 patient using stent removal and pyeloureterostomy using the native ureter. The mean percentage decrease in serum creatinine (Cr) level after stent implantation was 41% (range, 14%-63%). Nitinol ureteral stent implantation is an effective alternative for the treatment of ureteral stenosis in patients with chronic graft dysfunction or high surgical risk.

Neuromodulación de raíces sacras. Experiencia de nuestro centro 1998-2003. A propósito de 18 implantes definitivos de neuromodulación / Sacral root neuromodulation. Experience in our site: 1998-2003, concerning 18 definite neuromodulation implants

OBJETIVO: La neuromodulacion de raíces sacras es una técnica eficaz para el tratamiento de la Disfunción Miccional Crónica (DMC), refractaria a tratamientos convencionales. En la actualidad están surgiendo nuevas indicaciones en el ámbito urológico, como el dolor pélvico crónico y la cistitis intersticial. Diversos grupos de cirujanos digestivos están optando por esta técnica para el tratamiento de patología rectal (estreñimiento, disfunción esfinteriana). Este trabajo aporta nuestra experiencia en el tratamiento de pacientes con DMC y los resultados comparativos al año del implante de todos los pacientes. MATERIAL Y MÉTODOS: Desde diciembre de 1998 a julio del 2003 hemos realizados 18 implantes definitivos de neuromodulacion. La indicación principal fue la DMC, en un 62,5% de los pacientes. El seguimiento de los pacientes lo realizamos al mes, tres meses, y posteriormente cada seis meses. Este se realiza mediante diario miccional y cuestionario de calidad de vida. El implante del electrodo en los 16 primeros pacientes se ha realizado mediante cirugía abierta, mientras que los 2 siguientes se ha colocado el electrodo mediante técnica percutánea, utilizando el kit “Tined Lead”. RESULTADOS: Comparamos resultados al año del implante en todos los pacientes. Se han realizado 18 implantes de neuromodulación de los cuales 14 (77,7%) han sido en mujeres y 4 (22,3%) en varones. La edad media es de 52,56 años. La indicación del implante en un 72,2% de los pacientes fue por DMC, un 22,1% por incontinencia mixta (urinaria y fecal), y un 5,5% fue por cistopatía intersticial. La mejoría de los síntomas al año del implante, medidos por el calendario miccional y el cuestionario de calidad de vida fue de 76,4%. La mejoría clínica fue mayor en los pacientes con síntomas de urgencia, que los pacientes con predominio de la sintomatología de vaciado

OBJECTIVE: Sacral root neuromodulation is an effective technique for the treatment of Chronic Micturition Dysfunction (CMD) refractory to conventional therapy. New indications such as chronic pelvic pain and interstitial cystitis are currently making their way within the urologic setting. Several groups of gastric surgeons are now choosing this technique for the management of rectal diseases (constipation, sphincter dysfunction). This paper contributes our experience in the treatment of patients with CMD and the comparative results at one year from implant in all patients. MATERIAL AND METHODS: From December 1998 through July 2003, 18 neuromodulation definite implants were performed. The main indication was CMD in 62.5% patients. Follow up of patients was done at one month and three months, and every six months thereafter. Follow up is conducted through a micturition diary and QoL questionnaire. Electrode implant in the first 16 patients was achieved by open surgery. The next 2 patients had the electrode placed by a percutaneous technique using the “Tined Lead” kit. RESULTS: Results at one year after implant were compared in all patients. The total number of neuromodulation implants placed was 18, 14 (77.7%) of which were women and 4 (22.3%) men. Mean age was 52.56 years. Implant indication was CMD in 72.2% patients, mixed incontinence (urinary and faecal) in 22.1%, and interstitial cystic disease in 5.5%. Symptoms improvement at one year from implant, as determined by a micturition diary and QoL questionnaire was 76.4%. Clinical improvement was greater in patients with urgency symptoms than in patients with predominance of voiding symptoms

[Sacral root neuromodulation. Experience in our site: 1998-2003, concerning 18 definite neuromodulation implants]. / Neuromodulación de raíces sacras. Experiencia de nuestro centro 1998-2003. A propósito de 18 implantes definitivos de neuromodulación.

OBJECTIVE: Sacral root neuromodulation is an effective technique for the treatment of Chronic Micturition Dysfunction (CMD) refractory to conventional therapy. New indications such as chronic pelvic pain and interstitial cystitis are currently making their way within the urologic setting. Several groups of gastric surgeons are now choosing this technique for the management of rectal diseases (constipation, sphincter dysfunction). This paper contributes our experience in the treatment of patients with CMD and the comparative results at one year from implant in all patients. MATERIAL AND METHODS: From December 1998 through July 2003, 18 neuromodulation definite implants were performed. The main indication was CMD in 62.5% patients. Follow up of patients was done at one month and three months, and every six months thereafter. Follow up is conducted through a micturition diary and QoL questionnaire. Electrode implant in the first 16 patients was achieved by open surgery. The next 2 patients had the electrode placed by a percutaneous technique using the "Tined Lead" kit. RESULTS: Results at one year after implant were compared in all patients. The total number of neuromodulation implants placed was 18, 14 (77.7%) of which were women and 4 (22.3%) men. Mean age was 52.56 years. Implant indication was CMD in 72.2% patients, mixed incontinence (urinary and faecal) in 22.1%, and interstitial cystic disease in 5.5%. Symptoms improvement at one year from implant, as determined by a micturition diary and QoL questionnaire was 76.4%. Clinical improvement was greater in patients with urgency symptoms than in patients with predominance of voiding symptoms.

Recidiva tardía de carcinoma epidermoide de pene / Epidermoid pennis carcinoma recidive

OBJETIVO: Presentar un caso de recidiva de carcinoma epidermoide de pene a los 21 años de la cirugía. MÉTODO: Se trata de un paciente de 85 años con antecedentes de penectomía parcial por carcinoma epidermoide, que presenta lesión excrecente a nivel de glande de 1 mes de evolución. Se biopsia siendo el resultado carcinoma epidermoide por lo que se realiza penectomía total con uretrostomía cutánea. RESULTADO: El estudio histopatológico de la pieza confirmó un carcinoma epidermoide bien diferenciado (AU)

OBJETIVE: We report a recidive of pennis carcinoma after 21 years of surgery. METHODS: This is the case of a male of 85 years old, with parcial penectomy; by epidermoid carcinoma. In phisics exploration, that it displays excrecente lesion at level of glande of 1 month of evolution. Biopsy being the result of epidermoid carcinoma reason why is made. Total penectomy, a with cutaneus uretrostomy. RESULTS: The histopathological study of the piece, confirm a epidermoid carcinoma well differentiated (AU)

[Testicular torsion in the geriatric patient. Review of the literature apropos of a case]. / Torsión testicular en el paciente geriátrico. Y revisión de la literatura: a propósito de un caso.

Testicular torsion in adult, is an uncommonly etiology, but we should make differencial diagnosis in every person over thirty years old, with acute scrotum. The wrong diagnosis raises the incidence orchiectomy in adults for vascular etiology. We report a male of 74 years old with acute scrotum and review of the literature.

Torsión testicular en el paciente geriátrico y revisión de la literatura: a propósito de un caso / Testicular torsion in adults and literature revision: a propos of one case

La torsión testicular en el adulto, es una nosología infrecuente aunque debe de entrar dentro del diagnostico diferencial de cualquier adulto de mas de treinta años, con cuadro de escroto agudo. El retraso e incorrecto diagnóstico, aumenta la frecuencia de orquiectomías por procesos vasculares en el adulto frente al niño. Presentamos el caso de varón de 74 años con escroto agudo, y revisión de la literatura (AU)

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[Surgical management and complications of urinary stress incontinence: our experience in 385 patients operated on during the last 25 years]. / Manejo quirúrgico y complicaciones de la I.U.E: nuestra experiencia en 385 pacientes operadas en los últimos 25 años.

We present the results and complications found and compared in 2 large series of patients who underwent a surgical procedure to avoid Urinary Stress Incontinence in our hospital. From january of 1994 to december of 2001 we collected 195 patients with an average age of 57.9 y we compared them with a prior series of 189 patients collected between january of 1976 and december of 1993, with an average age of 53.6. The continence rate was similar in both series (70.8% pre-94 and 74.5% post 94), slight incontinence 22.7% pre-94 and 19.2% post-94 and for complete incontinence 6.3% pre-94 and 6.2% post-94. The Burch procedure was the most common and also shows the greatest effectiveness in our trial involving 113 cases and a continence rate of 74.3% in the first series and 144 cases and 77% respectively in the second series. The most common complications were very similar in both groups: tract urinary infection (5.2% and 9% first and second group), surgical wound infection (4.2% and 2.2% respectively). We conclude that in spite of the introduction of new and useful surgical procedure (TVT, periurethal substances injection...) the greatest long term success rate still corresponds to the Burch colposuspension.

Manejo quirúrgico y complicaciones de la I.U.E.: Nuestra experiencia en 385pacientes operadas en los últimos 25 años / Surgical management and urinary stress incontinence complications: our experience in 385 female operated patients during the last 25 years

Se presentan los resultados y complicaciones obtenidos y comparados en dos grandes series de pacientes operadas de Incontinencia Urinaria de Esfuerzo (I.U.E) en nuestro servicio. Desde enero de 1994 a diciembre de 2001 hemos recogido 195 pacientes con una edad media de 57,9 y las hemos comparado con una serie previa de 189 pacientes que comprende desde enero de 1976 hasta diciembre de 1993 con una edad media de 53,6 años. La tasa de pacientes continentes en ambas series fue similar (70,8 por ciento pre-94 y 74,5 por ciento post-94), leve incontinente en 22,7 por ciento pre-94 y 19,2 por ciento post-94 e incontinente 6,3 por ciento pre-94 y 6,2 por ciento post-94.La técnica de Burch es la más empleada y corresponde a la más eficaz en el estudio con 113 pacientes y un 74,3 por ciento de pacientes continentes en la primera serie y 144 pacientes con 77 por ciento continentes en la segunda serie. Las complicaciones más frecuentes fueron las mismas en las dos series: infección del tracto urinario (5,2 por ciento y 9 por ciento en primera y segunda serie) e infección de herida quirúrgica (4,2 por ciento y 2,2 por ciento respectivamente).Concluimos que a pesar de la introducción de nuevas y útiles técnicas correctoras (TVT, inyección de sustancias periuretrales...) la mayor tasa de éxito a largo plazo continúa siendo la colposuspensión tipo Burch (AU)

[Late recurrence of penile epidermoid carcinoma]. / Recidiva tardía de carcinoma epidermoide de pene.

OBJECTIVE: We report a recidive of penis carcinoma after 21 years of surgery. METHODS: This is the case of a male of 85 years old, with partial penectomy; by epidermoid carcinoma. In physics exploration, that it displays excrecente lesion at level of gland of 1 month of evolution. Biopsy being the result of epidermoid carcinoma reason why is made. Total penectomy, a with cutaneus uretrostomy. RESULTS: The histopathological study of the piece, confirm a epidermoid carcinoma well differentiated.