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.

[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.

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.

[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.

[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.

[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.

[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.