DHEAS repeated treatment improves cognitive and behavioral deficits after mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is characterized by diffused symptoms, which when combined are called "post-concussion syndrome". Dehydroepiandrosterone sulfate (DHEAS) is a neuroactive neurosteroid. Previously, we have reported that closed head mTBI causes long lasting cognitive deficits and depressive-like behavior. In the present study we describe the effects of DHEAS on the behavior of mice that suffered closed head mTBI. Following the induction of mTBI, mice were treated once a week with DHEAS (s.c. 20 mg/kg) and their performance in the passive avoidance test and the forced swimming test (FST) were evaluated 7, 30, 60 and 90 days post-injury. The most important interactions were between injury and injection (passive avoidance; p<0.001 and FST; p=0.001), meaning that DHEAS has beneficial effects only when given to injured animals. Our results demonstrate that the long-term cognitive and behavioral effects induced by mTBI may be improved by a repeated weekly treatment with DHEAS.

Mild traumatic brain injury induces persistent cognitive deficits and behavioral disturbances in mice.

Victims of mild traumatic brain injury (mTBI) do not show clear morphological brain defects, but frequently suffer from long-lasting cognitive deficits, emotional difficulties and behavioral disturbances. In the present study, we investigated the effects of experimental mTBI in mice on cognition, spatial and non-spatial tasks, and depressive-like behavior in mice. Experimental brain injury was induced using a concussive head trauma, which creates the TBI by a weight-drop device. Different groups of mice were tested at 7, 30, 60, and 90 days post-injury for cognitive function (the swim T-maze and the passive avoidance test) and for depression-like behavior (the forced swimming test). These tests have been used infrequently in the past in mTBI research. Significant differences were observed between the injured mice compared to the controls in both the swim T-maze (day 30: p < 0.001) and passive avoidance (day 30: p < 0.05) tests. In addition, a significant difference was detected in the forced swimming test between the injured mice and the controls (day 7: p < 0.05; day 90: p < 0.01), which showed a depressive- like state in the injured animals beginning 7 days post-injury. These results demonstrate that persistent deficits in these tests of cognitive learning abilities and emergence of depressive-like behavior in injured mice are similar to those reported in human post-concussion syndrome.

Age-dependent differential expression of BACE splice variants in brain regions of tg2576 mice.

Plaques found in the brains of patients suffering from Alzheimer's disease (AD) mainly consist of beta-amyloid (Abeta), which is produced by sequential cleaving of amyloid precursor protein (APP) by two proteolytic enzymes, beta- and gamma-secretases. Any change in the fine balance between these enzymes and their substrate may contribute to the etio-pathogenesis of AD. Indeed, the protein level and enzymatic activity of beta-secretase (BACE), but not its mRNA level, were found elevated in brain areas of AD patients who suffer a high load of Abeta plaque formation. Similarly, increased BACE activity but no mRNA change was observed in a transgenic mouse model of AD, tg2576, in which over expression of the Swedish mutated human APP leads to Abeta plaque formation and learning deficits. Based on the recent demonstration of four BACE splice variants with different enzymatic activity, the discrepancy between BACE activity and mRNA expression may be explained by the altered BACE alternative splicing. To test this hypothesis, we studied the expression of all BACE splice variants in different brain areas of tg2576 mice at age of 4 months and 1 year old. We found developmental and regional differences between wild-type and tg2576 mice. Our results indicate that over expression of APP in tg2576 mice leads to the altered alternative splicing of BACE and the increase of its enzymatically more active splice variant (I-501).

[Fournier's gangrene. Our experience over 10 years. A review of the literature]. / Gangrena de Fournier. Nuestra experiencia en los últimos 10 años. Revisión de la literatura.

OBJECTIVE: To report our experience over the last 10 years with Fournier's gangrene, an extensive fulminant infection of the perineoscrotal region, and to review the literature. METHODS: The medical records of 9 patients with Fournier's gangrene that had been diagnosed from January 1988 to December 1997 were reviewed. Patient age, etiology and predisposing factors, microbiological findings, duration of hospital stay, treatment and outcome were analyzed. RESULTS: The mean age of the patients was 53.8 years (range 43-71). The source of the gangrene was perirectal (22.22%), urinary (66.66%) and cutaneous (11.11%). Predisposing factors included diabetes mellitus, alcoholism, malnutrition and low socio-economic status. All patients were treated with surgical debridement and broad-spectrum antimicrobial therapy. Two patients underwent delayed reconstructive surgery. Cystostomy was performed in 100% of the cases. Two patients died from severe sepsis. CONCLUSIONS: Necrotizing fasciitis of the perineum and genitalia is a severe condition with a high morbidity and mortality. Good management is based on aggressive debridement, broad-spectrum antibiotics and intensive supportive care.

[Mitomycin C for the treatment of superficial tumors of the bladder (Tis-Ta-T1) with one or more risk factors. Argentinian Cooperative Group of Oncourology (GCAO)]. / Mitomicina-C para el tratamiento de los tumores superficiales de vejiga (Tis-Ta-T1) con uno o más factores de riesgo. Grupo Cooperativo Argentino de Oncourología (GCAO).

OBJECTIVES: To determine the efficacy and toxicity of intravesical mitomycin C in superficial bladder tumors (Tis Ta T1) completely resected with one or more risk factors. (Protocol U. 01/90). METHODS: The patients received six instillations weekly of 40 mg mitomycin C within 15 days post-TUR of a superficial bladder tumor with one or more risk factors: histological grade 3, tumor size more than 3 cm and/or multicentric lesion. The patients were evaluated by cystoscopy every three months for the first two years and every six months thereafter. Toxicity was evaluated according to Miller's score. Tumor recurrence, disease-free interval and survival were analyzed. RESULTS: 126 patients were entered into the study; of these, 110 were evaluable. At 18 months mean follow-up (range 6-36 months), 77 patients (70%) remain disease-free; the mean time to recurrence was 13.8 months. There were no differences between patients with one, two or three risk factors or those who received or did not receive previous treatments. The patients tolerated the treatment well; there were no dropouts or systemic toxicity. CONCLUSIONS: 1. At 18 months mean follow-up, 77 of 110 patients (70%) remain disease-free; 2. The mean time to recurrence was 13.8 months; 3. Local toxicity was minimal; 4. There were no dropouts due to toxicity; 5. Systemic toxicity was not observed.