Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling

In the present study, we investigated whether mild-intensity physical exercise represents a successful strategy to enhance spatial learning and memory and hippocampal plasticity in aging rats, as previously described for long-term exposure to running wheel or treadmill exercise. Aging Wistar rats were submitted to short bouts (4-6 min) of exercise treadmill during five consecutive weeks. This mild-intensity exercise program increased muscle oxygen consumption by soleus and heart in aging rats and reversed age-related long-term spatial learning and memory impairments evaluated in the water maze and step-down inhibitory avoidance tasks. Remarkably, the observed cognitive-enhancing properties of short bouts of exercise were accompanied by the activation of serine/threonine protein kinase (AKT) and cAMP response element binding (CREB) pro-survival signaling that culminates in the marked increase on the brain-derived neurotrophic factor (BDNF) mRNA expression and BDNF protein levels on the hippocampus of aging rats. Altogether, these results indicate that short bouts of exercise represent a viable behavioral strategy to improve cognition and synaptic plasticity in aging rats which should be taken into account in further studies addressing the effects of physical exercise in aging subjects.     

Evidence for oxidative stress in tissues derived from succinate semialdehyde dehydrogenase-deficient mice

Summary Animal models of inborn errors of metabolism are useful for investigating the pathogenesis associated with the corresponding human disease. Since the mechanisms involved in the pathophysiology of succinate semialdehyde dehydrogenase (SSADH) deficiency (Aldh5a1; OMIM 271980) are still not established, in the present study we evaluated the tissue antioxidant defences and lipid peroxidation in various cerebral structures (cortex, cerebellum, thalamus and hippocampus) and in the liver of SSADH-deficient mice. The parameters analysed were total radical-trapping antioxidant potential (TRAP) and glutathione (GSH) levels, the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as thiobarbituric acid-reactive substances (TBARS). We first observed that the tissue nonenzymatic antioxidant defences were significantly reduced in the SSADH-deficient animals, particularly in the liver (decreased TRAP and GSH) and in the cerebral cortex (decreased GSH), as compared to the wild-type mice. Furthermore, SOD activity was significantly increased in the liver and cerebellum, whereas the activity of CAT was significantly higher in the thalamus. In contrast, GPx activity was significantly diminished in the hippocampus. Finally, we observed that lipid peroxidation (TBARS levels) was markedly increased in the liver and cerebral cortex, reflecting a high lipid oxidative damage in these tissues. Our data showing an imbalance between tissue antioxidant defences and oxidative attack strongly indicate that oxidative stress is involved in the pathophysiology of SSADH deficiency in mice, and likely the corresponding human disorder. Competing interests: None declared References to electronic databases: Succinic semialdehyde dehydrogenase (SSADH) deficiency, OMIM 271980.     

Pharmacotherapy of overactive bladder: epidemiology and pathophysiology of overactive bladder

INTRODUCTION: Overactive bladder (OAB) describes complex symptoms, comprising of urinary urgency, with or without urinary incontinence, often with increased daytime frequency and nocturia in the absence of infection or other obvious etiology. OAB is highly prevalent and affects physical and mental health, activities of daily life and the quality of life of millions of adults. The pathophysiology of OAB and detrusor overactivity is still not completely known, but is most probably multifactorial. AREAS COVERED: The epidemiology and pathophysiology of OAB is reviewed. A literature search using PubMed from 2000 to 2010 was undertaken for this review with pertinent older papers referenced as needed to gain a clearer understanding of the epidemiology of OAB and related bladder pathophysiology, which it is hoped will lead to more effective and better-tolerated treatments for OAB. EXPERT OPINION: With recent advances in our understanding of the basic science of OAB, it is becoming clear that the control of bladder function is far more complex than previously believed. Recent research has highlighted several potential targets for the treatment of OAB, particularly within the mechanosensory pathways.     

Ileovesicostomy for adults with neurogenic bladders: complications and potential risk factors for adverse outcomes

AIMS: Risk factors for complications following ileovesicostomy have not been well defined. This study's purpose was to examine outcomes following ileovesicostomy in adults and identify possible risk factors that may contribute to post-operative complications. METHODS: Retrospective database review identified ileovesicostomy procedures from August 1999 to September 2003. Demographic, pre-operative, and post-operative data were extracted. Statistical analysis determined whether risk factors influenced outcomes of urethral continence, re-operation, and post-operative complications. Factors included age, tobacco use, diabetes, neurogenic bladder etiology, body mass index, pre-operative indwelling catheterization, or simultaneous procedures including pubovaginal sling/urethral closure. RESULTS: 50 adults status-post ileovesicostomy were identified. At last follow-up, 36 patients (72%) were continent per urethra. The incidence of complications decreased significantly from 3.38 per patient to 1.16 post-operatively (P < 0.0001). Twenty-seven averaged 1.52 inflammatory or infectious post-operative complications per patient, 19 averaged 1.47 stomal complications, and 11 averaged 2.09 ileovesicostomy mechanical obstructions. Overall, 27 required 2.85 re-operations or additional procedures following ileovesicostomy. Sub-group analysis identified BMI (P = 0.0569) as a possible risk factor. Differences in outcomes based on age, tobacco use, diabetes, neurogenic bladder etiology, pre-operative indwelling catheterization, or urethral closure were not significant. CONCLUSIONS: Ileovesicostomy is a valuable management option for adults with neurogenic bladder unable to perform intermittent catheterization. The incidence of urinary tract comorbid events significantly decreased following ileovesicostomy though the onset of other complications should be considered. The morbidity associated with ileovesicostomy requires careful patient selection, close long-term follow-up, and potential subsequent interventions to address post-operative complications.     

Education predicts quality of life among men with prostate cancer cared for in the Department of Veterans Affairs: a longitudinal quality of life analysis from CaPSURE

BACKGROUND: Previous findings have suggested that patient educational attainment is related to cancer stage at presentation and treatment for localized prostate cancer, but there is little information on education and quality of life outcomes. Patient education level and quality of life were examined among men diagnosed with prostate cancer and cared for within an equal-access health care system, the Department of Veterans Affairs Veterans Health Administration (VA). METHODS: Participants were 248 men with prostate cancer cared for in the VA and enrolled in CaPSURE. Repeated-measures analysis of variance was used to examine quality of life over time according to education level, controlling for age, ethnicity, income, site of clinical care, and year of diagnosis. RESULTS: Patients with lower levels of education tended to be younger, nonwhite, and have lower incomes. Controlling for age, ethnicity, income, year of diagnosis, and site, men with less formal education, compared with those with more, had worse functioning in the physical (P=.0248), role physical (P=.0048), role emotional (P=.0089), vitality (P=.0034), mental health (P=.0054), social function (P=.0056), and general health (P=.0002) domains and worse urinary (P=.003) and sexual (P=.0467) side effects. CONCLUSIONS: Men with less education experienced worse health-related quality of life across a wide range of domains and greater urinary and sexual symptoms than their peers who had more education. Clinicians should be aware that, even within an equal access to health care system, men with less education are vulnerable, having greater difficulty functioning in their daily lives after their prostate cancer treatment.