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- Gomez-Pinilla, Pedro J., et al.
(author)
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Effect of melatonin on age associated changes in guinea pig bladder function
- 2007
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In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 177:4, s. 1558-1561
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Journal article (peer-reviewed)abstract
- Purpose: The incidence of urinary incontinence increases with age but the cause and effect relationship between aging and altered bladder function is poorly understood. It was suggested that melatonin can ameliorate negative effects induced by aging by its free radical scavenging activity and its ability to decrease oxidative stress. We investigated the changes in bladder function evoked by aging and the possible benefits of melatonin treatment on age related bladder disturbances. Materials and Methods: Bladder function was assessed using cystometry in conscious, freely moving female guinea pigs. Animals were grouped according to age as young adults (4 months old) and senescents (18 to 20 months old). A group of senescent animals were treated with 2.5 mg kg(-1) day(-1) melatonin for 21 days. Results: Aging led to increased detrusor activity, as demonstrated by short micturition intervals, decreased bladder capacity and spontaneous contractions during the filling phase. During the voiding phase aged animals showed lower micturition pressures than young adults. Melatonin counteracted the cystometric changes in senescent animals and restored micturition parameters to those of young adults. Conclusions: These results show that in guinea pigs aging induces detrusor overactivity. Melatonin treatment improved age induced changes in bladder function. If similar effects can be demonstrated in humans, melatonin treatment may be a new approach to decrease the impact of age related bladder disorders.
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| 2. |
- Gomez-Pinilla, Pedro J, et al.
(author)
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Melatonin restores impaired contractility in aged guinea pig urinary bladder
- 2008
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In: Journal of Pineal Research. - : Blackwell Publishing Ltd. - 1600-079X .- 0742-3098. ; 44:4, s. 416-425
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Journal article (peer-reviewed)abstract
- Urinary bladder disturbances are frequent in the elderly population but the responsible mechanisms are poorly understood. This study evaluates the effects of aging on detrusor myogenic contractile responses and the impact of melatonin treatment. The contractility of bladder strips from adult, aged and melatonin-treated guinea pigs was evaluated by isometric tension recordings. Cytoplasmatic calcium concentration ([Ca2+](i)) was estimated by epifluorescence microscopy of fura-2-loaded isolated detrusor smooth muscle cells, and the levels of protein expression and phosphorylation were quantitated by Western blotting. Aging impairs the contractile response of detrusor strips to cholinergic and purinergic agonists and to membrane depolarization. The impaired contractility correlates with increased [Ca2+](i) in response to the stimuli, suggesting a reduced Ca(2+)sensitivity. Indeed, the agonist-induced contractions in adult strips were sensitive to blockade with Y27362, an inhibitor of Rho kinase (ROCK) and GF109203X, an inhibitor of protein kinase C (PKC), but these inhibitors had negligible effects in aged strips. The reduced Ca2+ sensitivity in aged tissues correlated with lower levels of RhoA, ROCK, PKC and the two effectors CPI-17 and MYPT1, and with the absence of CPI-17 and MYPT1 phosphorylation in response to agonists. Interestingly, melatonin treatment restored impaired contractility via normalization of Ca2+ handling and Ca2+ sensitizations pathways. Moreover, the indoleamine restored age-induced changes in oxidative stress and mitochondrial polarity. These results suggest that melatonin might be a novel therapeutic tool to palliate aging-related urinary bladder contractile impairment.
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| 3. |
- Bivalacqua, Trinity J., et al.
(author)
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Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1 alpha
- 2007
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In: BJU International. - 1464-4096 .- 1464-410X. ; 99:6, s. 1488-1494
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Journal article (peer-reviewed)abstract
- To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1 beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1 alpha to the erectile compartment on erectile function in a rat model of diabetes. Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMV beta gal or AdCMVPKG1 alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control. Compared to controls, AdCMV beta gal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1 alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1 alpha and PKG1 beta was lower in corporal tissue from DM AdCMV beta gal-transfected rats than in controls. PKG1 alpha expression was improved after AdCMVPKG1 alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1 alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control. PKG1 alpha and PKG1 beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1 alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1 alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.
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| 5. |
- Hedlund, P. O., et al.
(author)
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Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer : Part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5
- 2008
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In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 42:3, s. 220-229
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Journal article (peer-reviewed)abstract
- Objective. To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP, Estradurin®) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. Material and methods. In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240mg i.m. twice a month for 2months and thereafter monthly, or flutamide (Eulexin®) 250mg t.i.d. per os in combination with either triptorelin (Decapeptyl®) 3.75mg i.m. per month or on an optional basis bilateral orchidectomy. Results. At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). Conclusions. PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis. © 2008 Taylor & Francis.
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| 7. |
- Leps, J, et al.
(author)
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Long-term effectiveness of sowing high and low diversity seed mixtures to enhance plant community development on ex-arable fields
- 2007
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In: Applied Vegetation Science. - 1402-2001. ; 10:1, s. 97-110
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Journal article (peer-reviewed)abstract
- Questions: How is succession on ex-arable land affected by sowing high and low diversity mixtures of grassland species as compared to natural succession? How long do effects persist? Location: Experimental plots installed in the Czech Republic, The Netherlands, Spain, Sweden and the United Kingdom. Methods: The experiment was established on ex-arable land, with five blocks, each containing three 10 m x 10 m experiment tal plots: natural colonization, a low- (four species) and high-diversity (15 species) seed mixture. Species composition and biomass was followed for eight years. Results: The sown plants considerably affected the whole successional pathway and the effects persisted during the whole eight year period. Whilst the proportion of sown species (characterized by their cover) increased during the study period, the number of sown species started to decrease from the third season onwards. Sowing caused suppression of natural colonizing species, and the sown plots had more biomass. These effects were on average larger in the high diversity mixtures. However, the low diversity replicate sown with the mixture that produced the largest biomass or largest suppression of natural colonizers fell within the range recorded at the five replicates of the high diversity plots. The natural colonization plots usually had the highest total species richness and lowest productivity at the end of the observation period. Conclusions: The effect of sowing demonstrated dispersal limitation as a factor controlling the rate of early secondary succession. Diversity was important primarily for its 'insurance effect': the high diversity mixtures were always able to compensate for the failure of some species.
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