Purpose: Previous studies suggest that vascular endothelial growth factor (VEGF) circulating leve... more Purpose: Previous studies suggest that vascular endothelial growth factor (VEGF) circulating levels might improve identification of patients with prostate cancer but results are conflicting. Our aim was to compare serum VEGF levels across different prostate pathologies (including benign prostatic hyperplasia, prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer) in patients at high risk of prostate cancer. Materials and Methods: We consecutively enrolled 186 subjects with abnormal digital rectal examination and/or total PSA (tPSA) ≥ 2.5 ng/mL. Blood was collected before diagnostic ultrasound guided trans-rectal prostate biopsy, or any prostate oncology treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression was used to compute age-, tPSA-and free/total PSA-adjusted odds ratios (OR) and respective 95% confidence intervals (95% CI) for the association between serum VEGF and different prostatic pathologies. Results: Prostate biopsy main diagnoses were normal or benign prostatic hyperplasia (27.3%), prostatitis (16.6%), and prostatic cancer (55.0%). The median VEGF levels (ng/mL) in these groups were 178.2, 261.3 and 266.4 (p = 0.029), respectively, but no significant differences were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551). No independent association was observed between VEGF (3rd vs. 1st third) and prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95%: 0.64-3.26). Conclusions: In patients at high risk of prostate cancer, circulating VEGF levels have no clinical role in deciding which patients should be submitted to prostate biopsy. Prostatitis patients, often with higher PSA levels, also present high serum levels of VEGF, and their inclusion in control groups might explain the heterogeneous results in previous studies.
OBJECTIVETo evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bl... more OBJECTIVETo evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bladder volume at reflex micturition in rats with chronic urinary bladder inflammation.To evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bladder volume at reflex micturition in rats with chronic urinary bladder inflammation.MATERIALS AND METHODSOf three groups of female Wistar rats, group 1 received cyclophosphamide (75 mg/kg body weight) intraperitoneally every third day (cyclophosphamide is an antitumoral agent that induces bladder inflammation after urinary excretion of its metabolite, acrolein); group 2 comprised sham-inflamed rats that received saline instead of cyclophosphamide, and group 3 received cyclophosphamide, as group 1, every third day but plus 10 nmol/L resiniferatoxin intravesically, through a urethral catheter, at 7 days. At 8 days, under urethane anaesthesia, a needle was inserted in the bladder dome and saline infused at 6 mL/h for 2 h. Finally the animals were perfusion-fixed through the ascending aorta with 4% paraformaldehyde. Transverse sections cut from L6 spinal cord segments were immunoreacted for Fos protein and positive cells in the dorsal horn counted. In a further set of equal groups the bladders were prepared in the same way under urethane anaesthesia and after 30-min of stabilization, saline was infused at 6 mL/h and the volume evoking reflex micturition determined.Of three groups of female Wistar rats, group 1 received cyclophosphamide (75 mg/kg body weight) intraperitoneally every third day (cyclophosphamide is an antitumoral agent that induces bladder inflammation after urinary excretion of its metabolite, acrolein); group 2 comprised sham-inflamed rats that received saline instead of cyclophosphamide, and group 3 received cyclophosphamide, as group 1, every third day but plus 10 nmol/L resiniferatoxin intravesically, through a urethral catheter, at 7 days. At 8 days, under urethane anaesthesia, a needle was inserted in the bladder dome and saline infused at 6 mL/h for 2 h. Finally the animals were perfusion-fixed through the ascending aorta with 4% paraformaldehyde. Transverse sections cut from L6 spinal cord segments were immunoreacted for Fos protein and positive cells in the dorsal horn counted. In a further set of equal groups the bladders were prepared in the same way under urethane anaesthesia and after 30-min of stabilization, saline was infused at 6 mL/h and the volume evoking reflex micturition determined.RESULTSThe mean (Sd) number of positive c-fos cells per spinal cord section was 85 (21), 42 (9) (P = 0.002) and 55 (10) in groups 1 to 3, respectively; the values for group 2 and 3 were similar (P = 0.22) and statistically less than that of group 1 (P = 0.02). Reflex micturition occurred at, respectively, 0.26 (0.09), 0.49 (0.18) and 0.52 (0.11) mL, being similar in group 2 and 3 (P = 0.74) but lower in group 1 (P = 0.003).The mean (Sd) number of positive c-fos cells per spinal cord section was 85 (21), 42 (9) (P = 0.002) and 55 (10) in groups 1 to 3, respectively; the values for group 2 and 3 were similar (P = 0.22) and statistically less than that of group 1 (P = 0.02). Reflex micturition occurred at, respectively, 0.26 (0.09), 0.49 (0.18) and 0.52 (0.11) mL, being similar in group 2 and 3 (P = 0.74) but lower in group 1 (P = 0.003).CONCLUSIONIntravesical resiniferatoxin decreases c-fos expression and increases bladder capacity in chronically inflamed rat bladders. These findings suggest that desensitizing the vanilloid receptor type 1 by intravesical resiniferatoxin is relevant to the treatment of pain and voiding frequency in patients with chronic inflammatory bladder conditions.Intravesical resiniferatoxin decreases c-fos expression and increases bladder capacity in chronically inflamed rat bladders. These findings suggest that desensitizing the vanilloid receptor type 1 by intravesical resiniferatoxin is relevant to the treatment of pain and voiding frequency in patients with chronic inflammatory bladder conditions.
Previous studies suggest an association between total testosterone (tT) and prostate cancer, but ... more Previous studies suggest an association between total testosterone (tT) and prostate cancer, but results are conflicting and it is not clear if accounting for the tT levels improves the yielding of patient selection for prostatic biopsy. We evaluated the potential for tT levels and the tT/total PSA (tPSA) ratio to be used as diagnostic tools for prostate cancer and its relation with cancer aggressiveness. We measured tT, tPSA and free PSA (fPSA) in fasting blood samples of 1570 subjects consecutively referred for prostate biopsy due to abnormal digital rectal examination and/or elevated tPSA levels. These values were compared between groups defined according to the pathological results of the biopsy. No significant difference was observed in tT levels when comparing cases with prostate cancer, high grade prostate intraepithelial neoplasia, pathological prostatitis, benign prostatic hyperplasia or no alteration (median: 4.26 versus 4.44 versus 4.31 versus 4.16 pg/mL, respectively; p = 0.643). The tT/tPSA ratio had a better area under the curve than tT alone (0.62, 95% CI, 0.59-0.65 versus 0.50, 95% CI, 0.47-0.53), but worse than the f/tPSA ratio (0.70, 95% CI, 0.67-0.73). In multivariate analysis, using the median of distribution as cut-off no significant association was observed between tT or tT/tPSA and prostate cancer (OR = 1.06, 95% CI, 0.84-1.33; OR = 0.94, 95% CI, 0.70-1.27, respectively). The tT levels were not significantly different across Gleason score groups (p = 0.553). In patients suspected of having prostate cancer the tT levels are not useful to improve the yielding of patient selection for prostatic biopsy or to predict cancer aggressiveness.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
In recent times, basic and clinical data in the field of urology and in field-related technology ... more In recent times, basic and clinical data in the field of urology and in field-related technology have expanded immensely. In an era of rapid developments and innovations, there is an increasing need to update our knowledge and especially to guide our practice by innovations and evidence-based medicine. The recent flood of novel insights, treatment modalities, and clinical observations, in parallel with the speed and magnitude of technological advances and changes has major implications on our clinical practice and raises a significant number of questions for clinicians and patients. Because the problem of urologic diseases has reached epidemiologic dimensions, disease management prospects are sought from diverse sources.
In recent times, basic and clinical data in the field of urology and in field-related technology ... more In recent times, basic and clinical data in the field of urology and in field-related technology have expanded immensely. In an era of rapid developments and innovations, there is an increasing need to update our knowledge and especially to guide our practice by innovations and evidence-based medicine. The recent flood of novel insights, treatment modalities, and clinical observations, in parallel with the speed and magnitude of technological advances and changes has major implications on our clinical practice and raises a significant number of questions for clinicians and patients. Because the problem of urologic diseases has reached epidemiologic dimensions, disease management prospects are sought from diverse sources.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
In recent times, basic and clinical data in the field of urology and in field-related technology ... more In recent times, basic and clinical data in the field of urology and in field-related technology have expanded immensely. In an era of rapid developments and innovations, there is an increasing need to update our knowledge and especially to guide our practice by innovations and evidence-based medicine. The recent flood of novel insights, treatment modalities, and clinical observations, in parallel with the speed and magnitude of technological advances and changes has major implications on our clinical practice and raises a significant number of questions for clinicians and patients. Because the problem of urologic diseases has reached epidemiologic dimensions, disease management prospects are sought from diverse sources.
ABSTRACT Intravesical therapy with botulinum toxin type A (BTX-A) and vanilloids (capsaicin and r... more ABSTRACT Intravesical therapy with botulinum toxin type A (BTX-A) and vanilloids (capsaicin and resiniferatoxin) are actively investigated as potential treatments for lower urinary tract symptoms refractory to conventional therapy in patients with neurogenic detrusor overactivity. BTX-A cleaves soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in afferent and efferent nerve endings, impeding the fusion of synaptic vesicles with the neuronal membrane necessary for the release of neurotransmitters. Vanilloids desensitize the transient receptor potential vanilloid type 1 receptor and inactivate C-fibers. BTX-A intradetrusor injections are extremely effective for treating urinary incontinence, provide adequate protection of the upper urinary tract, and improve quality of life in patients with neurogenic detrusor overactivity. Therefore, BTX-A is currently the mainstay of intravesical therapy. However, despite promising results overall, the administration of these compounds, including BTX-A, remains an experimental procedure requiring further clinical studies.
For example, changes in the urothelium have recently been described and proposed to play a role i... more For example, changes in the urothelium have recently been described and proposed to play a role in NDO. As such, a better understanding of NDO has generated new opportunities to investigate novel therapeutic approaches for NDO.In the present paper, we aim to update recent data concerning SCI-induced LUT dysfunction and therapeutic approaches commonly used to deal with NDO. We make a brief description of LUT control and changes occurring after SCI, and refer to new therapeutic options, including vanniloids and botulinum toxin. Finally, we discuss mechanisms of spinal cord repair, an interesting and very active area of investigation that has obtained some promising results in the recovery of LUT control.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
The extracellular signal-regulated kinases 1 and 2 (ERK) cascade, member of the mitogen-activated... more The extracellular signal-regulated kinases 1 and 2 (ERK) cascade, member of the mitogen-activated protein kinases superfamily of signalling pathways, is one of the best characterized pathways as many protein interactions and phosphorylation events have been systematically studied. Traditionally, ERK are associated with the regulation of proliferation and differentiation as well as survival of various cell types. Their activity is controlled by phosphorylation on specific aminoacidic residues, which is induced by a variety of external cues, including growth-promoting factors.In the nervous system, ERK phosphorylation is induced by binding of neurotrophins to their specific tyrosine kinase receptors or by neuronal activity leading to glutamate release and binding to its ionotropic and metabotropic receptors. Some studies have provided evidence of its importance in neuroplastic events. In particular, ERK phosphorylation in the spinal cord was shown to be nociceptive-specific and its upregulation, occurring in cases of chronic inflammatory and neuropathic pain, seems to be of the utmost importance to behavioural changes observed in those conditions. In fact, experiments using specific inhibitors of ERK phosphorylation have proved that ERK directly contributes to allodynia and hyperalgesia caused by spinal cord injury or chronic pain. Additionally, spinal ERK phosphorylation regulates the micturition reflex in experimental models of bladder inflammation and chronic spinal cord transection.In this review we will address the main findings that suggest that ERK might be a future therapeutic target to treat pain and other complications arising from chronic pain or neuronal injury.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
During the acute phase of SCI, the extension and residual neurological deficits that will persist... more During the acute phase of SCI, the extension and residual neurological deficits that will persist after the waning of the spinal shock period are difficult to estimate on clinical grounds. Therefore, objective biomarkers able to estimate the extension of the lesion and the degree of neurological recovery are of great importance. Research has been focused on the detection of structural neuronal and glial proteins that leak from damaged cells, inflammatory proteins recruited to remove necrotic debris and more accurate neuroimaging methods that are able to discriminate the extension and functional consequences of the SCI. Urinary biomarkers are also being investigated to estimate functional changes that typically affect bladder function following SCI which can endanger patient's life in the long run. Future studies are needed to precisely characterize the composition and function of the glial scar that appears in the area of SCI and repeals axonal growth, therefore preventing axonal rewiring.
Purpose: Previous studies suggest that vascular endothelial growth factor (VEGF) circulating leve... more Purpose: Previous studies suggest that vascular endothelial growth factor (VEGF) circulating levels might improve identification of patients with prostate cancer but results are conflicting. Our aim was to compare serum VEGF levels across different prostate pathologies (including benign prostatic hyperplasia, prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer) in patients at high risk of prostate cancer. Materials and Methods: We consecutively enrolled 186 subjects with abnormal digital rectal examination and/or total PSA (tPSA) ≥ 2.5 ng/mL. Blood was collected before diagnostic ultrasound guided trans-rectal prostate biopsy, or any prostate oncology treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression was used to compute age-, tPSA-and free/total PSA-adjusted odds ratios (OR) and respective 95% confidence intervals (95% CI) for the association between serum VEGF and different prostatic pathologies. Results: Prostate biopsy main diagnoses were normal or benign prostatic hyperplasia (27.3%), prostatitis (16.6%), and prostatic cancer (55.0%). The median VEGF levels (ng/mL) in these groups were 178.2, 261.3 and 266.4 (p = 0.029), respectively, but no significant differences were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551). No independent association was observed between VEGF (3rd vs. 1st third) and prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95%: 0.64-3.26). Conclusions: In patients at high risk of prostate cancer, circulating VEGF levels have no clinical role in deciding which patients should be submitted to prostate biopsy. Prostatitis patients, often with higher PSA levels, also present high serum levels of VEGF, and their inclusion in control groups might explain the heterogeneous results in previous studies.
OBJECTIVETo evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bl... more OBJECTIVETo evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bladder volume at reflex micturition in rats with chronic urinary bladder inflammation.To evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bladder volume at reflex micturition in rats with chronic urinary bladder inflammation.MATERIALS AND METHODSOf three groups of female Wistar rats, group 1 received cyclophosphamide (75 mg/kg body weight) intraperitoneally every third day (cyclophosphamide is an antitumoral agent that induces bladder inflammation after urinary excretion of its metabolite, acrolein); group 2 comprised sham-inflamed rats that received saline instead of cyclophosphamide, and group 3 received cyclophosphamide, as group 1, every third day but plus 10 nmol/L resiniferatoxin intravesically, through a urethral catheter, at 7 days. At 8 days, under urethane anaesthesia, a needle was inserted in the bladder dome and saline infused at 6 mL/h for 2 h. Finally the animals were perfusion-fixed through the ascending aorta with 4% paraformaldehyde. Transverse sections cut from L6 spinal cord segments were immunoreacted for Fos protein and positive cells in the dorsal horn counted. In a further set of equal groups the bladders were prepared in the same way under urethane anaesthesia and after 30-min of stabilization, saline was infused at 6 mL/h and the volume evoking reflex micturition determined.Of three groups of female Wistar rats, group 1 received cyclophosphamide (75 mg/kg body weight) intraperitoneally every third day (cyclophosphamide is an antitumoral agent that induces bladder inflammation after urinary excretion of its metabolite, acrolein); group 2 comprised sham-inflamed rats that received saline instead of cyclophosphamide, and group 3 received cyclophosphamide, as group 1, every third day but plus 10 nmol/L resiniferatoxin intravesically, through a urethral catheter, at 7 days. At 8 days, under urethane anaesthesia, a needle was inserted in the bladder dome and saline infused at 6 mL/h for 2 h. Finally the animals were perfusion-fixed through the ascending aorta with 4% paraformaldehyde. Transverse sections cut from L6 spinal cord segments were immunoreacted for Fos protein and positive cells in the dorsal horn counted. In a further set of equal groups the bladders were prepared in the same way under urethane anaesthesia and after 30-min of stabilization, saline was infused at 6 mL/h and the volume evoking reflex micturition determined.RESULTSThe mean (Sd) number of positive c-fos cells per spinal cord section was 85 (21), 42 (9) (P = 0.002) and 55 (10) in groups 1 to 3, respectively; the values for group 2 and 3 were similar (P = 0.22) and statistically less than that of group 1 (P = 0.02). Reflex micturition occurred at, respectively, 0.26 (0.09), 0.49 (0.18) and 0.52 (0.11) mL, being similar in group 2 and 3 (P = 0.74) but lower in group 1 (P = 0.003).The mean (Sd) number of positive c-fos cells per spinal cord section was 85 (21), 42 (9) (P = 0.002) and 55 (10) in groups 1 to 3, respectively; the values for group 2 and 3 were similar (P = 0.22) and statistically less than that of group 1 (P = 0.02). Reflex micturition occurred at, respectively, 0.26 (0.09), 0.49 (0.18) and 0.52 (0.11) mL, being similar in group 2 and 3 (P = 0.74) but lower in group 1 (P = 0.003).CONCLUSIONIntravesical resiniferatoxin decreases c-fos expression and increases bladder capacity in chronically inflamed rat bladders. These findings suggest that desensitizing the vanilloid receptor type 1 by intravesical resiniferatoxin is relevant to the treatment of pain and voiding frequency in patients with chronic inflammatory bladder conditions.Intravesical resiniferatoxin decreases c-fos expression and increases bladder capacity in chronically inflamed rat bladders. These findings suggest that desensitizing the vanilloid receptor type 1 by intravesical resiniferatoxin is relevant to the treatment of pain and voiding frequency in patients with chronic inflammatory bladder conditions.
Previous studies suggest an association between total testosterone (tT) and prostate cancer, but ... more Previous studies suggest an association between total testosterone (tT) and prostate cancer, but results are conflicting and it is not clear if accounting for the tT levels improves the yielding of patient selection for prostatic biopsy. We evaluated the potential for tT levels and the tT/total PSA (tPSA) ratio to be used as diagnostic tools for prostate cancer and its relation with cancer aggressiveness. We measured tT, tPSA and free PSA (fPSA) in fasting blood samples of 1570 subjects consecutively referred for prostate biopsy due to abnormal digital rectal examination and/or elevated tPSA levels. These values were compared between groups defined according to the pathological results of the biopsy. No significant difference was observed in tT levels when comparing cases with prostate cancer, high grade prostate intraepithelial neoplasia, pathological prostatitis, benign prostatic hyperplasia or no alteration (median: 4.26 versus 4.44 versus 4.31 versus 4.16 pg/mL, respectively; p = 0.643). The tT/tPSA ratio had a better area under the curve than tT alone (0.62, 95% CI, 0.59-0.65 versus 0.50, 95% CI, 0.47-0.53), but worse than the f/tPSA ratio (0.70, 95% CI, 0.67-0.73). In multivariate analysis, using the median of distribution as cut-off no significant association was observed between tT or tT/tPSA and prostate cancer (OR = 1.06, 95% CI, 0.84-1.33; OR = 0.94, 95% CI, 0.70-1.27, respectively). The tT levels were not significantly different across Gleason score groups (p = 0.553). In patients suspected of having prostate cancer the tT levels are not useful to improve the yielding of patient selection for prostatic biopsy or to predict cancer aggressiveness.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
In recent times, basic and clinical data in the field of urology and in field-related technology ... more In recent times, basic and clinical data in the field of urology and in field-related technology have expanded immensely. In an era of rapid developments and innovations, there is an increasing need to update our knowledge and especially to guide our practice by innovations and evidence-based medicine. The recent flood of novel insights, treatment modalities, and clinical observations, in parallel with the speed and magnitude of technological advances and changes has major implications on our clinical practice and raises a significant number of questions for clinicians and patients. Because the problem of urologic diseases has reached epidemiologic dimensions, disease management prospects are sought from diverse sources.
In recent times, basic and clinical data in the field of urology and in field-related technology ... more In recent times, basic and clinical data in the field of urology and in field-related technology have expanded immensely. In an era of rapid developments and innovations, there is an increasing need to update our knowledge and especially to guide our practice by innovations and evidence-based medicine. The recent flood of novel insights, treatment modalities, and clinical observations, in parallel with the speed and magnitude of technological advances and changes has major implications on our clinical practice and raises a significant number of questions for clinicians and patients. Because the problem of urologic diseases has reached epidemiologic dimensions, disease management prospects are sought from diverse sources.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
In recent times, basic and clinical data in the field of urology and in field-related technology ... more In recent times, basic and clinical data in the field of urology and in field-related technology have expanded immensely. In an era of rapid developments and innovations, there is an increasing need to update our knowledge and especially to guide our practice by innovations and evidence-based medicine. The recent flood of novel insights, treatment modalities, and clinical observations, in parallel with the speed and magnitude of technological advances and changes has major implications on our clinical practice and raises a significant number of questions for clinicians and patients. Because the problem of urologic diseases has reached epidemiologic dimensions, disease management prospects are sought from diverse sources.
ABSTRACT Intravesical therapy with botulinum toxin type A (BTX-A) and vanilloids (capsaicin and r... more ABSTRACT Intravesical therapy with botulinum toxin type A (BTX-A) and vanilloids (capsaicin and resiniferatoxin) are actively investigated as potential treatments for lower urinary tract symptoms refractory to conventional therapy in patients with neurogenic detrusor overactivity. BTX-A cleaves soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in afferent and efferent nerve endings, impeding the fusion of synaptic vesicles with the neuronal membrane necessary for the release of neurotransmitters. Vanilloids desensitize the transient receptor potential vanilloid type 1 receptor and inactivate C-fibers. BTX-A intradetrusor injections are extremely effective for treating urinary incontinence, provide adequate protection of the upper urinary tract, and improve quality of life in patients with neurogenic detrusor overactivity. Therefore, BTX-A is currently the mainstay of intravesical therapy. However, despite promising results overall, the administration of these compounds, including BTX-A, remains an experimental procedure requiring further clinical studies.
For example, changes in the urothelium have recently been described and proposed to play a role i... more For example, changes in the urothelium have recently been described and proposed to play a role in NDO. As such, a better understanding of NDO has generated new opportunities to investigate novel therapeutic approaches for NDO.In the present paper, we aim to update recent data concerning SCI-induced LUT dysfunction and therapeutic approaches commonly used to deal with NDO. We make a brief description of LUT control and changes occurring after SCI, and refer to new therapeutic options, including vanniloids and botulinum toxin. Finally, we discuss mechanisms of spinal cord repair, an interesting and very active area of investigation that has obtained some promising results in the recovery of LUT control.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
The extracellular signal-regulated kinases 1 and 2 (ERK) cascade, member of the mitogen-activated... more The extracellular signal-regulated kinases 1 and 2 (ERK) cascade, member of the mitogen-activated protein kinases superfamily of signalling pathways, is one of the best characterized pathways as many protein interactions and phosphorylation events have been systematically studied. Traditionally, ERK are associated with the regulation of proliferation and differentiation as well as survival of various cell types. Their activity is controlled by phosphorylation on specific aminoacidic residues, which is induced by a variety of external cues, including growth-promoting factors.In the nervous system, ERK phosphorylation is induced by binding of neurotrophins to their specific tyrosine kinase receptors or by neuronal activity leading to glutamate release and binding to its ionotropic and metabotropic receptors. Some studies have provided evidence of its importance in neuroplastic events. In particular, ERK phosphorylation in the spinal cord was shown to be nociceptive-specific and its upregulation, occurring in cases of chronic inflammatory and neuropathic pain, seems to be of the utmost importance to behavioural changes observed in those conditions. In fact, experiments using specific inhibitors of ERK phosphorylation have proved that ERK directly contributes to allodynia and hyperalgesia caused by spinal cord injury or chronic pain. Additionally, spinal ERK phosphorylation regulates the micturition reflex in experimental models of bladder inflammation and chronic spinal cord transection.In this review we will address the main findings that suggest that ERK might be a future therapeutic target to treat pain and other complications arising from chronic pain or neuronal injury.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the... more Lower urinary tract symptoms and obstruction due to benign prostate hyperplasia: only part of the story According to the classic paradigm, in benign prostate hyperplasia (BPH), the increase in prostate volume obstructs urinary flow, causing lower urinary tract symptoms (LUTS). Prostatectomy removes the obstruction and therefore resolves LUTS.
During the acute phase of SCI, the extension and residual neurological deficits that will persist... more During the acute phase of SCI, the extension and residual neurological deficits that will persist after the waning of the spinal shock period are difficult to estimate on clinical grounds. Therefore, objective biomarkers able to estimate the extension of the lesion and the degree of neurological recovery are of great importance. Research has been focused on the detection of structural neuronal and glial proteins that leak from damaged cells, inflammatory proteins recruited to remove necrotic debris and more accurate neuroimaging methods that are able to discriminate the extension and functional consequences of the SCI. Urinary biomarkers are also being investigated to estimate functional changes that typically affect bladder function following SCI which can endanger patient's life in the long run. Future studies are needed to precisely characterize the composition and function of the glial scar that appears in the area of SCI and repeals axonal growth, therefore preventing axonal rewiring.
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Papers by Francisco Cruz