Hospital Of S Joao
Hospital Of S Joao
Frias B.,University of Porto |
Allen S.,University of Bristol |
Dawbarn D.,University of Bristol |
Charrua A.,University of Porto |
And 3 more authors.
Neuroscience | Year: 2013
Brain-derived neurotrophic factor (BDNF) is a neurotrophin (NT) known to participate in chronic somatic pain. A recent study has indicated that BDNF may participate in chronic cystitis at the peripheral level. However, the principal site of action for this NT is the central nervous system, most notably the spinal cord. The effects of centrally-acting BDNF on bladder function in normal animals and its central role during chronic cystitis are presently unknown. The present study was undertaken to clarify this issue. For that purpose, control non-inflamed animals were intrathecally injected with BDNF, after which bladder function was evaluated. This treatment caused short-lasting bladder hyperactivity; whereas chronic intrathecal administration of BDNF did not elicit this effect. Cutaneous sensitivity was assessed by mechanical allodynia as an internal control of BDNF action.To ascertain the role of BDNF in bladder inflammation, animals with cyclophosphamide-induced cystitis received intrathecal injections of either a general Trk receptor antagonist or a BDNF scavenger. Blockade of Trk receptors or BDNF sequestration notably improved bladder function. In addition, these treatments also reduced referred pain, typically observed in rats with chronic cystitis. Reduction of referred pain was accompanied by a decrease in the spinal levels of extracellular signal-regulated kinase (ERK) phosphorylation, a marker of increased sensory barrage in the lumbosacral spinal cord, and spinal BDNF expression.Results obtained here indicate that BDNF, acting at the spinal cord level, contributes to bladder hyperactivity and referred pain, important hallmarks of chronic cystitis. In addition, these data also support the development of BDNF modulators as putative therapeutic options for the treatment of chronic bladder inflammation. © 2013 IBRO.
Coelho A.,University of Porto |
Oliveira R.,University of Porto |
Cruz F.,University of Porto |
Cruz F.,Hospital Of S Joao |
Cruz C.D.,University of Porto
Experimental Neurology | Year: 2016
Spinal cord injury (SCI) often leads to neurogenic detrusor overactivity (NDO) due to sprouting of sensory afferents on the lumbosacral spinal cord. NDO is characterized by high frequency of voiding contractions and increased intravesical pressure that may lead to urinary incontinence. The latter has been described as one of the consequences of SCI that mostly decreases quality of life. Bladder wall injections of botulinum toxin A (Onabot/A) are an effective option to manage NDO. The toxin strongly impairs parasympathetic and sensory fibres coursing the bladder wall. However the robust parasympathetic inhibition may inhibit voiding contractions and cause urinary retention in patients that retain voluntary voiding. Here, we hypothesised that by restricting the toxin activity to sensory fibres we can improve NDO without impairing voiding contractions. In the present work, we assessed the effect of Onabot/A on sensory neurons in chronic (4 weeks) SCI rats by injecting the toxin intrathecally (IT), at lumbosacral spinal cord level. This route of administration was shown before to have an effect on bladder pain and contractility in an animal model of bladder inflammation. We found that IT Onabot/A led to a significant reduction in the frequency of expulsive contractions and a normalization of bladder basal pressure while maintaining voiding contractions of normal amplitude. Cleavage of SNAP-25 protein occurred mainly at the dorsal horn regions where most of the bladder afferents end. Cleaved SNAP-25 was not detected in motor or preganglionic parasympathetic neurons. A significant decrease in CGRP expression, a peptide exclusively present in sensory fibres in the spinal cord, occurred at the L5/L6 segments and associated dorsal root ganglia (DRG) after Onabot/A injection in SCI animals. Onabot/A strongly increased the expression of ATF3, a marker of neuronal stress, in L5/L6 DRG neurons. Taken together, our results suggest that IT Onabot/A has a predominant effect on bladder sensory fibres, and that such effect is enough to control NDO following chronic SCI. The mechanism of action of Onabot/A includes not only the cleavage of SNAP-25 in sensory terminals but also impairment of basic cellular machinery in the cell body of sensory neurons. © 2016 Elsevier Inc.
Fonseca J.,Hospital Beatriz Angelo |
Fonseca J.,British Hospital |
Martins da Silva C.,Hospital Of S Joao
Clinical Drug Investigation | Year: 2015
Lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) are common in aging men and can progress to acute urinary retention. Among the classes of agents recommended for patients with moderate to severe symptoms are α-adrenergic receptor (adrenoceptor) antagonists (α-blockers) and 5α-reductase inhibitors (5ARIs). This review provides a brief overview of the diagnosis and management of LUTS/BPH, focusing on the efficacy and tolerability of α-blockers approved for the treatment of LUTS/BPH, with particular emphasis on silodosin, a novel α-blocker. Of the older α1-blockers, alfuzosin, doxazosin and terazosin show little selectivity for the α1-adrenoceptor subtypes, while tamsulosin is moderately and silodosin is highly selective for the α1A subtype in preference to the α1B subtype. Highly selective α1A-receptor antagonists such as silodosin were developed specifically for the treatment of LUTS because non-selective antagonists were associated with cardiovascular adverse effects. Since α1A is predominantly expressed in the prostate, higher selectivity for α1A may account for lower blood pressure-related adverse effects. Silodosin is administered once daily and provides rapid improvements in the signs and symptoms of moderate to severe LUTS/BPH in male patients. As with other α-blockers, silodosin is generally well-tolerated and the most common adverse events seen are abnormal ejaculation, dizziness, headache, diarrhoea, nasal congestion and orthostatic hypotension. Unlike 5ARIs, α-blockers do not impair libido. Given the prevalence of LUTS/BPH and the efficacy and tolerability concerns with existing therapies, silodosin is a welcome addition to the pharmacological options for these patients. © 2015, Springer International Publishing Switzerland.
Lima C.F.,University of Porto |
Garrett C.,University of Porto |
Garrett C.,Hospital Of S Joao |
Castro S.L.,University of Porto
Journal of Clinical and Experimental Neuropsychology | Year: 2013
Does emotion processing in music and speech prosody recruit common neurocognitive mechanisms? To examine this question, we implemented a cross-domain comparative design in Parkinson's disease (PD). Twenty-four patients and 25 controls performed emotion recognition tasks for music and spoken sentences. In music, patients had impaired recognition of happiness and peacefulness, and intact recognition of sadness and fear; this pattern was independent of general cognitive and perceptual abilities. In speech, patients had a small global impairment, which was significantly mediated by executive dysfunction. Hence, PD affected differently musical and prosodic emotions. This dissociation indicates that the mechanisms underlying the two domains are partly independent. © 2013 Taylor & Francis.
Ferreira R.M.,University of Porto |
Machado J.C.,University of Porto |
Leite M.,University of Porto |
Carneiro F.,University of Porto |
And 2 more authors.
Histopathology | Year: 2012
Aims: To characterize the variation in virulence of Helicobacter pylori associated with CagA Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs, and to explore its relationship with the histopathological features of chronic gastritis and with the development of gastric carcinoma. Methods and results: A total of 169 H. pylori-infected patients with chronic gastritis and gastric carcinoma were studied. The presence of cagA and the number and type of EPIYA motifs were determined by polymerase chain reaction. Infection with strains harbouring two or more CagA EPIYA C motifs was associated with the presence of surface epithelial damage, and with atrophic gastritis and gastric carcinoma. The magnitude of risk for atrophic gastritis and gastric carcinoma increased with increasing number of EPIYA C motifs: strains with one EPIYA C motif conferred a risk (odds ratio [OR]) of 7.3 [95% confidence interval (CI) 2.1-25] for atrophic gastritis, whereas strains with two or more EPIYA C motifs conferred a risk (OR) of 12 (95% CI 2.5-58); strains with one EPIYA C motif conferred a risk (OR) of 17 (95% CI 5.4-55) for gastric carcinoma, whereas strains with two or more EPIYA C motifs conferred a risk (OR) of 51 (95% CI 13-198). Conclusions: Characterization of the number of H. pylori EPIYA C motifs is important in better defining gastric carcinoma risk. © 2012 Blackwell Publishing Ltd.
Pereira D.,University of Porto |
Garrett C.,Hospital Of S Joao
Acta Medica Portuguesa | Year: 2010
The etiology of Parkinson's disease (PD) remains in a certain part unknown. Both genetic susceptibility and environmental factors are sometimes considered to be putative contributors to its origin. Recent epidemiologic studies have focused on the possible role of environmental risk factors present during adult life or aging, once pure genetic forms of PD are rare. The purpose of this study was to investigate possible environmental and familial risk factors for PD. We performed a hospital based case-control study using 88 PD patients with neurologist confirmed diagnostic, and 176 sex, age, and residence similiar controls. Several possible risk factors were evaluated related to life style, past history, family history, occupational history and other exposures to potencial neurotoxin agents. Statistical differences, using a 95% confidence interval, were observed in positive family history of PD (p = 0,002), occupation category (p = 0,001), rural living (p = 0,037), living/working near a industry (p = 0,017), exposure to pesticides, herbicides and in-secticides (p < 0,001), coffee consumption (p = 0,036) and tea consumption (p = 0,001). Sex and age adjusted logistic regression showed as potencial risk factors, a positive family history of PD (odds ratio [OR] = 9,996; 95% confidence interval [CI] = 2,19-45,597), blue collar occupations (OR = 3,967; 95% CI = 1,670-9,426), exposure to pesticides, herbicides and insecticides (OR = 2,619 ; 95% CI = 1,170-5,862). An inverse relationship was found between tea consumption and the risk of PD (OR = 0,356; 95% CI = 0,174-0,727). The results of the study show that both familial and environmental factors may contribute to the development of PD. Like other studies suggest, PD is of unknown, but presumably multifactorial etiology. © 2010 CELOM.
Silva J.,Hospital Of S Joao |
Silva J.,Institute for Molecular and Cell Biology |
Silva C.M.,Hospital Of S Joao |
Silva C.M.,Institute for Molecular and Cell Biology |
And 2 more authors.
Current Opinion in Urology | Year: 2014
PURPOSE OF REVIEW: The pharmacological treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) is based on alpha-blockers and 5α-reductase inhibitors isolated or in combination. Silodosin, an alpha-1A specific alpha-blocker is the only innovation in these groups of agents. This classical paradigm is being challenged by antimuscarinics, 5-phosphodiesterase inhibitors (PDE5i) and β3- adrenoreceptor agonists. RECENT FINDINGS: Silodosin is effective in reducing BPH/LUTS, including nocturia and shows little cardiovascular adverse events. Antimuscarinic drugs isolated or in combination with alpha-blockers improve storage symptoms without any harmful effect to the voiding function. PDE5i alone improve BPH/LUTS. Combination of PDE5i with alpha-blockers provides better symptomatic control than alpha-blockers alone. A recent head-to-head comparison of tadalafil 5â€Šmg/day with tamsulosin 0. 4â€Šmg/day showed that these agents provided the same improvement in BPH/LUTS and, surprisingly, the same improvement in the urinary flow. In fact, previous studies with tadalafil had not shown any effect of tadalafil on flow. In addition, tadalafil but not tamsulosin improved sexual function. Mirabegron, the first β3-adrenoreceptor agonist, while improving BPH/LUTS in men with bladder outlet obstruction, do not decrease urinary flow or detrusor pressure. SUMMARY: The standard medical treatment for BPH/LUTS is still based on alpha-blockers, 5ARIs or its combination. In the future, it is expected that BPH/LUTS treatment will become individualized, according to the type of symptoms, presence of sexual dysfunction and risk of BPH progression. This will challenge our concept of standard treatment for BPH/LUTS. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Barroca H.,Hospital Of S Joao
Diagnostic Cytopathology | Year: 2010
Nephroblastoma is a success of paediatric oncologic therapy, yet, there are still some cases where favourable response to preoperative chemotherapy is not achieved. Fine needle biopsy has the role of diagnostic confirmation and, idyllically of predicting a response to preoperative chemotherapy. To advance in this aim, we retrieved a total of 14 nephroblastomas, (seven male patients and seven female with a mean age of 44.4 months), diagnosed in our department by fine needle biopsy and submitted afterward to chemotherapy and nephrectomy, in the last 10 years. Correlation between cytologic features, (morphology, cell death, and proliferation (Ki-67 labelling index), and post chemotherapy tumour evaluation was done. Cytologic pattern per se was not predictive of histologic tumour classification (P = 0.6061). We did not find any correlation between the percentage of necrosis and apoptosis (P = 0.682) in cytologic smears and histologic regressive changes but when both these two criteria coexisted in cytologic blastemal component of nephroblastomas, this fact seemed to lead to a favourable response of the tumour to chemotherapy. When evaluation of Ki-67 labelling index was done in the blastematous component present in the smears, divergent results were obtained. The small number of cases prevented any firm conclusions. By summing up, our results support the idea that there are probably two types of blastema in nephroblastoma with different "suicide" potential and chemotherapeutic response. Further studies should be performed to stratify the influence of necrosis, apoptosis, and proliferation in chemosensivity of nephroblastomas. © 2009 Wiley-Liss, Inc.
Cruz C.D.,University of Porto |
Coelho A.,University of Porto |
Antunes-Lopes T.,University of Porto |
Antunes-Lopes T.,Hospital Of S Joao |
And 2 more authors.
Advanced Drug Delivery Reviews | Year: 2015
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. © 2014 Elsevier B.V.
Santos L.C.,Hospital Of S Joao |
Abreu C.F.,Hospital Of S Joao |
Xerinda S.M.,University of Porto |
Tavares M.,University of Porto |
And 2 more authors.
Malaria Journal | Year: 2012
Background: In view of the close relationship of Portugal with African countries, particularly former Portuguese colonies, the diagnosis of malaria is not a rare thing. When a traveller returns ill from endemic areas, malaria should be the number one suspect. World Health Organization treatment guidelines recommend that adults with severe malaria should be admitted to an intensive care unit (ICU). Methods. Severe cases of malaria in patients admitted to an ICU were reviewed retrospectively (1990-2011) and identification of variables associated with in-ICU mortality performed. Malaria prediction score (MPS), malaria score for adults (MSA), simplified acute physiology score (SAPSII) and a score based on WHO's malaria severe criteria were applied. Statistical analysis was performed using StataV12. Results: Fifty nine patients were included in the study, all but three were adults; 47 (79,6%) were male; parasitaemia on admission, quantified in 48/59 (81.3%) patients, was equal or greater than 2% in 47 of them (97.9%); the most common complications were thrombocytopaenia in 54 (91.5%) patients, associated with disseminated intravascular coagulation (DIC) in seven (11.8%), renal failure in 31 (52.5%) patients, 18 of which (30.5%) oliguric, shock in 29 (49.1%) patients, liver dysfunction in 27 (45.7%) patients, acidaemia in 23 (38.9%) patients, cerebral dysfunction in 22 (37.2%) patients, 11 of whom with unrousable coma, pulmonary oedema/ARDS in 22 (37.2%) patients, hypoglycaemia in 18 (30.5%) patients; 29 (49.1%) patients presented five or more dysfunctions. The case fatality rate was 15.2%. Comparing the four scores, the SAPS II and the WHO score were the most sensitive to death prediction. In the univariate analysis, death was associated with the SAPS II score, cerebral malaria, acute renal and respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia. Age, partial immunity to malaria, delay in malaria diagnosis and the level of parasitaemia were not associated with death in this cohort. Conclusion: Severe malaria cases should be continued monitored in the ICUs. SAPS II and the WHO score are good predictors of mortality in malaria patients, but other specific scores deserve to be studied prospectively. © 2012 Santos et al; licensee BioMed Central Ltd.