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1.
Trials ; 21(1): 166, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046754

RESUMO

BACKGROUND: Urgency is a complaint of sudden, compelling desire to pass urine, which is difficult to defer, caused by involuntary contraction of the detrusor muscle during the bladder-filling stage. To enable detrusor inhibition, electrotherapy resources such as transcutaneous tibial nerve stimulation (TTNS) and parasacral transcutaneous electrical stimulation (PTES) have been used. The objective this study is to publish the study protocol that aims to investigate whether urgency decreases after treatment with both of the techniques. METHODS: This randomized controlled clinical trial will include 99 women, aged more than 18 years old, with urgency (score ≥ 8 in the Overactive Bladder-Validated 8-Question Awareness Tool [OAB-V8]). Women will be randomly allocated into three groups: TTNS, PTES, and placebo. The following questionnaires will be applied: the Anamnesis Record, the Incontinence Questionnaire Overactive Bladder, the King's Health Questionnaire, the 24-Hour Voiding Diary, and the OAB-V8, at four different time points: at baseline prior to the first session, at the 6th session, the 12th session and at follow-up. The current used for the transcutaneous electrical stimulation will be a symmetrical balanced biphasic pulsed current, for 12 sessions, twice a week, for 20 minutes. Qualitative variables will be displayed as frequency and percentage, quantitative variables as mean and standard deviation. Comparison of urgency severity among groups will be performed with a repeated measures ANOVA, considering the effect of the three groups and the four evaluations, and interactions among them. DISCUSSION: The present study aims to contribute evidence for a more in-depth discussion on electrode positioning for electrostimulation used in urgency treatment. It should be emphasized that, based on the possibility of confirming the hypothesis that urgency will decrease in a similar way after both treatments (TTNS and PTES), the PTES will be used as an option for positioning the electrodes alternatively to the tibial nerve region in special populations, such as amputees or people with severe lower limb sensory impairment. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC) ID: RBR-9rf33n, date of registration: 17 May 2018.


Assuntos
Estimulação Elétrica Nervosa Transcutânea/métodos , Bexiga Urinária Hiperativa/terapia , Incontinência Urinária de Urgência/terapia , Adulto , Eletrodos , Feminino , Seguimentos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sacro/inervação , Índice de Gravidade de Doença , Nervo Tibial/fisiopatologia , Estimulação Elétrica Nervosa Transcutânea/instrumentação , Resultado do Tratamento , Bexiga Urinária/inervação , Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/complicações , Bexiga Urinária Hiperativa/fisiopatologia , Incontinência Urinária de Urgência/diagnóstico , Incontinência Urinária de Urgência/etiologia , Incontinência Urinária de Urgência/fisiopatologia
2.
Neurourol Urodyn ; 38(5): 1212-1221, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30932250

RESUMO

AIMS: To evaluate the functional and molecular alterations of contractile and relaxant machinery in the bladder and urethra that lead to the underactive bladder (UAB) in old female mice. METHODS: Female young (3-months) and old (18-months) C57BL/6 mice were used. Urodynamic was assessed in awake and anaesthetized mice. Electrical-field stimulation (EFS) and concentration-response curves to contractile and relaxing agents in isolated bladders and urethras were performed. Messenger RNA (mRNA) expressions of muscarinic, adrenergic, and transient receptor potential vanilloid-4 (TRPV4), and of the enzymes tyrosine hydroxylase and neuronal nitric oxide synthase (nNOS) were determined. Bladder cyclic adenosine monophosphate (cAMP) levels were measured. RESULTS: Cystometry in old mice showed incapacity to produce bladder emptying. On filter paper, old mice showed reduced urinary spots. Compared to the young group, bladder contractions induced by EFS and carbachol were lower in old mice. The ß3 -adrenoceptor agonist mirabegron promoted higher bladder relaxation and elevation of cAMP levels in old mice. In old mice urethras, the α1a -adrenoceptor agonist phenylephrine produced higher contractions, but no differences were found for the NO donor sodium nitroprusside-induced relaxations. In old mice, increased mRNA expressions of ß3 - and α1a -adrenoceptors in bladder and urethra were found, respectively, whereas the muscarinic M2 and M3 receptors and ß2 -adrenoceptors did not change between groups. Reduced mRNA expressions of tyrosine hydroxylase and nNOS were found in old mouse urethras. Additionally, TRPV4 expression was reduced in bladder urothelium from old mice. CONCLUSION: Age-associated mouse UAB is the result of autonomic dysfunction at multiple levels leading to the less sensitive and overrelaxed bladder, along with urethral hypercontractility.


Assuntos
Envelhecimento/patologia , Sistema Nervoso Autônomo/fisiopatologia , Bexiga Inativa/fisiopatologia , Animais , AMP Cíclico/metabolismo , Estimulação Elétrica , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/efeitos dos fármacos , Receptores Adrenérgicos/efeitos dos fármacos , Receptores Muscarínicos/efeitos dos fármacos , Uretra/fisiopatologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiopatologia , Urodinâmica
3.
Auton Neurosci ; 217: 26-34, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30704972

RESUMO

The aims of the present study were to describe, in male rats, the anatomical organization of the major and accessory pelvic ganglia (MPG, AG; respectively), the interrelationship of the pelvic plexus components, and the morphometry of the pelvic postganglionic neurons. Anatomical, histochemical and histological studies were performed in anesthetized adult Wistar male rats. We found that the pelvic plexus consists of intricate neural circuits composed of two MPG, and three pairs of AG (AGI, AGII, AGIII) anatomically interrelated through ipsilateral and contralateral commissural nerves. Around 30 nerves emerge from each MPG and 17 from AGI and AGII. The MPG efferent nerves spread out preganglionic information to several pelvic organs controlling urinary, bowel, reproductive and sexual functions, while AG innervation is more regional, and it is confined to reproductive organs located in the rostral region of the urogenital tract. Both MPG and AG contain nerve fascicles, blood vessels, small intensely fluorescent cells, satellite cells and oval neuronal somata with one to three nucleoli. The soma area of AG neurons is larger than those of MPG neurons (p < 0.005). The MPG contains about 75% of the total pelvic postganglionic neurons. Our findings corroborated previous reports about MPG inputs, and add new information regarding pelvic ganglia efferent branches, AG neurons (number and morphometry), and neural interrelationship between the pelvic plexus components. This information will be useful in designing future studies about the role of pelvic innervation in the physiology and pathophysiology of pelvic functions.


Assuntos
Fibras Autônomas Pré-Ganglionares , Gânglios Autônomos/anatomia & histologia , Plexo Hipogástrico/anatomia & histologia , Nervos Espinhais/anatomia & histologia , Animais , Masculino , Ratos , Ratos Wistar , Bexiga Urinária/inervação
4.
Neurourol Urodyn ; 37(5): 1559-1566, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29357104

RESUMO

AIMS: The objective of this study was to evaluate the expression of bladder receptors in patients with defunctionalized bladder (DB) and to assess voiding behavior after refunctionalization. METHODS: A total of 68 pretransplant patients were divided in two groups: DB (diuresis <300 mL/24 h; n = 33) and NDB (non-DB; diuresis ≥300 mL/24 h; n = 35). A sample of mucosa and detrusor at the site of the future ureteral implantation was collected. The following receptors were assessed by real-time polymerase chain reaction (qRT-PCR): M2 , M3 , α1D , ß3 , P2X2 , P2X3 , TRPV1, TRPV4, TRPA1, and TRPM8. At 3, 6, and 12 months after transplant patients answered IPSS and ICIQ-OAB questionnaires and filled a 3-day 24 h frequency/volume chart (FVC) at 6 and 12 months. RESULTS: The expression of all receptors in the mucosa and in the detrusor was similar in both groups, except from α1D , which was overexpressed in the detrusor of DB relatively to NDB group. ICIQ-OAB symptom score was similar between the groups at 3, 6, and 12 months. There was a reduction of this score in both groups with time. The same pattern was found for IPSS score. Bother scores were similar between groups. No difference was observed for all FVC parameters between DB and NDB patients. CONCLUSION: Gene expression of bladder receptors involved in micturition control was similar in patients with or without DB. Bladder behavior had a similar pattern independently of pretransplant residual diuresis. These findings question the relevance of the term DB in pretransplant patients.


Assuntos
Transplante de Rim/efeitos adversos , Transplantados , Doenças da Bexiga Urinária/fisiopatologia , Micção , Adulto , Feminino , Expressão Gênica , Humanos , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Mucosa/efeitos dos fármacos , Período Pós-Operatório , Inquéritos e Questionários , Bexiga Urinária/inervação , Urodinâmica
5.
Einstein (Säo Paulo) ; 14(4): 541-546, Oct.-Dec. 2016. graf
Artigo em Inglês | LILACS | ID: biblio-840282

RESUMO

ABSTRACT Objective To determine adenosine 5’-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. Methods A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5’-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Results Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5’-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5’-triphosphate levels and no further increase in adenosine 5’-triphosphate was observed during bladder distension. Conclusion Adenosine 5’-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5’-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5’-triphosphate itself.


RESUMO Objetivo Determinar as concentrações extracelulares do 5’-trifosfato de adenosina no interstício dos segmentos medulares L6-S1, em condições basais ou durante a ativação mecânica e química das fibras aferentes vesicais. Métodos Um cateter de microdiálise foi implantado no sentido transversal na parte dorsal da medula espinal, entre os segmentos L6-S1 de ratas. O microdialisado foi coletado em intervalos de 15 minutos, durante 135 minutos, com os animais anestesiados. A concentração de 5’-trifosfato de adenosina nas amostras foi determinada mediante ensaio de bioluminescência. Em um grupo de animais (n=7), as amostras de microdialisado foram obtidas com a bexiga vazia, com distensão da bexiga para volume de 20 ou 40cmH2O, com solução salina, solução salina com ácido acético, ou solução salina com capsaicina. Em outro grupo (n=6), foi realizada com a bexiga distendida, e a solução para microdiálise continha o inibidor de ectonucleotidase ARL 67156. Resultados Os níveis extracelulares de trifosfato de adenosina no início do estudo foram 110,9±35,36fmol/15 minutos (média±EPM, n=13), e a distensão da bexiga causou um aumento nos níveis de 5’-trifosfato de adenosina, o que não foi observado após a distensão da bexiga com solução salina contendo capsaicina (10µM). A microdiálise com solução contendo ARL 67156 (1mM) foi associada com significante aumento dos níveis de trifosfato de adenosina extracelular, e nenhum aumento do trifosfato de adenosina foi observado durante a distensão da bexiga. Conclusão O 5’-trifosfato de adenosina está presente no interstício do segmento L6-S1 da medula espinal, é degradado por ectonucleotidases, e sua concentração aumentou com a ativação das fibras aferentes mecanossensíveis da bexiga, mas não das quimiossensíveis. O 5’-trifosfato de adenosina pode ter sido liberado das terminações centrais dos neurônios aferentes primários mecanossensíveis ou, mais provavelmente, de neurônios espinais intrínsecos, ou ainda de células gliais. Sua liberação parece ser modulada por fibras aferentes primárias da bexiga ativadas pela capsaicina ou pelo próprio 5’-trifosfato de adenosina.


Assuntos
Animais , Feminino , Ratos , Medula Espinal/química , Bexiga Urinária/inervação , Trifosfato de Adenosina/análise , Fibras Aferentes Viscerais , Microdiálise/métodos , Neurônios Aferentes/fisiologia , Medula Espinal/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Trifosfato de Adenosina/farmacologia , Ratos Sprague-Dawley , Medições Luminescentes , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/metabolismo
6.
Einstein (Sao Paulo) ; 14(4): 541-546, 2016.
Artigo em Inglês, Português | MEDLINE | ID: mdl-28076603

RESUMO

OBJECTIVE: To determine adenosine 5'-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. METHODS: A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5'-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. RESULTS: Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5'-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5'-triphosphate levels and no further increase in adenosine 5'-triphosphate was observed during bladder distension. CONCLUSION: Adenosine 5'-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5'-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5'-triphosphate itself. OBJETIVO: Determinar as concentrações extracelulares do 5'-trifosfato de adenosina no interstício dos segmentos medulares L6-S1, em condições basais ou durante a ativação mecânica e química das fibras aferentes vesicais. MÉTODOS: Um cateter de microdiálise foi implantado no sentido transversal na parte dorsal da medula espinal, entre os segmentos L6-S1 de ratas. O microdialisado foi coletado em intervalos de 15 minutos, durante 135 minutos, com os animais anestesiados. A concentração de 5'-trifosfato de adenosina nas amostras foi determinada mediante ensaio de bioluminescência. Em um grupo de animais (n=7), as amostras de microdialisado foram obtidas com a bexiga vazia, com distensão da bexiga para volume de 20 ou 40cmH2O, com solução salina, solução salina com ácido acético, ou solução salina com capsaicina. Em outro grupo (n=6), foi realizada com a bexiga distendida, e a solução para microdiálise continha o inibidor de ectonucleotidase ARL 67156. RESULTADOS: Os níveis extracelulares de trifosfato de adenosina no início do estudo foram 110,9±35,36fmol/15 minutos (média±EPM, n=13), e a distensão da bexiga causou um aumento nos níveis de 5'-trifosfato de adenosina, o que não foi observado após a distensão da bexiga com solução salina contendo capsaicina (10µM). A microdiálise com solução contendo ARL 67156 (1mM) foi associada com significante aumento dos níveis de trifosfato de adenosina extracelular, e nenhum aumento do trifosfato de adenosina foi observado durante a distensão da bexiga. CONCLUSÃO: O 5'-trifosfato de adenosina está presente no interstício do segmento L6-S1 da medula espinal, é degradado por ectonucleotidases, e sua concentração aumentou com a ativação das fibras aferentes mecanossensíveis da bexiga, mas não das quimiossensíveis. O 5'-trifosfato de adenosina pode ter sido liberado das terminações centrais dos neurônios aferentes primários mecanossensíveis ou, mais provavelmente, de neurônios espinais intrínsecos, ou ainda de células gliais. Sua liberação parece ser modulada por fibras aferentes primárias da bexiga ativadas pela capsaicina ou pelo próprio 5'-trifosfato de adenosina.


Assuntos
Trifosfato de Adenosina/análise , Microdiálise/métodos , Neurônios Aferentes/fisiologia , Medula Espinal/química , Bexiga Urinária/inervação , Fibras Aferentes Viscerais , Trifosfato de Adenosina/farmacologia , Animais , Feminino , Medições Luminescentes , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/metabolismo , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos
7.
Int Urogynecol J ; 26(6): 853-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25571865

RESUMO

INTRODUCTION AND HYPOTHESIS: Neosaxitoxin is a phycotoxin whose molecular mechanism of action shows a reversible inhibition of voltage-gated sodium channels at the axonal level, impeding nerve impulse propagation. This study was designed to evaluate the clinical efficacy of neosaxitoxin as a long-acting pain blocker in the treatment of bladder pain syndrome (BPS). METHODS: Five patients with a diagnosis of BPS received a total dose of 80 µg of neosaxitoxin in an isoosmotic solution of 0.9 % NaCl, pH 6.5. Infiltration was performed via cystoscopy under spinal anesthesia. Questionnaires were administered immediately before and 7, 30 and 90 days after the procedure to measure the patients' reported pain severity and quality of life. RESULTS: This study, for the first time, showed the effect of blocking the neuronal transmission of pain by local infiltration of neosaxitoxin into the bladder submucosa. All five patients successfully responded to the treatment. Furthermore, the analgesic effect lasted for the entire 90 days of follow-up without the need for a second infiltration, and no adverse reactions to neosaxitoxin were detected. CONCLUSIONS: Neosaxitoxin infiltration was shown to be a safe and effective intervention to control pain related to BPS. It was well tolerated by patients, who experienced extended pain relief and associated beneficial effects over a follow-up of 90 days. These results confirm the effectiveness of neosaxitoxin as a long-acting local pain blocker.


Assuntos
Bloqueadores Neuromusculares/uso terapêutico , Dor Intratável/tratamento farmacológico , Saxitoxina/análogos & derivados , Bexiga Urinária/inervação , Adulto , Cistoscopia , Feminino , Humanos , Pessoa de Meia-Idade , Bloqueadores Neuromusculares/administração & dosagem , Saxitoxina/administração & dosagem , Saxitoxina/uso terapêutico , Síndrome
8.
Neurourol Urodyn ; 30(7): 1392-402, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21661033

RESUMO

AIMS: Association between arterial hypertension and urinary bladder dysfunction has been reported in humans and spontaneously hypertensive rats. However, no study exists evaluating the bladder dysfunction in conditions of renovascular hypertension. The purpose of this study was to characterize the bladder dysfunction in two kidney-one clip (2K-1C) hypertensive rats. METHODS: A silver clip was placed around the renal artery of male Wistar rats. After 8 weeks, cystometric study, concentration-response curves to contractile and relaxant agents, frequency-dependent contractions, histomorphometry, muscarinic M(2) /M(3) mRNA expression and cyclic AMP measurements were performed. RESULTS: 2K-1C rats showed enhanced bladder volume, wall thickness and smooth muscle density. 2K-1C rats also exhibited increases in bladder capacity and non-void contractions, and decreases in the inter-contraction intervals. In isolated detrusor smooth muscle (DSM), contractions to carbachol and electrical-field stimulation (EFS) were significantly greater in 2K-1C rats. The Rho-kinase inhibitor Y27632 (10 µM) significantly reduced the carbachol-induced contractions in SHAM and 2K-1C rats, but DSM remained overactive in 2K-1C rats in presence of Y27632. Concentration-dependent contractions to the P2X receptor agonist α,ß-methylene ATP, KCl and extracellular Ca(2+) did not change between SHAM and 2K-1C groups. In 2K-1C rats, isoproterenol, metaproterenol and BRL 37-344 (non-selective, ß(2) - and ß(3) -selective adrenoceptor agonists, respectively) produced significantly lower relaxations and decreased cAMP levels, whereas relaxant responses to sodium nitroprusside and BAY 41-2272 remained unchanged. Muscarinic M(3) mRNA expression receptors were higher in 2K-1C group. CONCLUSIONS: Renovascular hypertensive rats exhibit bladder dysfunction that involves tissue remodeling and enhanced muscarinic M(3) -mediated contractions associated with reduced ß-adrenoceptor-mediated signal transduction.


Assuntos
Hipertensão Renovascular/complicações , Contração Muscular , Relaxamento Muscular , Músculo Liso/fisiopatologia , Doenças da Bexiga Urinária/etiologia , Bexiga Urinária/fisiopatologia , Agonistas Adrenérgicos beta/farmacologia , Animais , Agonistas Colinérgicos/farmacologia , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estimulação Elétrica , Hipertensão Renovascular/fisiopatologia , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/inervação , Músculo Liso/metabolismo , Músculo Liso/patologia , Fármacos Neuromusculares/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Agonistas do Receptor Purinérgico P2X/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor Muscarínico M3/genética , Transdução de Sinais , Fatores de Tempo , Regulação para Cima , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervação , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Doenças da Bexiga Urinária/metabolismo , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/fisiopatologia , Urodinâmica , Quinases Associadas a rho/antagonistas & inibidores
9.
Am J Physiol Renal Physiol ; 300(5): F1223-34, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21367919

RESUMO

The ankyrin-repeat transient receptor potential 1 (TRPA1) has been implicated in pathological conditions of the bladder, but its role in overactive bladder (OAB) following spinal cord injury (SCI) remains unknown. In this study, using a rat SCI model, we assessed the relevance of TRPA1 in OAB induced by SCI. SCI resulted in tissue damage, inflammation, and changes in bladder contractility and in voiding behavior. Moreover, SCI caused upregulation of TRPA1 protein and mRNA levels, in bladder and in dorsal root ganglion (DRG; L6-S1), but not in corresponding segment of spinal cord. Alteration in bladder contractility following SCI was evidenced by enhancement in cinnamaldehyde-, capsaicin-, or carbachol-induced bladder contraction as well as in its spontaneous phasic activity. Of relevance to voiding behavior, SCI induced increase in the number of nonvoiding contractions (NVCs), an important parameter associated with the OAB etiology, besides alterations in other urodynamic parameters. HC-030031 (TRPA1 antagonist) treatment decreased the number and the amplitude of NVCs while the TRPA1 antisense oligodeoxynucleotide (AS-ODN) treatment normalized the spontaneous phasic activity, decreased the cinnamaldehyde-induced bladder contraction and the number of NVCs in SCI rats. In addition, the cinnamaldehyde-induced bladder contraction was reduced by exposure of the bladder preparations to HC-030031. The efficacy of TRPA1 AS-ODN treatment was confirmed by means of the reduction of TRPA1 expression in the DRG, in the corresponding segment of the spinal cord and in the bladder, specifically in detrusor muscle. The present data show that the TRPA1 activation and upregulation seem to exert an important role in OAB following SCI.


Assuntos
Acetanilidas/farmacologia , Anquirinas/antagonistas & inibidores , Gânglios Espinais/efeitos dos fármacos , Oligonucleotídeos Antissenso/farmacologia , Purinas/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Bexiga Urinária Hiperativa/prevenção & controle , Bexiga Urinária/efeitos dos fármacos , Acroleína/análogos & derivados , Acroleína/farmacologia , Animais , Anquirinas/genética , Anquirinas/metabolismo , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Capsaicina/farmacologia , Carbacol/farmacologia , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiopatologia , Contração Muscular/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Canal de Cátion TRPA1 , Canais de Cátion TRPC , Bexiga Urinária/inervação , Bexiga Urinária/metabolismo , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/genética , Bexiga Urinária Hiperativa/metabolismo , Bexiga Urinária Hiperativa/fisiopatologia , Urodinâmica/efeitos dos fármacos
10.
Rio de Janeiro; s.n; 2011. 58 p. ilus.
Tese em Português | LILACS | ID: lil-601472

RESUMO

Lesões na inervação do trato urinário inferior ocasionado por traumatismo raquimedular afetam geralmente o músculo detrusor e o esfíncteres uretrais. Estas alterações acarretam problemas basicamente de incontinência urinária e aumento da pressão intravesical, decorrente deste traumatismo, trazendo consequências para o funcionamento do sistema urinário superior. Quantificar os elementos fibrosos da matriz extracelular e fibras musculares das bexigas neurogênicas hiper-reflexas comparando-as com bexigas normais. Foram utilizadas 6 amostras de bexigas neurogênicas de indivíduos que foram submetidos a cirurgia de reparação por cistoenteroplastia realizados pelo serviço de urologia do Hospital Municipal Souza Aguiar, estas amostras foram fixadas imediatamente em solução tamponada de formalina a 10%. O controle com amostras iguais as do estudo extraída de cadáveres cuja causa morte não relacionava-se ao sistema urogenital macroscópicamente. O material foi submetido as seguintes técnicas histoquímicas: H&E, van Gieson e Resorcina Fucsina resorcina de Weigert com prévia oxidação pela oxona. Imunohistoquímica: anti-elastina. A observação dos cortes corados pelo van Gieson demonstrou uma diminuição significativa do músculo liso de 13% e aumento do colágeno em 72% e as fibras do sistema elástico um aumento de 101%. Conclusão. Nas bexigas neurogênicas hiper-reflexas o músculo detrusor e os elementos fibrosos da matriz foram profundamente modificados. As fibras do sistema elástico foram as mais afetadas.


Lesions on lower urinary tract innervations caused by spinal cord injuries usually affect the detrusor muscle and urethral sphincter. Beside the smooth muscle fibers the collagen fibers and elastic system fibers, fibrous components of the extracellular matrix of the bladder wall, are strongly related to vesicle bladder compliance. For this reason the aim of this work is to quantify the fibrous elements of the extracellular matrix and muscle fibers of the neurogenic bladder hyperreflexia. Samples of neurogenic bladder were obtained from six men who had previously undergone surgical repair. The control group samples (n=6) were similarly obtained from patients whose deaths were not related to the urogenital system. The samples were stained using the following histochemical techniques: H&E, Van Gieson, Weigert and Sirius Red. Sections stained with Sirius Red were observed under polarization light microscopy to characterize possible different kinds of collagen. Immunohistochemical technique was used to characterize and quantify the elastic system fibers. Quantification analysis was performed by stereological methods. An increase of 72% of the collagen was observed. Nevertheless, the most significant difference observed was the raising of 101% of the elastic system fibers. Contrary the smooth muscle fibers showed a decrease of 13%. In the neurogenic bladder with detrusor hyperreflexia the fibrous elements of the extracellular matrix and smooth muscle fibers were greatly modified. The elastic system fibers seem to be the most affected in this disease.


Assuntos
Humanos , Masculino , Feminino , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinária/inervação , Bexiga Urinária/lesões , Imuno-Histoquímica , Incontinência Urinária/etiologia , Músculo Liso/citologia , Músculo Liso/inervação , Traumatismos da Medula Espinal/complicações , Vesícula Biliar/fisiopatologia
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