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1.
Oxid Med Cell Longev ; 2019: 5641645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531184

RESUMO

Purpose: This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR). Materials and Methods: Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-γ-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed. Results: Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. CSE expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR. Conclusions: These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Resistência à Insulina , Obesidade , Estresse Oxidativo , Canal de Cátion TRPA1/metabolismo , Doenças da Bexiga Urinária , Bexiga Urinária , Animais , Cistationina beta-Sintase , Cistationina gama-Liase , Masculino , Contração Muscular , Músculo Liso , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia , Ratos , Ratos Zucker , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/metabolismo , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/fisiopatologia
2.
Expert Opin Investig Drugs ; 28(9): 749-755, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399015

RESUMO

Introduction: In the lower urinary tract (LUT) several members of the TRP superfamily are involved in nociception and mechanosensory transduction. Animal studies have suggested a therapeutic potential of some of these channels, including TRPV1, TRPV4, TRPM8, TRPA1, and TRPM4, for treatment of bladder over- and underactivity and bladder pain disorders, but translation of this information to clinical application has been slow. Areas covered: An update on and discussion of current information on the potential clinical use of TRP channel agonists/antagonists in the treatment of different types of bladder dysfunction. The electronic databases PubMed and Scopus were used to identify relevant clinical and animal studies. Expert opinion: The therapeutic effect of TRPV1 channel desensitizing agonists (capsaicin, resiniferatoxin, given intravesically) has been convincingly demonstrated in some forms of bladder overactivity. However, so far, the potential of any of the small-molecule TRP channel blockers developed for non-bladder indications and tested in early human trials for safety has not been explored clinically in LUT dysfunction. The adverse effects of hyperthermia and reduction of noxious heat sensation of the first generation TRPV1 blockers have delayed development. Despite lack of translational information, TRP channels remain interesting targets for future LUT drugs.


Assuntos
Canais de Receptores Transientes de Potencial/agonistas , Canais de Receptores Transientes de Potencial/antagonistas & inibidores , Doenças da Bexiga Urinária/tratamento farmacológico , Animais , Desenvolvimento de Medicamentos/métodos , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/fisiopatologia , Dor/tratamento farmacológico , Dor/etiologia , Canais de Receptores Transientes de Potencial/metabolismo , Doenças da Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/fisiopatologia
3.
Biomed Res ; 40(4): 145-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413235

RESUMO

We investigated the mechanisms by which propiverine hydrochloride influenced bladder activity in rats with pelvic venous congestion (PC) and urinary frequency. To create PC rats, female rats were anesthetized with isoflurane and the bilateral common iliac veins and bilateral uterine veins were ligated. At 4 weeks after ligation, we assessed voiding behaviour, locomotor activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide metabolites (NOx). We also performed cystometry and measured mRNAs for nitric oxide synthase (NOS) and several receptors in the bladder wall. PC rats showed a decrease in locomotor activity and an increased frequency of urination. There was a decrease in endothelial NOS (eNOS), M3, and TRPV1 mRNA expression in the bladder wall, as well as an increase in inducible NOS (iNOS) mRNA. Administration of propiverine to PC rats increased locomotor activity to the level in sham rats, improved bladder function, decreased urinary 8-OHdG excretion, and increased urinary NOx excretion. In addition, propiverine increased neuronal NOS (nNOS) mRNA expression, and decreased expression of iNOS, M3 and TRPV1 mRNA in the bladder wall. Therefore, propiverine not only improved bladder dysfunction through its previously reported actions (anti-muscarinic effect, Ca antagonist effect, and inhibition of noradrenaline re-uptake), but also by reducing inflammation.


Assuntos
Benzilatos/farmacologia , Hiperemia/tratamento farmacológico , Doenças da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperemia/metabolismo , Hiperemia/patologia , Hiperemia/fisiopatologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Óxido Nítrico Sintase Tipo I/biossíntese , Óxido Nítrico Sintase Tipo III/biossíntese , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV/biossíntese , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Doenças da Bexiga Urinária/metabolismo , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/fisiopatologia
4.
Low Urin Tract Symptoms ; 11(4): 232-240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207098

RESUMO

OBJECTIVE: This study evaluated the effect of human umbilical cord blood mononuclear cells (HUCB-MNCs) on bladder dysfunction in streptozotocin (STZ; 35 mg/kg, i.v.)-induced diabetic rats. METHODS: Adult male Sprague-Dawley rats (n = 30) were equally divided into three groups: control group, STZ-diabetic group, and HUCB-MNC-treated group (1 × 106 cells). HUCB-MNCs were isolated by density gradient centrifugation from eight healthy donors and injected into the corpus cavenosum in STZ-diabetic rats 4 weeks after the induction of diabetes. Studies were performed 4 weeks after HUCB-MNC or vehicle injection. In vitro organ bath studies were performed on bladder strips, whereas protein expression of hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and α-smooth muscle actin (SMA) in the bladder and the ratio of smooth muscle cells (SMCs) to collagen were determined using western blotting and Masson trichrome staining. RESULTS: Neurogenic contractions of detrusor smooth muscle strips were 55% smaller in the diabetic group than control group (P < 0.05); these contractions were normalized by HUCB-MNC treatment. In addition, HUCB-MNC treatment restored the impaired maximal carbachol-induced contractile response in detrusor strips in the diabetic group (29%; P < 0.05). HUCB-MNC treatment improved the KCl-induced contractile response in the diabetic bladder (68%; P < 0.05), but had no effect on ATP-induced contractile responses. Increased expression of HIF-1α and VEGF protein and decreased expression of α-SMA protein and the SMC/collagen ratio in diabetic rats were reversed by HUCB-MNC. CONCLUSION: Administration of HUCB-MNCs facilitates bladder function recovery, which is likely related to downregulation of HIF-1α expression and attenuation of fibrosis in STZ-diabetic rats.


Assuntos
Diabetes Mellitus Experimental/complicações , Sangue Fetal/citologia , Leucócitos Mononucleares/fisiologia , Doenças da Bexiga Urinária/etiologia , Actinas/metabolismo , Animais , Western Blotting , Sangue Fetal/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Contração Muscular/fisiologia , Músculo Liso/fisiopatologia , Ratos , Ratos Sprague-Dawley , Bexiga Urinária/metabolismo , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/terapia , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Int Braz J Urol ; 45(4): 681-685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184453

RESUMO

OBJECTIVE: The objective of bladder augmentation (BA) is to create a low-pressure reservoir with adequate capacity. Despite its benefits, the use of intestinal patches in bladder enlargement provides a high risk of developing complications and BA with demucosalised bowel represents a potential alternative. Therefore, this study evaluated urological parameters and long-term clinical follow-up of patients submitted to nonsecretory BA in a single center with 25 years of experience. MATERIALS AND METHODS: Patients treated with BA underwent urological evaluation, which included history, physical examination and urodynamic study. The main urodynamic parameters (bladder capacity and bladder compliance) were assessed in the pre and postoperative moments, and compared by the Wilcoxon Signed Rank test. The main long-term complications were described. RESULTS: 269 patients (mean age 14±13 years, 47% male) underwent BA with the use of demucolised intestinal segments. Among the patients in the sample, 187 (69.52%) had neurogenic bladder, 68 (25.28%) had bladder exstrophy, nine had tuberculosis (3.34%), four had a posterior urethral valve (1.49%) and one with hypospadia (0.37%). After the surgical procedure, a significant increment in both urodynamic parameters was found, with a 222% increase in bladder capacity and 604% in bladder compliance (p < 0.001 in both analyzes). Mean follow-up time ranged from 2 to 358 months, with a median of 72 months (IQR 74-247). Among all patients, 5 presented spontaneous perforation. CONCLUSION: The study showed statistically signifi cant increase in both compliance and bladder capacity after non-secretory BA, with a low rate of severe complications.


Assuntos
Doenças da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Resultado do Tratamento , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/reabilitação , Urodinâmica , Adulto Jovem
6.
Mol Med Rep ; 19(4): 2716-2728, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720140

RESUMO

Due to the rising abuse of ketamine usage in recent years, ketamine­induced urinary tract syndrome has received increasing attention. The present study aimed to investigate the molecular mechanism underlying ketamine­associated cystitis in a mouse model. Female C57BL/6 mice were randomly divided into two groups: One group was treated with ketamine (100 mg/kg/day of ketamine for 20 weeks), whereas, the control group was treated with saline solution. In each group, micturition frequency and urine volume were examined to assess urinary voiding functions. Mouse bladders were extracted and samples were examined for pathological and morphological alterations using hematoxylin and eosin staining, Masson's trichrome staining and scanning electron microscopy. A cDNA microarray was conducted to investigate the differentially expressed genes following treatment with ketamine. The results suggested that bladder hyperactivity increased in the mice treated with ketamine. Furthermore, treatment with ketamine resulted in a smooth apical epithelial surface, subepithelial vascular congestion and lymphoplasmacytic aggregation. Microarray analysis identified a number of genes involved in extracellular matrix accumulation, which is associated with connective tissue fibrosis progression, and in calcium signaling regulation, that was associated with urinary bladder smooth muscle contraction. Collectively, the present results suggested that these differentially expressed genes may serve critical roles in ketamine­induced alterations of micturition patterns and urothelial pathogenesis. Furthermore, the present findings may provide a theoretical basis for the development of effective therapies to treat ketamine­induced urinary tract syndrome.


Assuntos
Sinalização do Cálcio , Matriz Extracelular/metabolismo , Ketamina/efeitos adversos , Doenças da Bexiga Urinária/etiologia , Doenças da Bexiga Urinária/metabolismo , Animais , Biomarcadores , Peso Corporal , Modelos Animais de Doenças , Feminino , Camundongos , Modelos Biológicos , Membrana Mucosa/metabolismo , Membrana Mucosa/patologia , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/fisiopatologia
7.
Physiology (Bethesda) ; 34(2): 150-162, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30724129

RESUMO

Autonomic nerves are attractive targets for medical therapies using electroceutical devices because of the potential for selective control and few side effects. These devices use novel materials, electrode configurations, stimulation patterns, and closed-loop control to treat heart failure, hypertension, gastrointestinal and bladder diseases, obesity/diabetes, and inflammatory disorders. Critical to progress is a mechanistic understanding of multi-level controls of target organs, disease adaptation, and impact of neuromodulation to restore organ function.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Terapia por Estimulação Elétrica/métodos , Cardiopatias/terapia , Animais , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/terapia , Terapia por Estimulação Elétrica/instrumentação , Gastroenteropatias/fisiopatologia , Gastroenteropatias/terapia , Cardiopatias/fisiopatologia , Humanos , Inflamação/fisiopatologia , Inflamação/terapia , Obesidade/fisiopatologia , Obesidade/terapia , Estimulação da Medula Espinal/instrumentação , Estimulação da Medula Espinal/métodos , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/terapia , Estimulação do Nervo Vago/instrumentação , Estimulação do Nervo Vago/métodos
8.
Int Urogynecol J ; 30(4): 589-594, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30710159

RESUMO

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the functional outcomes and urodynamic findings after laparoscopic sacrocolpopexy (LSC) in patients with stages II-IV pelvic organ prolapse (POP). METHODS: In this single-center prospective study, we evaluated 63 women (mean age 62.5 ± 7.5 years) women with symptomatic and advanced POP (stage II-IV) who underwent LSC without concomitant anti-incontinence surgery. The preoperative evaluation incuded history, clinical examination, and urodynamic testing. Women were followed up at 1, 3, 6, and 12 months after surgery and then annually using history, examination, and uroflowmetry. At 6 months, we performed urodynamic testing. To evaluate urinary symptoms, we used the Urogenital Distress Inventory (UDI)-6 questionnaire before and 6 months after surgery. RESULTS: Median follow- up was 22 months (range 8-48). After surgery, maximum flow (Qmax) significantly improved compared with baseline (14.17 ± 2.3 vs 27 ± 8.4 ml/s; p = 0.02), and the percentage of patients with elevated postvoid residual (PVR) significantly decreased (33.3% vs 11.1%; p = 0.001). Detrusor overactivity and bladder outlet obstruction disappeared in 73.6% and 85.7% of patients, respectively, while detrusor underactivity persisted in 66.6% of women. Twenty women (31.7%) reported stress urinary incontinence (SUI) before surgery (14 clinically evident and 6 as occult form), which persisted in only 7/20 (11%) patients following LSC, with no de novo cases. The most common preoperative symptoms were voiding symptoms, present in 42/63 (66.6%) patients, which resolved in 36 (85.7%). The overactive bladder syndrome disappeared in 60% of women, with no de novo cases. Results were reflected by a significant decrease in UDI-6 score from a median of 16 (0-45) at baseline to 5.5 (0-17) at the final follow-up (p = 0.001). The domain on storage symptoms (median 3 vs 1) and voiding symptoms (median 3 vs 1) of UDI-6 showed an improvement after surgery (p = 0.001). CONCLUSIONS: The urodynamic finding showed that LSC in women with advanced POP provides good functional outcomes.


Assuntos
Prolapso de Órgão Pélvico/complicações , Prolapso de Órgão Pélvico/cirurgia , Doenças da Bexiga Urinária/fisiopatologia , Incontinência Urinária por Estresse/fisiopatologia , Urodinâmica , Vagina/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Laparoscopia , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/fisiopatologia , Período Pós-Operatório , Período Pré-Operatório , Sacro/cirurgia , Inquéritos e Questionários , Doenças da Bexiga Urinária/etiologia , Obstrução do Colo da Bexiga Urinária/etiologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/fisiopatologia , Bexiga Inativa/etiologia , Bexiga Inativa/fisiopatologia , Incontinência Urinária por Estresse/etiologia
9.
BMC Complement Altern Med ; 19(1): 41, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717724

RESUMO

BACKGROUND: This study aimed to elucidate the effects and mechanisms of Radix Linderae (RL) extracts on a mouse model of diabetic bladder dysfunction (DBD), especially on later decompensated phase. METHODS: Male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) after 4 weeks of high-fat diet (HFD) feeding. DBD mouse models (later decompensated phase) were developed by 12-weeks persistent hyperglycemia and then treated with RL extracts for 4 weeks. During administration, the fasting blood glucose (FBG) test was performed once a week. Four weeks later, oral glucose tolerance test (OGTT), voided stain on paper (VSOP), and urodynamic alteration were explored. We also performed haematoxylin and eosin (H&E) and Masson's trichrome staining to observe the histology of the bladder. Then, the contractile responses to α, ß-methylene ATP, capsaicin (CAP), KCl and carbachol were measured. Moreover, qPCR assay was performed to analyse the bladder gene expression levels of M3 receptors and TRPV1. RESULTS: The diabetic mice exhibited higher FBG, OGTT and urine production, and no substantial alteration was observed after RL treatment. Urodynamic test showed the maximum bladder capacity (MBC), residual volume (RV) and bladder compliance (BC), as well as the decrement of voided efficiency (VE) and micturition volume (MV), remarkably increased in the DBD mice. Furthermore, RL treatment significant improved urodynamic urination, with lower MBC, RV, and, BC, as well as higher VE and MV, as compared with the model groups. The wall thickness of the bladder and the ratio of smooth muscle/collagen remarkably increased, and RL could effectively attenuate the pathological change. The response of bladder strips to the stimulus was also reduced in the DBD mice, and RL treatment markedly increased the contraction. Furthermore, the gene expression levels of M3 receptors and TRPV1 were down-regulated in the bladders of the diabetic mice, whereas RL treatment retrieved those gene expression levels. CONCLUSIONS: RL extracts can improve the bladder voiding functions of the DBD model mice in later decompensated phase, and underlying mechanisms was associated with mediating the gene expression of M3 receptors and TRPV1 in the bladder instead of improving blood sugar levels.


Assuntos
Diabetes Mellitus Experimental/complicações , Medicamentos de Ervas Chinesas , Lindera/química , Doenças da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Raízes de Plantas , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/fisiopatologia
10.
J Pediatr Surg ; 54(10): 2107-2111, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30686521

RESUMO

AIM: To assess the long-term urologic outcomes in follow-up of patients of sacrococcygeal teratoma (SCT) using urodynamic study (UDS) in addition to clinical and radiologic evaluation. METHODS: A prospective study of clinical, radiological and urodynamic evaluation in patients with SCT who underwent resection between January 2002-June 2015 and were followed up till January 2016 was conducted. RESULTS: Total 57 patients, 42 (73.7%) females and 15 (26.3%) males with 35 (62.4%) following treatment for benign and 22 (38.5%) for malignant disease were included. Twenty-eight of 57 (49.12%) had urological problems. Clinical complaints in 21 (36.8%) patients included stress urinary incontinence-14 (66.7%), enuresis-9 (42.9%), and poor stream or dribbling of urine-6 (28.6%). Eight of 51 patients (15.7%) had abnormal ultrasound findings, which included contracted, trabeculated thick walled bladder (3), bilateral hydronephrosis (3) and significant post void residue (PVR) (6). Seven of 57 underwent micturating cystourethrogram (MCU), 5 had an abnormal report[significant PVR (4), small trabeculated bladder (3), reflux (2) and large capacity bladder (1)]. Urodynamic study was done in 27 patients, 18/27 (66.7%) had abnormalities. Six patients without any clinical or ultrasonographic abnormalities had abnormal UDS. Total 28 (49.12%) had urological comorbidities. Three patients had overactive bladder, five dysfunctional voiding, one underactive bladder and one had giggle incontinence. Children were managed by behaviour therapy and pharmacotherapy. CONCLUSION: Urodynamic evaluation could detect abnormalities in patients who had no urinary complaints or abnormality on ultrasound. The abnormalities have a potential for progressive upper tract damage. Urodynamics should be an integral part of urological surveillance in patients operated for SCT. TYPE OF STUDY: Prognostic study. LEVEL OF EVIDENCE: Level II (Prospective cohort study).


Assuntos
Neoplasias da Coluna Vertebral/cirurgia , Teratoma/cirurgia , Urodinâmica/fisiologia , Adolescente , Terapia Comportamental/métodos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hidronefrose/diagnóstico , Hidronefrose/fisiopatologia , Lactente , Masculino , Estudos Prospectivos , Região Sacrococcígea , Neoplasias da Coluna Vertebral/fisiopatologia , Teratoma/fisiopatologia , Ultrassonografia , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/fisiopatologia , Incontinência Urinária/diagnóstico , Incontinência Urinária/fisiopatologia
11.
J Pediatr Surg ; 54(4): 825-830, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29960741

RESUMO

PURPOSE: To assess the efficacy of combined transcutaneous interferential (IF) electrical stimulation and pelvic floor muscle training through biofeedback on non-neuropathic urinary incontinence in children. METHODS: This prospective study comprised of 46 anatomically and neurologically normal children (9 boys, 37 girls; mean age of 8.4 ±â€¯2.2 years old) with non-neuropathic urinary incontinence. All children were evaluated by kidney and bladder ultrasounds, uroflowmetry with electromyography (EMG), a complete voiding diary and a dysfunctional voiding scoring questionnaire at the baseline. Children were randomly allocated into two treatment groups including group A (n = 23) who underwent biofeedback therapy in addition to IF electrical stimulation and group B (n = 23) who received only biofeedback therapy. Re-evaluation was performed 6 months and one year after completion of the treatment sessions. RESULTS: Improvement of non-neuropathic urinary incontinence was significantly higher in group A in comparison to group B at two follow ups (P < 0.05). Daytime incontinence was improved in 19/23(82%) and 13/23(56.5%) of children in groups A and B respectively after the treatment (P < 0.01). There was no significant difference in uroflowmetry measures between two groups after the treatment. CONCLUSIONS: Combination of biofeedback therapy and transcutaneous IF electrical stimulation is a potential effective modality in treating non-neuropathic urinary incontinence in children. LEVEL OF EVIDENCE: Type of study: Treatment study. Level I: Randomized controlled trials with adequate statistical power to detect differences (narrow confidence intervals) and follow up >80%.


Assuntos
Biorretroalimentação Psicológica/métodos , Terapia por Exercício/métodos , Diafragma da Pelve/fisiopatologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Incontinência Urinária/terapia , Criança , Terapia Combinada , Eletromiografia , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Doenças da Bexiga Urinária/fisiopatologia
12.
J Mol Neurosci ; 68(3): 357-367, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30259317

RESUMO

Neural injury, inflammation, or diseases commonly and adversely affect micturition reflex function that is organized by neural circuits in the CNS and PNS. One neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1), and its cognate receptor, PAC1 (Adcyap1r1), have tissue-specific distributions in the lower urinary tract. PACAP and associated receptors are expressed in the LUT and exhibit changes in expression, distribution, and function in preclinical animal models of bladder pain syndrome (BPS)/interstitial cystitis (IC), a chronic, visceral pain syndrome characterized by pain, and LUT dysfunction. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency and somatic (e.g., hindpaw, pelvic) sensitivity in preclinical animal models and a transgenic mouse model that mirrors some clinical symptoms of BPS/IC. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction following urinary bladder inflammation.


Assuntos
Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Doenças da Bexiga Urinária/metabolismo , Transtornos Urinários/metabolismo , Micção , Animais , Humanos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Transdução de Sinais , Doenças da Bexiga Urinária/fisiopatologia , Transtornos Urinários/fisiopatologia
13.
Tissue Eng Part A ; 25(11-12): 855-866, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30191762

RESUMO

IMPACT STATEMENT: The search for an ideal "off-the-shelf" biomaterial for augmentation cystoplasty remains elusive and current scaffold configurations are hampered by mechanical and biocompatibility restrictions. In addition, preclinical evaluations of potential scaffold designs for bladder repair are limited by the lack of tractable large animal models of obstructive bladder disease that can mimic clinical pathology. The results of this study describe a novel, minimally invasive, porcine model of partial bladder outlet obstruction that simulates clinically relevant phenotypes. Utilizing this model, we demonstrate that acellular, bi-layer silk fibroin grafts can support the formation of vascularized, innervated bladder tissues with functional properties.


Assuntos
Fibroínas/química , Regeneração , Tecidos Suporte/química , Doenças da Bexiga Urinária , Animais , Modelos Animais de Doenças , Feminino , Suínos , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/psicologia , Doenças da Bexiga Urinária/terapia , Urodinâmica
14.
J Urol ; 201(4): 802-809, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30248344

RESUMO

PURPOSE: Hinman syndrome is a rare disease with urodynamic findings and a clinical course resembling neuropathic bladder, without a neuropathic etiology. Diffusion tensor imaging is a special technique of magnetic resonance imaging that has recently been used to evaluate the peripheral nerves but has been demonstrated to be applicable for evaluation of the lumbosacral plexus. We examined the lumbosacral plexus using diffusion tensor imaging, which has not previously been reported in patients with Hinman syndrome. MATERIALS AND METHODS: The study included 12 patients who fulfilled criteria for Hinman syndrome, with severe bladder dysfunction on urodynamics, renal scarring on scintigraphy and no pathological findings on magnetic resonance imaging. The 12 subjects serving as controls required pelvic or spinal magnetic resonance imaging for reasons other than spinal abnormalities. Evaluation was performed with a 3.0 Tesla magnetic resonance imaging system and 16-channel body coil. Tractography was done to examine the lumbosacral plexus. Fractional anisotropy and mean diffusivity were computed and compared between groups for the right and left plexuses. RESULTS: Mean fractional anisotropy was 0.24 and 0.35 for the right plexus in patients and controls, respectively, and 0.24 and 0.36 for the left plexus. Mean diffusivity was 1.39 for the right and left plexuses in patients, and 1.28 for the right and left plexuses in controls (p <0.001 for all). CONCLUSIONS: Our study focusing on the lumbosacral plexus as a possible origin of neuropathy revealed abnormal findings in patients with Hinman syndrome resembling nerve injury series. This is the first known study to provide data showing that Hinman syndrome may have a neuropathic etiology.


Assuntos
Imagem de Tensor de Difusão/métodos , Plexo Lombossacral/diagnóstico por imagem , Bexiga Urinaria Neurogênica/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Doenças Raras , Índice de Gravidade de Doença , Síndrome , Doenças da Bexiga Urinária/diagnóstico por imagem , Doenças da Bexiga Urinária/fisiopatologia , Bexiga Urinaria Neurogênica/fisiopatologia , Urodinâmica/fisiologia
15.
Urology ; 123: 1-6, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30352207

RESUMO

Diabetic bladder dysfunction affects almost half of all diabetic patients, making it one of the most common complications of diabetes mellitus. The clinical presentation of diabetic bladder dysfunction can be varied and may be extremely bothersome to patients, negatively impacting their quality of life. Despite this, it remains understudied and under-represented in the medical literature. This review summarizes the current literature on pathophysiology, clinical presentation, urodynamic findings, evaluation, and management. Through this, we hope to provide guidance to clinicians involved with the management of this condition.


Assuntos
Complicações do Diabetes , Doenças da Bexiga Urinária , Animais , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/terapia , Modelos Animais de Doenças , Humanos , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/terapia
16.
Int Urol Nephrol ; 51(1): 73-78, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30478812

RESUMO

OBJECTIVES: Pregnancy is associated with many functional changes of the urinary bladder. It was reported that most of healthy women complain from urinary symptoms during pregnancy. The parasympathetic system is mainly mediating bladder emptying. The aim of the study is to investigate the cholinergic effect and the role of acetylcholinesterase in the bladder during pregnancy. METHODS: Sixteen rats were used in the present study as control group (non-pregnant) and pregnant group (18-20 days pregnant). Isolated urinary smooth muscle strips were suspended in organ baths filled with Krebs' solution for isometric tension recording. RESULTS: Electric field stimulation (EFS), (0.1-40 Hz), of the control and pregnant bladder preparations produced frequency-dependent contractions. Atropine (1 µM) inhibited EFS-induced contractions in the two groups by 65% and 50% respectively indicating the response of cholinergic innervation. Neostigmine significantly enhanced EFS responses, confirming its selectivity for inhibiting acetylcholinesterase which is responsible for termination of acetylcholine. Concentration-response curves for acetylcholine were reduced in pregnant group than control. Concentration-response curves for ATP were increased in pregnant group than control. Neostigmine augmented concentration-response curves for acetylcholine in control and pregnant groups. The effect of neostigmine on acetylcholine contractile responses in pregnancy group was higher than in control. CONCLUSIONS: Urinary bladder dysfunction during pregnancy might be due to augmentation of acetylcholinesterase effect. This will lead to the decrease in response to cholinergic stimuli. New pharmaceutical drugs specifically affecting the enzyme in the bladder can help in avoiding the unpleasant urinary symptoms during pregnancy.


Assuntos
Acetilcolinesterase/metabolismo , Atropina/farmacologia , Neostigmina/farmacologia , Complicações na Gravidez , Doenças da Bexiga Urinária , Bexiga Urinária , Animais , Inibidores da Colinesterase/farmacologia , Modelos Animais de Doenças , Feminino , Parassimpatolíticos/farmacologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/metabolismo , Complicações na Gravidez/fisiopatologia , Ratos , Receptores Muscarínicos/metabolismo , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervação , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/tratamento farmacológico , Doenças da Bexiga Urinária/metabolismo , Doenças da Bexiga Urinária/fisiopatologia
17.
Neuromodulation ; 22(6): 697-702, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30506765

RESUMO

OBJECTIVES: Incomplete spinal cord injury (SCI) accounts for two-thirds of all SCIs in clinical practice. Preclinical research on the effect of sacral neuromodulation (SNM) on bladder function, however, has been focused only on animal models of complete SCI. We aimed to evaluate the effect of early SNM on bladder responses in a rat model of incomplete SCI. MATERIALS AND METHODS: Altogether, 21 female Sprague-Dawley rats were equally assigned to control (CTR), SCI + sham stimulation (SHAM), and SCI + SNM (SNM) groups. In the SHAM and SNM groups, incomplete SCI was created by producing a moderate contusion with an NYU-MASCIS impactor at the T9-T10 level of the spine, with needle electrodes implanted bilaterally into the S2 or S3 sacral foramen. Only SNM group underwent electrical stimulation for 28 days, beginning on day 7 after SCI. Cystometry was performed 35 days after SCI. RESULTS: Although the interval between voiding contractions was significantly longer in the SHAM group than the CTR group (25.5 ± 1.4 vs. 12.5 ± 1.7 min; p < 0.05), there were no significant differences between the SNM group (16.5 ± 1.5 min) and the CTR group. Maximum voiding contraction pressure did not differ among the groups. The SNM group had a significantly lower frequency (3.5 ± 0.5 vs. 14.6 ± 2.0; p < 0.05) and maximum pressure (11.4 ± 6.2 vs. 21.3 ± 1.8 cmH2 O; p < 0.05) of nonvoiding contractions than the SHAM group. CONCLUSIONS: Our results provide experimental evidence that early SNM treatment may prevent or diminish bladder dysfunctions (e.g., detrusor overactivity, abnormal micturition reflex) in a clinical condition of incomplete SCI.


Assuntos
Modelos Animais de Doenças , Sacro/fisiologia , Traumatismos da Medula Espinal/terapia , Estimulação da Medula Espinal/métodos , Doenças da Bexiga Urinária/terapia , Animais , Contusões , Feminino , Ratos , Ratos Sprague-Dawley , Sacro/inervação , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiologia , Doenças da Bexiga Urinária/etiologia , Doenças da Bexiga Urinária/fisiopatologia
18.
Eur Rev Med Pharmacol Sci ; 22(20): 6575-6582, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30402828

RESUMO

OBJECTIVE: We aimed at investigating changes in the expression and physiological function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in interstitial cells of Cajal (ICC) in diabetic state. MATERIALS AND METHODS: Twenty adult female Sprague-Dawley (SD) rats were randomly assigned to control and Zucker diabetic fatty (ZDF) group. The protein and mRNA expression of HCN isoforms and C-kit in the rat bladders were detected using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). The bladder contraction was evaluated using a bladder smooth muscle strip test. Whole cell patch-clamp techniques were used to detect the activity of HCN channels. Immunofluorescent staining was used to the positive expression of HCN and C-kit in ICC. RESULTS: cAMP, as HCN channel-specific stimulant, could increase the frequency and amplitude of spontaneous contractions in both group, while cAMP inducing contraction of ZDF rats, was still significantly lower compared with the control group. Acute bladder ICCs were isolated by collagenase digestion. Classic Ih current pattern was recorded on ICCs while Ih current amplitude of ICCs from ZDF diabetic rats was significantly lower than the control group. The expression and mRNA of HCN1-4 isoforms in ZDF diabetic rats were both significantly lower compared with the control group. Meanwhile, the number of c-kit positive cells in ZDF diabetic rats showed no significant differences compared with controls. The morphological structure of ICC in the bladder of ZDF rats was relatively loose and the number of their cell process was apparently decreased. CONCLUSIONS: The structure of ICCs in ZDF rats was relatively loose, their connection to each other was also diminished. The expression of HCN was down-regulated and its response to cAMP was also decreased. HCN channels in bladder ICCs might regulate detrusor contraction. Changes in HCN expression and activity in bladder ICCs might be one of the most important mechanisms of diabetic cystopathy.


Assuntos
Complicações do Diabetes/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Células Intersticiais de Cajal/metabolismo , Contração Muscular , Músculo Liso/metabolismo , Doenças da Bexiga Urinária/metabolismo , Bexiga Urinária/metabolismo , Urodinâmica , Animais , Complicações do Diabetes/patologia , Complicações do Diabetes/fisiopatologia , Feminino , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Células Intersticiais de Cajal/patologia , Músculo Liso/patologia , Músculo Liso/fisiopatologia , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos Sprague-Dawley , Ratos Zucker , Transdução de Sinais , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/fisiopatologia
20.
Neurourol Urodyn ; 37(5): 1549-1558, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29667730

RESUMO

AIMS: Succinate and its receptor, GPR91, have been implicated in different aspects of metabolic syndrome. As GPR91 is expressed in the urinary bladder, the aim of this study is to show the effect of chronically increased succinate levels on bladder function. MATERIALS AND METHODS: Healthy Sprague-Dawley (SD) rats and hypertensive Dahl rats received an intraperitoneal injection of either saline or succinate (50 mg/kg) daily for a period of 4 weeks. Conscious cystometry was performed at the end of this period. Bladders were collected and used for contractility studies and morphological assessment. Two-way ANOVA was performed to compare between the two strains and student t-tests to compare treatment groups within each strain. RESULTS: Compared to SD rats, Dahl rats showed signs of bladder dysfunction. Succinate treatment led to higher urinary succinate levels and lower bladder capacities compared to saline-treated animals. In SD rats, this was associated with higher collagen content, lower GPR91 expression and an altered bladder nerve profile in the bladder. In succinate-treated Dahl rats, detrusor contractility was reduced and associated with decreased cholinergic innervation and increased collagen content. CONCLUSIONS: It is suggested that succinate negatively affects bladder function via effects through its receptor, GPR91, and that its effects are enhanced in the presence of metabolic disturbance. These findings contribute to our understanding of the pathophysiology of bladder dysfunction, specifically in a metabolic syndrome setting.


Assuntos
Síndrome Metabólica/fisiopatologia , Succinatos/uso terapêutico , Doenças da Bexiga Urinária/tratamento farmacológico , Doenças da Bexiga Urinária/fisiopatologia , Animais , Colágeno/metabolismo , Masculino , Síndrome Metabólica/complicações , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiopatologia , Sistema Nervoso Parassimpático/efeitos dos fármacos , Ratos , Ratos Endogâmicos Dahl , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas-G/biossíntese , Receptores Acoplados a Proteínas-G/genética , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/etiologia
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