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1.
Pediatr Surg Int ; 36(7): 763-772, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32458130

RESUMO

INTRODUCTION: Bladder Bowel Dysfunction (BBD) has been described in patients with Down's Syndrome (DS). Our aim was to report the incidence, demographics, presentation, complications and management of the bladder in DS patients with BBD. METHODS: A systematic review was performed using PRISMA guidelines and search terms "{[(trisomy 21) OR down's syndrome]} AND [("non-neurogenic") OR voiding dysfunction]" in the search engines MEDLINE and SCOPUS. We also include a case series from two paediatric urology centres. RESULTS: A total of 38 patients with BBD and DS were included. Mean age was 12 years (newborn to 21 years), the male:female ratio was 2:1. Functional constipation (90%), recurrent urinary tract infections (38%) and enuresis were common at presentation (56%), while over 56% patients required surgical intervention. Medical treatment and behavioral modification were less successful while intermittent catheterisation did not work. CONCLUSION: This study reviews the largest cohort of patients with BBD in DS. It is common with serious consequences requiring operative intervention. Usual interventions are unreliable due to poor compliance. Early identification and management protect the renal tract. Regular screening for urogenital anomalies in DS is currently not performed. We recommend a thorough history of bladder function in DS patients to identify these cases early.


Assuntos
Síndrome de Down/complicações , Doenças da Bexiga Urinária/complicações , Doenças da Bexiga Urinária/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Constipação Intestinal/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/terapia , Adulto Jovem
2.
Am J Physiol Renal Physiol ; 318(4): F901-F910, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32116016

RESUMO

The signaling pathways and effectors that drive the response of the bladder to nonmalignant insults or injury are incompletely defined. Interrogation of biological systems has been revolutionized by the ability to generate high-content data sets that capture information on a variety of biomolecules in cells and tissues, from DNA to RNA to proteins. In oncology, such an approach has led to the identification of cancer subtypes, improved prognostic capability, and has provided a basis for precision treatment of patients. In contrast, systematic molecular characterization of benign bladder disorders has lagged behind, such that our ability to uncover novel therapeutic interventions or increase our mechanistic understanding of such conditions is limited. Here, we discuss existing literature on the application of omics approaches, including transcriptomics and proteomics, to urinary tract conditions characterized by pathological tissue remodeling. We discuss molecular pathways implicated in remodeling, challenges in the field, and aspirations for omics-based research in the future.


Assuntos
Genômica , Análise de Célula Única , Biologia de Sistemas , Doenças da Bexiga Urinária/genética , Doenças da Bexiga Urinária/metabolismo , Bexiga Urinária/metabolismo , Animais , Epigênese Genética , Epigenômica , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Fenótipo , Proteômica , Transcriptoma , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/fisiopatologia
3.
Neurourol Urodyn ; 39(2): 586-593, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31868966

RESUMO

AIMS: To determine the effects of early sacral neuromodulation (SNM) and pudendal neuromodulation (PNM) on lower urinary tract (LUT) function, minipigs with complete spinal cord injury (cSCI) were analyzed. SNM and PNM have been proposed as therapeutic approaches to improve bladder function, for example after cSCI. However, further evidence on efficacy is required before these methods can become clinical practice. METHODS: Eleven adults, female Göttingen minipigs with cSCI at vertebral level T11-T12 were included: SNM (n = 4), PNM (n = 4), and SCI control (SCIC: n = 3). Tissue from six healthy minipigs was used for structural comparisons. Stimulation was started 1 week after cSCI. Awake urodynamics was performed on a weekly basis. After 16 weeks follow-up, samples from the urinary bladder were taken for analyses. RESULTS: SNM improved bladder function with better capacities and lower detrusor pressures at voiding and avoided the emergence of detrusor sphincter dyssynergia (DSD). PNM and untreated SCI minipigs had less favorable outcomes with either DSD or constant urinary retention. Structural results revealed SCI-typical fibrotic alterations in all cSCI minipigs. However, SNM showed a better-balanced distribution of smooth muscle to connective tissue with a trend towards the reduced progression of bladder wall scarring. CONCLUSION: Early SNM led to an avoidance of the emergence of DSD showing a more physiological bladder function during a 4 month follow-up period after cSCI. This study might pave the way for the clinical continuation of early SNM for the treatment of neurogenic LUT dysfunction after SCI.


Assuntos
Plexo Lombossacral/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Doenças da Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/terapia , Bexiga Urinária/fisiopatologia , Animais , Feminino , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/terapia , Músculo Liso/patologia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/complicações , Suínos , Porco Miniatura , Resultado do Tratamento , Doenças da Bexiga Urinária/etiologia , Retenção Urinária/fisiopatologia , Retenção Urinária/terapia , Urodinâmica
5.
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
6.
Neurourol Urodyn ; 38(8): 2104-2111, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31396992

RESUMO

AIMS: In recent years, the human brain-bladder control network has been visualized in different functional magnetic resonance imaging (fMRI) studies. The role of the brainstem and suprapontine regions has been elucidated. Especially the pontine region and the periaqueductal gray, as the central structures of the micturition circuit, were demonstrated. Detrusor sphincter dyssynergia (DSD) is a common problem in patients with neurological diseases. Residual urine and consecutive urinary tract infections with the risk of kidney damage remain a problem. In the present study, we used fMRI of the brain to compare the activation sites of patients with DSD with those of our previously published healthy controls with special emphasis on the brainstem region. METHODS: fMRI was performed in 11 patients with DSD who had an urge to void due to a filled bladder. In a nonvoiding model, they were instructed to contract or to relax the pelvic floor muscles repetitively. RESULTS: In patients with DSD, we could reproduce the activation sites found in healthy subjects, showing the regions in the brainstem as well as the other micturition-related areas. The activation of the pontine region was more rostral/dorsal compared with the healthy volunteers. CONCLUSION: Interestingly, we detected the well-known activation in the pontine region in the patients in the dorsal/rostral part compared with the more ventral activation in the healthy volunteers, suggesting that the L-region of the pontine micturition center is more prominent in cases of DSD.


Assuntos
Encéfalo/diagnóstico por imagem , Doenças da Bexiga Urinária/diagnóstico por imagem , Adulto , Idoso , Encéfalo/fisiopatologia , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças da Bexiga Urinária/fisiopatologia , Micção/fisiologia
7.
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
8.
Spinal Cord ; 57(12): 1084-1093, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31383950

RESUMO

STUDY DESIGN: Cross-sectional study OBJECTIVES: To determine clinical factors associated with telomere length in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center, Boston, MA. METHODS: Two hundred seventy-eight participants with chronic SCI provided blood samples for measurement of C-reactive protein (CRP), interleukin-6 (IL-6), and telomere length, completed respiratory health questionnaires, underwent dual X-ray absorptiometry (DXA) to assess body fat, and completed spirometry. High-throughput real-time PCR assays were used to assess telomere length in leukocyte genomic DNA. Linear regression models were used to assess cross-sectional associations with telomere length. RESULTS: Telomere length was inversely related to age (p < 0.0001). In age-adjusted models, gender, race, injury duration, %-total and %-trunk fat, body mass index (BMI), %-predicted forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), chronic cough or phlegm, CRP, IL-6, wheeze, smoking, diabetes, heart disease, chronic obstructive pulmonary disease (COPD), skin ulcer, urinary tract infection (UTI), or chest illness history were not significantly associated with telomere length. There was a suggestive age-adjusted association between persons with the most severe SCI (cervical motor complete and AIS C) and shorter telomere length (p = 0.055), an effect equivalent to ~8.4 years of premature aging. There were similar age-adjusted associations with telomere length between persons using a wheelchair (p = 0.059) and persons with chronic urinary catheter use (p = 0.082) compared to persons without these characteristics. CONCLUSIONS: Our results suggest that clinical characteristics such as decreased mobility and bladder dysfunction that are common in individuals with more severe SCI are associated with shorter telomere length.


Assuntos
Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/fisiopatologia , Homeostase do Telômero/fisiologia , Telômero/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Traumatismos da Medula Espinal/epidemiologia , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/epidemiologia , Doenças da Bexiga Urinária/fisiopatologia , Cadeiras de Rodas/efeitos adversos , Cadeiras de Rodas/tendências
9.
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
10.
J Neurophysiol ; 122(3): 1136-1146, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31314637

RESUMO

The internal surface of the urinary bladder is covered by the urothelium, a stratified epithelium that forms an impermeable barrier to urinary solutes. Increased urothelial permeability is thought to contribute to symptom generation in several forms of cystitis by sensitizing bladder afferents. In this report we investigate the physiological mechanisms that mediate bladder afferent hyperexcitability in a rat model of cystitis induced by overexpression in the urothelium of claudin-2 (Cldn2), a tight junction-associated protein upregulated in bladder biopsies from patients with interstitial cystitis/bladder pain syndrome. Patch-clamp studies showed that overexpression of Cldn2 in the urothelium sensitizes a population of isolectin GS-IB4-negative [IB4(-)] bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials. Gene expression analysis revealed a significant increase in mRNA levels of the delayed-rectifier voltage-gated K+ channel (Kv)2.2 and the accessory subunit Kv9.1 in this population of bladder sensory neurons. Consistent with this finding, Kv2/Kv9.1 channel activity was greater in IB4(-) bladder sensory neurons from rats overexpressing Cldn2 in the urothelium than in control counterparts. Likewise, current density of TTX-S voltage-gated Na+ (Nav) channels was greater in sensitized neurons than in control counterparts. Significantly, guangxitoxin-1E (GxTX-1E), a selective blocker of Kv2 channels, blunted the repetitive firing of sensitized IB4(-) sensory neurons. In summary, our studies indicate that an increase in the activity of TTX-S Nav and Kv2/Kv9.1 channels mediates repetitive firing of sensitized bladder sensory neurons in rats with increased urothelial permeability.NEW & NOTEWORTHY Hyperexcitability of sensitized bladder sensory neurons in a rat model of interstitial cystitis/bladder pain syndrome (IC/BPS) results from increased activity of tetrodotoxin-sensitive voltage-gated Na+ and delayed-rectifier voltage-gated K+ (Kv)2/Kv9.1 channels. Of major significance, our studies indicate that Kv2/Kv9.1 channels play a major role in symptom generation in this model of IC/BPS by maintaining the sustained firing of the sensitized bladder sensory neurons.


Assuntos
Dor/fisiopatologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/fisiologia , Células Receptoras Sensoriais/fisiologia , Doenças da Bexiga Urinária/fisiopatologia , Canais de Sódio Disparados por Voltagem/fisiologia , Animais , Cistite Intersticial/fisiopatologia , Modelos Animais de Doenças , Feminino , Ratos , Ratos Sprague-Dawley
11.
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
12.
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
13.
Am J Physiol Renal Physiol ; 317(1): F197-F206, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066574

RESUMO

Cytotoxic chemotherapy is the foundation for the treatment of the wide variety of childhood malignancies; however, these therapies are known to have a variety of deleterious side effects. One common chemotherapy used in children, doxorubicin (DOX), is well known to cause cardiotoxicity and cardiomyopathy. Recent studies have revealed that DOX impairs skeletal and smooth muscle function and contributes to fatigue and abnormal intestinal motility in patients. In this study, we tested the hypothesis that systemic DOX administration also affects detrusor smooth muscle (DSM) function in the urinary bladder, especially when administered at a young age. The effects on the DSM and bladder function were assessed in BALB/cJ mice that received six weekly intravenous injections of DOX (3 mg·kg-1·wk-1) or saline for the control group. Systemic DOX administration resulted in DSM hypertrophy, increased voiding frequency, and a significant attenuation of DSM contractility, followed by a slower relaxation compared with the control group. Gene expression analyses revealed that unlike DOX-induced cardiotoxicity, the bladders from DOX-administered animals showed no changes in oxidative stress markers; instead, downregulation of large-conductance Ca2+-activated K+ channels and altered expression of myosin light-chain kinase coincided with reduced myosin light-chain phosphorylation. These results indicate that in vivo DOX exposure caused DSM dysfunction by dysregulation of molecules involved in the detrusor contractile-relaxation mechanisms. Collectively, our findings suggest that survivors of childhood cancer treated with DOX may be at increased risk of bladder dysfunction and benefit from followup surveillance of bladder function.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Sintomas do Trato Urinário Inferior/induzido quimicamente , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Cadeias Leves de Miosina/metabolismo , Miosinas de Músculo Liso/metabolismo , Doenças da Bexiga Urinária/induzido quimicamente , Bexiga Urinária/efeitos dos fármacos , Urodinâmica/efeitos dos fármacos , Fatores Etários , Animais , Feminino , Hipertrofia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Sintomas do Trato Urinário Inferior/metabolismo , Sintomas do Trato Urinário Inferior/patologia , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Camundongos Endogâmicos BALB C , Quinase de Cadeia Leve de Miosina/metabolismo , Fosforilação , Transdução de Sinais , Fatores de Tempo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/metabolismo , Doenças da Bexiga Urinária/patologia , Doenças da Bexiga Urinária/fisiopatologia
14.
J Pediatr Urol ; 15(3): 226.e1-226.e5, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31014982

RESUMO

Bowel and bladder dysfunction (BBD) refers to a heterogeneous group of voiding disorders, accounting for an estimated 40% of pediatric urology visits. Symptoms of BBD include enuresis, urgency, and urinary retention, often accompanied by constipation. The aim of this pilot study was to explore whether a pupillary response can be characterized for BBD, by examining the pupillary light reflex (PLR) before and after voiding among patients with BBD. A total of 28 patients aged from 7 to 21 years were recruited from the Wetting, Infections, and Stooling Help clinic at Children's National Medical Center. An infrared pupilometer was used to assess the PLR. Both baseline static and dynamic pupillometry assessments were obtained before and after voiding. Measurements were also taken after 5 min in the supine position, followed by 5 min standing to induce an orthostatic stressor. Visual inspection of the graphed data revealed a characteristic shape in 11 of 28 patients with voiding symptoms. In these 11 patients, the redilation arm of the PLR shows a 'notch,' or a brief reconstriction of the pupil before resting pupil size is reestablished (figure). This feature of the PLR has not been seen in previous and parallel studies using pupillometry to evaluate other populations. The results of this study suggest that a subset of patients with BBD may have a significant perturbation of autonomic regulation, identifiable through analysis of the PLR. To our knowledge, this 'notch' during redilation has not been previously described or seen in other patient populations and may represent a distinctive and readily identifiable physiologic marker of disease. These results are broadly aligned with results of other studies that have examined ANS activity in patients with BBD, although further study is needed to confirm the results of this pilot study and to assess relative contributions of sympathetic and parasympathetic function in producing pupillary abnormalities. This study has several limitations, including the small sample size, the absence of data on severity and duration of symptoms, and the absence of a control group of patients without any voiding symptoms. A simple tool for diagnosing BBD and for monitoring response to treatment could significantly improve the quality of treatment for one of the most common pediatric urologic complaints. Given the heterogeneity of symptoms under the BBD umbrella, pupillometric data could guide selection of treatment options, as well as assess adequacy of response to pharmacologic therapy.


Assuntos
Enteropatias/etiologia , Intestinos/fisiopatologia , Disautonomias Primárias/complicações , Pupila/fisiologia , Reflexo Pupilar/fisiologia , Doenças da Bexiga Urinária/etiologia , Bexiga Urinária/fisiopatologia , Adolescente , Criança , Defecação/fisiologia , Feminino , Humanos , Enteropatias/fisiopatologia , Masculino , Projetos Piloto , Disautonomias Primárias/fisiopatologia , Doenças da Bexiga Urinária/fisiopatologia , Micção/fisiologia , Adulto Jovem
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
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