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1.
Nihon Yakurigaku Zasshi ; 155(2): 74-79, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32115481

RESUMO

Recently, hydrogen sulfide (H2S) has been recognized as the third gasotransmitter besides nitric oxide and carbon monoxide, and it has been reported that H2S exhibits various physiological functions such as neuromodulation and vasorelaxation. In the lower urinary tract (bladder and prostate), it is reported that donors of H2S induce contraction of the rat detrusor and relaxation of the pig bladder neck. These reports suggest a possibility that H2S may have site-specific effects on the bladder. However, the detailed functions of H2S in each part of the bladder are still unclear. In addition, there is no report showing physiological roles of H2S in the prostate. In this article, we will review the distribution of enzymes related to H2S biosynthesis and physiological roles of H2S in the lower urinary tract based on reports from our and other groups. We will also introduce a possibility that H2S can be a new therapeutic target against lower urinary tract symptoms (LUTS) based on our data from spontaneously hypertensive rats (SHRs), which develop hypertension-mediated LUTS.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Próstata/fisiologia , Bexiga Urinária/fisiologia , Animais , Masculino , Ratos , Ratos Endogâmicos SHR , Suínos
2.
Vet Clin North Am Exot Anim Pract ; 23(1): 103-114, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759442

RESUMO

Reptile kidneys maintain a constant extracellular environment within the body. They excrete waste products, maintain normal concentrations of salt and water, regulate acid-base balance, and produce hormones and vitamins. The kidneys contain nephrons consisting of glomeruli designed to filter the plasma, Bowman capsules that collect the filtrate, and tubules that resorb most of the filtered water and nutrients while excreting waste metabolites. A Loop of Henle is absent. Therefore, reptile kidneys cannot produce a hypertonic urine. The urinary bladder (if present) and cloaca excrete and absorb additional fluids and electrolytes. A renal portal system is present in all reptiles.


Assuntos
Répteis/fisiologia , Animais , Rim/metabolismo , Répteis/anatomia & histologia , Ureia/análise , Ácido Úrico/análise , Bexiga Urinária/anatomia & histologia , Bexiga Urinária/fisiologia
3.
BJOG ; 127(2): 193-201, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469215

RESUMO

OBJECTIVE: To characterise the bladder microbiota of continent adult women. DESIGN: Cross-sectional study of adult women who contributed catheterised urine samples, completed validated symptom questionnaires, and provided demographic data. SETTING: US academic medical centre. POPULATION: Well-characterised continent adult women. METHODS: Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing. MAIN OUTCOME MEASURES: Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen). RESULTS: The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P < 0.001) and Escherichia (P = 0.005) urotypes were more common in younger and older women, respectively. CONCLUSIONS: For urobiome research, enhanced culture methods and/or DNA sequencing are the preferred techniques for bacterial detection. The interpretation of clinical tests, such as the standard urine culture, should incorporate the knowledge that some women have Gardnerella or Escherichia urotypes without evidence of any clinical disorder. Clinical care strategies should preserve or restore the beneficial effects of the native urobiome, as disruption of that microbial community could result in unintended vulnerability to uropathogen invasion or opportunistic pathogen overgrowth. Longitudinal studies of urobiome responses to therapies should be encouraged. TWEETABLE ABSTRACT: In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice.


Assuntos
Microbiota/genética , Bexiga Urinária/microbiologia , Sistema Urinário/microbiologia , Urina/microbiologia , Adulto , Estudos Transversais , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactobacillus/genética , Microbiota/fisiologia , Pessoa de Meia-Idade , RNA Ribossômico 16S , Análise de Sequência de DNA , Bexiga Urinária/fisiologia
4.
PLoS One ; 14(12): e0225821, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31790475

RESUMO

Traditional urodynamics have poor correlation with urological symptoms. Ambulatory urodynamics may improve this correlation but the need for a transurethral catheter and the time-consuming nature of this examination limits its use. Therefore, the objective of this study was to develop a wireless real-time bladder pressure measurement device for repeated and prolonged-term measurement of bladder behavior in awake pigs. The Bladder Pill is an intravesical device with a pressure microsensor and a 3-dimensional inductive coupling coil for energy supply. A corresponding external coil provides wireless power transmission and real-time communication of bladder pressure data. To test the correlation between the pressure data measured by the device and by standard methods, we compared static water column pressures with this device and water-filled urodynamic catheter systems. In vivo assessment of awake voiding by the pill was done by introducing the bladder pill into the bladder of Göttingen minipigs. An air-charged urodynamic catheter was introduced transurethrally as control for pressure measurements. The optimal physical configuration of the pill was investigated to maximize the containment in the bladder. We used two versions of external signal receivers (one waistband and one rectangular frame) to test the optimal external signal capture. Next to that, we performed short-term and medium-term comparative pressure studies. The in vitro static pressure measurement demonstrated a mean difference of less than 1 cm H2O between the methods. The optimal design of the pill for maximal retainment in the bladder proved to be a pigtail configuration. The bending of the device during bladder contractions caused offset of 2.7 +/- 1.4 cm H2O (mean +/- SD) on the pressure measurements. The rectangular frame performed signal capture during 5 consecutive voids with a good correlation of the pressure measurements. The device can be inserted through the urethra and is retrieved using string or endoscopic extraction. In conclusion, wireless long-term measurement of bladder pressure is demonstrated and yields comparable results to current available catheter methods of measurement in a pig model.


Assuntos
Equipamentos e Provisões , Bexiga Urinária/fisiologia , Micção/fisiologia , Vigília/fisiologia , Tecnologia sem Fio/instrumentação , Animais , Feminino , Suínos , Porco Miniatura
5.
BMC Palliat Care ; 18(1): 109, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805921

RESUMO

BACKGROUND: Malignant Ascites (MA) is a therapeutic dilemma significantly impairing patients' quality of life (QoL). The Sequana Medical alfapump System (AP), a subcutaneous, externally rechargeable, implantable device, continually draining ascites via the urinary bladder, has been well established in liver cirrhosis, but not yet in MA. The AP-system was evaluated in cancer patients in reducing the need for large volume paracentesis (LVP). METHODS: A retrospective multicentre evaluation of all eligible patients who received an AP for MA-palliation was performed. AP was evaluated for its ability to reduce LVP and cross-correlated with adverse events (AE), survival and retrospective physician-reported QoL. RESULTS: Seventeen patients with median age of 63 years (range: 18-81), 70.6% female, across 7 primary tumour types were analysed. Median duration of AP-implantation was 60 min (range: 30-270) and median post-implantation hospital stay: 4 days (range: 2-24). Twelve protocol-defined AE occurred in 5 patients (29.4%): 4 kidney failures, 4 pump/catheter-related blockages, 3 infections/peritonitis and 1 wound dehiscence. Median ascitic volume (AV) pumped daily was 303.6 ml/day (range:5.6-989.3) and median total AV drained was 28 L (range: 1-638.6). Median patient post-AP-survival was 111 days (range:10-715) and median pump survival was 89 days (range: 0-715). Median number of paracenteses was 4 (range: 1-15) per patient pre-implant versus 1 (range: 0-1) post-implant (p = 0.005). 71% of patients were reported to have an improvement of at least one physician reported QoL-parameters. CONCLUSIONS: AP appears to be effective in palliating patients with MA by an acceptable morbidity profile. Its broader implementation in oncology services should be further explored. TRIAL REGISTRATION: NCT03200106; June 27, 2017.


Assuntos
Ascite/terapia , Drenagem/instrumentação , Bexiga Urinária/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/psicologia , Drenagem/métodos , Drenagem/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Cuidados Paliativos/tendências , Qualidade de Vida/psicologia , Estudos Retrospectivos
6.
J Vis Exp ; (153)2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31840657

RESUMO

Previous studies have established the release of chemical substances from flat bladder mucosa sheets affixed in Ussing chambers and exposed to changes in hydrostatic pressure or mechanical stretch and from cultured urothelial cells upon hydrostatic pressure changes, stretch, cell swelling, or drag forces, and in bladder lumen at end of filling. Such findings led to the assumption that these mediators are also released in suburothelium (SubU)/lamina propria (LP) during bladder filling, where they affect cells deep in the bladder wall to ultimately regulate bladder excitability. There are at least two obvious limitations in such studies: 1) none of these approaches provide direct information about the presence of mediators in SubU/LP, and 2) the stimuli used are not physiological and do not recapitulate authentic filling of the bladder. Here, we discuss a procedure that enables direct access to the suburothelial surface of the bladder mucosa in the course of bladder filling. The murine detrusor-free preparation we created closely resembles filling of the intact bladder and allows pressure-volume studies to be performed on the bladder in the absence of confounding signaling from spinal reflexes and detrusor smooth muscle. Using the novel detrusor-free bladder model, we recently demonstrated that intravesical measurements of mediators cannot be used as a proxy to what has been released or present in the SubU/LP during bladder filling. The model enables examination of urothelium-derived signaling molecules that are released, generated by metabolism and/or transported into the SubU/LP during the course of bladder filling to transmit information to neurons and smooth muscle of the bladder and regulate its excitability during continence and micturition.


Assuntos
Contração Muscular/fisiologia , Músculo Liso/fisiologia , Bexiga Urinária/fisiologia , Animais , Pressão Hidrostática , Camundongos , Transdução de Sinais , Micção
7.
PLoS One ; 14(10): e0223705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600317

RESUMO

OBJECTIVES: To investigate effects of postural changes and bladder distention on intrabladder pressure whilst estimating intra-abdominal pressure in horses. DESIGN: Two-year cohort study. Patients admitted for elective surgical procedures unrelated to gastrointestinal or genitourinary tract. SETTING: School of Agricultural and Veterinarian Sciences, Jaboticabal, SP, Brazil. ANIMALS: 20 adult horses, 11 males (stallions and geldings) and 9 females; between 3.5 and 12 years, weighing 350 to 500 kg. INTERVENTIONS: Intra-abdominal pressure was directly-recorded through abdominocentesis at the ventral midline with a fluid-filled system. Intrabladder pressure was obtained from a bladder catheter with the fluid-filled system zeroed at the level of the tuber ischia with patients in dorsal recumbency or pubic symphysis if in lateral recumbency. MEASUREMENTS AND MAIN RESULTS: Body position directly influenced intra-abdominal pressure. In dorsal recumbency, intra-abdominal pressure differed (p < 0.05) from intrabladder pressure at end-inspiration and end-expiration regardless of whether the bladder was empty or distended. There was no correlation nor association between the two pressures in this body position. In lateral recumbency a difference (p <0.05) between intra-abdominal pressure and intrabladder pressure was recorded at end-inspiration with the bladder distended with 25 ml, and at end-expiration for distension volumes of 25 ml and 50 ml. There was a strong correlation between both pressures for left and right lateral recumbency, regardless of the distension volume. Ordinary least product (OLP) regression analysis showed no fixed or proportional bias between both pressures for distension volume of 50 ml, at both end-inspiration and end-expiration. CONCLUSIONS: Indirect assessment of equine intra-abdominal pressure cannot be made in dorsal recumbency. For that purpose, patients should be in left lateral recumbency with the bladder distended with 50 ml. Values can be recorded at end-inspiration or end-expiration. RESTRICTION: Occlusion of the catheter tip by the bladder wall when minimally distended.


Assuntos
Abdome/fisiologia , Cavalos/fisiologia , Pressão , Bexiga Urinária/fisiologia , Animais , Procedimentos Cirúrgicos Eletivos , Feminino , Masculino , Análise Multivariada , Postura , Análise de Regressão
8.
Eur J Pharmacol ; 864: 172727, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600494

RESUMO

The combination of a ß3-adrenoceptor agonist and an antimuscarinic agent was revealed to be more effective than monotherapy for patients with overactive bladder and in animal models. However, its influence on voiding functions has not been well documented. Therefore, during intermittent-cystometry, we studied the effects of vibegron (a novel ß3-adrenoceptor agonist) and imidafenacin (an antimuscarinic agent) alone to determine their dose levels for the combination study. Then, the effects of the combination on voiding functions were investigated in urethane-anesthetized rats (1.0 g/kg s.c.). Independently, vibegron (0.3-3 mg/kg, i.v.) and imidafenacin (0.001 and 0.003 mg/kg, i.v.) dose-dependently increased bladder capacity and voided volume, without affecting voiding functions such as residual volume, voiding efficiency, and micturition pressure. However, vibegron also increased bladder compliance. The combination of vibegron (3 mg/kg) and imidafenacin (0.003 mg/kg) significantly increased bladder capacity and voided volume when compared to those with monotherapy using each individually. The combination did not change residual volume, voiding efficiency, and micturition pressure, compared to those in the vehicle group. We identified no responses in resiniferatoxin (RTX)-treated rats, as opposed to those identified after administering vibegron (3 mg/kg), imidafenacin (0.003 mg/kg), or both to non-RTX-treated rats. These outcomes might have resulted from the combination of the increased effect of vibegron on bladder compliance and the inhibitory effect of both vibegron and imidafenacin on the activation of bladder afferent nerves.


Assuntos
Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Imidazóis/farmacologia , Antagonistas Muscarínicos/farmacologia , Pirimidinonas/farmacologia , Pirrolidinas/farmacologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiologia , Anestesia , Animais , Interações Medicamentosas , Feminino , Ratos , Ratos Sprague-Dawley
9.
mSphere ; 4(5)2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484739

RESUMO

Urgency urinary incontinence (UUI) and overactive bladder (OAB) can both potentially be influenced by commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various components of the nervous system, eventually resulting in contraction of the detrusor muscle during micturition. This study models host responses to various urogenital bacteria, first by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined Ca2+ influx, gene expression, and alpha smooth muscle actin deposition assays. Organisms such as Escherichia coli and Gardnerella vaginalis were found to strongly induce Ca2+ influx and contraction, whereas Lactobacillus crispatus and L. gasseri did not induce this response. Additionally, supernatants from lactobacilli impeded Ca2+ influx and contraction induced by uropathogens. Upon further investigation of factors associated with purinergic signaling pathways, the Ca2+ influx and contraction of cells correlated with the amount of extracellular ATP produced by E. coli Certain lactobacilli appear to mitigate this response by utilizing extracellular ATP or producing inhibitory compounds that may act as a receptor agonist or Ca2+ channel blocker. These findings suggest that members of the urinary microbiota may be influencing UUI or OAB.IMPORTANCE The ability of uropathogenic bacteria to release excitatory compounds, such as ATP, may act as a virulence factor to stimulate signaling pathways that could have profound effects on the urothelium, perhaps extending to the vagina. This may be countered by the ability of certain commensal urinary microbiota constituents, such as lactobacilli. Further understanding of these interactions is important for the treatment and prevention of UUI and OAB. The clinical implications may require a more targeted approach to enhance the commensal bacteria and reduce ATP release by pathogens.


Assuntos
Trifosfato de Adenosina/metabolismo , Bactérias/metabolismo , Cálcio/metabolismo , Miofibroblastos/citologia , Bexiga Urinária/microbiologia , Actinas/fisiologia , Bactérias/patogenicidade , Linhagem Celular , Colágeno/fisiologia , Humanos , Lactobacillales , Microbiota , Contração Muscular , Miofibroblastos/microbiologia , Simbiose , Bexiga Urinária/fisiologia , Urotélio/citologia
10.
Prog Urol ; 29(11): 567-571, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31473103

RESUMO

AIMS: The aims of the study were to evaluate the reproducibility of bladder voiding efficiency (BVE) between free flow (FF) and intubated flow(IF) in old women, and to search for a relationship of this index with complaint and urodynamic diagnosis. METHODS: Urodynamic tracings of non-neurologic women referred for investigation of various lower urinary tract symptoms (LUTS) were analyzed. Urodynamic study included one FF followed by one cystometry and IF. Post void residual volume (PVR) was measured using a Bladder-scan. Exclusion criteria were voided volume<100ml and prolapse of grade>2. RESULTS: One hundred and ninety women met the study criteria. The mean age was 74±6 years [65-96years]. The main complaint was urinary incontinence: stress (26), urge (53) and mixed (56). Forty-four women had various complaints without incontinence. Overall BVE IF (77.6±25.8) was significantly lower than BVE FF (90.4±15.3) (P<.0001). Age sub-groups stratification led similar results. BVE IF was significantly lower than BVE FF in women with incontinence whatever the cause. Urodynamic diagnosis was posed according to the ICS/IUGA recommendations and 2 sub-groups defined according with involvement of detrusor. BVE IF was significantly lower than BVE FF for detrusor dysfunction, except for detrusor overactivity. CONCLUSION: In this large cohort of old non-neurologic women studied urodynamically for a variety of LUTS, BVE is higher when evaluated from a FF whatever age and for complaint of urinary incontinence. In addition, a low BVE value from an IF may suggest a detrusor dysfunction. LEVEL OF EVIDENCE: 4.


Assuntos
Sintomas do Trato Urinário Inferior/fisiopatologia , Bexiga Urinária/fisiologia , Micção/fisiologia , Urodinâmica/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Retrospectivos
11.
Fisioter. Pesqui. (Online) ; 26(3): 285-290, jul.-set. 2019. tab
Artigo em Português | LILACS | ID: biblio-1039890

RESUMO

RESUMO A incontinência urinária (IU) está associada à ocorrência de quedas em idosos e pode ter relação com déficits no controle postural. O objetivo deste trabalho é comparar o controle postural estático, na condição de olhos abertos e fechados, e o risco de quedas entre idosas com IU e idosas sem IU. A amostra foi dividida em dois grupos: idosas com IU (n=21, idade=65,33±4,57 anos) e idosas sem IU (n=19, idade=66,37±5,26 anos). As características da perda urinária do grupo com IU foram avaliadas por meio do International Consultation on Incontinence Questionnaire: Short Form (ICIQ-SF). O controle postural estático dos grupos foi mensurado pelo deslocamento do centro de pressão (COP) por meio de uma plataforma de força; e o risco de quedas foi avaliado pelo teste timed up and go. Para a análise estatística, foi utilizado o teste U de Mann-Whitney e o teste qui-quadrado. A maioria das participantes com IU perdiam urina em pequena quantidade e todas perdiam em baixa frequência. Não foi observada diferença entre os grupos em relação às variáveis do COP (p>0,05) e o risco de quedas (p=0,082). Entretanto, na análise intragrupos, houve diferença na velocidade do COP de ambos os grupos na comparação olhos abertos versus olhos fechados (p<0,05). Não houve diferença no controle postural estático e no risco de quedas entre idosas com e sem IU.


RESUMEN La incontinencia urinaria (IU) está asociada con la presencia de caídas en los ancianos y puede estar relacionada con déficits en el control postural de ellos. El presente estudio tuvo como objetivo comparar el control postural estático con los ojos abiertos y con los ojos cerrados y el riesgo de caídas entre mujeres ancianas con IU y mujeres ancianas sin IU. La muestra se dividió en dos grupos: ancianas con IU (n=21, edad=65,33±4,57 años) y ancianas sin IU (n=19, edad=66,37±5,26 años). Las características de pérdida urinaria en el grupo con IU se evaluaron utilizando el International Consultation on Incontinence Questionnaire: Short Forma (ICIQ-SF). El control postural estático de los grupos se midió por el desplazamiento del centro de presión (COP) por medio de una plataforma de fuerza; y el riesgo de caídas fue evaluado por el test del timed up and go. En el análisis estadístico, se utilizaron la prueba U de Mann-Whitney y la prueba de Chi-cuadrado. La mayoría de las participantes con IU perdieron una pequeña cantidad de orina y todas la perdieron a baja frecuencia. No se observó diferencia entre los grupos en relación con las variables COP (p>0,05) y el riesgo de caídas (p=0,082). Sin embargo, en el análisis intragrupo hubo una diferencia en la velocidad de COP de ambos grupos en la comparación ojos abiertos versus ojos cerrados (p<0,05). No hubo diferencias en el control postural estático y en el riesgo de caídas entre las ancianas con y sin IU.


ABSTRACT Urinary incontinence (UI) is associated with the occurrence of falls in older people and may be related to failure in the postural control of older people. This study aims to compare static postural control under eyes-closed and eyes-open conditions as well as the risk of falls in older women with UI and without UI. The sample was divided in two groups: a group of older women with UI (n=21, age=65.33±4.57 years) and a group of older women without UI (n=19, age=66.37±5.26 years). The urinary loss characteristics of the UI group were evaluated with use of the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF). The static postural control of the groups was measured using displacement of center of pressure (COP) through a force platform and the risk of falls was evaluated with the Timed Up and Go test (TUG). Statistical analysis was performed using Mann Whitney's U-Testand the chi-square test. Most participants with UI lost urine in small amounts and at low frequency. No difference was observed between the groups with respect to COP variables (p>0.05) and risk of falls (p=0.082). However, in the intragroup analysis, a difference was observed in the COP velocity of both groups comparing open and closed eyes (p<0.05). No difference was observed in the static postural control and risk of falls in older women with and without UI.


Assuntos
Humanos , Feminino , Idoso , Incontinência Urinária/fisiopatologia , Acidentes por Quedas , Equilíbrio Postural/fisiologia , Bexiga Urinária/fisiologia , Bexiga Urinária/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais
12.
Am J Physiol Renal Physiol ; 317(5): F1183-F1188, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411072

RESUMO

We assessed the effects of limited application of sacral neurostimulation (SNS) during bladder filling on bladder capacity using our previously published SNS model in rats. Female Sprague-Dawley rats (n = 24) were urethane anesthetized (1.2 g/kg sc) and implanted with jugular venous and transvesical bladder catheters. L6/S1 nerve trunks were isolated bilaterally, and two electrodes were placed on each exposed nerve. True bladder capacity (TBC) was determined using stable single-fill cystometrograms. In the first series of experiments, SNS was applied at the onset of bladder filling for 25%, 50%, 75%, and 100% of the previous control filling cycle duration (n = 10). In the second series of experiments, SNS was applied during the first, second, third, and fourth 25% and the first and second 50% of the control fill. In the first series, a significant increase in TBC was observed only when SNS was applied for 75% or 100% of the control fill duration (30% and 35%, respectively, P < 0.05). In the second series, significant increases in TBC only occurred during the fourth 25% period and second 50% period (32% and 43%, respectively, P < 0.001). Results from the second series also revealed an increase in subsequent single-fill bladder capacities (TBC) only when SNS was applied during the second 50% of the prior fill cycle. These data indicate that the application of SNS during the final 50% of the bladder fill cycle is necessary and sufficient for increasing bladder capacity.


Assuntos
Estimulação Elétrica/métodos , Sacro , Nervos Espinhais/fisiologia , Bexiga Urinária/fisiologia , Urodinâmica/fisiologia , Animais , Feminino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Bexiga Urinária/inervação
13.
Exp Neurol ; 322: 113033, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31400304

RESUMO

Dysfunction of the lower urinary tract (LUT) is prevalent in neurological disorders, including multiple sclerosis, stroke, spinal cord injury and neurodegenerative conditions. Common symptoms include urgency, incontinence, and urinary retention. Recent advances in neuromodulation have resulted in improved treatments for overactive bladder symptoms of urgency, frequency, and nocturia. However, there are presently no treatments available for the induction of voiding to overcome urinary retention. We demonstrate that transcutaneous spinal cord stimulation (TSCS), a non-invasive intervention, applied over the thoracolumbar spine in neurologically intact rhesus macaques can activate the LUT, including activation of the bladder detrusor muscle, the urethral sphincter and pelvic floor muscles. Urodynamic studies show improved voiding efficiency and decreased post-voiding residual volumes in the bladder, while maintaining coordinated activity in the detrusor and sphincter with physiologic detrusor peak pressure, contraction duration, and urine flow rate remaining unchanged. We conclude that TSCS may represent a novel approach to activate the LUT and enable voiding in select neurological conditions.


Assuntos
Estimulação da Medula Espinal , Uretra/fisiologia , Bexiga Urinária/fisiologia , Micção/fisiologia , Urodinâmica/fisiologia , Animais , Feminino , Macaca mulatta
14.
Am J Physiol Renal Physiol ; 317(5): F1154-F1163, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31461351

RESUMO

Tachykinins (TKs) are involved in both the physiological regulation of urinary bladder functions and development of overactive bladder syndrome. The aim of the present study was to investigate the signal transduction pathways of TKs in the detrusor muscle to provide potential pharmacological targets for the treatment of bladder dysfunctions related to enhanced TK production. Contraction force, intracellular Ca2+ concentration, and RhoA activity were measured in the mouse urinary bladder smooth muscle (UBSM). TKs and the NK2 receptor (NK2R)-specific agonist [ß-Ala8]-NKA(4-10) evoked contraction, which was inhibited by the NKR2 antagonist MEN10376. In Gαq/11-deficient mice, [ß-Ala8]-NKA(4-10)-induced contraction and the intracellular Ca2+ concentration increase were abolished. Although Gq/11 proteins are linked principally to phospholipase Cß and inositol trisphosphate-mediated Ca2+ release from intracellular stores, we found that phospholipase Cß inhibition and sarcoplasmic reticulum Ca2+ depletion failed to have any effect on contraction induced by [ß-Ala8]-NKA(4-10). In contrast, lack of extracellular Ca2+ or blockade of voltage-dependent Ca2+ channels (VDCCs) suppressed contraction. Furthermore, [ß-Ala8]-NKA(4-10) increased RhoA activity in the UBSM in a Gq/11-dependent manner and inhibition of Rho kinase with Y-27632 decreased contraction force, whereas the combination of Y-27632 with either VDCC blockade or depletion of extracellular Ca2+ resulted in complete inhibition of [ß-Ala8]-NKA(4-10)-induced contractions. In summary, our results indicate that NK2Rs are linked exclusively to Gq/11 proteins in the UBSM and that the intracellular signaling involves the simultaneous activation of VDCC and the RhoA-Rho kinase pathway. These findings may help to identify potential therapeutic targets of bladder dysfunctions related to upregulation of TKs.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Músculo Liso/fisiologia , Receptores da Neurocinina-2/fisiologia , Bexiga Urinária/fisiologia , Quinases Associadas a rho/metabolismo , Animais , Cálcio/metabolismo , Antagonistas de Estrogênios/farmacologia , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Deleção de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Contração Muscular/efeitos dos fármacos , Taquicininas/metabolismo , Tamoxifeno/farmacologia , Quinases Associadas a rho/genética
15.
J Clin Neurosci ; 68: 342-343, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31331745

RESUMO

The periaqueductal grey area and sensory thalamus are thought to be important nuclei involved in the supraspinal bladder control network. Deep brain stimulation of the periqueductal grey area has been shown to increase bladder capacity in the human. In a single patient, we have recorded local field potential signals from implanted deep brain stimulation electrodes within the sensory thalamus during filling cystometry with periaqueductal grey area deep brain stimulation in the ON and OFF states. In the OFF stimulation state, we demonstrate correlations between bladder volume and oscillations in the high gamma frequency band in the sensory thalamus. Stimulation of the periaqueductal grey area abolishes this correlated activity in the gamma frequency band and also suppresses oscillations within the sensory thalamus in the alpha frequency band. These findings support the involvement of the sensory thalamus in the afferent limb of bladder-related brain networks. They also suggest that periaqueductal grey area deep brain stimulation may disrupt the normal processing of afferent signals within the sensory thalamus which may be related to the effect of stimulation on bladder capacity.


Assuntos
Estimulação Encefálica Profunda , Substância Cinzenta Periaquedutal/fisiologia , Tálamo/fisiologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Membro Fantasma/terapia
16.
Biol Pharm Bull ; 42(7): 1064-1068, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257280

RESUMO

Distigmine bromide (distigmine) is a reversible carbamate cholinesterase (ChE) inhibitor. Its principle clinical application is in the treatment of myasthenia gravis. Distigmine is also used as a remedy for dysuria and glaucoma. Its effectiveness in the management of dysuria has been demonstrated in several clinical reports. Distigmine may improve (enhance) urinary bladder smooth muscle (UBSM) contraction during micturition by inhibiting acetylcholine (ACh) decomposition. However, the pharmacological effects of distigmine on UBSM have not been adequately studied so far. In this review article, we summarize the reported effects of distigmine on the contractile responses elicited by exogenous and endogenous ACh in isolated UBSM preparations. We also discuss the effects of distigmine on the UBSM basal tone and the contractile response of UBSM to ATP, which is co-released with ACh from parasympathetic nerve terminals.


Assuntos
Inibidores da Colinesterase/farmacologia , Músculo Liso/efeitos dos fármacos , Compostos de Piridínio/farmacologia , Bexiga Urinária/efeitos dos fármacos , Animais , Humanos , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Neurotransmissores/fisiologia , Bexiga Urinária/fisiologia , Vasoconstrição/efeitos dos fármacos
17.
J Acupunct Meridian Stud ; 12(5): 166-171, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31351218

RESUMO

Twenty-five Thoroughbred jumper geldings suffered back soreness with poor performance, and 5 control horses were assessed by archived computer data, clinical examination, and laboratory analyses of complete blood picture, serum enzymes, and cortisol level, before and after cloprostenol-pharmacopuncture. The 25 diseased horses before therapy showed significant increases in aspartate aminotransferase and creatine phosphokinase with clinical pains scored mild in 15 horses, moderate in 9 horses, and severe in one horse, without changes in the hormonal and hematological data. After therapy, they responded by an increase of heart rate (57.8 ± 4.3 bpm), body temperature (38.5 ± 0.7°C), respiration rate (28.3 ± 2.1 bpm), and capillary refilling time (CRT) (1.0 ± 0.0). On the 2nd day, a significant decrease in the mean levels of aspartate aminotransferase and creatine phosphokinase (P = 0.001) was detected, while on the 4th day, they mimed the level of the 5 controls, and on the 6th day, they showed a significant decrease (P = 0.002). The serum cortisol level showed a significant increase on the 6th day of treatment (P = 0.013). The blood picture showed significant increases in red blood cells, mean corpuscular volume, platelets, white blood cells, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean platelet volume, platelet distribution width, lymphocytes, plateletcrit, and large platelet concentration ratio (P < 0.05) and nonsignificant changes in hematocrit, granulocytes, and midocytes. The improved blood parameters, enzymes, hormones, and performance progress after cloprostenol-pharmacopuncture proved its effectiveness in treating back soreness in athletic horses.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/veterinária , Dor nas Costas , Cloprostenol/uso terapêutico , Doenças dos Cavalos/terapia , Animais , Dor nas Costas/terapia , Dor nas Costas/veterinária , Cavalos , Bexiga Urinária/fisiologia
18.
PLoS One ; 14(7): e0220381, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31344120

RESUMO

Circadian expression rhythms of clock gene products in the bladder are reportedly hindered by clock gene abnormalities. However, the role of clock gene products in various pathological lower urinary tract conditions is unknown. The present study examined the relationship between clock genes and voiding dysfunction in spontaneous hypertensive rats (SHR). The voluntary voiding behavior study using metabolic cages was performed in 18-weeks old male Wistar rats (control group, n = 36) and SHR (SHR group, n = 36) under 12-h light/12-h dark conditions. Bladders were harvested every 4 h at six time points (n = 6 for each time point for each group), and we analyzed the messenger RNA (mRNA) expression of several clock genes: period 2 (Per2), cryptochrome 2 (Cry2), brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), nuclear receptor subfamily 1, group D, member 1 (Rev-erbα), mechanosensors: transient receptor potential vanilloid channel 1 (TRPV1), TRPV4, Piezo1, and vesicular nucleotide transporter (VNUT) using real-time polymerase chain reaction. Though 24-h urination frequency for both light and dark periods was significantly higher in the SHR group, urine volume per voiding was significantly lower versus control. In controls, urine volume per voiding was significantly lower during the dark period (active phase) than the light period (rest phase); this parameter did not significantly differ between active and rest phases for SHR. SHR bladders showed significantly higher expression of Cry2 and Clock during the active phase compared to controls. In the SHR group, TRPV1, TRPV4, Piezo1, and VNUT mRNA levels were significantly higher during the active phase compared to the control group. We speculate that Cry2 and Clock may be contributing factors in the decrease of bladder capacity during the active phase in SHR through increase of TRPV1, TRPV4, Piezo1, and VNUT expression, but further research will be necessary to elucidate the precise mechanisms.


Assuntos
Proteínas CLOCK/genética , Ritmo Circadiano/genética , Hipertensão/genética , Bexiga Urinária/metabolismo , Animais , Proteínas CLOCK/metabolismo , Perfilação da Expressão Gênica , Hipertensão/metabolismo , Hipertensão/patologia , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Bexiga Urinária/fisiologia
19.
Eur J Pharmacol ; 860: 172552, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31326376

RESUMO

Localisation of platelet-derived growth factor receptor-α (PDGFRα) (+) cells expressing small-conductance Ca2+-activated K+ (SK3) channels in the urinary bladder was investigated, while putative roles of SK3 (+) PDGFRα (+) cells in suppressing detrusor smooth muscle (DSM) spontaneous activity were explored. In guinea-pig bladder, immunohistochemistry for SK3 channels, PDGFRα or vimentin was examined, as were the effects of purinergic agonists on spontaneous phasic contractions (SPCs). In bladder of PDGFRα-GFP mice, the effects of purinergic agonists on intracellular Ca2+ signaling in PDGFRα (+) cells or DSM cells in situ and SPCs were investigated. SK3 (+) cells co-expressing PDGFRα or vimentin were distributed in DSM bundles but not inter-bundle spaces or lamina propria. SK3 (+) cells had a stellate- or spindle-shape cell body extending processes. MRS2365 (100 nM or 1 µM), a P2Y1 agonist, caused a transient contraction without inhibiting SPCs in both DSM and lamina propria. In PDGFRα-GFP mice bladder, MRS2365, (100 nM), ADP (100 µM) or ATP (100 µM) increased the Ca2+ level of PDGFRα (+) cells without suppressing spontaneous Ca2+ transients in neighboring DSM cells, and also failed to suppress SPCs. Preferential localisation of SK3 positive PDGFRα (+) cells in DSM bundles appears to indicate their functional interaction with DSM cells. However, increases in Ca2+ level of PDGFRα (+) cells upon purinergic stimulation are not associated with the inhibition of Ca2+ or contractile activity in DSM cells. Thus, it is unlikely that the SK3-dependent hyperpolarisation generated in SK3 expressing PDGFRα (+) cells is transmitted to DSMs to suppress their excitability.


Assuntos
Regulação da Expressão Gênica , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Bexiga Urinária/citologia , Animais , Sinalização do Cálcio/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Cobaias , Masculino , Camundongos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Agonistas Purinérgicos/farmacologia , Bexiga Urinária/fisiologia
20.
Low Urin Tract Symptoms ; 11(4): 224-231, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31298501

RESUMO

OBJECTIVES: A non-invasive protocol was previously developed using three-dimensional ultrasound and a sensation meter to characterize real-time bladder sensation. This study the protocol by measuring the effects of fill rateand ultrasound probe pressure during oral hydration. METHODS: Healthy volunteers with no urinary symptoms (based on International Consultation on Incontinence Questionnaire on Overactive Bladder surveys) were recruited into an oral hydration study. Throughout two complete fill-void cycles, participants drank 2 L Gatorade G2 (The Gatorade Company, Inc., Chicago, Illinois) and used a touch-screen sensation meter to record real-time bladder sensation (0%-100%). The study was repeated three times, once per week (Visits A, B, and C). In Visits A and B, ultrasound was used to measure bladder volume every 5 minutes. Ultrasound was not used in Visit C except at 100% capacity. Volume data from Visit B were used to estimate volumes throughout the fills in Visit C. Sensation-capacity curves were generated for each fill for comparative analysis. RESULTS: Ten participants completed three visits (60 total fills). Increased fill rate led to decreased sensation throughout filling, andultrasound probe pressure led to increased sensation. Participants reported higher sensation at low volumes during Fill 1 of Visit A before training with the sensation meter. Sensation curves with intermittent ultrasound showed repeatability for Fill 2 in Visits A and B. Fill rate and ultrasound probe pressure affect real-time bladder sensation during oral hydration. CONCLUSIONS: This study demonstrated repeatability of real-time bladder sensation during a two-fill oral hydration protocol with ultrasound.


Assuntos
Sensação/fisiologia , Bexiga Urinária/fisiologia , Ingestão de Líquidos , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Ultrassonografia , Bexiga Urinária/diagnóstico por imagem , Urodinâmica , Adulto Jovem
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