RESUMEN

A 60-year-old man was examined at a local clinic for difficulty in urinating, and was diagnosed with prostatic hypertrophy. He was referred to our department because his prostate-specific antigen (PSA) level was elevated (276 ng/ml). His Gleason score was 4＋3, there was one bone metastasis in the left ileac bone, and multiple lung metastases were present. The patient was accordingly diagnosed with stage D2 prostate cancer. Lutenizing hormone-releasing hormone (LH-RH) analogue treatment was initiated in April 1999, and 9 months later the PSA level had decreased to 4.3 ng/ml. Six years and 9 months after the start of hormone therapy, the cancer had developed into castration-resistant prostate cancer and the PSA level had risen to 43.8 ng/ml. Paclitaxel-carboplatin therapy was therefore initiated. Eight months after the start of chemotherapy, the PSA level had decreased to 25.9 ng/ml, but 6 years and 1 month later it had risen to 925 ng/ml, and the chemotherapy was discontinued. Docetaxel-predonine therapy was initiated in March 2012. Three months after the start of chemotherapy, the PSA level had decreased to 3.1 ng/ml, and the bone metastasis was reduced.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Neoplasias de la Próstata/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Carboplatino/administración & dosificación , Carboplatino/farmacología , Docetaxel , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Prednisolona/administración & dosificación , Taxoides/administración & dosificación

RESUMEN

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Antichollnergic agents are anticipated to diminish storage symptoms, as well as nocturia. Nevertheless, the effect of this treatment on polyuria related to nocturia is not clear. By subgroup analysis of the data set from a phase III clinical trial of antimuscarinic agent for OAB patients in Japan, imidafenacin was found to improve nocturia with a reduction in nocturnal polyuria. This study adds the effects and underlying mechanism of antimuscarinic agents decreasing urine production through inhibition of C-fibre in the bladder of water-leaded rats. OBJECTIVE: To evaluate the effects and underlying mechanisms of antimuscarinic agents used to decrease in urine production in water-loaded rats. SUBJECTS AND METHODS: Urine production was measured using a cystostomy catheter in female Sprague-Dawley rats every 2 h. The effect of the antimuscarinic agents atropine, tolterodine and imidafenacin on urine production was investigated under water-loaded conditions, which were induced by i.p. injection of 15 mL saline. Blood samples were collected to determine the levels of antidiuretic hormone (ADH), aldosterone (ALD), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) before, and 2 and 8 h after, antimuscarinic agent administration. To induce desensitization of C-fibre afferent nerves, resiniferatoxin (RTX)was injected s.c. or intravesically 2 days before experiments. RESULTS: Urine production increased and reached its maximum 2 h after 15 mL saline injection. Imidafenacin and tolterodine decreased urine production in water-loaded rats, but ADH, ALD, ANP and BNP levels were not different between imidafenacin-treated and vehicle-treated rats. The inhibitory effect on urine production was not found in RTX-treated rats. Atropine did not reduce urine production. CONCLUSION: These results suggest that antimuscarinic agents decrease urine volume through C-fibres in the bladder; thus, antimuscarinics with inhibitory effects on C-fibres could be beneficial for nocturia with nocturnal polyuria.

Asunto(s)

Antagonistas Muscarínicos/farmacología , Fibras Nerviosas Amielínicas/efectos de los fármacos , Nocturia/tratamiento farmacológico , Poliuria/tratamiento farmacológico , Vejiga Urinaria/inervación , Urodinámica/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Femenino , Nocturia/fisiopatología , Poliuria/fisiopatología , Ratas , Ratas Sprague-Dawley , Vejiga Urinaria/efectos de los fármacos

RESUMEN

OBJECTIVE: To investigate the efficacy and safety of a combination treatment with α(1)-blockers and antimuscarinics for detrusor overactivity in rats. METHODS: Rats with detrusor overactivity caused by a cerebral infarction were divided into four groups that received an i.v. administration of tamsulosin (0.1-1000 µg/kg); solifenacin (0.01-0.3 mg/kg); combined low doses of tamsulosin (0.008, 0.1 µg/kg) and solifenacin (0.01 mg/kg); or solifenacin (0.1, 0.3, 1.0 mg/kg) at 1-h intervals during the continuous administration of tamsulosin (0.01 µg/kg/h). RESULTS: Both tamsulosin alone and solifenacin alone significantly increased bladder capacity in cerebral infarcted rats, but these effects were reduced in rats pretreated with resiniferatoxin. The combined low dose of tamsulosin and solifenacin resulted in a significant increase in bladder capacity compared to mono-administration of 0.01 mg/kg solifenacin (68.8 vs 19.8% of control value, respectively). In the group receiving solifenacin at 1-h intervals, solifenacin dose-dependently decreased bladder contraction duration and a significant reduction in bladder contraction pressure (by 35.0% of control value) was found at the highest dose (1.0 mg/kg). However, no reduction in bladder contraction duration was found even at the highest dose of solifenacin when co-administered with tamsulosin. CONCLUSION: α(1)-Blockers and antimuscarinic agents have an additive ameliorative effect on detrusor overactivity when co-administered at low doses. α(1)-Blockers prevent the reduction in bladder contraction duration induced by a high-dose administration of antimuscarinic agents.

Asunto(s)

Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Antagonistas Muscarínicos/uso terapéutico , Quinuclidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Tetrahidroisoquinolinas/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Diterpenos/farmacología , Quimioterapia Combinada , Femenino , Infarto de la Arteria Cerebral Media/complicaciones , Antagonistas Muscarínicos/farmacología , Contracción Muscular/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Quinuclidinas/farmacología , Ratas , Ratas Sprague-Dawley , Succinato de Solifenacina , Estadísticas no Paramétricas , Sulfonamidas/farmacología , Tamsulosina , Tetrahidroisoquinolinas/farmacología , Vejiga Urinaria/patología , Vejiga Urinaria/fisiopatología , Vejiga Urinaria Hiperactiva/etiología

RESUMEN

PURPOSE: We previously reported that cyclooxygenase inhibitors improved storage function in rats with detrusor overactivity caused by cerebral infarction via C-fiber suppression but the precise mechanism underlying this effect remained unclear. In this study we investigated the effects of cyclooxygenase inhibitors on stretch evoked adenosine triphosphate and prostaglandin E(2) release from bladder epithelium. MATERIALS AND METHODS: Whole bladders excised from normal rats were fixed vertically in an organ bath filled with Krebs solution. Bladders were infused with 0.3 ml Krebs solution (baseline), followed by 0.9 ml vehicle or 1.5 ml vehicle/drug solution, or 0.3 ml protamine sulfate (Wako Pure Chemical Industries, Osaka, Japan), followed by 0.3 ml prostaglandin E(2) (Nacalai Tesque, Kyoto, Japan). Solutions were allowed to stand for 10 minutes and collected. Adenosine triphosphate and prostaglandin E(2) concentrations were measured by luciferin-luciferase assay and enzyme-linked immunoassay, respectively. RESULTS: Adenosine triphosphate and prostaglandin E(2) release from bladder epithelium was increased by distention in volume dependent fashion. A 100 µM dose of the nonselective cyclooxygenase inhibitors FYO-750, ketoprofen and indomethacin significantly suppressed the increased adenosine triphosphate and prostaglandin E(2) release. Inhibition of adenosine triphosphate release by 100 µM FYO-750 and indomethacin was antagonized by prostaglandin E(2) co-injection. Prostaglandin E(2) increased adenosine triphosphate release in a nondistending condition, and the 1 µM of the selective EP1 and EP3 receptor antagonists ONO-8711 and ONO-AE5-599, respectively, significantly suppressed the increased adenosine triphosphate release. CONCLUSIONS: Results indicate that cyclooxygenase inhibitors suppress adenosine triphosphate release from bladder epithelium via decreasing prostaglandin E(2). EP1 and/or EP3 receptors appear to participate in this effect.

Asunto(s)

Adenosina Trifosfato/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Dinoprostona/metabolismo , Vejiga Urinaria/metabolismo , Urotelio/metabolismo , Animales , Fenómenos Biomecánicos , Femenino , Ratas , Ratas Sprague-Dawley , Vejiga Urinaria/fisiología , Urotelio/fisiología

RESUMEN

Although sunitinib shows a high response rate in patients with untreated metastatic renal cell carcinoma (mRCC), quite a few patients show no therapeutic effect. Therefore, it is crucial to distinguish the patients who respond to sunitinib from those who do not as early as possible after the administration of the therapy. We herein report a case of mRCC in which (11)C-acetate (AC) positron emission tomography (PET) showed an early therapeutic effect of sunitinib treatment 4 weeks after its administration.

RESUMEN

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C-fiber afferent nerves. α1A -adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A -adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.

RESUMEN

PURPOSE: Impaired melatonin production is involved in disruption of the normal circadian pattern of sleep, which leads to nocturia in older adults. Melatonin improves nocturia. We hypothesized that melatonin could alleviate urinary frequency by suppressing the brain micturition center. We investigated the central contribution of melatonin to bladder function and urine volume. MATERIALS AND METHODS: Cystometry was done in conscious female Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan). We examined the effect of melatonin alone (4.3 x 10(-1) to 4.3 x 10 pmol intracerebroventricularly) or with the gamma-aminobutyric acid(A) antagonist bicuculline (5.0 x 10(-5) mg/kg intravenously) on bladder function. The influence of melatonin (4.3 x 10 pmol intracerebroventricularly) on urine volume was investigated in water loaded rats. Blood samples were collected to determine antidiuretic hormone, atrial natriuretic peptide and brain natriuretic peptide 4 hours after melatonin administration. RESULTS: Melatonin significantly increased bladder capacity dose dependently by 27.0%, 40.8% and 63.5% at 4.3 x 10(-1), 4.3 and 4.3 x 10 pmol, respectively, but had no significant effect on bladder contraction pressure. Bicuculline inhibited the melatonin induced increases in bladder capacity. Melatonin decreased urine volume in water loaded rats but plasma antidiuretic hormone, atrial natriuretic peptide and bladder contraction pressure were not changed. CONCLUSIONS: Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.

Asunto(s)

Bicuculina/farmacología , Agonistas del GABA/farmacología , Melatonina/farmacología , Vejiga Urinaria/efectos de los fármacos , Micción/efectos de los fármacos , Urodinámica/efectos de los fármacos , Análisis de Varianza , Animales , Factor Natriurético Atrial/sangre , Relación Dosis-Respuesta a Droga , Femenino , Péptido Natriurético Encefálico/sangre , Ratas , Ratas Sprague-Dawley , Cateterismo Urinario , Vasopresinas/sangre

RESUMEN

PURPOSE: Cyclooxygenase inhibitors decrease micturition frequency in animals with bladder inflammation but to our knowledge the influence of cyclooxygenase inhibitors on detrusor overactivity has not been investigated. We evaluated the effects, and the site and mechanism of action of cyclooxygenase inhibitors on detrusor overactivity induced by cerebral infarction. MATERIALS AND METHODS: Cerebral infarcted rats underwent cumulative intravenous administration of the selective cyclooxygenase-1 inhibitor SC-560 (Sigma), the selective cyclooxygenase-2 inhibitor rofecoxib (Kemprotec, Middlesbrough, United Kingdom) or the nonselective cyclooxygenase inhibitor FYO-750 hourly plus a single intravenous administration of SC-560, rofecoxib or SC-560 plus rofecoxib. To evaluate the site of action cerebral infarcted rats underwent single intracerebroventricular or intrathecal administration of FYO-750. To evaluate the mechanism of action FYO-750 was intravenously administered in diuretic rats or cerebral infarcted rats pretreated with resiniferatoxin. RESULTS: For cumulative administration SC-560 (0.3 mg/kg), rofecoxib (0.3 mg/kg) and FYO-750 (0.1 to 1 mg/kg) significantly increased bladder capacity. For single administration neither SC-560 (0.03 mg/kg) nor rofecoxib (0.03 mg/kg) affected bladder capacity but SC-560 plus rofecoxib significantly increased bladder capacity vs vehicle. Intracerebroventricular and intrathecal administration of FYO-750 did not affect bladder capacity. FYO-750 did not affect urinary production in diuretic rats and the effects of FYO-750 were blocked by resiniferatoxin except at the highest drug dose. CONCLUSIONS: Results indicate that cyclooxygenase inhibitors improve detrusor overactivity caused by cerebral infarction by suppressing peripheral C fiber's without affecting urinary production. The nonselective cyclooxygenase inhibitor showed more potent efficiency than the selective cyclooxygenase-1 or the cyclooxygenase-2 inhibitor alone.

Asunto(s)

Inhibidores de la Ciclooxigenasa/uso terapéutico , Lactonas/uso terapéutico , Pirazoles/uso terapéutico , Sulfonas/uso terapéutico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Animales , Infarto Cerebral/complicaciones , Inhibidores de la Ciclooxigenasa/farmacología , Femenino , Lactonas/farmacología , Fibras Nerviosas Amielínicas/efectos de los fármacos , Pirazoles/farmacología , Ratas , Ratas Sprague-Dawley , Sulfonas/farmacología , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Hiperactiva/etiología

RESUMEN

Hematuria is a commonly encountered symptom of a wide spectrum of diseases, including calculi, tumors, and vascular abnormalities. In rare cases, hematuria is caused by life-threatening vascular diseases. When hematuria is encountered, physicians sometimes fail to include vascular diseases in the differential diagnosis because of their rare association with hematuria. Likewise, radiologists often fail to do so because of the low frequency of occurrence of these diseases. Multidetector computed tomography performed with the bolus injection technique should be the first-line diagnostic test when vascular disease is suspected. Radiologists should be familiar with the various imaging findings of hematuria caused by vascular disease. They should also be familiar with the management options (including endovascular techniques) for hematuria caused by vascular disease, since in some cases affected patients can be treated with interventional procedures.

Asunto(s)

Hematuria/diagnóstico por imagen , Hematuria/etiología , Tomografía Computarizada por Rayos X/métodos , Enfermedades Urológicas/complicaciones , Enfermedades Urológicas/diagnóstico por imagen , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Raras/complicaciones , Enfermedades Raras/diagnóstico por imagen

RESUMEN

Muscarinic receptor antagonists are used clinically for their therapeutic peripheral effects on bladder function. However, these agents may also act on central muscarinic receptors, especially in individuals with compromised blood-brain barrier function. We compared the effects of atropine and tolterodine, agents that do and do not readily cross the blood-brain barrier, respectively, administered peripherally (intravenous [i.v.]) and centrally (intracerebroventricular [i.c.v.]) on cystometrography in conscious rats after cerebral infarction induced by middle cerebral artery occlusion or sham surgery. We hypothesized that tolterodine would produce greater improvement in bladder capacity and less impairment in bladder contractility and that the effects of both agents would be greater in rats with cerebral infarction and sham-operated rats after peripheral administration, but that tolterodine and atropine would exert similar effects after central administration. Bladder capacity was markedly reduced following cerebral infarction. Low-dose i.v. tolterodine (or=20 nmol/kg) significantly increased bladder capacity but also significantly increased residual volume and decreased bladder contraction pressure. Tolterodine was significantly more efficacious than atropine in increasing bladder capacity, whereas atropine produced significantly greater increases in residual volume and reductions in bladder contraction pressure; these treatment group differences were also observed in sham-operated animals. Tolterodine and atropine administered i.c.v. significantly increased bladder capacity following cerebral infarction or sham surgery; however, this was accompanied by significantly increased residual volume and decreased bladder contraction time. The decrease in bladder contraction time was significantly smaller after tolterodine vs atropine. Peripherally acting muscarinic receptor antagonists may be preferable to centrally acting agents for minimizing adverse events, such as incomplete bladder emptying, even in individuals with compromised blood-brain barrier function.

Asunto(s)

Atropina/uso terapéutico , Compuestos de Bencidrilo/uso terapéutico , Cresoles/uso terapéutico , Infarto de la Arteria Cerebral Media/complicaciones , Antagonistas Muscarínicos/farmacología , Fenilpropanolamina/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Micción/efectos de los fármacos , Animales , Atropina/administración & dosificación , Compuestos de Bencidrilo/administración & dosificación , Cresoles/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Infarto de la Arteria Cerebral Media/fisiopatología , Inyecciones Intraventriculares , Antagonistas Muscarínicos/administración & dosificación , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Fenilpropanolamina/administración & dosificación , Ratas , Ratas Sprague-Dawley , Tartrato de Tolterodina , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria Hiperactiva/etiología , Vejiga Urinaria Hiperactiva/fisiopatología , Cateterismo Urinario

RESUMEN

This chapter critically reviews the literature on surgery for stress urinary incontinence (SUI) and pelvic organ prolapse (POP), and medical treatment for overactive bladder in women. The midurethral polypropylene sling was reported to provide a durable option with significant improvement. The tension-free vaginal tape (TVT) procedure is based on a theory of pathophysiology of stress incontinence presented by Petros and Ulmsten. In their "integral theory" impairment of the pubourethral ligament is one of the primary cause of SUI. The transobturator sling was found to be effective in SUI patients with less incidence of perioperative complications and voiding difficulties. Prolapse of the uterus/vaginal apex and posterior vaginal wall may also be found in women with stress incontinence. There are many procedures for the correction of POP. Transvaginal repair of anterior and posterior compartment prolapse with polypropylene mesh has been developed in recent years. It is necessary to assess and compare the current quality of outcomes.

Asunto(s)

Urología/tendencias , Femenino , Humanos , Japón , Vejiga Urinaria Hiperactiva/terapia , Incontinencia Urinaria de Esfuerzo/terapia , Prolapso Uterino/terapia

RESUMEN

Iliac artery-ureteral fistula (IAUF) is a rare entity that has a potential risk of life-threatening hemorrhage. It is difficult to diagnose and treat appropriately. Conventional treatment for the disease consists of surgical ligation and vascular reconstruction or coil embolization. Surgical treatment is usually difficult for patients with several risk factors. In recent years, endovascular stent-graft treatment for iliac artery pseudoaneurysm has been reported. The present report describes two cases in which endovascular covered stent-graft treatment was successfully applied to treat IAUF, with good clinical outcomes.

Asunto(s)

Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/cirugía , Fístula/terapia , Arteria Ilíaca/diagnóstico por imagen , Arteria Ilíaca/cirugía , Stents/efectos adversos , Enfermedades Ureterales/terapia , Ureterostomía , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Cistectomía , Humanos , Hidronefrosis/terapia , Linfoma/cirugía , Masculino , Suturas/efectos adversos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento

Asunto(s)

Huesos/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Radiofármacos , Acetatos , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Radioisótopos de Carbono , Humanos , Masculino

RESUMEN

AIMS: Alpha1-blockers improve voiding symptoms through the reduction of prostatic and urethral smooth muscle tone; however, the underlying mechanism of improvement of storage symptoms is not known. Using a rat model of detrusor overactivity caused by cerebral infarction (CI), we undertook the present study to determine whether the effect of an alpha1-blocker, naftopidil, is dependent on the suppression of C-fiber afferents. METHODS: To induce desensitization of C-fiber bladder afferents, we injected resiniferatoxin (0.3 mg/kg, RTX) sub-cutaneously to female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO) (RTX-CI rats). As controls we used rats without RTX treatment (CI rats). MCAO and insertion of a polyethylene catheter through the bladder dome were performed under halothane anesthesia. We investigated the effects on cystometrography (CMG) of intravenous (i.v.), intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of naftopidil in conscious CI rats. RESULTS: Bladder capacity (BC) was markedly reduced after MCAO in both RTX-CI and CI rats. I.v. administration of naftopidil significantly increased BC in CI rats without an increase in residual volume, but it had no effects on BC in RTX-CI rats. I.t. administration of naftopidil significantly increased BC in CI but not in RTX-CI rats. CONCLUSIONS: These results suggest that naftopidil has an inhibitory effect on C-fiber afferents in the lumbosacral spinal cord, improving BC during the storage phase.

Asunto(s)

Antagonistas Adrenérgicos alfa/farmacología , Hipertonía Muscular/tratamiento farmacológico , Naftalenos/farmacología , Fibras Nerviosas Amielínicas/efectos de los fármacos , Piperazinas/farmacología , Vejiga Urinaria/efectos de los fármacos , Antagonistas de Receptores Adrenérgicos alfa 1 , Animales , Diterpenos/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Inyecciones Intravenosas , Inyecciones Intraventriculares , Inyecciones Espinales , Hipertonía Muscular/fisiopatología , Fibras Nerviosas Amielínicas/fisiología , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/fisiología , Neurotoxinas/farmacología , Ratas , Ratas Sprague-Dawley , Vejiga Urinaria/inervación , Vejiga Urinaria/fisiología

RESUMEN

PURPOSE: To investigate the role of glutamate receptors in overactive bladder (OAB) caused by cerebral infarction (CI) we examined the effects of 2 different types of receptors antagonists on OAB induced by left middle cerebral artery (MCA) occlusion. MATERIALS AND METHODS: Female rats were intravenously injected with dizocilpine, an NMDA (N-methyl-D-aspartate) receptor antagonist, or NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide), an AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist, before or after MCA occlusion. Awake rats were cystometrically examined for 8 hours. Detrusor strips were evaluated for force development in response to dizocilpine and NBQX. RESULTS: In CI rats without pretreatment bladder capacity (BC) was significantly decreased after MCA occlusion and remained consistently below half that of pre-occlusion capacity. Dizocilpine (0.5 mg/kg intravenously) administered before MCA occlusion blocked the decrease in BC in awake rats 5 to 8 hours after MCA occlusion. In CI rats pretreated with NBQX (10 or 30 mg/kg intravenously) BC was not different from that in rats without pretreatment. Increasing doses of dizocilpine (0.01 to 10 mg/kg) or NBQX (0.1 to 30 mg/kg) increased rat BC 2 hours after MCA occlusion. NBQX did not change the BC of sham operated rats. No differences in the contractile response to dizocilpine or NBQX of detrusor strips from sham operated and CI rats were observed. CONCLUSIONS: These results indicate that NMDA receptor has an essential role in the development of OAB after CI. AMPA receptor antagonist cannot block the development of OAB. However, AMPA receptor antagonist temporally inhibits OAB after it is established by CI.

Asunto(s)

Infarto Cerebral/complicaciones , Receptores de Glutamato/fisiología , Enfermedades de la Vejiga Urinaria/etiología , Enfermedades de la Vejiga Urinaria/fisiopatología , Animales , Maleato de Dizocilpina/farmacología , Relación Dosis-Respuesta a Droga , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Quinoxalinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores AMPA/antagonistas & inhibidores , Receptores de Glutamato/efectos de los fármacos

RESUMEN

PURPOSE: It has been reported that the opiate receptor system in the spinal cord is involved in bladder and urethral function. We determined whether U-50488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide), a kappa opioid receptor agonist, could decrease detrusor-sphincter dyssynergia (DSD) and, thus, improve voiding efficiency in conscious, spinal cord injured (SCI) rats. MATERIALS AND METHODS: Experiments were done in female Sprague-Dawley rats in which the spinal cord was completely transected at the T6-8 level 4 weeks prior to performing cystometry while conscious and held in a restraining cage. Experiments were also performed in normal spinal cord rats. Saline was infused (0.1 ml per minute) via the cystostomy catheter into the bladder. Voiding efficiency was determined by measuring voided and residual volumes. After performing a control cystometrogram increasing doses of U-50488 (0.01, 0.1, 1 and 10 mg/kg) were administered intravenously at 1-hour intervals. The effects of nor-binaltorphimine dihydrochloride, a kappa opioid receptor antagonist, on U-50488 induced changes in voiding parameters were also examined. RESULTS: A high dose of U-50488 (1 to 10 mg/kg) significantly decreased contraction amplitude and bladder capacity (p <0.01 to 0.05) in normal spinal cord and SCI rats. A low dose of U-50488 (0.01 mg/kg) increased voiding efficiency by 32.7% without decreasing bladder capacity in SCI rats. Nor-binaltorphimine hydroparameters counteracted the effect of U-50488 induced changes. CONCLUSIONS: These results suggest that the kappa opioid receptor system is related to DSD caused by spinal cord injury. The kappa opioid receptor agent is believed to have therapeutic potential for treating DSD associated with SCI.

Asunto(s)

Receptores Opioides/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Vejiga Urinaria/fisiopatología , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero/farmacología , Animales , Femenino , Ratas , Ratas Sprague-Dawley , Receptores Opioides/efectos de los fármacos , Vejiga Urinaria/efectos de los fármacos