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Hironobu Akino

Publications and source records attributed to Hironobu Akino.

16 recordsLinked to original sources
PubMed2007

Identification of alpha-1L and alpha-1A adrenoceptors in human prostate by tissue segment binding.

PURPOSE: Silodosin (KMD-3213 or [(-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide]) (Kissei Pharmaceutical Co., Ltd., Matsumoto, Japan) is a selective antagonist for alpha-1A and alpha-1L adrenoceptors. Using this tritiated ligand the 2 alpha-1 adrenoceptors were examined in binding studies with intact tissue segments and membrane preparations of human prostate, and compared with functionally identified alpha-1 adrenoceptor. MATERIALS AND METHODS: Binding assays with tissue segments and membrane preparations of human prostate samples were performed using [3H]-silodosin and binding affinities for various drugs were estimated. In functional experiments antagonist affinities were evaluated from the inhibitory potency against the contractile response to noradrenaline. RESULTS: [3H]-silodosin bound to intact segments and membrane preparations of human prostate with subnanomolar affinity. [3H]-silodosin binding sites in intact segments were divided into 2 distinct components with different affinities for prazosin and RS-17053 (N-[2(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl1H-indole-3-ethanamine hydrochloride) (Research Biochemicals International, Natick, Massachusetts), while binding in membrane preparations showed single high affinity for these drugs. [3H]-silodosin binding sites also showed high affinity for silodosin and tamsulosin but low sensitivity to BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione) (Research Biochemicals International) in intact segments and in membrane preparations. In functional experiments silodosin and tamsulosin potently inhibited the contractile response to noradrenaline but prazosin, RS-17053 and BMY 7378 showed low antagonistic affinity. CONCLUSIONS: The current binding studies in human prostate samples clearly show that alpha-1L and alpha-1A adrenoceptors coexist as pharmacologically distinct entities in intact tissues but not in crude membrane preparations. Also, alpha-1 adrenoceptors involved in the contractile response to noradrenaline are the alpha-1L subtype.

Humans↗
PubMed2007

Improvement in bladder storage function by tamsulosin depends on suppression of C-fiber urethral afferent activity in rats.

PURPOSE: Alpha(1)-blockers improve voiding symptoms by decreasing prostatic and urethral smooth muscle tone. However, to our knowledge the mechanism underlying improvements in storage symptoms is not known. Topical application of prostaglandin E(2) to the rat lower urinary tract stimulates the micturition reflex. Using an animal model we investigated whether the alpha(1)-blocker tamsulosin (Astellas Pharma, Tokyo, Japan) acts on C-fiber afferent activity and, if so, the location of this effect. MATERIALS AND METHODS: To induce desensitization of C-fiber afferent activity resiniferatoxin (0.3 mg/kg) was subcutaneously injected in female Sprague-Dawley rats 2 days before experiments. Simultaneous recordings of urethral pressure and rhythmic bladder pressure were made with the rats under urethane anesthesia. Prostaglandin E(2) (0.4 mg/ml) was continuously administered intravesically or intraurethrally to rats pretreated with resiniferatoxin (resiniferatoxin rats) or rats without pretreatment (nonresiniferatoxin rats). We investigated the effects on the micturition reflex of intravenous (2.2 x 10(-1) to 2.2 x 10(3) nM/kg) or intrathecal (0.001 to 0.1 nmol) administration of tamsulosin. RESULTS: The bladder contraction interval was markedly decreased after intravesical or intraurethral administration of prostaglandin E(2) in nonresiniferatoxin rats but it was unchanged in resiniferatoxin rats. This effect was antagonized by the EP1 receptor antagonist ONO-8711 (6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]-5Z-hexenoic acid). Intravenous administration of tamsulosin significantly increased the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2) but it had no effect on nonresiniferatoxin rats receiving intravesical prostaglandin E(2). Intrathecal administration of tamsulosin produced a slight and insignificant increase in the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2). CONCLUSIONS: These results suggest that prostaglandin E(2) enhances the micturition reflex through C-fiber afferents and tamsulosin had an inhibitory effect on the C-fiber urethral afferent nerves, thereby improving bladder storage function.

Adrenergic alpha-Antagonists↗
PubMed2006

Improvement of bladder storage function by alpha1-blocker depends on the suppression of C-fiber afferent activity in rats.

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.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2005

Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats.

PURPOSE: We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically. MATERIALS AND METHODS: To induce C-fiber bladder afferent nerve desensitization resiniferatoxin (RTX) (0.3 mg/kg) was injected subcutaneously in female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO). As controls, we used rats treated with ethanol and saline vehicle (VEH). Insertion of a polyethylene catheter through the bladder dome and MCAO were performed using halothane anesthesia. The effects of intravenous (0.2 to 2000 nM/kg) or intravesical (0.2 or 2 nM) tolterodine, an antimuscarinic agent, on cystometrography were investigated in conscious rats with a cerebral infarct (CI). Tolterodine was instilled intravesically for 30 minutes and cystometry was repeated. RESULTS: Bladder capacity (BC) was markedly decreased after MCAO in RTX treated (RTX-CI) and VEH treated (VEH-CI) rats. Low tolterodine doses (0.2 or 2 nM/kg) significantly increased BC in VEH-CI rats without increasing residual volume but it had no effects on BC in RTX-CI rats. At the highest dose (2,000 nM/kg) the drug significantly decreased bladder contraction pressure and increased residual volume in RTX-CI and VEH-CI rats. Intravesical administration of tolterodine (0.2 or 2 nM) significantly increased BC in VEH-CI rats. However, tolterodine had no effect on BC in RTX-CI rats. CONCLUSIONS: These results suggest that at low doses tolterodine exerts an inhibitory effect on C-fiber bladder afferent nerves, thereby, improving BC during the storage phase.

Administration, Intravesical↗
PubMed2005

Direct effect of CoC12 and NiCl2 on citrate uptake by the rat renal brush border membrane.

Co and Ni are essential but relatively rare elements as to organisms. In the mammalian membrane, these metals are transported by the same carrier proteins. The aim of this study was to investigate the direct effects of CoCl2 and NiCl2 on citrate uptake by rat renal brush border membrane vesicles (BBMV). BBMV were prepared by the divalent cation precipitation methods, and citrate uptake was measured by the Millipore rapid membrane filtration technique. The time course of citrate uptake during 120-min of incubation with 1 mM CoCl2 and NiCl2 showed a rapid significant inhibition at the early phase and a slight recover at the late phase. Incubation for 1 min of BBMV with 1, 5 and 25 mM CoCl2 and NiCl2, respectively, significantly inhibited citrate uptake in a concentration-dependent manner compared with that of 0 mM. We discuss these findings from the point of view that Co and Ni are located in Group VIII of the periodic table.

Animals↗
PubMed2005

[Pathophysiology and treatment of the overactive bladder syndrome in an aged male patient with voiding difficulty: pharmacological treatment].

Pharmacolgical treatment is the main stay in the treatment of overactive bladder (OAB). However, it can be difficult to treat the patients with OAB and voiding difficulty. The present patient was a 75-year-old male, who had wet OAB and voiding difficulty with slight enlargement of the prostate (ultrasound-estimated prostate volume; 28 ml) and a medical history of cerebral infarction. The analysis of clinical data gained from the patients with lower urinary tract symptoms in our institution suggested that the etiology of OAB in this patient was neurogenic bladder with high probability (nearly 80%), and the probability of the existence of bladder outlet obstruction (BOO) was approximately 40%. Given the high probability of the neurogenic OAB, the first-line therapy should be a pharmacological treatment. If he had BOO, the treatment should start with alpha-adrenoceptor blockers, and also the combination of anticholinergic drugs and alpha-blockers would be beneficial. If he had impaired detrusor contractility, we have no evidence-based proposal for his treatment.

Adrenergic alpha-Antagonists↗
PubMed2004

Role of glutamate receptors in the development and maintenance of bladder overactivity after cerebral infarction in the rat.

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.

Animals↗
PubMed2004

Roles of opiate in lower urinary tract dysfunction associated with spinal cord injury in rats.

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.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2004

Prognostic value of nuclear area index in patients with bladder cancer.

BACKGROUND: To assess the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal transitional cells in patients with bladder cancer, who have undergone radical cystectomy. METHODS: Measurements of the nuclear areas of cancer and normal transitional cells were carried out on the histological slides of 73 patients with bladder cancer. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the cause-specific survival of the patients was examined. RESULTS: The median values of MNA and NAI in the 73 patients were 39 micro m2 and 1.2, respectively. Cause-specific survival rates of the patients were calculated according to stage (T1-2 vs T3-4), grade (grade 2 vs grade 3), MNA (<39 micro m2 vs>/=39 micro m2) and NAI value (<1.2 vs>/=1.2). Using univariate analysis, all these parameters were statistically significant prognostic factors. However, by multivariate analysis, NAI was the only independent variable for the survival of the patients (P < 0.01). Cause-specific survival rates of patients with NAI values of less than 1.2 were significantly higher than those with NAI values of 1.2 or more, in both grade 2 and grade 3 tumors. CONCLUSIONS: These results suggest that NAI could provide improved prognostic information for patients with bladder cancer.

Adult↗
PubMed2003

RNA synthesis in pons necessary for maintenance of bladder overactivity after cerebral infarction in rat.

PURPOSE: The maintenance of long lasting bladder overactivity caused by cerebral infarction is believed to require transcription in the pontine micturition center. Therefore, we examined the influence of the RNA synthesis inhibitor actinomycin D (Banyu Pharmaceutical Co., Ltd., Tokyo, Japan) on bladder overactivity induced by left middle cerebral artery occlusion. MATERIALS AND METHODS: Rats under halothane anesthesia were injected with actinomycin D or vehicle (mannitol) into the bilateral dorsal pontine tegmentum, followed by middle cerebral artery occlusion. Awake rats were cystometrically examined for 12 hours. The expression of c-fos and zif268 mRNA in the dorsal pontine tegmentum was monitored with real-time polymerase chain reaction. RESULTS: Injection of actinomycin D produced a significant decrease in bladder capacity in sham operated rats but bladder capacity returned to control levels before sham operation within 6 hours. In cerebral infarcted rats pretreated with vehicle bladder capacity was significantly decreased after middle cerebral artery occlusion and it remained consistently below half of pre-occlusion capacity. Actinomycin D blocked the decrease in bladder capacity in cerebral infarcted rats. In actinomycin D treated cerebral infarcted rats bladder capacity gradually recovered and returned to the control level before middle cerebral artery occlusion within 10 hours. Actinomycin D suppressed an increase in c-fos mRNA expression 1 hour after middle cerebral artery occlusion as well as in zif268 3 hours after occlusion. Administering actinomycin D 0.5 or 1 hour after middle cerebral artery occlusion also suppressed bladder overactivity until at least 10 hours after occlusion but injection 3 hours after occlusion did not. CONCLUSIONS: These results indicate that an RNA synthesis inhibitor can prevent a late stage of bladder overactivity. Transcription in the dorsal pontine tegmentum was found to be necessary to maintain the long lasting bladder overactivity caused by cerebral infarction.

Animals↗
PubMed2003

[Transcatheter arterial embolization with n-butyl 2-cyanoacrylate (hystoacryl) for renal arteriovenous malformation: case report].

A 22-year-old woman presented with sudden onset gross hematuria. Drip infusion pyelography and enhanced computerized tomography yielded no unusual findings. Renal angiography demonstrated an arteriovenous malformation (AVM) in the central portion of the right kidney. Superselective transcatheter arterial embolization (TAE) of the AVM was performed with a steel coil, and hematuria disappeared after TAE. However, severe gross hematuria developed again six days later. Second renal arteriography revealed the formation of the collateral vessels. By using n-butyl 2-cyanoacrylate (NBCA), TAE for AVM was performed successfully. She has been free of hematuria during the one-year follow-up.

Adult↗
PubMed2002

Prognostic value of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging for patients with prostate cancer.

PURPOSE: The purpose of this study was to investigate the prognostic value of measuring glucose metabolism of primary prostate cancer lesions, using 2-Deoxy-2-[F-18]Fluoro-D-Glucose positron emission tomography (FDG-PET). PROCEDURES: Forty-two patients with prostate cancer were investigated with FDG-PET, and standardized uptake value (SUV) of the prostate was calculated. After PET study, radical prostatectomy was performed in 17 patients (RPT group), and endocrine therapy in 25 patients (ET group). Relapse-free survival curves were created by the Kaplan-Meier method. RESULTS: In the RPT group, the patients with high SUV had a poorer prognosis compared to those with low SUV (P = 0.033). In the ET group, the patients with high SUV were likely to have a poorer prognosis with low significance at a level of P = 0.087. CONCLUSIONS: FDG-PET appeared to have a defined prognostic value for patients with prostate cancer undergoing radical prostatectomy, and more patients need to be studied for patients undergoing endocrine therapy.

Journal Article↗
PubMed2002

Overactive bladder--experimental aspects.

Supra-pontine lesions resulting from neurological disorders such as vascular disease, Parkinson's disease, or Alzheimer type senile dementia lead to an increase in bladder activity. This is due in part to the removal at the cortical inhibitory control of the micturition center in the brain stem - i.e. the pontine micturition center (PMC) - and in part to facilitation of excitatory control. These inhibitory or excitatory controls consist of several neurotransmitter systems, including glutamate, dopamine, gamma-aminobutyric acid (GABA), and acetylcholine. Bladder overactivity caused by cerebral infarction is mediated by upregulation of N-methyl-D-aspartate (NMDA) glutamatergic and D2 dopaminergic excitatory mechanisms, and by downregulation of NMDA glutamatergic and Ml muscarinic inhibitory mechanisms in the brain. Bladder overactivity associated with Parkinson's disease is reportedly induced by a loss of input to the D1 dopaminergic receptor. Furthermore, bladder overactivity caused by Alzheimer type dementia is thought to be mediated by downregulation of M1 muscarinic inhibitory mechanisms. Development of bladder overactivity following cerebral infarction is mediated by activation of the NMDA receptor and accompanied by an increase in c-fos, zif268 and COX-2 mRNA expression in the dorsal pontine tegmentum.

Animals↗
PubMed2002

Direct effect of vanadium on citrate uptake by rat renal brush border membrane vesicles (BBMV).

Vanadium pentoxide is used as a catalyst and a ferrovanadium alloy ingredient in automotive steels and in jet engines and airframes. In addition, vanadium is found in fuel oils. Thus, occupational exposures to vanadium pentoxide and trioxide may occur during the cleaning of oil-fired ship boilers, and from oil-fired power station boilers. Occupational exposure to vanadium pentoxide induces green tongue, asthmatic symptoms and albuminuria with cast. Urinary citrate is freely filtered at the glomerulus, and its reabsorption in the proximal tubule is the major determinant of the rate of renal excretion. In this study, we exposed rat renal brush border membrane vesicles (BBMV) to vanadium pentoxide and examined their citrate uptake characteristics. The preincubation of BBMV with 1 mM V2O5 for 8 hours significantly inhibited citrate uptake compared with that of BBMV without V2O5, preincubation. These findings indicate that the preincubation of BBMV with vanadium pentoxide results in a time-dependent inhibition of citrate uptake by BBMV. These findings might contribute to nephrotoxicity in vanadium exposure.

Animals↗
PubMed2002

11C-acetate PET imaging of prostate cancer.

UNLABELLED: 11C-Acetate can act as a probe of tissue metabolism through entry into catabolic or anabolic metabolic pathways as mediated by acetyl-coenzyme A. The uptake of (11)C-acetate in prostate cancer was investigated to determine whether this tracer has potential in tumor identification. METHODS: Twenty-two patients with prostate cancer underwent PET after intravenous administration of 740 MBq (11)C-acetate. Eighteen of the 22 patients were also investigated with (18)F-FDG PET. Standardized uptake values (SUVs) for each tumor were investigated for tracer activity at 10-20 min after (11)C-acetate and 40-60 min after (18)F-FDG administration. RESULTS: Adenocarcinoma of the prostate showed variable uptake of (11)C-acetate, with SUVs ranging from 3.27 to 9.87. In contrast, SUVs for (18)F-FDG ranged from 1.97 to 6.34. By visual inspection, (11)C-acetate accumulation in primary prostate tumors was positive in all patients, whereas (18)F-FDG accumulation was positive in only 15 of 18 patients. (11)C-Acetate PET in a patient with lymph node metastasis showed high intrapelvic accumulation corresponding to metastatic sites. Similarly, 2 patients with bone metastases were (11)C-acetate avid. CONCLUSION: (11)C-Acetate shows marked uptake in prostate cancer and is more sensitive in detection of prostate cancer than is (18)F-FDG PET. (11)C-Acetate represents a new tracer for detection of prostate cancer with PET, measuring radiopharmaceutical uptake pathways that are different from those measured by (18)F-FDG.

Acetates↗