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Biomedical subjects

D Ishii

Publications and source records attributed to D Ishii.

At least 19 recordsLinked to original sources

Urodynamics in a rat neurogenic bladder model with a unilateral electrolytic lesion of the basal forebrain.

OBJECTIVE: To investigate the changes in bladder function in rats with an electrolytic lesion of the right basal forebrain (RBF) and to determine the effects of AH-9700, a novel sigma receptor ligand, on cystometry in RBF-lesioned rats. MATERIALS AND METHODS: A lesion was made electrolytically in the RBF of male Wistar rats. At 7 or 8 days after the lesion or sham surgery, continuous cystometry was performed in awake rats. In addition, contractile responses to electrical field stimulation or carbachol were measured in isolated bladder strips, as were the forebrain contents of acetylcholine, monoamine neurotransmitters and their metabolites. RESULTS: RBF-lesioned rats showed a remarkable increase in voiding frequency, with a decrease in voiding threshold pressure but no change in voiding pressure, compared with sham-operated rats. However, contractile responses in bladder strips isolated from RBF-lesioned rats were no different from those in strips isolated from sham-operated rats. In RBF-lesioned rats, the contents of acetylcholine, dopamine, 4-dihidroxyphenylacetic acid and homovanillic acid were significantly decreased in the right forebrain. AH-9700 dose-dependently decreased the voiding frequency and increased the threshold pressure in RBF-lesioned rats. Anti-muscarinic agents (oxybutynin and propiverine) also decreased the voiding frequency, but their effects were less potent than that of AH-9700. CONCLUSIONS: The RBF-lesioned rat may be a useful model for the neurogenic bladder of supraspinal origin. Moreover, AH-9700 effectively improves bladder dysfunction in this model.

Animals↗

Effects of AH-9700, (+)-pentazocine, DTG and oxybutynin on micturition in anesthetized rats with acetone-induced cystitis.

We investigated the effects of AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl] pyrrolidine fumarate; a novel sigma receptor ligand), (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG) (two typical sigma receptor ligands), and oxybutynin (a currently used anti-pollakiuria drug) on cystometrograms in anesthetized rats with 30% acetone-induced cystitis. Compared to sham-treated rats, acetone-treated cystitis models exhibited an increase in urinary frequency during continuous filling cystometry. Intravenous administration of AH-9700 (1-5 mg/kg), (+)-pentazocine or DTG to the rats with cystitis dose-dependently prolonged micturition intervals and increased the micturition threshold pressure. Oxybutynin (1 mg/kg. i.v.) also extended micturition intervals, but decreased the micturition pressure. These results indicate that AH-9700, (+)-pentazocine and DTG improve abnormal frequent urination caused by acetone-induced cystitis in a manner different from that of oxybutynin.

Acetone↗

Pharmacological actions of AH-9700 on micturition reflex in anesthetized rats.

In radioligand binding assays, AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl]pyrrolidine fumarate) had high affinity for sigma receptors and moderate affinity for muscarinic receptors. The affinity of AH-9700 for sigma(1) receptors was significantly reduced in the presence of 5'-guanylyl-imidodiphosphate (GppNHp). In isolated bladder strips of rats, AH-9700 inhibited carbachol-induced contractions. In anesthetized rats, i.v. administration of AH-9700 and typical sigma receptor ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), but not oxybutynin, dose-dependently inhibited rhythmic isovolumetric reflex bladder contractions. AH-9700 and oxybutynin suppressed the amplitude of rhythmic bladder contractions. On the other hand, at doses lower than used i.v., the i.c.v. administration of AH-9700 or the sigma receptor ligands inhibited rhythmic bladder contractions without suppressing the amplitude. This inhibitory effect of AH-9700 was markedly reduced by pretreatment with i.c.v. pertussis toxin. These results suggest that AH-9700 exerts a marked anti-micturition reflex effect through central sigma receptors possibly related to pertussis toxin-sensitive Gi/o-proteins and a moderate spasmolytic effect based on its peripheral anti-muscarinic activity.

Anesthesia↗

Pharmacological effect of amezinium on urethra and bladder of rabbits.

The pharmacological effect of amezinium on the urethra and bladder of rabbits was investigated. Amezinium produced concentration-dependent contractions in isolated urethral strips. The maximum response was approximately 30% of that caused by norepinephrine (NE). The concentration-response curve of NE was shifted to the left by amezinium. Moreover, amezinium enhanced the relaxative effect of NE on carbachol-induced contractions in isolated bladder strips. In anesthetized rabbits, amezinium significantly increased the intraurethral pressure (IUP) but produced only slight increases in mean blood pressure (MBP). Pre-treatment with amezinium ehhanced NE-induced increases in IUP index and MBP. The enhancing effect on the IUP index lasted much longer than that on MBP. In a stress incontinence model amezinium significantly inhibited the incontinence after an i.v. infusion of a low dose of NE. This effect was antagonized by pre-treatment with prazosin. These results suggest that amezinium may produce an excellent effect for stress incontinence, especially mixed, without severe adverse events such as sudden hypertension.

Animals↗

Effects of (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), sigma (sigma) ligands, on micturition in anaesthetized rats.

The effects of two sigma (sigma) binding site ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), on bladder functions were examined in rats. Cystometry using urethane-anaesthetized rats showed that (+)-pentazocine (1 - 5 mg kg(-1), i.v.) and DTG (1 - 5 mg kg(-1), i.v.) prolonged micturition intervals, indicating increased bladder capacity and raised the threshold pressure. The effects of (+)-pentazocine (2 mg kg(-1), i.v. ) on micturition were not influenced by naloxone (0.5 mg kg(-1), i.v. ), which antagonized similar effects of morphine (2 mg kg(-1), i.v.). When administered intracerebroventricularly (i.c.v.), DTG (1 microg) and (+)-pentazocine (30 microg) prolonged micturition intervals with increased threshold pressure on the cystometrogram. In isolated bladder detrusor strips of rats, (+)-pentazocine (3 microM) and DTG (1 microM) did not affect contractile responses to electrical field stimulation. A higher concentration of DTG (3 microM) slightly suppressed the response induced by 30 Hz stimulation. The effects of (+)-pentazocine and DTG on micturition were abolished by pre-treatment with pertussis toxin (PTX, 1 microg, i.c.v.). These results indicate that typical sigma ligands, such as (+)-pentazocine and DTG, increase bladder capacity in anaesthetized rats. Moreover, the mechanism by which sigma ligands change the urinary storage properties in rats may involve pathways in which the function of Gi/o proteins is necessary.

Anesthesia↗

[The role of uninhibited bladder in antireflux surgery. Special reference to reflux recurrence and diverticulum formation].

A retrospective study on antireflux surgery for primary vesicoureteral reflux at Hokkaido University Hospital was performed. One hundred and seventy-nine patients (299 ureters) underwent antireflux surgery in these 17 years and 7 months. When the period was divided into 3, success rate was 96.5, 93.8 and 100 per cent, respectively. Overall success rate was 96.6 per cent. There was a combined failure or complication in 9 patients. The records of these 9 were reviewed in detail. Three were believed to be a technical error: 2 stricture and one persistent reflux. The remaining 6 were all children except one and had no clear reason for failure: 2 persistent reflux and 4 contralateral appearance of reflux ("missing VUR"). Four of these 6 patients were characterized by voiding dysfunction, namely uninhibited bladder. In 3 patients reflux disappeared spontaneously by administration of anticholinergic agent. In many of these, vesical diverticulum formation was also noted to precede or to coincide with recurrence or appearance of reflux. Thus other 3 patients with diverticulum formation after antireflux surgery were added and re-evaluated. All 3 children had voiding dysfunction with uninhibited bladder. Diverticulum formation was believed to be related to uninhibited bladder in at least one child. It seems that the child with uninhibited bladder and reflux is particularly at risk for failure or complication of antireflux surgery. Patients with symptoms of voiding dysfunction deserve a complete evaluation, including cystoscopy and urodynamics.

Child↗

Multiple detection system for the high-resolution microcolumn size-exclusion chromatographic separation of proteins with a slurry-packed capillary column.

A multiple (triple) detection system with one detector and recorder each was developed for the high-resolution size-exclusion chromatographic separation of proteins with a slurry packed capillary column. Fused-silica capillary columns of length 1, 2.5 and 6 m and I.D. 0.26 mm were connected in this order by joining each end of the shorter column to the top of the longer column through flow-through cells installed side-by-side on a cell block in the detector. By this means it was possible to record the chromatograms three times with one injection. This system is convenient for comparing the chromatograms obtained with different plate numbers and for effecting very high-resolution separations.

Chromatography, Gel↗

Rat insulin-like growth factor II gene. A single gene with two promoters expressing a multitranscript family.

We have characterized the single-copy rat gene encoding the protein precursor of insulin-like growth factor II (pre-pro-rIGF-II) that is located downstream from and in the same transcriptional orientation as the homologous insulin II gene (5'-insulin-IGF-II-3'). This gene consists of at least three coding exons and utilizes two promoters that generate alternate 5' non-coding exons. Multiple transcripts from both promoters appear primarily in fetal or neonatal tissues (in all of the developmental stages and tissues that we have examined), but they are extremely rare or undetectable in adult tissues, with the exception of the brain and the spinal cord. These transcripts, which exhibit characteristic developmental profiles in various tissues, differ both in the presence of one of the alternate 5' non-coding exons and in the length of their fourth exon. The possible occurrence of differential splicing or differential polyadenylation (or both) in this region is discussed.

Animals↗

Direct coupling of micro high-performance liquid chromatography with fast atom bombardment mass spectrometry. II. Application to gradient elution of bile acids.

A new system without a moving belt has been developed for direct coupling of micro high-performance liquid chromatography with fast atom (xenon or argon) bombardment mass spectrometry. The structure of the interface was basically the same as used previously, but the mass spectrometer was modified by adding both a liquid nitrogen trap between the ion source housing and the diffusion pump, and a position adjuster for the interface. Stable ionization of the solute in a glycerol matrix is achieved at flow-rates below 2 microliter/min. The system was applied to the analysis of bile acids by gradient elution chromatography. Steady baselines were observed in the mass chromatograms.

Bile Acids and Salts↗

The efficient use of microcolumns in chromatographic systems.

Microcolumn techniques involving pre-column concentration and post-column derivatization make good use of micro-scale high-performance liquid chromatography. The efficient use of microcolumns is illustrated by some applications to the analysis of amino acids, bile acids and catecholamines. The potential of new detector techniques based on the multichannel photodiode array detector, and on immobilized enzyme post-column reaction systems with fluorimetric detection, is also discussed.

Journal Article↗

[Female primary urethral tumors].

Our experience on treatment of female urethral tumors is presented. Nineteen female patients with primary urethral tumors were treated at our University Hospital during the 31 years since 1953. Ten of the patients had carcinoma (6 had squamous cell carcinoma, 2 had adenocarcinoma and 2 had transitional cell carcinoma) and the other 9 patients had benign urethral neoplasms. Although the patients with urethral carcinomas did not always undergo standardized treatment, 5 patients were treated with distal urethrectomy, 3 with urethrectomy, 1 with total cystourethrectomy and the other patient with TUR. Three patients were lost to follow up, the other females were alive, 4 months to 7 years after treatment excluding one patient who died of disseminated disease 1 year after TUR. Since primary female urethral malignancies are rare diseases, there is still controversy as to the choice of treatment for the disease because of the poor prognosis even after an operation. Our experience is not enough to conclude on the best choice of treatment, but more extensive operation including puboosteotomy is recommended in the latest literature.

Adenocarcinoma↗

Analysis of bile acids by micro high-performance liquid chromatography with postcolumn enzyme reaction and fluorometric detection.

Free and conjugated bile acids in human sera were analyzed by micro high-performance liquid chromatography with detection by an immobilized hydroxysteroid dehydrogenase postcolumn reaction and a spectrofluorometer. Bile acids could be effectively collected on a precolumn, 10 X 0.2 mm I.D., packed with silica-ODS (octadecylsilane), by passing a dilute phosphate solution of a serum through it. The detection limit was 0.13-0.28 pmole for a single-to-noise ratio of 2. An amount of 0.1 ml of serum was enough for analysing each bile acid in it.

3-Hydroxysteroid Dehydrogenases↗