Tomoyuki Ueda

Allergy to laboratory animals: an epidemiological study

A large cross sectional survey was carried out using a self administered questionnaire to examine the prevalence of laboratory animal allergy (LAA) and the factors associated with its development. Out of 5641 workers who were exposed to animals at 137 laboratory animal facilities in Japan, 23.1% had one or more allergic symptoms related to laboratory animals. The commonest symptom as rhinitis. About 70% of LAA subjects developed symptoms during their first three years of exposure. Atopy (past and family history), the number of animal species handled, and the time spent in handling correlated significantly with the development of LAA as did some types of job. A close relation between nasal symptoms and exposure to rabbits and between skin symptoms and exposure to rats were found. LAA subjects developed symptoms most quickly to rabbits.

Effect of naftopidil, an alpha1D/A-adrenoceptor antagonist, on the urinary bladder in rats with spinal cord injury.

AIMS Alpha1D-adrenoceptors (α1D-ARs) located in the spinal cord are involved in the control of lower urinary tract function. In order to clarify the effect of α1D-ARs on storage function in the spinal cord, we examined the effect of oral administration and intrathecal injection of the α1D/A-AR antagonist, naftopidil, on bladder activity, as well as the effect of naftopidil on bladder wall histology, in female rats with spinal cord injury (SCI). MAIN METHODS Adult female Sprague-Dawley rats with Th9-10 spinal cord transection were used. In SCI rats with or without 5mg/day of naftopidil for 4weeks, bladder activity was examined via continuous cystometry. In other SCI rats, bladder activity was examined before and after intrathecal injection of naftopidil. In addition, bladder wall histology was compared between SCI rats with or without oral administration of naftopidil for 4weeks. KEY FINDINGS Oral administration of naftopidil decreased the number of non-voiding contractions (NVCs). Intrathecal injection of naftopidil prolonged the interval between voiding contractions, decreased the maximum voiding contraction pressure and the number of NVCs, and increased bladder capacity without affecting the residual urine volume. Oral administration of naftopidil also decreased bladder wall fibrosis. SIGNIFICANCE The α1D/A-AR antagonist naftopidil might act on the bladder and spinal cord to improve detrusor hyperreflexia in the storage state in SCI female rats. Naftopidil also suppressed bladder wall fibrosis, suggesting that it may be effective for the treatment of neurogenic lower urinary tract dysfunction after SCI.

Spinal mechanism of micturition reflex inhibition by naftopidil in rats

AIM We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. METHODS The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. KEY FINDINGS Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01-1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. SIGNIFICANCE Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system.

High-dose tranilast administration to rats creates interstitial cystitis-like symptoms with increased vascular permeability.

AIM We investigated whether the high-dose administration of tranilast could be used to create an animal model of interstitial cystitis (IC). Then, we used this model to assess the relationship between IC and changes in the vascular permeability of the bladder. MAIN METHODS Female rats were divided into the following 4 groups: a control group, a tranilast group, a carbazochrome group and a combination (tranilast+carbazochrome) group. Continuous cystometry, bladder distension, and the Evans blue dye extravasation test were performed 4weeks after drug administration. Locomotor activity, the plasma TGF-β1 level, and collagen fibers in the bladder wall were also examined in the control and tranilast groups. KEY FINDINGS The interval between bladder contractions was shorter and the leakage of Evans blue dye into the bladder wall was greater in the tranilast group than in the control group. Glomerulations of the bladder wall after bladder distention and thinning of the collagen fiber layer in the bladder were observed in the tranilast group. Locomotor activity in darkness and the plasma TGF-β1 level were both lower in the tranilast group than in the control group. In the combination group, the leakage of Evans blue dye was greater than in the control group; however, it was less prominent than in the tranilast group. SIGNIFICANCE These results suggest that high-dose administration of tranilast to rats can create an IC-like rat model and that an increase in the vascular permeability of the bladder wall may be one cause of IC symptoms.

Propiverine increases urethral wall catecholamine levels and bladder leak point pressure in rats

To investigate whether propiverine has a noradrenaline re‐uptake inhibitor and whether it acts on the lumbosacral cord or the urethral wall. In addition, we aimed to examine the effect of propiverine on leak point pressure in rats.

Effects of silodosin on bladder activity in rats with frequent urination induced by pelvic venous congestion

To examine the effects of silodosin on bladder activity using female rats with frequent urination induced by pelvic venous congestion.

Pelvic venous congestion with castration causes chronic prostatitis in rats

To determine whether castration combined with pelvic congestion could cause chronic prostatitis, and to examine the effect of eviprostat in this rat model.

Action of naftopidil on spinal serotonergic neurotransmission for inhibition of the micturition reflex in rats

We examined the mechanism of action of naftopidil, an α1D/A blocker, on spinal descending serotonergic neurotransmission for the micturition reflex.

Naftopidil Improves Symptoms in a Rat Model of Tranilast‐Induced Interstitial Cystitis

The effect of naftopidil on symptoms of tranilast‐induced interstitial cystitis (IC) was examined in rats.

Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous congestion

The α1D/A receptor antagonist, naftopidil, inhibits micturition reflex by acting on various different sites. We examined the effects of naftopidil on bladder activity and changes in the induced urinary frequency using female rats with pelvic venous congestion (PC). Twenty-four female rats were divided into sham, PC, and PC/naftopidil groups. After anesthetizing rats in the PC and PC/naftopidil groups, the bilateral common iliac veins and uterine veins were ligated. Rats in the sham and PC groups were fed a standard diet, while rats in the PC/naftopidil group were fed diets containing 0.04% naftopidil. After 4 weeks of treatment, locomotor activity, urinary nitric oxide metabolites (NOx), continuous cystometry, and plasma monoamine measurements were performed. PC rats exhibited a decrease of locomotor activity, a shorter interval between bladder contractions on continuous cystometry, and decreased urinary NOx and plasma serotonin levels than the sham rats. The PC/naftopidil rats exhibited an increase of locomotor activity, a longer interval between bladder contractions, and increased urinary NOx and plasma serotonin levels. Therefore, naftopidil might improve bladder dysfunction induced by pelvic venous congestion due to several actions in the central nervous system and bladder tissue, as well as acting as an α1 blocker to cause pelvic venous dilation.