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Narihiko Hayashi

Publications and source records attributed to Narihiko Hayashi.

3 recordsLinked to original sources

The effect of FK1706 on erectile function following bilateral cavernous nerve crush injury in a rat model.

PURPOSE: We investigated the neurotrophic effect of FK1706 on erectile recovery following bilateral cavernous nerve crush injury in a rat model. MATERIALS AND METHODS: A total of 28 male Sprague-Dawley rats were randomly divided into 4 equal groups. Seven animals underwent sham operation and subcutaneous vehicle injection, whereas 21 underwent bilateral cavernous nerve crush injury followed by vehicle injection alone, or by low (0.1 mg/kg) or high (1.0 mg/kg) dose FK1706 treatment. Injections were continued 5 days weekly for 8 weeks. Erectile function was then assessed by cavernous nerve electrostimulation and penile tissue was evaluated immunohistochemically. RESULTS: No erectile dysfunction was identified in the sham treated group (mean maximal intracavernous pressure +/- SEM 106.8 +/- 6.4 cm H(2)O), whereas nerve injury significantly decreased ICP to 17.9 +/- 7.0 cm H(2)O. FK1706 facilitated neural and erectile recovery in a concentration dependent manner with a mean ICP in the high dose FK treatment group of 80.1 +/- 7.8 cm H(2)O compared with 44.1 +/- 12.9 cm H(2)O in the low dose group. Similar stepwise findings were observed using mean area under the curve data. Sham treated animals showed regular axon sizes and shapes with homogenous GAP-43 and neurofilament staining, whereas injured axons showed irregular shapes, sizes and staining patterns. FK1706 treatment restored axon shape and staining patterns. Injury significantly decreased nicotinamide adenine dinucleotide phosphate staining and FK1706 treatment showed a nonsignificant trend toward increased staining. CONCLUSIONS: Bilateral cavernous nerve crush causes reproducible erectile dysfunction, consistent with prior experiments. High dose subcutaneous FK1706 therapy promotes significant neuroregeneration and erectile function recovery.

Animals↗

Improving erectile function by silencing phosphodiesterase-5.

PURPOSE: We investigated whether phosphodiesterase-5 (PDE5) can be down-regulated by a specific small interfering RNA (siRNA) and whether this would improve erectile function. MATERIALS AND METHODS: A PDE5 siRNA encoding oligonucleotide was inserted into pSUPER-retro vector, resulting in the siRNA expressing construct, pPDE5-silencer. The construct was packaged into oncoretroviral particles and then transduced into rat cavernous smooth muscle cells (CSMCs). Cells were examined for PDE5 expression by reverse transcriptase-polymerase chain reaction, Western blotting and immunofluorescence microscopy. Cells were then treated with 10 microM sodium nitroprusside (SNP) and examined for cyclic guanosine monophosphate (cGMP) at 0, 10, 30, 60 and 240 minutes. The siRNA expressing cassette was transferred from the oncoretrovirus to lentivirus, which was then injected into rat penises. Three months later erectile function was examined by electrostimulation and PDE5 expression in cavernous smooth muscle was determined by immunohistochemistry. RESULTS: CSMCs transfected with pPDE5-silencer (CSMC plus siRNA) showed an 88.2% decrease in PDE5 compared with CSMCs transfected with control vector (CSMCs plus vector). Within 10 minutes of SNP treatment cells (CSMCs, CSMCs plus vector and CSMCs plus siRNA) showed similar sharp increases in cGMP. However, while cGMP levels in CSMCs and CSMCs plus vector returned to almost baseline in 1 hour, the cGMP level in CSMCs plus siRNA remained high even 4 hours after SNP treatment. Rats injected with the siRNA expressing lentivirus showed increased electrostimulated erectile function, as measured by peak intracorporeal pressure and the intracorporeal pressure increase, compared with rats injected with control lentivirus. PDE5 expression was decreased in the siRNA treated cavernous smooth muscle. CONCLUSIONS: PDE5 expression could be decreased by siRNA, resulting in prolonged cGMP accumulation and improved erection.

3',5'-Cyclic-GMP Phosphodiesterases↗

[Clinical study of unilateral intravaginal testicular torsion and anatomicalcomparative study of bilateral testes in orchiopexy].

Fourty-eight patients were operated on for unilateral intravaginal testicular torsion at Yokohama Red Cross Hospital during the period between July 1976 and December 2001. Orchiopexy was carried out on 20 out of 48 patients. Only 8 patients could receive orchiopexy within 8 hours after the onset of symptoms. Although, 24 of the 48 patients had visited a medical doctor within 8 hours after the onset. Therefore, the less the testes might be sacrificed if these patients could be immediately sent to a clinic with an urologic speciality. The contralateral uninvolved testis has been said to require orchiopexy because it has an anatomical structure similar to the testis with torsion. However, the contralateral testes in 5 out of 20 patients with ipsilateral orchiopexy turned out to have a normal anatomical structure according to our classification of intravaginal testicular torsion. This suggests that no orchiopexy is necessary if the contralateral uninvolved testis has a normal anatomical structure from the standpoint of torsion type.

Adult↗