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Biomedical subjects

T Sakurada

Publications and source records attributed to T Sakurada.

At least 55 records · Page 3Linked to original sources
PubMed1999

Contribution of spinal mu1-opioid receptors to morphine-induced antinociception.

To determine the role of mu-opioid receptor subtypes, mu1 and mu2, in antinociception induced by intrathecal (i.t.) or intracerebroventricular (i.c.v.) injection of morphine, we assessed the effect of naloxonazine, a selective antagonist at mu1-opioid receptors. The antinociceptive effects of morphine were measured using four different nociceptive tests. The selective mu1 antagonist, naloxonazine (35 mg/kg, s.c.), 24 h before testing antagonized the antinociceptive effect of morphine on responses to chemical and thermal stimuli to a greater extent than that on responses to mechanical stimuli, as judged from ED50 values. The present results suggest that the antinociceptive activity of both i.t. and i.c.v. morphine on responses to chemical and thermal stimuli may be mediated through the mu1-opioid receptor subtype (naloxonazine-sensitive sites). These findings may be interpreted as indicative of the existence of mu1-receptor subtypes capable of mediating antinociception not only in supraspinal sites but also in spinal sites.

Analgesics↗
PubMed1999

Spinal actions of GR73632, a novel tachykinin NK1 receptor agonist.

Behavioral characterization of GR73632, a newly synthesized tachykinin NK1 receptor agonist, was examined in mice. Intrathecal (IT) injection of GR73632 in the spinal subarachnoid space of mice elicited a dose-dependent behavioral syndrome, consisting of scratching, biting and licking. The time course of the response to GR73632 was almost similar to that of substance P. GR73632 evoked much more licking and biting than did substance P, that in turn caused less scratching. GR73632 was approximately 200-fold more potent than substance P in inducing the characteristic behavioral response. The GR73632-induced behavioral response was inhibited by IT co-administration of CP-96,345, a non-peptide NK1 receptor antagonist, but not its inactive enantiomer CP-96,344. CP-96,345, co-injected IT with substance P, also inhibited the behavioral response to substance P. These results demonstrate that the scratching, biting and licking response induced by IT GR73632 may be mediated by the NK1 receptor in the spinal cord. These findings suggest that GR73632 may be useful as a tachykinin NK1 receptor agonist and also for evaluating spinal pharmacological activities of NK1 receptor antagonists.

Animals↗
PubMed1999

Major metabolites of substance P degraded by spinal synaptic membranes antagonize the behavioral response to substance P in rats.

Substance P (SP) was degraded by synaptic membranes of rat spinal cord. Cleavage products were separated by reversed phase high performance liquid chromatography and identified by amino acid composition analyses. Major products of SP were phenylalanine, SP(1-4), SP(1-6), SP(1-7), SP(10-11), and SP(8-9). Both the degradation of SP and the accumulation of the major cleavage products were strongly inhibited by a metal chelator, o-phenanthroline, and also by specific inhibitors of endopeptidase-24.11, thiorphan, and phosphoramidon. Thus, endopeptidase-24.11 plays a major role in SP degradation in the rat spinal cord. N-Terminal fragments, SP(1-7) and SP(1-4), detected after incubation with spinal synaptic membranes were examined in vivo for antagonism against the scratching, biting, and licking response induced by intrathecal (IT) injection of SP (3.0 nmol) in rats. When IT coadministered with SP, SP(1-7) and SP(1-4) produced a significant inhibition of behavioral response to SP with ED50 of 135.0 pmol and 6.2 nmol, respectively. These results suggest that the degradation of SP in the spinal cord is not only responsible for inactivation of parent peptide, but may also lead to the formation of N-terminal SP-fragments which are shown to display a novel physiological function.

Animals↗
PubMed1999

Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK1 receptors.

1. Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P-containing neurons by using i.t. injection of tachykinin neurokinin (NK)1 receptor antagonists and substance P (SP) antiserum. 2. Nociceptin-induced behavioural response was evoked significantly 5 - 10 min after i.t. injection and reached a maximum at 10 - 15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 0.375 - 30.0 fmol, and the maximum effect was observed at 3.0 fmol. 3. The behavioural response elicited by nociceptin (3.0 fmol) was dose-dependently inhibited by intraperitoneal (i.p.) administration of morphine. 4. The NK1 receptor antagonists, CP-96,345, CP-99,994 and sendide, inhibited nociceptin-induced behavioural response in a dose-dependent manner. A significant antagonistic effect of [D-Phe7, D-His9]SP (6 - 11), a selective antagonist for SP receptors, was observed against nociceptin-induced response. The NK2 receptor antagonist, MEN-10376, had no effect on the response elicited by nociceptin. 5. Pretreatment with SP antiserum resulted in a significant reduction of the response to nociceptin. No significant reduction of nociceptin-induced response was detected in mice pretreated with NKA antiserum. 6. The N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK-801) and D(-)-2-amino-5-phosphonovaleric acid (APV) (D-APV), and L-NG-nitro arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, failed to inhibit nociceptin-induced behavioural response. 7. off present results suggest that SP-containing neurons in the mouse spinal cord may be involved in elicitation of scratching, biting and licking behaviour following i.t. injection of nociceptin.

Aggression↗
PubMed1999

Nociceptin (1 - 7) antagonizes nociceptin-induced hyperalgesia in mice.

Nociceptin and its N-terminal fragment, nociceptin (1 7), were administered intrathecally (i.t.) into conscious mice. Nociceptin (3.0 fmol) produced a significant reduction in the nociceptive thermal threshold (hyperalgesia) measured as the tail-flick and paw-withdrawal responses. Nociceptin (1-7), injected i.t., at 150-1200 fmol had no significant effect. However, when nociceptin (1-7) (150 1200 fmol) was injected simultaneously with nociceptin (3.0 fmol), nociceptin-induced hyperalgesia was significantly reduced. Analgesia induced by a high dose (1200 pmol) of nociceptin was not antagonized by co-administration of nociceptin (1-7) (1200 fmol). These results suggest that N-terminal fragments of nociceptin formed endogenously could modulate the hyperalgesic action of nociceptin in the spinal cord.

Amino Acid Sequence↗
PubMed1999

Ruptured distal aortic arch aneurysm associated with arteriosclerosis obliterans.

A 73-year-old man with a ruptured distal aortic arch aneurysm into the pericardial space, mediastinum and right pleural space is described. The patient underwent a successful total aortic arch replacement using deep hypothermia, systemic circulatory arrest and selective cerebral perfusion. Extracorporeal circulation was established with right axillar arterial perfusion due to arteriosclerosis obliterans (ASO). Presentation and management are discussed.

Aged↗
PubMed1999

[Axillary artery perfusion for the extensive arterial vascular disease].

Usefulness of axillar artery perfusion for the cases with severe systematic atherosclerosis was reported. It is generally accepted that the femoral artery is a common arterial cannulation site when performing the surgery of ascending aorta and total aortic arch. However, atheroembolism is one of the most severe complication for the patients with extensive arterial vascular disease by using femoral arterial perfusion. Axillar artery perfusion can prevent these complications, and the perfusion through the artificial graft anastomosed to the axillar artery can also avoid the malperfusion of the vertebral artery and axillar artery. We concluded that the axillar artery perfusion via artificial graft is useful alternative for aortic surgery.

Aged↗
PubMed1999

[Mitral valve annuloplasty with U-shaped flexible band using Duran ring].

To preserve the physiologic function and correct annular dilatation, U-shaped flexible band was applied for mitral valve annuloplasty in 6 cases. U-shaped flexible band was made by cutting Duran ring to the proper length of posterior annulus using Carpentier-Edwards ring sizer. Echocardiographic mitral regurgitation decreased from 3.8 +/- 0.4 to 0.7 +/- 0.5 after repair. All patients discharged without any complications. This annuloplasty method is effective for mitral insufficiency.

Aged↗
PubMed1999

Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord.

We previously reported that the intraplantar (i.pl.) application of nociceptin/orphanin FQ (N/OFQ) at extremely low doses elicited a nociception through a substance P (SP) release from nociceptor endings. In the present study, the nociception induced by SP (and N/OFQ) was abolished by intrathecal (i.t.) injection of neurokinin(1) (SP receptor) antagonist, suggesting the involvement of the stimulation of nociceptive primary SP neuron and SP release into spinal synapses. On the other hand, similar low doses of N/OFQ (i.t.) exerted nociceptive responses, characterized by scratching, biting, and licking, and these responses were blocked by an neurokinin(1) antagonist (i.t.) or capsaicin pretreatment or in tachykinin 1 gene knockout mice (tac1(-/-) mice), suggesting that N/OFQ receptor (NOR) also exists on the spinal terminals of SP neurons. When wide ranges of N/OFQ doses were used, a typical bell-shaped dose-response relationship was observed in both peripheral and central nociception tests. Furthermore, N/OFQ (1 nmol) administered i.pl. blocked SP (i.pl.)-induced flexor responses, which were abolished by pertussis toxin pretreatment or in NOR gene knockout (NOR(-/-)) mice. On the other hand, N/OFQ administered i.t. blocked SP (i.t.)-induced scratching, biting, and licking in capsaicin-pretreated and tac1(-/-) mice, and this antinociception was abolished in NOR(-/-) mice. All these findings suggest that N/OFQ has biphasic actions depending on doses in the nociceptors and spinal synapses and has postsynaptic antinociceptive actions in spinal cord by modulating SP signaling.

Analgesics↗
PubMed1999

[Graft replacement from ascending aorta to descending aorta with endovascular stent graft under median sternotomy].

We reported a 62-year-old man with DeBakey IIIa dissecting aortic aneurysm involving distal aortic arch who underwent graft replacement from ascending to descending aorta using a endovascular stent graft. Median sternotomy was carried out, because of severe pleural adhesion. Endovascular stent graft composed of 30 mm Gianturco Z stent and 24 mm woven Dacron graft was inserted to descending aorta with the aid of hypothermia, systemic circulation arrest and selective cerebral perfusion. Transesophageal echocardiography was used to measure the diameter and the length of descending aorta and the graft. And ascending and total aortic arch replacement was performed with four branched woven Dacron graft. Postoperative chest CT and aortography showed satisfactory reconstruction with the thrombosed false lumens. We think placement of stent graft to descending aorta through median sternotomy is useful method when left thoracotomy is impossible or distal anastomotic site is too far for the anastomosis.

Aortic Dissection↗
PubMed1998

Antiemetic effects of sendide, a peptide tachykinin NK1 receptor antagonist, in the ferret.

The antiemetic activity of sendide, a new peptide tachykinin NK1 receptor antagonist, against cisplatin-induced emesis was investigated using ferrets. The frequency of cisplatin (10 mg/kg, i.p.)-induced retching (104.6 +/- 14.3/6 h) and vomiting (19.0 +/- 3.0/6 h) was significantly reduced by pretreatment with sendide (3.0 mg/kg, s.c.) (14.0 +/- 8.1/6 h and 1.8 +/- 1.2/6 h, respectively). Intravenous bolus injection of substance P (1-10 microg/kg) or 5-hydroxytryptamine (5-HT) (10-50 microg/kg) produced a dose-dependent increase in the abdominal afferent vagus nerve activity. The change from pre-injection level in the afferent nerve activity induced by substance P (1 microg/kg, i.v.) (453.7 +/- 51.5%) was significantly reduced by pretreatment with either sendide (100 microg/kg, i.v.) (276.1 +/- 50.1%, P < 0.05) or granisetron, a 5-HT3 receptor antagonist (1 mg/kg, i.v.) (146.3 +/- 14.0%, P < 0.01). The amount of 5-HT released into the solution during a 1-h exposure to 2-methyl-5-HT (10(-6) M), a 5-HT3 receptor agonist, was significantly increased (317.9 +/- 46.7%, P < 0.05) compared with that of the control tissues (160.4 +/- 8.1%). The 2-methyl-5-HT-induced 5-HT release was significantly inhibited by administration of sendide (10(-6) M) (174.0 +/- 21.6%, P < 0.05) or granisetron (10(-6) M) (186.6 +/- 27.3%, P < 0.05). Since sendide does not penetrate the central nervous system, these results suggest that the antiemetic effects of sendide are due to the inhibition of NK1 and 5-HT3 receptors on the emetic peripheral detector sites.

Animals↗
PubMed1998

Stereoselective blood-brain barrier transport of histidine in rats.

The transport characteristics of l- and d-histidine through the blood-brain barrier (BBB) were studied using cultured rat brain microvascular endothelial cells (BMEC). l-Histidine uptake was a saturable process. A decrease in incubation temperature from 37 to 0 degreesC or the addition of metabolic inhibitors (DNP and rotenone) reduced the uptake rate of l-histidine. Ouabain, an inhibitor of (Na+, K+)-ATPase, also reduced uptake of l-histidine. Moreover, the substitution of Na+ with choline chloride and choline bicarbonate in the incubation buffer decreased the initial l- and d-histidine uptake rates. These results suggested that l-histidine is actively uptaken by a carrier-mediated mechanism into the BMEC, with energy supplied by Na+. However, l-histidine uptake at 0 degreesC was not completely inhibited, and it was reduced in the presence of an Na+-independent System-L substrate, BCH, suggesting facilitated diffusion (the Na+-independent process) by a carrier-mediated mechanism into the BMEC. l-histidine uptake in rat BMEC also appeared to be System-N mediated since uptake was inhibited by glutamine, aspargine and l-glutamic acid gamma-monohydroxamate. System-N mediated transport was not pH sensitive. d-histidine transport was also studied in rat BMEC. d-histidine transport by rat BMEC has similar characteristics to l-histidine. However, System-N transport did not play a role in d-histidine uptake. The uptake of l-histidine was also greater than that of the d-isomer, indicating the stereoselective uptake of histidine in rat BMEC.

Animals↗
PubMed1998

[A case of Stanford type A acute aortic dissection associated with a distal aortic arch atherosclerotic aneurysm].

We report a rare case of Stanford type A acute aortic dissection associated with a distal aortic arch atherosclerotic aneurysm. A 71-year-old female was referred to us with the diagnosis of thrombosed Stanford type A acute aortic dissection, however on the next day transesophageal echocardiography revealed the false lumen has been recanalized. In the operation, there was a distal aortic arch atherosclerotic aneurysm which was unidentified at the preoperation. It is very rare that the dissection originated from atherosclerotic aneurysm and proceeded to proximal and distal portion of the aorta.

Acute Disease↗
PubMed1998

Venous aneurysm of the cephalic vein: report of a case.

We herein report the rare case of a 41-year-old Japanese woman in whom a venous aneurysm in the left cephalic vein was excised under local anesthesia. Histological examination revealed significant diminution in the number and size of muscle and elastic fibers in the aneurysm wall. Conceivably, a combination of endophlebohypertrophy and a congenital focal defect of the elastic and muscle fibers might have contributed to the development of this venous aneurysm.

Adult↗
PubMed1998

Involvement of spinal NMDA receptors in capsaicin-induced nociception.

Intraplantar injection of capsaicin into the mouse hindpaw produced an acute nociceptive response. The involvement of N-methyl-D-aspartate (NMDA) receptors was examined by intrathecal administration of various excitatory amino acid (EAA) receptor antagonists. The selective and competitive NMDA receptor antagonists, D(-)-2-amino-5-phosphono-valeric acid (APV) and (+/-)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphoric acid (CPP), were most potent in inhibiting the nociceptive response induced by capsaicin (ED50, 0.23 nmol and 0.12 nmol). The noncompetitive NMDA receptor antagonist dizocilpine (MK-801) and the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) had similar effects on the capsaicin-induced nociception (ED50, 2.90 and 7.98 nmol), while ketamine and 7-chlorokynurenic acid were without effect. Ifenprodil, an antagonist at the receptor-coupled polyamine site, showed a significant reduction of the nociceptive response (ED50, 13.8 nmol). The inhibitory effects of APV, CPP, MK-801, and ifenprodil were reversed by co-administration of NMDA. Coadministration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) or kainate resulted in a marked reduction of CNQX-induced antinociception. The present results suggest that the NMDA receptor plays a key role in spinal nociceptive processing as measured by the capsaicin test in mice. This nociceptive test may be useful for evaluating competitive NMDA antagonists.

Animals↗
PubMed1998

Intrathecal administration of p-hydroxymercuribenzoate or phosphoramidon/bestatin-combined induces antinociceptive effects through different opioid mechanisms.

The antinociceptive effect of intrathecally (i.t.) administered protease inhibitors was tested against capsaicin (800 ng) injected into the dorsal surface of a hindpaw. Both p-hydroxymercuribenzoate (2-8 nmol), a cysteine protease inhibitor, and phosphoramidon (1-4 nmol), an endopeptidase 24.11 inhibitor in the presence of bestatin (0.25 nmol) an aminopeptidase inhibitor, administered i.t. 60 min prior to the injection of capsaicin produced a dose-dependent reduction of the capsaicin-induced paw licking and biting response. p-Hydroxymercuribenzoate (4 nmol)-induced antinociception was significantly antagonized by nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by naltrindole, a selective delta-opioid receptor antagonist. On the other hand, phosphoramidon (4 nmol) /bestatin-induced antinociception was significantly antagonized by naltrindole, but not by nor-binaltorphimine. The results indicate that the antinociceptive effect of p-hydroxymercuribenzoate may be due to the inhibition of a cysteine protease degrading endogenous dynorphins whereas phosphoramidon in the presence of bestatin blocks the degradation of enkephalins.

Animals↗
PubMed1998

A case of episodic angioedema associated with blood eosinophilia: upregulated C5a receptor expression on eosinophils.

A 47-year-old woman was admitted to hospital complaining of swelling and pain of the extremities, accompanied by high fever and generalized erythema. Laboratory examination showed marked blood eosinophilia with elevation of IgM, IgE, and C-reactive protein. All autoantibodies examined were negative. The heart and lungs showed no untoward findings. Biopsies of the skin and muscle revealed cellular infiltration of eosinophils around small blood vessels. Quantitation of C5a receptor (C5aR) expression by flow cytometry using anti-C5aR antibody showed upregulated expression of C5aR on blood eosinophils but downregulated expression on neutrophils. The abnormal C5aR expression on eosinophils and neutrophils became normal after spontaneous resolution of symptoms and blood eosinophilia. The possibility that C5aR expression on granulocytes is related to the pathogenesis of this syndrome may be considered.

Angioedema↗