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Biomedical subjects

Takafumi Hayashi

Publications and source records attributed to Takafumi Hayashi.

At least 19 recordsLinked to original sources

Possible involvement of dynorphin A-(1-17) release via mu1-opioid receptors in spinal antinociception by endomorphin-2.

The antinociception induced by i.t. or i.c.v. administration of endomorphins is mediated via mu-opioid receptors. However, although endomorphins do not have an appreciable affinity for kappa-opioid receptors, pretreatment with the kappa-opioid receptor antagonist norbinaltorphimine markedly reduces the antinociceptive response to i.c.v. or i.t. administered endomorphin-2 but not endomorphin-1. These results suggest that endomorphin-2 initially stimulates mu-opioid receptors, which subsequently induce the release of dynorphins that act on kappa-opioid receptors to produce antinociception. The present study was performed in mice to determine whether the release of dynorphins by i.t. administered endomorphin-2 is mediated through mu-opioid receptors to produce antinociception. Intrathecal pretreatment with an antiserum against dynorphin A-(1-17), but not against dynorphin B-(1-13) or alpha-neoendorphin, dose-dependently prevented the paw-withdrawal inhibition by endomorphin-2. The pretreatments with these antisera did not affect the endomorphin-1- or [D-Ala(2),MePhe(4),Gly(ol)(5)]enkephalin-induced paw-withdrawal inhibition. The attenuation of endomorphin-2-induced antinociception by i.t. pretreatment with an antiserum against dynorphin A-(1-17) or s.c. pretreatment with norbinaltorphimine was blocked dose-dependently by s.c. pretreatment with the mu-opioid receptor antagonist beta-funaltrexamine or the mu(1)-opioid receptor antagonist naloxonazine at ultra-low doses that are ineffective against mu-opioid receptor agonists. These results suggest that the spinal antinociception induced by endomorphin-2 is mediated through the stimulation of a distinct subtype of mu(1)-opioid receptor that induces the release of the endogenous kappa-opioid peptide dynorphin A-(1-17) in the spinal cord.

Analgesics, Opioid↗

Differential inhibitory effects of mu-opioids on substance P- and capsaicin-induced nociceptive behavior in mice.

The antinociceptive mechanisms of the selective mu-opioid receptor agonists [D-Ala2,NMePhe4,Gly(ol)5]enkephalin (DAMGO), H-Tyr-D-Arg-Phe-beta-Ala-OH (TAPA) or H-Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA-NH2) against substance P (SP)- or capsaicin-elicited nociceptive behaviors was investigated in mice. DAMGO, TAPA or TAPA-NH2 given intrathecally inhibited the nociceptive behaviors elicited by intrathecally administered SP or capsaicin, and these antinociceptive effects were completely eliminated by intrathecal co-administration with D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective mu-opioid receptor antagonist. Pretreatment subcutaneously with naloxonazine, a selective mu1-opioid receptor antagonist, partially attenuated the antinociceptive effect of TAPA-NH2, but not DAMGO and TAPA, against SP. However, the antinociception induced by TAPA, but not DAMGO and TAPA-NH2, against capsaicin was significantly inhibited by naloxonazine. On the other hand, co-administration intrathecally with Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), a selective mu2-opioid receptor antagonist, significantly attenuated the antinociceptive effects of DAMGO, but not TAPA and TAPA-NH2, against capsaicin, while the antinociceptions induced by three opioid peptides against SP were significantly inhibited by D-Pro2-Tyr-W-MIF-1. These results suggest that differential inhibitory mechanisms on pre- and postsynaptic sites in the spinal cord contribute to the antinociceptive effects of the three mu-opioid peptides.

Analgesics, Opioid↗

Double contours and craniofacial morphology.

This study was done to try to clarify the relationship between double contours and craniofacial morphology. The study sample included 56 pre-orthodontic patients with signs and symptoms of temporomandibular joint (TMJ) disorders. A comparison of craniofacial structures was done on 32 subjects with bilateral condylar bone change (BBC group: 28 female and 4 male) and 24 subjects with no condylar bone change (NBC group: 21 female and 3 male). The BBC showed significantly greater antegonial and ramus notch depths, as well as significantly more retruded mandibles, shorter ramus heights, and larger mandibular plane angles than the NBC. BBC subjects with bilateral double contours showed significantly more retruded mandibles, larger antegonial notch depth, and shorter lengths from the Sella to the Articulare than BBC subjects with no double contours. The study showed that important relationships exist between the presence of double contours and mandibular morphology and TMJ position.

Adolescent↗

Condylar bone change and sagittal incisal and condylar paths during mandibular protrusive excursion.

This study showed significant differences in sagittal condylar and incisal path angles during mandibular protrusive excursion, as well as flattening of the condylar path related to the existence and type of condylar bone change. Twenty-eight (28) patients with signs and symptoms of TMJ disorders were studied, using a six-degrees-of-freedom measuring device and helical CT. Sagittal incisal and condylar path angles at two mm and three mm condylar path lengths (CPL) were significantly shorter in the bilateral condylar bone change (BBC), compared to the no bone change (NBC) group. Also, NBC incremental sagittal condylar path angles from three to five mm CPL and NBC condylar path curvature at five mm CPL were both significantly larger than in BBC. Comparing types of bone change, incremental sagittal condylar path angles from three to five mm CPL was significantly less in osteophyte than in NBC or erosion groups. Condylar path curvature at five mm CPL was also significantly less in osteophyte than in NBC.

Dental Occlusion↗

Craniofacial morphology and inclination of the posterior slope of the articular eminence in female patients with and without condylar bone change.

This study investigated the association of craniofacial and glenoid fossa shapes and temporomandibular joint (TMJ) pathology in 39 orthodontic patients with signs and symptoms of TMJ disorders, using helical CT scans. Cephalometric measurements showed that 21 subjects with bilateral condylar bone change (BBC) had significantly smaller SNB angles, ramus heights and S-Ar/N-Ba ratios, as well as larger mandibular plane angles and lower anterior facial height than the 18 subjects with no condylar bone change (NBC). The average posterior slope of the left and right articular eminence in their central and lateral sections was significantly steeper in NBC than in BBC. Condylar bone change might, therefore, not only be related to the morphology of the mandible, but also of the glenoid fossa and cranial base. This appears to reflect adaptive changes in the condyle, articular eminence and cranial base in response to changes in loading.

Adolescent↗

Differential involvement of mu 1-opioid receptors in dermorphin tetrapeptide analogues-induced antinociception.

The involvement of putative mu(1)-opioid receptors in the antinociception induced by the dermorphin tetrapeptide analogues Try-D-Arg-Phe-beta-Ala (TAPA) and Tyr-D-Arg-Phe-beta-Ala-NH(2) (TAPA-NH(2)) was determined in mice, using a tail-pressure test and a formalin test. TAPA and TAPA-NH(2) injected i.c.v. and i.t. produced dose-dependent antinociception in both assays. In the tail-pressure test, the antinociception induced by i.c.v. or i.t. injected TAPA, but not TAPA-NH(2), was significantly attenuated by pretreatment with naloxonazine, a selective antagonist for putative mu(1)-opioid receptors. Moreover, naloxonazine also significantly attenuated the antinociception induced by i.c.v. injected TAPA, but not TAPA-NH(2), in the formalin test. In contrast, the antinociception induced by both TAPA and TAPA-NH(2) given i.t. was significantly attenuated by pretreatment with naloxonazine in the formalin test. The present results suggest that TAPA and TAPA-NH(2) should be considered selective agonists for putative mu(1)- and mu(2)-opioid receptors, respectively. The C-terminal amidation of TAPA-NH(2) may be critical for distinguishing between putative mu(1)- and mu(2)-opioid receptors.

Analgesics↗

The relationship between morphological changes of the condyle and condylar position in the glenoid fossa.

AIMS: To investigate whether condylar morphological changes influence the condyle position in the glenoid fossa as well as the amount of condylar movement from the intercuspal position (IP) to the reference position (RP). METHODS: Helical computed tomography was used for precise measurement of the joint spaces at IP and RP in 22 subjects (mean age 22.7 years). Subjects were divided into 2 groups, those without condylar bone changes (n = 11) and those with condylar bone changes (n = 11). The latter group was further subdivided into a flattening subgroup and an osteophyte subgroup, according to the type of condylar bone change. RESULTS: There were no significant differences in the width of the anterosuperior or posterosuperior joint spaces at IP between either the 2 groups or the 2 subgroups. On the other hand, during condylar movement from IP to RP, the condyles moved significantly more superiorly and posterosuperiorly in the bone-change group than in the no-bone-change group. There was also greater absolute horizontal condylar movement between IP and RP in the bone-change group. In addition, within the bone-change group, the type of condylar bone change influenced the amount of condylar movement. Joints with osteophyte formation showed the most superior, posterosuperior, and absolute horizontal movement from IP to RP. CONCLUSION: The findings that condyles of the bone-change group, especially those with osteophyte formation, were located significantly more anteroinferiorly in the glenoid fossa at IP than RP than the condyles of the no-bone-change group suggest that condylar IP-RP positional changes might be related to condylar shape alteration.

Adult↗

Degradation of endomorphin-2 at the supraspinal level in mice is initiated by dipeptidyl peptidase IV: an in vitro and in vivo study.

Endomorphin-2 (Tyr-Pro-Phe-PheNH(2)) was discovered as an endogenous ligand for the mu-opioid receptor. The physiological function of endomorphin-2 as a neurotransmitter or neuromodulator may cease through the rapid enzymatic process in the synapse of brain, as for other neuropeptides. The present study was conducted to examine the metabolism of endomorphin-2 by synaptic membranes prepared from mouse brain. Major metabolites were free tyrosine, free phenylalanine, Tyr-Pro and PheNH(2). Both the degradation of endomorphin-2 and the accumulation of major metabolites were inhibited by specific inhibitors of dipeptidyl peptidase IV, such as diprotin A and B. On the other hand, the accumulation of Phe-PheNH(2) and Pro-Phe-PheNH(2) was increased in the presence of bestatin, an aminopeptidase inhibitor, whereas that of free phenylalanine and PheNH(2) was decreased. Furthermore, purified dipeptidyl peptidase IV hydrolyzed endomorphin-2 at the cleavage site, Pro(2)-Phe(3) bond. Thus, degradation of endomorphin-2 by brain synaptic membranes seems to take place mainly through the cleavage of Pro(2)-Phe(3) bond by dipeptidyl peptidase IV, followed by release of free phenylalanine and PheNH(2) from the liberated fragment, Phe-PheNH(2) by aminopeptidase. We have also examined that the effect of diprotin A on the antinociception induced by intracerebroventricularly administered endomorphin-2 in the mouse paw withdrawal test. Diprotin A simultaneously injected with endomorphin-2 enhanced endomorphin-2-induced antinociception. These results indicate that dipeptidyl peptidase IV may be an important peptidase responsible for terminating endomorphin-2-induced antinociception at the supraspinal level in mice.

Aminopeptidases↗

The clinical significance of follow-up sonography in the detection of cervical lymph node metastases in patients with stage I or II squamous cell carcinoma of the tongue.

OBJECTIVE: We sought to assess the reliability of repeated sonography in the detection of cervical lymph node metastases at the earliest stage during a follow-up period in patients with stage I or stage II carcinoma of the tongue. STUDY DESIGN: Eighteen consecutive patients with stage I or II squamous cell carcinoma of the tongue were included. When possible, every patient was examined with sonography approximately every 2 weeks during the follow-up period. RESULTS: With repeated sonography on 18 patients, 7 metastatic nodes of 7 patients (39%) meeting our criteria were found. With the use of computed tomography, we diagnosed 10 nodes (including the 7 nodes observed with sonography) in these 7 patients as metastatic. A histopathologic examination revealed that 12 nodes in the same 7 patients had metastatic foci. For sonography, the sensitivity per node was 58%, whereas that of computed tomography was 83%. CONCLUSIONS: Follow-up sonography enabled the detection of all patients who had subsequent subclinical lymph node metastases. However, the sensitivity of sonography in the detection of smaller metastatic nodes was lower than that of computed tomography.

Aged↗

Maxillary odontogenic keratocyst with respiratory epithelium: a case report.

We report a case of odontogenic keratocyst with a respiratory epithelial lining and a malformed impacted tooth in the maxilla of a 39-year-old Japanese female who suffered from swelling symptoms for half a year. CT examinations revealed an air-filled cystic lesion with an impacted tooth crown in the maxillary bone which expanded to the nasal cavity as well as to the maxillary sinus. Histopathologically, the surgically removed cyst wall consisted of fibrous granulation tissue with a lining of parakeratinized squamous epithelium as well as ciliated pseudostratified epithelium and with retention of desquamated keratin materials in the lumen. The impacted tooth was malformed lacking a root portion. We discuss the frequency of respiratory epithelium in odontogenic keratocysts.

Adult↗

The relationship between retruded contact position and intercuspal position in patients with TMJ osteoarthritis.

This study was conducted to investigate the relationship between posterior mandibular excursion movement and temporomandibular joint osteoarthntis (TMJ OA) in 25 orthodontic patients with Angle Class I and Class II, using a six degrees-of-freedom measuring device and helical computed tomography. There were significant differences found in three-dimensional length, antero-posterior, absolute latero-medial and supero-inferior incisal, and condylar intercuspal position (IP)-retruded contact position (RCP) slides between bilateral, unilateral, and no condylar bone change groups. With respect to the types of condylar bone change, there were significant differences found in three-dimensional length, antero-postenor, and absolute latero-medial condylar IP-RCP slides between flattening, erosion and osteophyte groups. These results suggest that large three-dimensional, not only incisal but also condylar, IP-RCP slides might be related to the uni-/bilaterality and kind of TMJ pathosis, which might make such slides useful as clinical indices of TMJ OA.

Adult↗

Non-contrast-enhanced CT findings of high attenuation within metastatic cervical lymph nodes in patients with stage I or II tongue carcinoma during a follow-up period.

We present the non-contrast-enhanced CT finding of high attenuation within metastatic regional lymph nodes in two patients with stage I or II tongue carcinoma during a follow-up period. The attenuation values of these lesions were approximately 70 HU or more. One patient had a level I node, and the other had a level II node. Contrast-enhanced CT failed to reveal these hyperattenuated areas within the nodes. Histopathologic examination revealed that these hyperattenuated areas were strongly correlated with the area of marked keratinization of metastatic foci. If contrast-enhanced CT had been the only imaging technique used, these lesions might have been overlooked. The clinician should be aware of the characteristic findings of non-contrast-enhanced, as well as contrast-enhanced, CT when investigating lymph node metastases at an early stage in patients with stage I or II tongue carcinoma during the follow-up period.

Aged↗

Possible involvement of tachykinin NK(1) and NMDA receptors in histamine-induced hyperalgesia in mice.

Intrathecal (i.t.) injection of histamine elicited a significant hyperalgesic response as assayed by the tail-flick test. This hyperalgesic effect peaked at 15 min following i.t. administration of histamine (800 pmol) and returned to control level with 30 min. Hyperalgesia produced by histamine was inhibited dose-dependently by i.t. co-administration of the histamine H(1) receptor antagonist, d-chlorpheniramine, but not the histamine H(2) receptor antagonist, ranitidine. The tachykinin NK(1) receptor antagonists, (+)-[(2S,3S)-3-(2-methoxy-benzyl-amino)-2-phenylpiperidine] (CP-99,994), and [Tyr(6), D-Phe(7), D-His(9)]substance P-(6-11) (sendide), inhibited histamine-induced hyperalgesic response in a dose-dependent manner. A significant antagonistic effect of [D-Phe(7), D-His(9)]substance P-(6-11), a selective antagonist for substance P receptors, was observed against histamine-induced hyperalgesic response. The tachykinin NK(2) receptor antagonist, Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Lys-NH(2) (MEN-10,376), had no effect on hyperalgesia elicited by histamine. The competitive N-methyl-D-aspartate (NMDA) receptor antagonists, and D-(-)-2-amino-5-phosphonovaleric acid (D-APV), (+/-)-3-(2-carboxypiperazin-yl)propyl-1-phosphoric acid (CPP), the noncompetitive NMDA receptor antagonist dizocilpine (MK-801), and L-N(G)-nitro arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, markedly inhibited histamine-induced hyperalgesic response. The present results suggest that hyperalgesic response induced by i.t. injection of histamine may be mediated by tachykinin NK(1) receptors, but not NK(2) receptors in the spinal cord. In addition, spinal NMDA receptor-NO system may also contribute to elicitation of hyperalgesia following i.t. injection of histamine.

Animals↗

Enhanced antinociception by intrathecally-administered morphine in histamine H1 receptor gene knockout mice.

We previously reported that histamine H(1) receptor gene knockout mice (H1KO) showed lower spontaneous nociceptive threshold to pain stimuli when compared to wild-type mice. The objective of the present study was to examine the antinociceptive effect of intrathecally-administered morphine in H1KO mice. The antinociceptive effects of morphine were examined using assays for thermal (tail-flick, hot-plate, paw-withdrawal), mechanical (tail-pressure) and chemical nociception (formalin and capsaicin tests) using H1KO and wild-type mice. In these nociceptive assays, intrathecally-administered morphine produced significant antinociceptive effects in wild-type mice. The antinociceptive effect produced by intrathecally administered morphine was enhanced in the knockout mice. We also examined the effect of an histamine H(1) receptor antagonist, an active (d-) isomer of chlorpheniramine, on morphine-induced antinociception in ICR mice. The intrathecal co-administration of d-chlorpheniramine enhanced the effect of morphine in all nociceptive assays examined. The pharmacological experiments using d-chlorpheniramine further substantiate the evidence for the histamine H(1) receptor-mediated suppression of morphine-induced antinociception. These results suggest that existing H(1) receptors play an inhibitory role in morphine-induced antinociception at the spinal cord level.

Analgesics↗

Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone.

To determine if different subtypes of mu-opioid receptors were involved in antinociception induced by endomorphin-1 and endomorphin-2, the effect of pretreatment with various mu-opioid receptor antagonists beta-funaltrexamine, naloxonazine and 3-methylnaltrexone on the inhibition of the paw-withdrawal induced by endomorphin-1 and endomorphin-2 given intracerebroventricularly (i.c.v.) were studied in ddY male mice. The inhibition of the paw-withdrawal induced by i.c.v. administration of endomorphin-1, endomorphin-2 or DAMGO was completely blocked by the pretreatment with a selective mu-opioid receptor antagonist beta-funaltrexamine (40 mg/kg), indicating that the antinociception induced by all these peptides are mediated by the stimulation of mu-opioid receptors. However, naloxonazine, a mu1-opioid receptor antagonist pretreated s.c. for 24h was more effective in blocking the antinociception induced by endomorphin-2, than by endomorphin-1 or DAMGO given i.c.v. Pretreatment with a selective morphine-6 beta-glucuronide blocker 3-methylnaltrexone 0.25mg/kg given s.c. for 25 min or co-administration of 3-methylnaltrexone 2.5 ng given i.c.v. effectively attenuated the antinociception induced by endomorphin-2 given i.c.v. and co-administration of 3-methylnaltrexone shifted the dose-response curves for endomorphin-2 induced antinociception to the right by 4-fold. The administration of 3-methylnaltrexone did not affect the antinociception induced by endomorphin-1 or DAMGO given i.c.v. Our results indicate that the antinociception induced by endomorphin-2 is mediated by the stimulation of subtypes of mu-opioid receptor, which is different from that of mu-opioid receptor subtype stimulation by endomorphin-1 and DAMGO.

Analgesics↗

Endomorphin analogues containing D-Pro2 discriminate different mu-opioid receptor mediated antinociception in mice.

The antagonistic actions of D-Pro(2)-endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice. D-Pro(2)-endomorphin-1 and D-Pro(2)-endomorphin-2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. When D-Pro(2)-endomorphin-1 (0.05-0.1 pmol) was injected simultaneously with i.t. endomorphin-1 (5.0 nmol) or endomorphin-2 (5.0 nmol), antinociception induced by endomoprhin-1 was reduced significantly, whereas endomorphin-2-induced antinociception was not affected by D-Pro(2)-endomorphin-1. Antinociception induced by i.t. endomorphin-2 (5.0 nmol) was reduced significantly by its analogue, D-Pro(2)-endomorphin-2 (100 pmol), but not by D-Pro(2)-endomorphin-1. D-Pro(2)-endomorphin-1. D-Pro(2)-endomorphin-1 also antagonized the antinociceptive effect of i.t. DAMGO, a mu-opioid receptor agonist, whereas D-Pro(2)-endomorphin-2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containing D-Pro(2) are able to discriminate the antinociceptive actions of mu(1)- and mu(2)-opioid receptor agonists at the spinal cord level.

Analgesics↗

Differential antinociceptive effects induced by intrathecally-administered endomorphin-1 and endomorphin-2 in mice.

Two highly selective mu-opioid receptor (MOP-R) agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), have been identified and postulated to be endogenous ligands for MOP-R. Experiments were designed to determine the involvement of subtypes of MOP-R on the antinociceptive effects of EM-1 or EM-2 using the paw withdrawal test. The intrathecal (i.t.) injection of EM-1 and EM-2 produced dose-dependent antinociception in mice 1 min after the injection. Subcutaneous (s.c.) pretreatment with naloxonazine (NLZ), a selective MOP1-R antagonist, dose-dependently antagonized the antinociceptive effect of EMs. The antinociceptive effect of EM-2 was more sensitive to NLZ than that of EM-1. The selective heroin/morphine-6beta-glucuronide antagonist 3-methoxynaltrexone (3-MNT) blocked EM-2-induced antinociception, but not EM-1-induced antinociception. The dose-response curve of EM-2 was shifted threefold to the right by pretreatment with s.c. 3-MNT at a dosage of 0.25 mg/kg. EM-2-induced antinociception was attenuated by pretreatment with s.c. nor-binaltorphimine and naltrindole, whereas the effect of EM-1 was not affected. Moreover, the antinociceptive effect of EM-2 was attenuated by i.t. pretreatment with antisera against dynorphin A(1-17) or methionine-enkephalin. These results suggest that EM-2-induced antinociception may be mediated by the subtype of MOP-R, which is sensitive to NLZ and 3-MNT, and by subsequent release of dynorphin A(1-17) and methionine-enkephalin in the spinal cord.

Analgesics, Opioid↗

Postoperative mandibular stability after orthognathic surgery in patients with mandibular protrusion and mandibular deviation.

Skeletal stability and temporomandibular joint (TMJ) signs and symptoms were analyzed in 23 patients in whom mandibular protrusion and mandibular deviation had been corrected using bilateral sagittal split ramus osteotomy (BSSRO group, n = 10) and unilateral SSRO and intraoral vertical ramus osteotomy (USSRO+IVRO group, n = 13). Miniplate fixation was used in SSRO but no fixation was used in IVRO. The ratio of condylar bony change was 30.4% (7/23) and all condylar bony changes were seen on the deviated side. All preoperative signs and symptoms of TMJ disorders (4/13 patients in the USSRO+IVRO group and 2/10 patients in the BSSRO group) disappeared after surgery. Comparing the USSRO+IVRO group and the BSSRO group, in patients without condylar bony change, the mandible in both groups was stable anteriorly and horizontally after surgery, even though there was a larger horizontal mandibular movement in the USSRO+IVRO group during surgery. Comparing patients with condylar bony change versus no condylar bony change in the USSRO+IVRO group, postoperative horizontal mandibular displacement was significantly larger in the condylar bony change group than in the no condylar bony change group. These results support the idea that USSRO+IVRO can be useful in correcting mandibular deviation as well as improving signs and symptoms of TMJ disorders. However, it also seems important to be aware of the possibility of horizontal mandibular relapse in patients with condylar bony change.

Adolescent↗