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Biomedical subjects

A Kotani

Publications and source records attributed to A Kotani.

At least 37 records · Page 2Linked to original sources
PubMed2000

Development of novel lipophilic derivatives of DADLE (leucine enkephalin analogue): intestinal permeability characateristics of DADLE derivatives in rats.

PURPOSE: The objective of this study is to examine the intestinal permeability of novel lipophilic derivatives of DADLE (Tyr-D-Ala-Gly-Phe-D-Leu), an enkephalin analogue, using isolated rat intestinal membranes. METHODS: The novel lipophilic derivatives of DADLE were synthesized by chemical modification with various fatty acids at the C terminus. The pharmacological activities of these DADLE derivatives were assessed by a hot plate test. The intestinal permeability of these derivatives was estimated by the in vitro Ussing chamber method. RESULTS: We obtained four different DADLE derivatives including acetyl-DADLE (DADLE-C2), butyryl-DADLE (DADLE-C4), caproyl-DADLE (DADLE-C6), and caprylyl-DADLE (DADLE-C8). All the derivatives of DADLE had at least 75% of the activity of native DADLE, suggesting that chemical modification of DADLE at the C terminus did not markedly affect its pharmacological activity. These DADLE derivatives were more stable than native DADLE in jejunal and colonic homogenates. A "bell-shaped" profile was observed between the apparent permeability coefficients (Papp) of DADLE derivatives and lipophilicity. In particular, DADLE-C4 had the greatest permeability characteristics across the intestinal membrane of the acyl derivatives studied in this experiment. The permeability of DADLE-C4 across the jejunal membrane was further improved in the presence of puromycin, amastatin, and sodium glycocholate (NaGC), all at a concentration of 0.5 mM. CONCLUSIONS: We suggest that the combination of chemical modification with butyric acid and the application of a protease inhibitor are effective for improving the absorption of DADLE across the intestinal membrane.

Animals↗
PubMed1999

Enhanced permeability of insulin across the rat intestinal membrane by various absorption enhancers: their intestinal mucosal toxicity and absorption-enhancing mechanism of n-lauryl-beta-D-maltopyranoside.

We have examined the in-vitro permeability characteristics of insulin in the presence of various absorption enhancers across rat intestinal membranes and have assessed the intestinal toxicity of the enhancers using an in-vitro Ussing chamber method. The absorption enhancing mechanism of n-lauryl-beta-D-maltopyranoside was studied also. The permeability of insulin across the intestinal membranes was low in the absence of absorption enhancers. However, the permeability was improved in the presence of enhancers such as sodium glycocholate and sodium deoxycholate in the jejunum, and sodium glycocholate, sodium deoxycholate, n-lauryl-beta-D-maltopyranoside, sodium caprate and ethylenediaminetetraacetic acid (EDTA) in the colon. Overall, the absorption enhancing effects were greater on the colonic membrane than on the jejunal membrane. The intestinal membrane toxicity of these enhancers was characterized using the release of cytosolic lactate dehydrogenase from the colonic membrane. A marked increase in the release of lactate dehydrogenase was observed in the presence of sodium deoxycholate and EDTA. The release of lactate dehydrogenase in the presence of these absorption enhancers was similar to that seen with sodium dodecyl sulphate (SDS), used as a positive control, indicating high toxicity of these enhancers to the intestinal membrane. In contrast, sodium glycocholate and sodium caprate caused minor releases of lactate dehydrogenase, similar to control levels, suggesting low toxicity. In addition, the amount of lactate dehydrogenase in the presence of n-lauryl-beta-D-maltopyranoside was much less than that seen with sodium deoxycholate, EDTA and SDS. Therefore, sodium glycocholate, sodium caprate and n-lauryl-beta-D-maltopyranoside are useful absorption enhancers due to their high absorption enhancing effects and low intestinal toxicity. To investigate the absorption enhancing mechanisms of n-lauryl-beta-D-maltopyranoside, the transepithelial electrical resistance (TEER), voltage clamp experiments and the circular dichroism spectra were studied. n-Lauryl-beta-D-maltopyranoside decreased the TEER values in a dose-dependent manner, suggesting that the enhancer may open the tight junctions of the epithelium, thereby increasing the permeability of insulin via a paracellular pathway. This speculation was supported by the findings that 20 mM n-lauryl-beta-D-maltopyranoside produced a greater increase in the paracellular flux rate than in the transcellular flux rate by the voltage clamp studies. Evaluating the circular dichroism spectra we found that insulin oligomers were not dissociated to monomers by the addition of n-lauryl-beta-D-maltopyranoside, but dissociation did occur with the addition of sodium glycocholate. Thus, the dissociation of insulin was not a major factor in the absorption enhancing effect of n-lauryl-beta-D-maltopyranoside. These findings provide basic information to select the optimal enhancer for the intestinal delivery of peptide and protein drugs including insulin.

Algorithms↗
PubMed1998

Evaluation of disk capture with a splint repositioning appliance: clinical and critical assessment with MR imaging.

OBJECTIVE: The purpose of this study was to evaluate disk repositioning clinically and through use of magnetic resonance imaging after the insertion of a disk repositioning appliance. STUDY DESIGN: Seventy-four patients with 82 temporomandibular joints showing middle to late opening movement click and closing movement click near maximum intercuspation were treated with a mandibular full-coverage repositioning splint. These joints were assessed clinically and by means of magnetic resonance imaging for disk recapture. RESULTS: According to clinical assessment, 75.6% (62/82) of the joints were treated successfully; no click was observed from the splinted mandibular position. When compared with the results of magnetic resonance imaging assessment, clinical assessment showed an accuracy rate of 91.5%, although the incidence of the false negatives was high (40%). CONCLUSIONS: The results of this study showed that about 70% of reducing displaced disks were captured with use of the disk repositioning appliance. And it was also suggested that magnetic resonance imaging is helpful to evaluate disk repositioning therapy.

Adolescent↗
PubMed1998

Change of position of the temporomandibular joint disk with insertion of a disk-repositioning appliance.

OBJECTIVE: We report alteration of the temporomandibular joint disk and the condyle position through the construction of a mandibular full-coverage occlusal appliance (often referred to as a disk repositioning appliance). STUDY DESIGN: Forty-five joints with displaced disks with reduction were available for the study. We assessed these joints for disk recapture and the change of disk position with insertion of the appliance using magnetic resonance imaging. RESULTS: Of the 41 joints that had a recaptured disk with insertion of the splint, 25 slid in a posterior direction, although the amount of movement was negligible. No disk slid posteriorly in the joints without splint capture. CONCLUSIONS: On the basis of our results, we conclude that many of the occasionally displaced disks might have moved backward with successful treatment involving a disk-repositioning splint. However, the amount of the movement was negligible.

Adolescent↗
PubMed1998

Effects of various protease inhibitors on the stability and permeability of [D-Ala2,D-Leu5]enkephalin in the rat intestine: comparison with leucine enkephalin.

The effects of various protease inhibitors on the stability of leucine enkephalin (Leu-Enk) and [D-Ala2,D-Leu5] enkephalin (DADLE) were investigated, and the permeability of these peptides was also examined in an in vitro Ussing chamber. Captopril, thiorphan, bacitracin, bestatin, puromycin, amastatin, and sodium glycocholate (Na-GC) were chosen as protease inhibitors. Regional differences in the stability of Leu-Enk and DADLE were observed, and the rank order of the stability of these peptides was colon > duodenum > ileum > jejunum. Na-GC, amastatin, and puromycin were effective protease inhibitors for improving the stability of these peptides, although captopril and thiorphan did not improve the stability of Leu-Enk. In the transport studies, Leu-Enk did not cross the intestinal membrane in the absence of protease inhibitors, but its transport was improved in the presence of Na-GC. In addition, Na-GC, amastatin, and puromycin improved the permeability of DADLE in both jejunum and colon, while the permeability of DADLE was not improved by the addition of captopril, thiorphan, and bestatin. Furthermore, the permeability of 6-carboxyfluorescein, a poorly absorbable and stable compound, was also improved in the presence of Na-GC and bacitracin at a concentration of 10 mM. These findings indicated that amastatin, puromycin, and Na-GC at a concentration of 0.5 mM might increase the permeability of DADLE due to the improved stability of DADLE in the donor site. However, Na-GC and bacitracin at a concentration of 10 mM had absorption-enhancing activities which might be also related to the enhanced permeability of DADLE across the intestinal membrane.

Animals↗
PubMed1997

Clinical effect of full coverage occlusal splint therapy for specific temporomandibular disorder conditions and symptoms.

PURPOSE: The purpose of this retrospective study was to evaluate the effect of maxillary full-coverage occlusal splint (stabilization splint) therapy for specific temporomandibular disorders and their symptoms/signs. MATERIAL AND METHODS: This study assessed the outcome of 232 patients who were suffering from chronic pain on movements, joint noise except reciprocal clicking, and difficulty of mouth opening. All were treated with the stabilization splint alone. RESULTS: The total remission rate was 41% and, including those reporting some improvement, the rate was 84%. The presence of displaced disk significantly decreased the success rate. However, the presence or absence of radiographic changes in the temporomandibular joint did not influence the treatment outcome. CONCLUSION: From this study, it is suggested that the stabilization splint therapy may be a useful treatment modality in treatment of temporomandibular disorders, especially for the patients without clinical evidence of displaced disk.

Adolescent↗
PubMed1997

In vivo study of calcium phosphate cements: implantation of an alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide cement paste.

alpha-Tricalcium phosphate (alpha-TCP)/dicalcium phosphate dibasic (DCPD)/tetracalcium phosphate monoxide (TeCP) cement was implanted in paste form into soft tissue (rate subcutaneous sockets) and bone tissue (defects in rabbit mandibles) to evaluate the setting behaviour of the cement and tissue responses to the cement. A histological study of the soft tissue implants revealed thin fibrous capsule formation, the appearance of multinucleated giant cells on and close to the cement surface, and small clusters of the cement near the main part of the set cement which were formed by the migration of the paste while setting. X-ray diffraction (XRD) analysis of the implanted cement showed peaks for hydroxyapatite (HA) which increased as the implant period increased. Histology and microradiography of the bone tissue implants showed well-set cement without migration, active bone formation around the cement and direct bone union to it. However, the cement disappeared from the implant site in 4 of 16 specimens where intense bleeding seemed to wash away the implants while setting. From the results of the present study, we concluded that the cement is well tolerated, especially by bone tissue. This may be related to the fact that the cement sets producing HA. The cement is a promising material as a bone substitute; however, there is a problem of migration while setting in soft tissue and of exclusion from the bone defects by intense bleeding.

Animals↗
PubMed1997

In vivo study of a calcium phosphate cement consisting of alpha-tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate monoxide.

Prehardened calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted in rabbit mandibles and back muscles, and studied histologically and microradiographically. In the mandibles, new bone formation occurred around the implants and increased in quantity the longer the implant period lasted. Histology, microradiography and scanning electron microscopy (SEM) demonstrated direct contact of bone and cement. Bone response to this cement was essentially the same as to hydroxyapatite (HA) ceramics, known as a biocompatible bone substitute. Material resorption was recognized, which increased with the implant period and was greater in the surface bound by soft tissue than the surface bound by bone tissue. In the back muscles, however, no calcified tissue formation occurred. Resorption proved to be faster than in the case of the mandible implants. It was concluded that the cement, in prehardened form, has good biocompatibility and is a promising material as a bone substitute.

Animals↗
PubMed1997

Effects of different absorption enhancers on the permeation of ebiratide, an ACTH analogue, across intestinal membranes.

The permeation of ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), a novel ACTH analogue, across the intestinal mucosae has been examined by use of isolated intestinal membranes from rats in a modified Ussing chamber. Regional differences were observed in the permeation of ebiratide across intestinal membranes; the order of membrane permeability was jejunum > ileum > duodenum > colon. Overall, the permeation of ebiratide was relatively poor. The effects of various absorption enhancers were examined to increase the intestinal permeability to ebiratide. Sodium glycocholate and sodium caprate had no significant enhancing effect on the permeability of the jejunal membrane, but significantly enhanced the permeation of ebiratide through the colonic membrane. On the other hand, N-dodecyl-beta-D-maltopyramoside (LM) significantly enhanced the permeation of ebiratide through both jejunal and colonic membranes. In general, the absorption-enhancing effects of these agents were more predominant in the colon than in the jejunum. Membrane damage by the absorption enhancers was evaluated by measuring the amount of protein released from the intestinal membrane. It was found that all the absorption enhancers slightly increased the amount of protein released, but that the amounts of protein released in the presence of these enhancers were much less than in the presence of ethylenediaminetetraacetic acid (EDTA), used as a positive control. These findings suggest that the absorption enhancers, especially LM might be useful adjuvants for improving the intestinal absorption of peptide and protein drugs, including ebiratide.

Adrenocorticotropic Hormone↗
PubMed1996

Spontaneous dissecting aneurysm of the anterior cerebral artery: report of two cases.

BACKGROUND: Dissecting aneurysms of the vertebrobasilar artery have been increasingly reported. However, those of the anterior circulation are still rare lesions. Those confined to the anterior cerebral artery are extremely rare and their clinical features are not well known. CASE REPORT: Two cases of spontaneous dissecting aneurysm of the anterior cerebral artery are described. Both patients are middle-aged males and presented with ischemic attacks, although they were lacking any factors correlated to atherosclerosis. Definite diagnosis was made by angiography, which demonstrated characteristics of dissecting aneurysm, such as "double lumen" and "string sign." Serial angiography was performed and revealed dynamic changes during the time course. Nonsurgical therapy was utilized and both patients achieved good recovery. CONCLUSION: Most of the dissecting aneurysms confined to the anterior cerebral artery present with ischemic attacks. Although their etiology remains uncertain, such aneurysms may be a potent cause of occlusive diseases of the anterior cerebral artery, especially in relatively young males lacking any factors correlated to atherosclerosis.

Adolescent↗
PubMed1996

Giant basilar artery aneurysm with intramural hemorrhage and then disastrous hemorrhage: case report.

OBJECTIVE AND IMPORTANCE: Intracranial giant aneurysms have been considered to grow by recurrence of intramural hemorrhage of the aneurysmal wall. However, it remains uncertain whether rupture of giant aneurysms is brought about by the same mechanism that causes the rupture of smaller saccular aneurysms. It is also unclear whether intramural hemorrhage is correlated with the rupture of giant aneurysms. CLINICAL PRESENTATION: A 67-year-old woman was admitted with symptoms of gait disturbance and dementia. Computed tomographic scans revealed a large mass located in the prepontine region and extending into the third ventricle as well as moderate dilatation of the lateral ventricles. Angiography demonstrated a giant basilar tip aneurysm and multiple aneurysms located in the bilateral anterior and middle cerebral arteries. INTERVENTION: Ventriculoperitoneal shunting was scheduled, but subarachnoid and intraventricular hemorrhage occurred and the patient died. Computed tomographic scans, performed immediately before the disastrous hemorrhage, displayed intramural hemorrhage in the wall of the giant basilar tip aneurysm. Ventricular drainage was performed, but the patient died. CONCLUSION: It seems probable that intramural hemorrhage of the aneurysmal wall may cause both the growth and rupture of intracranial giant aneurysms.

Aged↗
PubMed1995

Pitfalls in the treatment of delayed lymph-node metastases after control of small tongue carcinomas.

Between 1985 and 1992, 13 patients were treated for delayed lymph-node metastases that developed after obtaining control of primary lesions of the tongue. These lesions were treated primarily by radiotherapy or surgical resection; cervical metastases were treated mainly by delayed radical neck dissection (RND). Seven of the 13 patients survived with no evidence of recurrence. The other six patients developed tumors in the neck, and five of these patients died due to uncontrollable disease. In all but one patient, recurrence appeared between the site of the primary lesion and the region of RND, the oral floor and/or the parapharyngeal space. None of the patients with recurrence received radiotherapy in the area between the primary lesion and the site of RND. In contrast, there was no recurrence in patients who received external irradiation to the primary lesion and upper cervical lymph nodes. This review emphasizes the need to direct more attention to the area between the site of the primary lesion and the regional lymph nodes in patients receiving treatment for delayed metastases associated with small carcinomas of the tongue.

Adult↗
PubMed1995

Ruptured aneurysm at the origin of duplication of the middle cerebral artery--case report.

A 28-year-old male presented with a rare case of an aneurysm at the origin of duplication of the middle cerebral artery manifesting as subarachnoid hemorrhage. Preoperative angiography revealed duplication of the right middle cerebral artery and an aneurysm at its origin, which was successfully clipped. He was discharged with no neurological deficits. Congenital factors may be more important in the etiology of aneurysms associated with this anomaly.

Adult↗
PubMed1995

Age-related changes of male mouse submandibular gland: a morphometric and radioautographic study.

The DNA synthesis and the changes of cell population kinetic of aging male mouse submandibular glands were studied by light and electron microscopic radioautography from embryonic day 19 to 21 months postnatal. At the embryonic day 19, the gland consisted of developing acinar cells (49%), intercalated duct (ICD) (37%), juxta-acinar (JA) (3%) and striated duct (SD) cells (11%). At birth, JA cells increased rapidly to 32%, thereafter decreased gradually. At 1 month of age, granular convoluted tubule cells appeared and increased rapidly in number with age. They reached a maximum at 6 month after birth. Then they appeared to decrease gradually from 6 to 21 months. The most conspicuous feature of the aged submandibular glands was the regressive changes of the granular ducts. The extent and height of the granular ducts as well as the content of mature secretory granules decreased. These changes may play an important role during the development of mice, because the granular duct synthesizes many biological factors. The 3H-thymidine labeling index of each cell type of male mouse submandibular glands reached a peak 1 day after birth and decreased with aging. The labeling index of intercalated duct cells was higher than the others and persisted for a long time. On the other hand, the labeling indices of the other cells were significantly depressed at one week after birth. From these observations on morphology, it was also shown that ICD cells were concerned with the generation of the other cell types.

Aging↗