Biomedical subjects

Shinichi Kikuchi

Publications and source records attributed to Shinichi Kikuchi.

45 records · Page 3Linked to original sources

PubMed2002

Exogenous tumor necrosis factor-alpha induces abnormal discharges in rat dorsal horn neurons.

STUDY DESIGN: An electrophysiologic study to examine effects of exogenous application of tumor necrosis factor-alpha (TNF-alpha ) activities and nociresponses of dorsal horn neurons in the spinal cord at L5. OBJECTIVES: To investigate the role of TNF-alpha in the induction and development of hyperalgesia in neural mechanisms responsible for a radicular pain. SUMMARY OF BACKGROUND DATA: TNF-alpha is found in the herniated disc and known to play a pivotal role in the development of inflammatory hyperalgesia; however, it is not known whether TNF-alpha causes abnormal discharge in the dorsal horn neurons and enhances nociresponse. METHODS: Single-unit activities of neurons in the L5 superficial dorsal horn were extracellularly recorded, using 28 urethane-anesthetized rats. The wide dynamic range and nociceptive-specific neurons activated by stimulation of the hind paw were selected. Effects of exogenous TNF-alpha were examined regarding 1) spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) responses of wide dynamic range neurons to noxious stimulation, and 3) morphologic changes in the dorsal root ganglion. RESULTS: Application of TNF-alpha to the nerve root induced 1) a significant increase in spikes/sec in spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) enhanced responses of wide dynamic range neurons to noxious stimulation, and 3) inflammatory changes in the ganglion. CONCLUSION: These results suggest the possibility that TNF-alpha produced in the vicinity of nerve roots due to disc herniation might cause ectopic discharges in primary afferent fibers and thereby induce the prolonged excitation in pain-processing neurons responsible for radicular pain.

Action Potentials↗

PubMed2002

Nerve vasculature changes induced by serotonin under chronic cauda equina compression.

STUDY DESIGN: An analysis of nerve vascular changes in nerve roots induced by serotonin in chronically compressed nerve roots. OBJECTIVES: To assess the hypotheses that serotonin might have a vasoconstrictive effect in chronically compressed nerve roots. SUMMARY OF BACKGROUND DATA: The 5-hydroxytryptamine 2A receptor is involved in serotonin-induced activation or sensitization of sensory nerve terminals. Serotonin exerts complex effects on pain and hyperalgesia through various receptor subtypes located at various levels of the pain transmission system. Serotonin induces endothelium-dependent contraction in vascular diseases. However, there is no knowledge regarding a response of nerve vasculature induced by serotonin in chronically compressed nerve roots. METHODS: A total of 45 dogs were used. A plastic balloon was placed under the lamina L7 and inflated to 10 mm Hg and left for 1 week. Four experimental groups were used: no operation (Group A, n = 15), the balloon was placed under the lamina but not inflated (Group B, n = 10), the balloon was inflated to 10 mm Hg for 1 week and the pressure was released just before the measurement (Group C, n = 10), and the balloon was inflated to 10 mm Hg for 1 week and inflation was maintained during the measurements (Group D, n = 10). The blood vessels of the second or third sacral nerve were defined after an intra-arterial injection of 0.5 micromol/L or 1.0 micromol/L serotonin using a specially designed operation microscope equipped with a video camera. In all groups 0.5 micromol/L serotonin (each group, n = 5) or 1.0 micromol/L serotonin (each group, n = 5) was injected. In Group A (n = 5) saline was injected. The measurements of diameter of observed blood vessels and blood flow index were performed on video recordings. All statistical assessments were performed by Wilcoxon signed-ranks test and Fisher's PLSD. RESULTS: In Group A, the diameter of blood vessels and blood flow did not change after administration of saline. In the noncompression groups (Groups A and B) the diameter of blood vessels and blood flow increased after injection of 0.5 micromol/L serotonin. In compression groups (Groups C and D) the blood vessels contracted after injecting 0.5 micromol/L serotonin and blood flow decreased. There was a significant difference in the diameter of blood vessels and blood flow between noncompression and compression groups (P < 0.01). There was no difference regarding diameter of blood vessels between released compression (Group C) and maintained compression during measurement group (Group D). In all groups blood vessels contracted and blood flow decreased after injecting 1.0 micromol/L. In electron microscopic observation tight junction of endothelial cells was destroyed in chronically compression nerve roots. DISCUSSION: The present study demonstrated that serotonin had a vasodilative effect on the intact nerve roots, whereas there was a vasoconstrictive effect to the chronically compressed nerve roots. There was no difference in the diameter of blood vessels between released compression and maintained compression during measurement group. Results suggested that dysfunction of endothelial cells induced by serotonin rather than mechanical compression itself might lead to contraction of blood vessels under chronic compression. CONCLUSION: Serotonin had a vasoconstrictive effect on the chronically compressed nerve roots.

Animals↗

PubMed2002

Dexamethasone decreases blood flow in normal nerves and dorsal root ganglia.

STUDY DESIGN: An experimental physiologic and histologic study of dexamethasone effects on peripheral nerves. OBJECTIVE: To characterize the effect of topically applied 0.4% dexamethasone on acute changes in nerve blood flow and subsequent histologic changes in rat sciatic nerve fibers. SUMMARY OF BACKGROUND DATA: Dexamethasone is an anti-inflammatory glucocorticoid used clinically to reduce the neural consequences of inflammation. Several reports of accidental injury to nerves after steroid injections have raised questions about the mechanisms involved in dexamethasone-induced neurotoxic injury. METHODS: Nerve blood flow studies using a laser Doppler flowmeter were conducted in animals with stable temperature and arterial pressure. Dexamethasone 0.4%, 0.1 mL was applied topically to rat sciatic nerve in the following protocol groups: 1) nerve blood flow recording every 5 minutes for 30 minutes, and 2) initial nerve blood flow recording and repeat recording at 4 hours. Three additional animals had 30-minute nerve blood flow recordings in which normal saline was substituted for dexamethasone; these animals were used for control and to assure that the experimental preparation was viable throughout the observational period. Additional groups of two animals each received dexamethasone but were used only for neuropathologic observation at 2, 4, and 6 days after treatment. Neuropathologic studies were conducted on glutaraldehyde-fixed, plastic-embedded tissue. RESULTS: Application of saline to the exposed sciatic nerves did not significantly change nerve blood flow from baseline values. Nerve blood flow values remained constant throughout the observational period. Dexamethasone, however, significantly reduced nerve blood flow in both the 30-minute and 4-hour groups. Some animals showed an initial transient increase in blood flow before nerve blood flow began to steadily decline to the final values reported. Neuropathologic changes were minimal and consisted only of edema and occasional subperineurial activation of Schwann cells. No demyelination or degeneration was seen. CONCLUSION: Dexamethasone causes statistically significant reductions in normal nerve blood flow at 30 minutes and 4 hours after topical application; however, the reduction is on average below the threshold for causing ischemic changes in the structure of peripheral nerve fibers.

Administration, Topical↗

PubMed2002

Epidural application of nucleus pulposus enhances nociresponses of rat dorsal horn neurons.

STUDY DESIGN: An electrophysiologic study to examine responses of dorsal horn neurons in the rat L5 spinal cord to noxious stimuli after disc herniation or application of the nucleus pulposus to the L5 nerve root. OBJECTIVES: To investigate the pathogenic role of nucleus pulposus in the neural mechanism underlying sciatica and low back pain. SUMMARY OF BACKGROUND DATA: Application of the nucleus pulposus to the lumbar nerve root induced morphologic, vascular, and functional changes in the nerve root, suggesting that some factors in the nucleus pulposus may be implicated in the pathogenesis of chronic changes. However, it has not been studied whether the epidural application of nucleus pulposus enhances nociresponses of pain-processing neurons in the superficial dorsal horn of the spinal cord. METHODS: Extracellular recordings were made from the L5 dorsal horn neurons in 20 Wistar rats. The wide-dynamic-range (WDR) neurons activated by electric stimulation of the ipsilateral footpad of hindpaw were selected, and their responses to noxious and innocuous stimulation were examined after L5-L6 disc herniation onto the L5 nerve root (Group A) and application of the autologous nucleus pulposus (Group B) or fat tissues (Groups C and D). RESULTS: The herniation of the nucleus pulposus (Group A) and application of the autologous nucleus pulposus (Group B) to the nerve root remarkably enhanced responses of WDR neurons to noxious stimuli for hours, whereas application of fat tissue scarcely enhanced nociresponses (Groups C and D). CONCLUSIONS: Results suggest that somewhat pathogenic factors in the nucleus pulposus may have a crucial role in the induction of hyperalgesia. This may help to elucidate the reason why a severe pain is sometimes induced without a visually identified protrusion.

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PubMed2002

Cooling decreases fos-immunoreactivity in the rat after formalin injection.

The effects of cooling on inflammatory response after injection of formalin in rats were examined by counting Fos-labeled cells in the dorsal horn of the spinal cord and evaluating swelling. A small amount of dilute formalin was injected into the right hindpaw of rats. The rats were divided into Cooling (-) and Cooling (+) groups and Fos-labeled cells in the spinal cord and paw volumes were compared between the two groups. In the Cooling (+) group, Fos-labeled cells were reduced significantly and the peak time of expression was delayed compared with the Cooling (-) group. Paw volumes were significantly smaller in the Cooling (+) group than in the Cooling (-) group. These results suggest that cooling therapy is effective by delaying the progress of inflammatory reactions and provides extra time for administration of analgesics or implementation of other clinical treatments.

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PubMedDate not supplied

An anatomic study of the sacral hiatus: a basis for successful caudal epidural block.

STUDY DESIGN: An anatomic study of the sacral hiatus using isolated sacra. OBJECTIVES: To clarify the anatomic variations of the sacral hiatus using the bony landmarks of the sacrum for improving the reliability of caudal epidural block (CEB). BACKGROUND DATA: The CEB has been widely used for the diagnosis and treatment of lumbar spinal disorders. The reliability of CEB is 70%-80% in the literatures. The cause of failure of CEB may depend on anatomic basis. METHODS: A total of 92 isolated sacra were used in this study. The bony landmarks were sacral hiatus and sacral cornua. Morphologic types of the sacral hiatus were classified using these landmarks. Also, location of the apex of sacral hiatus, diameter of the sacral canal at the apex of sacral hiatus, and the distance between bilateral cornua were measured. Two orthopedic surgeons performed measurements independently. RESULTS: Forty-two percent of the cases have both hiatus and cornu. Four percent of the cases showed the absent hiatus. The apex of sacral hiatus existed at the level of S4 vertebrae in 64% of the cases. The average diameter of the sacral canal was 6.0 +/- 1.9 mm. The average distance of bilateral sacral cornua was 10.2 +/- 0.35 mm. There were closed hiatus in 3% of cases. CONCLUSIONS: The sacral hiatus has anatomic variations. Understanding of these variations may improve the reliability of CEB.

Adult↗

PubMedDate not supplied

The effect of initial graft tension in anterior cruciate ligament reconstruction on the mechanical behaviors of the femur-graft-tibia complex during cyclic loading.

BACKGROUND: Initial graft tension influences clinical results of anterior cruciate ligament reconstruction. HYPOTHESIS: Under repetitive loading conditions, the effect of initial graft tension on the biomechanical behavior of the femur-graft-tibia complex may depend on the graft and the fixation. STUDY DESIGN: Ex vivo biomechanical laboratory study. METHODS: After anterior cruciate ligament reconstruction, initial graft tension of 20, 80, or 140 N was applied to the complex for 2 minutes. Then, a cyclic force-relaxation test was performed for 5000 cycles so that the graft was stretched by 2 mm. RESULTS: In a patellar tendon graft with interference screws, the average peak load values at the 5000 th cycle were 105, 157, and 205 N for the complexes with initial tension of 20, 80, and 140 N, respectively. In a flexor tendon graft with interference screws, the values were 27, 41, and 39 N. In a flexor tendon graft with Endobutton fixation, the values were 17, 40, and 77 N. CONCLUSIONS: Considering the tension of the normal anterior cruciate ligament (16 to 87 N), an initial tension of 20 N appears to be high enough for a patellar tendon graft. For a flexor tendon graft with interference screws, an increase in initial tension above 80 N has no biomechanical advantages.

Animals↗

PubMedDate not supplied

Inhibitory effects on pulmonary metastases of low-dose consecutive administration of cisplatin on sarcoma-bearing mice.

Low-dose consecutive CDDP administrations have been reported to be effective in cancer treatment. We studied the inhibitory effects on pulmonary metastasis of bolus versus low-dose consecutive administration of CDDP chemotherapy for sarcoma-bearing mice, and evaluated the differences in responses to two types of therapy. Significant reductions (p < 0.01) in the number of pulmonary metastases were observed in the low-dose consecutive administration group compared to the control group, and in the bolus group compared to the control group. No significant difference in the number of metastases between the low-dose consecutive administration group and the bolus group was observed (p = 0.43). This study suggests that low-dose consecutive CDDP administration would be as effective as bolus CDDP administration, which is currently popular. Also, low-dose consecutive CDDP administrations may contribute to the attenuation of the adverse drug reactions expected by patients with bone and soft tissue tumors who are undergoing chemotherapy.

Animals↗

PubMedDate not supplied

Establishment and characterization of a new cell line, FPS-1, derived from human undifferentiated pleomorphic sarcoma, overexpressing epidermal growth factor receptor and cyclooxygenase-2.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is among the most common soft tissue sarcomas in adults. In order to improve its aggressive course or prognosis and establish new therapeutic methods, molecular genetic and biological characterizations of UPS are required. MATERIALS AND METHODS: A new human UPS cell line (FPS-1) was established from UPS of the upper arm of a 79-year-old man. The cell line has been maintained for over 14 months with more than 60 passages. FPS-1 cells were characterized using molecular biological methods. RESULTS: FPS-1 cells showed the same morphological and immunophenotypical characteristics as the primary tumor. Cytogenetic and molecular analyses revealed a nonsense mutation in exon 6 of the p53 gene. Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) were expressed in FPS-1 cells. CONCLUSION: FPS-1 cells might be useful for investigating biological behavior and developing new molecular targeting antitumor drugs for UPS with EGFR or COX-2 expression.

Aged↗