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Biomedical subjects

T Mashimo

Publications and source records attributed to T Mashimo.

At least 19 recordsLinked to original sources

Prism adaptation to optical deviation alleviates pathologic pain.

BACKGROUND: The human visual and somatosensory systems are interdependent. Using a visual subjective body-midline (SM) judgment task, we previously confirmed that pathologic pain and deafferentation can modify visuospatial perception, indicating that altered somatosensory experience can modify visual perception. Conversely, in the present study we investigated whether a change in visual experience can modify perception of pathologic pain. METHODS: We used prism adaptation (PA) to modify subjects' visual experience. Five patients with complex regional pain syndrome (CRPS) adapted to wedge prisms, producing a 20-degree visual displacement toward the unaffected side. Further, we used several types of prisms in a longitudinal single-case study. Wearing prismatic goggles, the subjects performed a target-pointing task once a day for 2 weeks. We evaluated pain intensity and visual SM judgment to measure the adaptive aftereffects at three time points: before PA (pre-test), immediately after the first PA exposure (IA-test), and after a 14-day sequence of PA exposure (post-test). RESULTS: PA toward the unaffected side alleviated pathologic pain and other CRPS pathologic features, when measured at post-test. None of the IA-test results showed an analgesic effect. In the longitudinal study, sham PA and 5-degree PA did not produce any effects, and PA toward the affected side actually exacerbated the subjective pain. CONCLUSIONS: Our findings suggest that vision can influence pathologic pain, and preliminarily suggest that prism adaptation has a direction-specific and reproducible effect on not only pathologic pain but also other CRPS pathologic features. Thus, prism adaptation may be a viable cognitive treatment for CRPS.

Adaptation, Physiological↗

Pathologic pain distorts visuospatial perception.

Spatial perception is achieved by integrating multisensory information. Using visual subjective body midline (vSM) judgments in patients with unilateral limb pain (complex regional pain syndrome [CRPS]), we found that their vSM deviated toward the affected side; however, deafferentation of the affected limb caused a transient pain decrease and a transient shift of the vSM deviation toward the unaffected side. Our results indicate that the persistent pain state in CRPS distorts visuospatial perception.

Adaptation, Physiological↗

Ketamine and thiopental sodium: individual and combined neuroprotective effects on cortical cultures exposed to NMDA or nitric oxide.

BACKGROUND: An N-methyl-D-aspartate (NMDA) blocker, ketamine, has been shown to be neuroprotective both in vivo and in vitro. However, ketamine is not commonly recommended for use in patients suffering from cerebral ischaemia because of its adverse neurological effects. We hypothesized that combined administration of ketamine and thiopental sodium (TPS) would be highly effective in protecting cerebral cortical neurones from ischaemia, with possibly reduced dosages. METHODS: We examined the degree of neuroprotection provided by various concentrations of ketamine and TPS, alone and in combination, in cortical cultures exposed to NMDA or a nitric oxide-releasing compound (NOC-5) for 24 h. The survival rate (SR) of E16 Wistar rat cortical neurones was evaluated using photomicrographs before and after exposure to these compounds. RESULTS: The SRs of cortical neurones exposed to 30 microM NMDA or NOC-5 were 15.0 (3.8)%, 12.8 (3.1)%, respectively. Higher doses (5, 10 and 50 microM) but not lower doses (<1 microM) of ketamine improved SRs [57.9 (2.2)%, 61.1 (5.4)%, 76.7 (3.0)%, respectively] against NMDA but not NOC. Enhanced survival was observed with combined administration of 5 or 10 microM ketamine and 50 microM TPS [SR 71.3 (4.8)%, 74.7 (3.7)%, respectively, P<0.05 if ketamine alone, P<0.01 if TPS alone], against NMDA-induced neurotoxicity in vitro. Only the highest dose of TPS (50 microM) improved survival after NOC exposure. This neuroprotection was not influenced by ketamine. CONCLUSIONS: These data indicate that a low, clinically relevant dose of ketamine offer significant neuroprotection during prolonged exposure to NMDA but not to NOC. Combinations of reduced doses of ketamine and TPS exhibited enhanced neuroprotection against NMDA-induced neurotoxicity. Hence, combinations of these two common i.v. anaesthetics agents could be developed to protect the brain from ischaemia.

Anesthetics, Dissociative↗

Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons.

Two cold-sensitive transient receptor potential (TRP) channels, TRPA1 and TRPM8, have been identified and considered interesting because of their possible roles in thermosensation, nociception and other functions. Recently, we have reported that the phosphorylation of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase occurred in primary afferent neurons in response to noxious heat stimulation of the peripheral tissue, i.e. activity-dependent activation of extracellular signal-regulated protein kinase and p38 in dorsal root ganglion neurons. In the present study, we investigated the phosphorylation of extracellular signal-regulated protein kinase, p38, and c-Jun N-terminal kinase in the rat dorsal root ganglion by cold stimulation using immunohistochemistry. Cold stimuli (28-4 degrees C) were applied by immersion of the hind paw into a water bath (six times of 10 s stimulation and 10 s interval, total 2 min). Noxious cold stimulation induced phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38, but not phosphorylated-c-Jun N-terminal kinase, in small to medium diameter sensory neurons with a peak at 2 min after stimulation. We found that a cold stimulation at 4 degrees C showed a marked increase in the number of activated neurons. Furthermore, double staining for phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38 showed no colocalization in the dorsal root ganglion neurons. We then performed double-labeling experiments for TRPA1 and TRPM8 mRNA and phosphorylation of mitogen-activated protein kinase. The majority of phosphorylated-extracellular signal-regulated protein kinase-positive neurons also expressed TRPM8 mRNA, whereas phosphorylated-p38 heavily colocalized with TRPA1 mRNA after noxious cold stimulation. Our data suggest that the noxious, but not innocuous, cold stimulation in vivo induced differential activation of extracellular signal-regulated protein kinase and p38 pathways in each subpopulation containing TRPA1 or TRPM8 in dorsal root ganglion.

Animals↗

Transition to a virtually incompressible oxide phase at a shock pressure of 120 GPa (1.2 Mbar): Gd3Ga5O12.

Cubic, single-crystal, transparent Gd(3)Ga(5)O(12) has a density of 7.10 g/cm(3), a Hugoniot elastic limit of 30 GPa, and undergoes a continuous phase transition from 65 GPa to a quasi-incompressible (QI) phase at 120 GPa. Only diamond has a larger Hugoniot elastic limit. The QI phase of is more incompressible than diamond from 170 to 260 GPa. Electrical conductivity measurements indicate the QI phase has a band gap of 3.1 eV. Gd(3)Ga(5)O(12) can be used to obtain substantially higher pressures and lower temperatures in metallic fluid hydrogen than was achieved previously by shock reverberation between Al(2)O(3) disks.

Journal Article↗

Primary motor cortex stimulation within the central sulcus for treating deafferentation pain.

Nine patients with post-stroke pain, six with brachial plexus injuries, two with phantom limb pain, one with spinal cord injury, and one with brain stem injury were treated with a modified motor cortex stimulation (MCS) protocol. Preoperative pharmacological tests were performed with phentolamine, lidocaine, ketamine, thiopental, morphine, and placebo. We placed a grid electrode in the subdural space to decide upon the best stimulation point for pain relief over a few weeks with the purpose of determining the placement of a Resume electrode. In five patients, Resumes were implanted in the interhemispheric fissure to reduce lower extremity pain. In five other patients, Resumes were placed within the central sulcus to stimulate area 4 and area 3b. In addition, electrodes were also placed on the surface of the precentral gyrus. Fourteen of the 19 patients showed pain reduction (6 excellent, 3 good, and 5 fair) using the MCS with our results indicating area 4 within the central sulcus to be the optimal stimulation point for pain relief. We speculate that conventional method may sometimes fail to stimulate area 4 and that focal stimulation of the primary motor cortex within the central sulcus may improve the efficacy of this treatment. Our pharmacological tests show that patients with ketamine sensitivity seem to be good candidates for MCS. Test stimulation with a subdural multi-grid electrode and Resumes in the cetral sulcus were helpful in locating the best stimulation point for pain relief.

Adult↗

Expression of hepatocyte growth factor in primary sensory neurons of adult rats.

We examined the expression of hepatocyte growth factor (HGF) mRNA and its receptor, c-met mRNA, in the dorsal root ganglia (DRG) and spinal cord of naive adult rats using in situ hybridization histochemistry (ISHH) and the reverse transcription-polymerase chain reaction (RT-PCR) technique. HGF mRNA was expressed in 25.0% of DRG neurons and 80.5% of HGF mRNA-positive neurons expressed trkA mRNA. In the lumbar spinal cord, c-met mRNA signals were observed in the superficial layer of dorsal horn. These results suggest that the HGF/cMet system may be involved in sensory transmission.

Animals↗

Neuroprotective effect of hypothermia at defined intraischemic time courses in cortical cultures.

Many experimental and clinical studies have shown that hypothermia confers cerebroprotective benefits against ischemic insults. Because of the many conflicting reports on hypothermic neuroprotection, we undertook this cellular study to identify the optimal temperature or a range of temperatures for maximal neuroprotection at different times (6-24 hr) during ischemic insults. Cultured Wistar rat cortical neurons were exposed to oxygen deprivation at defined times and temperatures (37 degrees C normothermia, 32 degrees C mild hypothermia, 27 degrees C moderate hypothermia, 22 degrees C deep hypothermia, and 17 degrees C profound hypothermia). The survival rate of neurons was evaluated by assessing viable neurons on photomicrographs. The normothermic group demonstrated a significantly lower survival rate of cultured neurons (6 hr, 80.3% +/- 2.7%; 12 hr, 56.1% +/- 2.1%; 18 hr, 34.2% +/- 1%; 24 hr, 18.1% +/- 2.2%) compared to hypothermic groups (P < 0.001). The survival rate for the profound hypothermic group was significantly reduced (P < 0.01) compared to other hypothermic groups (at 17 degrees C: 12 hr, 85.9% +/- 2.5%, 18 hr, 74.7% +/- 3.7%, 24 hr, 58.7% +/- 2.7%). Almost equal survival rates were observed among mild, moderate, and deep hypothermic groups following <18 hr exposure to hypoxia, but the deep hypothermic group showed a significantly higher survival rate (84.1% +/- 1.6%; P < 0.001) when subjected to hypoxia for 24 hr. In conclusion, hypothermia offers marked neuroprotection against hypoxia, but attenuation of neuronal cell death was less with profound hypothermia compared to mild, moderate, and deep hypothermia. Deep hypothermia affords maximal protection of neurons compared to mild and moderate hypothermia during long-lasting hypoxia (>18 hr).

Animals↗

NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model.

Pro-inflammatory cytokines have been shown to be involved in the genesis, persistence, and severity of neuropathic pain following nerve injury. The transcription factor, nuclear factor-kappa B (NF-kappaB), plays a pivotal role in regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF-kappaB in the pathogenesis of neuropathic pain, using a gene-based approach of NF-kappaB decoy, we tested whether the activated NF-kappaB affected pain behavior via the expression of inflammatory mediators. Single endoneurial injections of NF-kappaB decoy, at the site of nerve lesion, significantly alleviated thermal hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury. This finding suggests that a perineural inflammatory cascade, that involves NF-kappaB, is involved in the pathogenesis of neuropathic pain.

Animals↗

Expression of HGF and cMet in the peripheral nervous system of adult rats following sciatic nerve injury.

Hepatocyte growth factor (HGF) exhibits neurotrophic properties on different types of neuron, including motor, sensory and parasympathetic neurons. We demonstrate that sciatic nerve ligation induces an increase of the HGF receptor, c-met, mRNA in the distal segment of the sciatic nerve to the ligation site and a delayed elevation in the proximal segment. Immunohistochemical analysis revealed co-localization of cMet and GFAP and indicates that Schwann cells express cMet in the sciatic nerve after injury. HGF mRNA was detected in the spinal cord and DRG, and nerve injury did not alter the expression. These data demonstrate that the expression of HGF and cMet in the peripheral nervous system shows the unique pattern of regulation following nerve injury.

Animals↗

Inhibitory effect of theophylline on recombinant GABA(A) receptor.

Convulsions due to systemic toxicity are a major and frequently fatal side effect of theophylline. The cause of theophylline-induced convulsions is not clear, but antagonism of the inhibitory nervous system may be implicated, so we examined the effects of theophylline on GABA-induced currents using recombinant GABA(A) receptor (GABA(A)-R). Theophylline dose-dependently inhibited GABA-induced currents: the IC50 value was 1841+/-63 microM and Hill coefficient 1.09+/-0.03. The inhibitory action of theophylline on GABA-induced currents was competitive and voltage dependent. The inhibition of GABA-induced currents by theophylline may be a primary mechanism underlying theophylline-induced convulsions.

Animals↗

The effects of propofol on NMDA- or nitric oxide-mediated neurotoxicity in vitro.

Acute brain ischemia causes neurotoxic cascades including NMDA receptors and NO. Propofol, an i.v. anesthetic, is thought to have a neuroprotective effect. We investigated the influence of propofol on NMDA/NO neurotoxicity using Shibuta's established model of primary brain cultures. Cortical neurons prepared from E16 were used after 13-14 days in culture. The neurons were exposed to various concentrations of propofol with NMDA or NO-donor. The survival rates of neurons exposed to 30 microM NMDA with or without 300 microM propofol were 12.1 +/- 2.2% and 11.9 +/- 2.2%, respectively. The survival rates exposed to 30 microM NO-donor with or without 300 microM propofol were 11.2 +/- 4.2% and 14.0 +/- 3.9%, respectively. These results suggest that neuroprotective effect of propofol is limited and propofol does not offer advantages over thiopental against NMDA/NO-induced cytotoxicity.

Animals↗

Identification of tumor metastasis suppressor region on the short arm of human chromosome 20.

Acquisition of metastatic ability by prostate cancer cells is the hallmark of their lethal trait and outcome. However, the genetic alterations underlying the clinical progression and pathogenesis of prostate cancer are not well understood. Several studies involving loss of heterozygosity (LOH) and comparative genomic hybridization analysis have identified distinctively altered regions on various human chromosomes, and genomic imbalance of chromosome 20 was implicated in progression and recurrence of prostate tumors. To examine the role of chromosome 20 in prostate neoplasms, we introduced this chromosome into highly metastatic rat prostate cancer cells using the microcell-mediated chromosome transfer technique. Introduction of the chromosome resulted in significant suppression of the metastatic ability of the hybrid cells, by as much as 98%, without any interference with the in vivo growth rate or tumorigenicity of primary tumor in SCID mice. Our STS-PCR analysis on 10 hybrid clones indicates that the suppressor activity of chromosome 20 is located in the p11.23-12 region. Further examination of the hybrid clones by experimental metastasis assay and histologic analysis as well as Matrigel invasion assay suggests the involvement of the suppressor region at an early stage of invasion and extravasation. We also investigated the status of the chromosome 20 suppressor region in pathology specimens from human prostate cancer patients and detected the frequent loss of this region in high-grade tumors. These results suggest the presence of a putative suppressor gene on human chromosome 20 that is functionally involved in development of prostate cancer metastases.

Aged↗

Premedication modifies the quality of sedation with propofol during regional anesthesia.

PURPOSE: To determine the effects of diazepam or clonidine on the quality of sedation with propofol during regional anesthesia. METHODS: In a prospective randomised, controlled, double-blinded study, 60 patients undergoing elective gynecological surgery were studied. They were given premedication with 0.15-mg clonidine (Group-CL, n=20), 5-mg diazepam (Group-DZ, n = 20), or placebo (Group-P, n = 20) po. After spinal anesthesia was established, sedation was provided with propofol and controlled using a five-point sedation score at 3, "eyes closed but rousable to command", and 4, "eyes closed but rousable to mild physical stimulation". During sedation, blinded anesthesiologist recorded occurrence of complications. At two hours after end of sedation, patients were asked if they had intraoperative dream and memory. RESULTS: The loading dose, steady-state infusion rate, and overall mean infusion rate in Group-CL were 0.80 mg x kg(-1), 2.35 mg x kg(-1) x hr(-1) and 2.89 mg x kg(-1) x hr(-1), compared with 0.97 mg x kg(-1), 3.13 mg x kg(-1) x hr(-1) and 3.59 mg x kg(-1) x hr(-1) in Group-DZ, and 1.38 mg x kg(-1), 4.10 mg x kg(-1) x hr(-1) and 4.36 mg x kg(-1) x hr(-1) in Group-P, respectively. Indices of both Group-CL (P < 0.001) and Group-DZ (P < 0.05) were smaller than those of Group-P Moreover, clonidine reduced the incidence of uncontrolled movement (P < 0.01), while diazepam reduced the incidence of intraoperative memory and increased the incidence of dream (P < 0.05). Premedication did not affect the incidence of other complications. CONCLUSION: Both premedicants reduced propofol requirements and exerted beneficial effects on the incidence of some complications during sedation with propofol as an adjunct to regional anesthesia.

Adult↗

The effect of positive end-expiratory pressure and continuous positive airway pressure on the oxygenation and shunt fraction during one-lung ventilation with propofol anesthesia.

STUDY OBJECTIVE: To evaluate the effect of positive end-expiratory pressure (PEEP) and continuous positive airway pressure (CPAP) on the oxygenation and shunt fraction during one-lung ventilation (OLV). DESIGN: Prospective clinical study. SETTING: Inpatient thoracic surgery and anesthesia clinic at an University hospital. PATIENTS: 15 patients with esophageal cancer who were scheduled for radical surgery. INTERVENTIONS: Arterial oxygenation, shunt fraction, and hemodynamics were evaluated at 20 min after the start of operation, at 20 minutes after the initiation of OLV under zero end-expiratory pressure (ZEEP), 20 minutes after the application of 4 cm PEEP to the dependent lung, at 20 minutes after OLV under ZEEP, 20 minutes after the application of 4 cm CPAP to the nondependent lung, and again under ZEEP, and after the combined application of PEEP and CPAP to the dependent and nondependent lungs. MEASUREMENTS AND MAIN RESULTS: There were no significant changes in mean pulmonary artery pressure, mean arterial blood pressure, heart rate, mixed venous partial pressure of oxygen, or arterial and mixed venous saturation of oxygen (SVO(2)) during this study. Arterial partial pressure of oxygen (pO(2)) increased and shunt fraction values decreased significantly after the application of PEEP (pO(2); 197.8 +/- 32.9 mmHg, Qs/Qt; 22.9 +/- 5.6%), CPAP (pO(2); 212.6 +/- 15.9 mmHg, Qs/Qt; 22.8 +/- 5.9%), and combination of PEEP and CPAP (pO(2); 222.0 +/- 42.8 mmHg, Qs/Qt; 24.1 +/- 6.4%) compared with ZEEP (pO(2); 128.1 +/- 37.5 mmHg, Qs/Qt; 33.2 +/- 6.8% ). But there were no significant differences regarding oxygenation and shunt fraction during PEEP, CPAP, or the combination of PEEP and CPAP. CONCLUSIONS: The application of PEEP to the dependent lung, CPAP to the nondependent lung, and the combination of PEEP and CPAP, are useful for improving oxygenation and decreasing Qs/Qt.

Adult↗

Diabetes attenuates the minimum anaesthetic concentration (MAC) and MAC-blocking adrenergic response reducing actions of clonidine in rats.

BACKGROUND: It is well known that clonidine, an alpha2 agonist, reduces anaesthetic requirement and attenuates haemodynamic responses against noxious stimuli. However, the diabetic state is known to affect several functions of alpha2 adrenoceptors. We investigated the effects of streptozotocin (STZ)-induced diabetes mellitus (DM) on these beneficial actions of clonidine in halothane-anaesthetized rats. METHODS: The rats were randomly assigned to one of three groups: diabetes (n=24, induced by 50 mg x kg(-1) IV STZ), diabetes treated with insulin (n=24), or control (n=24). We evaluated the effects of clonidine on minimum anaesthetic concentration (MAC) and minimum concentration of halothane needed to suppress cardiovascular responses evoked by a noxious stimulus (MAC-blocking adrenergic responses: MAC-BAR) in each group. MAC and MAC-BAR of halothane were determined by the tail clamp method. MAC-BAR was defined as the MAC which attenuated haemodynamic responses within 10% following the tail clamp. RESULTS: The diabetic state decreased MAC of halothane by approximately 10%, while MAC-BAR of halothane had been little affected. In the diabetes group, MAC reducing action of clonidine (30 and 100 microg x kg(-1), IV) was completely abolished and MAC-BAR reducing action of clonidine was partially reduced (30 but not 100 microg x kg(-1), IV). Insulin treatment preserved these actions of clonidine. CONCLUSION: It is suggested that the diabetic state attenuates the beneficial actions of clonidine and that insulin treatment of diabetes preserves these actions of clonidine.

Adrenergic alpha-Agonists↗

Evaluation of diagonal earlobe crease as a marker of coronary artery disease: the use of this sign in pre-operative assessment.

In this study, we examined the usefulness of the earlobe crease sign as a marker of coronary artery disease in the pre-operative assessment of patients. We were interested in evaluating this sign for use in emergency patients. We investigated 530 patients, aged > 40 years, undergoing elective surgery. If the electrocardiogram was abnormal or the patient reported symptoms suggesting coronary artery disease, further cardiac examinations were performed. Patients who demonstrated evidence of coronary artery disease in the additional investigations or had a clear history of coronary artery disease were classified as the abnormal coronary group. Other patients with no history and/or normal investigations were classified as the normal coronary group. The assessment of earlobe crease sign was performed prior to anaesthesia, and the sensitivity, specificity and positive predictive value of this sign were calculated. We found that the sensitivity and specificity was high regardless of age, except for specificity in patients > 70 years old. The data suggest that the earlobe crease sign may be a useful marker for the presence of coronary artery disease in patients undergoing emergency operations in which little or no history and investigations are available. However, more work is required to assess the use of this sign in other ethnic groups.

Adult↗