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Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 199 records · Page 11Linked to original sources

Anterior decompression with single segmental spinal interbody fusion for lumbar burst fracture.

STUDY DESIGN: The clinical and radiologic records for seven patients with lumbar burst fracture who underwent anterior decompression with single segmental interbody fusion were reviewed. OBJECTIVE: To determine the clinical results obtained with this method and its influence on the intervertebral disc degeneration inferior to the fusion. SUMMARY OF BACKGROUND DATA: Some patients with Denis' type B fracture can tolerate one-segment anterior fusion. However, there is no reliable information in the literature regarding the juxtafusional disc degeneration after one-segment fusion. METHODS: Seven patients with type B lumbar burst fractures, including four with cleavage fracture of the lower endplate, underwent anterior single segmental fusion; three patients underwent surgery with no instrumentation, and four underwent surgery with Kaneda instrumentation. The mean follow-up period lasted 85 months. The kyphosis angle and inferior intervertebral disc height adjacent to the fusion were measured before and after surgery. Pain and working status were evaluated using the scales proposed by Denis et al. RESULTS: Significant correction loss was obtained 1 year after surgery in the patients in whom no instrumentation was used (7.3 +/- 0.6 degrees), compared with the correction loss in patients whose surgery included the use of instrumentation (0.3 +/- 0.5 degree; P = 0.00001). No further correction losses were seen in either group at the final follow-up examination. No marked reduction in disc height was observed in any patient, including the four patients with cleavage fracture of the lower endplate. All patients returned to their previous occupation; five patients were rated as P1 (no pain) and W1 (returned to heavy labor), and two patients were rated as P2 (minimal pain) and W2 (return to heavy labor with lifting restrictions) at the final follow-up examination. CONCLUSIONS: There was slight correction loss within 1 year when no instrumentation was used, but this deformity did not affect the clinical results. The results provided no evidence that cleavage fracture of the lower endplate accelerates degeneration of the adjacent intervertebral disc.

Adolescent↗

Induction of human leukocyte antigen (HLA)-A2-restricted and MAGE-3-gene-derived peptide-specific cytolytic T lymphocytes using cultured dendritic cells from an HLA-A2 esophageal cancer patient.

BACKGROUND AND OBJECTIVES: Using peripheral blood mononuclear cells (PBMCs) from a 10-year survivor with established human leukocyte antigen (HLA)-A2(+) and MAGE-3(+) esophageal cancer cell line (KYSE-170), we examined the induction of HLA-A2-restricted and MAGE-3-gene-derived peptide (FLWGPRALV, amino acids 271-279)-specific cytolytic T lymphocytes (CTLs). METHODS: Autologous dendritic cells (DCs) cultured with granulocyte-macrophage colony stimulating factor and interleukin-4 were used as antigen presenting cells. PBMCs were stimulated by peptide-pulsed DCs in vitro. RESULTS: PBMC cocultured with FLWGPRALV-pulsed DCs could induce the relevant peptide-specific CTLs, which had tumor necrosis factor production and specific cytotoxicity against relevant peptide-pulsed autologous DCs (34%, effector:target ratio = 40:1). Moreover, they showed specific cytotoxicity against the autologous esophageal cancer cell line KYSE-170 (17%, effector:target ratio = 40:1). CONCLUSIONS: These results suggest that FLWGPRALV-pulsed cultured DCs would be a potent candidate for peptide vaccine against HLA-A2(+) and MAGE-3(+) esophageal cancer.

Antigen-Presenting Cells↗

Keishi-bukuryo-gan prevents the progression of atherosclerosis in cholesterol-fed rabbit.

In this study, we examined whether in vivo keishi-bukuryo-gan (a Kampo formulation) could prevent the progression of atherosclerosis in cholesterol-fed rabbits, an animal model for hypercholesterolaemia. Sixteen male Japanese white rabbits (2 kg body weight) were divided into two groups. Group A (n = 8) was fed standard rabbit chow containing 1% cholesterol for 8 weeks. Group B (n = 8) was fed standard rabbit chow containing 1% cholesterol and 1% keishi-bukuryo-gan for 8 weeks. At the end of the experiment, average plasma concentrations of total-cholesterol and IDL-cholesterol were 2055.9 +/- 201.8 mg/dL and 408.1 +/- 62.6 mg/dL in group A and 1950.5 +/- 126.3 mg/dL and 407.6 +/- 56.6 mg/dL in group B, respectively. The percentage of the surface area of the total thoracic aorta with visible plaque was significantly reduced by keishi-bukuryo-gan administration; group A was 33.2% +/- 5.3% and group B was 14.3% +/- 2.9%. beta-very low density lipoprotein (VLDL) and low density lipoprotein (LDL) isolated from cholesterol fed rabbits treated with keishi-bukuryo-gan (group B) were shown to be highly resistant to oxidative modification by cupric ion. Sera isolated from rabbits administered keishi-bukuryo-gan had reduced lipid peroxide formation compared with those from rabbits without keishi-bukuryo-gan. Thus, keishi-bukuryo-gan prevents the progression of atherosclerosis in cholesterol-fed rabbits in vivo by limiting oxidative LDL modification.

Animals↗

Effect of Choto-san, a kampo medicine, on impairment of passive avoidance performance in mice.

In mice with procephalic ischaemia loading, disrupted passive avoidance retention performance was dose-dependently improved by Choto-san, but this effect was antagonized by NAN-190, a serotonin1A receptor antagonist. In mice with decreased intracerebral serotonin concentration, Choto-san prevented disturbance in acquiring a passive avoidance response after scopolamine administration, but did not influence the decreased serotonin concentration. These results suggested that Choto-san showed the anti-amnestic effect based on the stimulation of serotonin1A receptors.

Animals↗

Effect of extract prepared from the roots of Paeonia lactiflora on endothelium-dependent relaxation and antioxidant enzyme activity in rats administered high-fat diet.

This study examined the effect of Paeoniae Radix (PR) on endothelial function and the activity of superoxide dismutase (SOD) of erythrocytes in rats administered a high-fat diet. Administration of the extract of PR increased the endothelium-dependent relaxation and the activities of SOD compared with high the cholesterol diet group significantly. Hypercholesterolaemia induced an increase of endothelial superoxide anion and endothelial dysfunction. Paeoniae Radix is suggested to have a protective effect on endothelial cells and their function.

Animals↗

Long-acting calcium channel antagonist pranidipine prevents ventricular remodeling after myocardial infarction in rats.

The purpose of this study was to examine the effects of the long-acting calcium channel antagonist pranidipine on ventricular remodeling, systolic and diastolic cardiac function, circulating humoral factors, and cardiac mRNA expression in myocardial infarcted rats. Myocardial infarction (MI) was produced by ligation of the coronary artery in Wistar rats. Three mg/kg per day of pranidipine was randomly administered to the infarcted rats. Hemodynamic measurements, Doppler echocardiographic examinations, analyses of the plasma levels of humoral factors, and myocardial mRNA expression were performed at 4 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 24.2 +/- 1.2mmHg and 5.4 +/- 0.6 mmHg. Pranidipine reduced LVEDP and CVP to 13.6 +/- 1.4mmHg (P < 0.01) and 2.5 +/- 0.4mmHg (P < 0.01). The weight of the left and right ventricles in MI was significantly higher than in the sham-operated rats (sham, 2.02 +/- 0.04 and 0.47 +/- 0.02g/kg; MI, 2.18 +/- 0.05 and 0.79 +/- 0.04g/ kg; P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3mm (P < 0.01) (sham, 6.4 +/- 0.3mm). Pranidipine prevented an increase in the weight of the left and right ventricles (2.02 +/- 0.04 and 0.6 +/- 0.03g/kg, P < 0.01) and LVDd (7.9 +/-0.2mm, P < 0.01 to MI). Plasma renin activity (PRA), and plasma epinephrine, norepinephrine, and dopamine concentrations in MI were higher than those of the sham-operated rats. Pranidipine decreased the PRA and plasma cathecolamine levels of the myocardial infarcted rats to the level of the sham-operated rats. Moreover, the rats in MI showed systolic dysfunction, shown by decreased fractional shortening (sham, 31 +/- 2% vs MI, 15 +/- 1%; P < 0.01) and diastolic dysfunction shown by the E-wave deceleration rate (sham, 12.8 +/- 1.1 m/s2; MI, 32.6 +/- 2.1 m/s2; P < 0.01). Pranidipine significantly prevented systolic and diastolic dysfunction. The increases in beta-myosin heavy chain (MHC), alpha-skeletal actin, and atrial natriuretic polypeptide mRNAs in the noninfarcted left ventricle and right ventricle at 4 weeks after the myocardial infarction were significantly suppressed by the treatment with pranidipine. On the other hand, depressed alpha-MHC was restored to normal levels by pranidipine in both regions. In conclusion, pranidipine prevents the left ventricular remodeling process accompanied by systolic and diastolic dysfunction, and inhibits abnormal cardiac gene expression after myocardial infarction.

Analysis of Variance↗

Transfer function analysis of the circulation in patients undergoing sevoflurane anesthesia.

PURPOSE: The effects of sevoflurane anesthesia on the interactions between heart rate, blood pressure and respiration were assessed using transfer function analysis. METHODS: Nine ASA 1 or 2 patients undergoing elective surgery were involved. They were paralysed and their lungs were mechanically ventilated during sevoflurane anesthesia. Instantaneous heart rate (IHR) from electrocardiogram, instantaneous lung volume (ILV) by respiratory inductive plethysmography and mean blood pressure (MBP) by arterial tonometry were obtained during conscious state, and 1MAC and 2MAC of sevoflurane anesthesia. Transfer function analysis for the relationships between ILV and IHR, ILV and MBP, MBP and IHR were made for five minute periods during which the respiratory rate was varied in a standardized fashion. RESULTS: In awake patients transfer magnitudes for the relationships between ILV and IHR and between MBP and IHR in the 0.04-0.5Hz frequency band were 8.9 +/- 7.7 bpm x l(-1) and 0.95 +/- 0.44 bpm x mmHg(-1) respectively. Sevoflurane 2MAC decreased these values to 1.2 +/- 0.7 (P = 0.014) and 0.26 +/- 0.14 (P < 0.01) respectively, but phases were not affected. Neither transfer magnitudes nor phases between ILV and MBP were affected during sevoflurane anesthesia. Coherence for the relationships between ILV and IHR and between MBP and IHR were decreased during 1MAC sevoflurane anesthesia but not affected during 2MAC sevoflurane anesthesia. CONCLUSIONS: The interactions between heart rate, blood pressure and respiration were altered by sevoflurane anesthesia. These findings could be explained by the attenuation of autonomic nervous system activity.

Adult↗

Heart rate and blood pressure power spectral analysis during calcium channel blocker induced hypotension.

PURPOSE: To observe heart rate (HRV) and blood pressure variability (BPV) as indices of neurocirculatory responses to induced hypotension with diltiazem and/or nicardipine for hip surgery. METHODS: Thirty-six ASA I-II patients received diltiazem (group D, n = 12), nicardipine (group N, n = 12) or combination of diltiazem/nicardipine (group DN, n = 12). The intensity of HRV and BPV, was determined by spectral analysis of HRV and BPV before anesthesia (T0), just before induced hypotension (T1), and at 10 and 30 min after the start of induced hypotension (T2 and T3, respectively). The logarithmic HRV and BPV were integrated: sympathetic and parasympathetic mediated low frequency area (0.06-0.1 Hz, LF), parasympathetic related high frequency area (0.15-0.4 Hz, HF) and total frequency area (0.01-0.4 Hz). Blood loss was assessed by weighing gauzes and measuring suction. RESULTS: Group DN had less blood loss (466 +/- 46 ml, mean +/- SEM) than group D (733 +/- 100 ml, P < 0.05). Diltiazem (11.4 +/- 0.9 microg x kg(-1) x min(-1)), and combination of diltiazem (0.25 +/- 0.01 mg x kg(-1)) and nicardipine (5.9 +/- 0.9 microg x kg(-1) x min(-1)) decreased LF-HRV at T2 and T3 (P < 0.05 vs T0 and T1), while nicardipine (8.1 +/- 0.8 microg x kg(-1) x min(-1)) showed increase in LF-HRV at T2 (P < 0.05 vs T1). HF-HRV unchanged through hypotension except for a decrease in group N at T3 (P < 0.05 vs T1). There were no increases in HF-BPV, and LF-BPV, except for a diltiazem induced decrease in LF-BPV at T3 (P < 0.05 vs T0 and T1). CONCLUSION: Group D and group DN can be used for deliberate hypotension without an increase in sympathetically mediated LF-HRV.

Adult↗

Is the use of catecholamine before ischemic arrest safe? Effect of catecholamine on rat heart ischemia/reperfusion injury.

Using an isolated working heart model, we studied the effects of dopamine, adrenaline, or noradrenaline pretreatment on ischemia/reperfusion injury. Hearts from Wistar rats were perfused in the first 20-minute working mode, 15 minutes in Langendorff mode, and in the second 20-minute working mode. Hearts were treated with dopamine (0.52 and 2.60 mmol/L), adrenaline (16 and 80 nmol/L), or noradrenaline (16 and 80 nmol/L) during the second working perfusion, then arrested with St. Thomas' Hospital cardioplegic solution and subjected to global ischemia (37 degrees C or 20 degrees C). During reperfusion, recoveries of cardiac function and creatine kinase leakage were measured. At 37 degrees C, dopamine and adrenaline had a harmful effect at both doses; noradrenaline was harmful at a high dose but beneficial at a low dose. At 20 degrees C, adrenaline, dopamine, and noradrenaline had a harmful effect at high doses but no harmful effect at low doses. To determine the role of beta adrenergic stimulation before ischemia, a dose-response study was undertaken with isoprotelenol and milrinone at 37 degrees C. Combined pretreatment with isoprotelenol and milrinone accelerated ischemia/reperfusion injury dose-dependently. Preischemic beta adrenergic stimulation thus plays a significant role in the deleterious effect of catecholamine pretreatment at high doses. At low doses, however, the effect of the inotropic agent could be changed depending on ischemic temperature. Our results suggest that catecholamine should not be given at high doses before ischemia, regardless of temperature during ischemia.

Adrenergic beta-Agonists↗

BDM (2,3-butanedione monoxime), an inhibitor of myosin-actin interaction, suppresses myofibrillogenesis in skeletal muscle cells in culture.

During the initial phase of myofibrillogenesis in developing muscle cells, the majority of thin filaments lie parallel to, and exhibit correct polarity and spatial position with thick filaments, as in mature myofibrils. Since myosin is known to function as an accelerator of actin polymerization in vitro, it has been postulated that myosin-actin interaction is important in the initial phase of myofibrillogenesis. To clarify further the role of actin-myosin interaction in myofibril formation during development, BDM (2, 3-butanedione 2-monoxime), an inhibitor of myosin ATPase, was applied to primary cultures of skeletal muscle to inhibit myosin activity during myofibrillogenesis, and myofibril formation was examined. When 10 mM BDM was added to the myotubes just after fusion and the cultures were maintained for a further 4 days, cross-striated myofibrils were scarcely observed by fluorescence microscopy when examined by staining with antibodies to actin, myosin, troponin and alpha-actinin, whereas in the control myotubes not exposed to BDM, typical sarcomeric structures were detected. Electron microscopy revealed a disorganized arrangement of myofilaments and incomplete sarcomeric structures in the BDM-treated myotubes. Thus, formation of cross-striated myofibrils was remarkably suppressed in the BDM-treated myotubes. When the myotubes cultured in BDM-containing media were transferred to control media, sarcomeric structures were formed in 2-3 days, suggesting that the inhibitory effect of BDM on myotubes is reversible. These results suggest that actin-myosin interaction plays a critical role in the early process of myofibrillogenesis.

Actins↗

Gait analysis following varus osteotomy of the femur for hip osteoarthritis.

The purpose of this study was to evaluate differences in the gait patterns of healthy and osteoarthritic hips, and changes in these patterns after intertrochanteric varus osteotomy of the femur, in relation to the strength of the muscles around the hip joint. We measured the strength ratio of hip abductor muscles, temporal and distance factors, and pelvic movement, and carried out dynamic electromyography (EMG) in 24 women who underwent unilateral varus osteotomy of the femur for hip osteoarthritis (OA), 30 non-surgically-treated women with hip OA, and 54 healthy women. The stance phase time was shorter and the strength ratio of hip abductor muscles was lower in the operated patients than these values in the other two groups, changes in pelvic obliquity and tilt were smaller, and changes in the percent maximum voluntary contraction of the gluteus medius and tensor fascia latae muscles were greater than these values in the healthy subjects. This study showed the postoperative reappearance of the simulated conditions in the hip before varus osteotomy of the femur, providing evidence that the pelvis was horizontally maintained during walking due to the decreased stance phase time and increased performance of the hip abductor muscles achieved after this procedure.

Adult↗

Hybrid functional electrical stimulation for energy-efficient restoration of standing-up motion.

OBJECTIVE: To find the most energy-efficient standing-up motion for quadriceps and to restore that motion in a person with complete paraplegia by using hybrid functional electrical stimulation. DESIGN: Nonrandomized control trial. SETTING: A referral center and institutional practice providing outpatient care. PARTICIPANTS: Twenty-nine volunteer samples were used to collect normal data. One patient with complete paraplegia received treatment for the restoration of standing-up motion. MAIN OUTCOME MEASUREMENTS: Joint angles and ground reaction forces were investigated during the standing-up motion with arms crossed in front of the chest with an ankle-foot orthosis set at various angles. The electromyogram (EMG) was performed during the standing-up motion with and without the orthosis. The energy costs of quadriceps during the standing-up motion were calculated using a mathematical model. Standing-up motion in a person with complete paraplegia was restored and then analyzed by measuring the vertical ground reaction force and the hip and knee angles. RESULTS: Quadriceps energy cost was lowest (p < .05) in subjects wearing the ankle-foot orthosis set at neutral with a flat sole line. In the integrated EMG the peak value of rectus femoris contraction was larger with the orthosis than without it (p < .05). A patient with complete paraplegia was able to stand up smoothly from a wheelchair based on stimulation patterns obtained from healthy subjects. CONCLUSIONS: Energy-efficient standing-up motion in a patient with complete paraplegia was restored when the patient used an ankle-foot orthosis set at neutral with a flat sole line.

Adult↗

Muscle fatigue from intermittent stimulation with low and high frequency electrical pulses.

OBJECTIVE: To evaluate muscle fatigue resulting from intermittent low frequency and high frequency stimulation for the application of closed-loop control in functional electrical stimulation (FES). DESIGN: Nonrandomized trial. SETTING: General community, a referral center, institutional practice, and ambulatory care. PATIENTS: Twenty healthy nondisabled men volunteered for the normal muscle group. Four paraplegic men with implanted percutaneous intramuscular electrodes for FES volunteered for the paralyzed muscle group. INTERVENTION: The stimulation frequency was set at low (20 Hz) or high (100 Hz). Stimulation was administered in 4-second bursts at the start of 60-second, 120-second, and 240-second periods (duty cycles of 1/15, 1/30, and 1/60, respectively). MAIN OUTCOME MEASUREMENTS: Knee extensor torques were measured during intermittent electrical stimulation. A strength decrement index (SDI) was used to assess muscle fatigue. Actual knee extensor torques in the paraplegic men were also measured with an isokinetic dynamometer. RESULTS: Muscle fatigue was significantly greater at 20 Hz than at 100 Hz for both the nondisabled and the paraplegic subjects (p < .0001). Muscle fatigue at the 1/15 cycle was significantly reduced (p < .01). CONCLUSIONS: Muscle fatigue was greater at the lower frequency (20 Hz) than at the higher frequency (100 Hz) during intermittent electrical stimulation, suggesting that intermittent high frequency stimulation may be valuable in the development of closed-loop control strategies for FES.

Adult↗

Efficacy of Choto-san on vascular dementia and the protective effect of the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death.

Two different multicenter studies on the efficacy of Choto-san on patients with vascular dementia, one a well-controlled but non-double blind (60 patients), the other a double-blind controlled study (139 patients), were performed. In the well-controlled study, Choto-san was superior in global improvement rating, utility rating and improvement of subjective symptoms, psychiatric symptoms and disturbance in daily living activities. In the double-blind study, with more objective criteria than the well-controlled study, Choto-san was also superior in global improvement rating, utility rating and improvement of subjective symptoms, psychiatric symptoms and disturbance in daily living activities. These results suggest that Choto-san is effective in the treatment of vascular dementia. Uncaria sinensis (OLIV.) HAVIL. (US) is the main medicinal plant composing Choto-san. Glutamate-induced cell death of cultured cerebellar granule cells was protected by the application of water extract of US in a dose-dependent manner, and concentrations of 10(-5) to 10(-4) g/ml had a significant effect compared to exposure to glutamate only. Further, the increase of 45Ca2+ influx into cells by glutamate was also blocked by the water extract in a dose-dependent manner. These results suggest that US has a protective effect on glutamate-induced neuronal death in cultured cerebellar granule cells through the inhibition of Ca2+ influx.

Activities of Daily Living↗

Elevated serum L-selectin levels and abnormal regulation of L-selectin expression on leukocytes in atopic dermatitis: soluble L-selectin levels indicate disease severity.

BACKGROUND: L-selectin mediates leukocyte rolling on endothelium at sites of inflammation, suggesting that L-selectin may be involved in the development of cutaneous lesions of atopic dermatitis (AD). After leukocyte activation, L-selectin is rapidly shed from the cell surface. OBJECTIVE: The purpose of this study was to assess leukocyte L-selectin expression and quantitate levels of serum soluble L-selectin (sL-selectin) in patients with AD. METHODS: Serum sL-selectin levels in patients with AD (n = 70), contact dermatitis (n = 18), and psoriasis (n = 23), as well as normal control subjects (n = 30), were examined by using an ELISA. The L-selectin expression on leukocytes in heparinized blood samples from patients with AD (n = 18) and normal control subjects (n = 10) was also examined by flow cytometry. RESULTS: Serum levels of sL-selectin in patients with AD were significantly higher than those found in normal control subjects. Furthermore, sL-selectin levels correlated positively with disease severity and total serum IgE levels in AD. The expression of L-selectin on B cells, monocytes, and neutrophils was significantly decreased in patients with AD compared with normal control subjects, although those on CD4(+) or CD8(+) T cells from patients with AD were similar to those from normal control subjects. CONCLUSION: Elevated sL-selectin levels and the abnormal expression of L-selectin on some leukocyte subsets in patients with AD may correlate with inflammation associated with AD. Furthermore, the level of sL-selectin may be a useful immunologic indicator for disease activity in AD.

Adolescent↗

Fast and slow recovery phases of goldfish behavior after transection of the optic nerve revealed by a computer image processing system.

As the goldfish is a common experimental animal for vision research, including psychophysical behavior, it is very important to quantitatively score fish behavior. We have previously developed a computer image processing system which can acquire the positional coordinates of goldfish moving freely in an aquarium and determine turning directions (go straight, right or left turn). In the present study, an algorithm to determine tilting angles of moving goldfish was constructed. We also made histograms for quantifying the interaction between pairs of goldfish (two-point distance). By using these histograms, we estimated the time-course of behavioral regeneration after optic nerve transection in goldfish. Control goldfish showed an equal percentage of right or left turns and maintained an upright position in a dorsoventral axis. When the optic nerve of a goldfish was unilaterally sectioned, the goldfish showed predominant turning and slight tilting toward the intact eye. The abnormal turning and tilting behaviors lasted for 10-14 days and then gradually decreased, returning to control behaviors by one month after the unilateral transection. When the optic nerve of a single goldfish was bilaterally sectioned, it did not show any preferential turning and tilting behavior, which is similar to what was observed in control goldfish. However, the trace maps showed that, after bilateral sectioning, fish preferred to cross the center of the tank, which was unlike control fish. In control pairs, one goldfish chased the other with a fixed small range of two-point distances. However, in pairs of goldfish with bilateral transection of the optic nerve, the blind goldfish behaved independently of each other, with a long two-point distance. The long two-point distance of the blind goldfish lasted for at least two months and then slowly returned to control two-point distance by four months after bilateral transection. Such fast and slow recovery in goldfish behaviors evoked after unilateral and bilateral transection of the optic nerve is discussed with respect to reconnection of regenerating optic nerves in the fish central nervous system. This computer image processing system is a useful tool with which we can quickly and easily quantify fish behavior.

Algorithms↗

Synthesis and in vivo evaluation of [11C]SA6298 as a PET sigma1 receptor ligand.

The potential of a 11C-labeled selective sigma1 receptor ligand, 1-(3,4-dimethoxyphenethyl)-4-[3-(3,4-dichlorophenyl)propyl]piperazine ([11C]SA6298), was evaluated as a positron emission tomography (PET) ligand for mapping sigma, receptors in the central nervous system and peripheral organs. [11C]SA6298 was synthesized by methylation of the desmethyl SA6298 with [11C]CH3I, with the decay-corrected radiochemical yield of 39 +/- 5% based on [11C]CH3I and with the specific activity of 53 +/- 17 TBq/mmol within 20 min from end of bombardment (EOB). In mice, the uptake of [11C]SA6298 was significantly decreased by carrier loading in the brain, liver, spleen, heart, lung, small intestine, and kidney in which sigma receptors are present as well as in the skeletal muscle. Pretreatment with SA6298 also blocked the uptake of [11C]SA6298 by these organs except for the small intestine, but significant displacement of [11C]SA6298 by posttreatment with SA6298 was observed only in the heart, lung, and muscle. In the blocking study with one of the eight sigma receptor ligands, including haloperidol, SA6298, NE-100, (+)-pentazocine, SA4503, (-)-pentazocine, (+)-3-PPP, and (+)-SKF 10,047 (in the order of the affinity for sigma1 receptor subtype), only SA6298 and an analog SA4503 significantly reduced the brain uptake of [11C]SA6298 to approximately 80% of the control, but the other six ligands did not. Peripherally, the uptake of [11C]SA6298 by the organs described above was decreased predominantly by SA6298 or SA4503, but the blocking effects of the other five ligands except for NE-100 depended on their affinity for sigma1 receptors. The saturable brain uptake of [11C]SA6298, approximately 20%, was also observed by tissue dissection method in rats and by PET in a cat. Ex vivo autoradiography of the rat brain showed a high uptake in the cortex and thalamus. In the cat brain a relatively high uptake was found in the cortex, thalamus, striatum, and cerebellum. These results have indicated a receptor-mediated uptake of the tracer to some extent in the brain and peripheral organs. However, the tracer has a limited potential for the PET study of the brain receptors because of a relatively high nonspecific binding.

Animals↗

Stepwise ethanolysis of tuna oil using immobilized Candida antarctica lipase.

Ethanolysis of fish oil under mild conditions has been strongly desired for preparing the starting materials for the purification of ethyl docosahexaenoate. Thus, we attempted ethanolysis of tuna oil using immobilized Candida antarctica lipase. The immobilized lipase was inactivated in the presence of 2 3 molar equivalent of ethanol against the total fatty acids in tuna oil. To avoid such inactivation, the first step of ethanolysis was conducted at 40 degrees C in a mixture of tuna oil and 1 3 molar equivalent of ethanol using 4% immobilized lipase. After a 10-h reaction, ethanol was consumed and 33% of tuna oil was converted to its corresponding ethyl esters (E-FAs). The reactant is named Gly/E-FA33. The lipase was not inactivated in the presence of 2 3 molar equivalent of ethanol against the total fatty acids in Gly/E-FA33. These findings and the consideration of several factors affecting ethanolysis of tuna oil led to the development of the two- and three-step ethanolyses. The two-step reaction was performed as follows: the first step was carried out at 40 degrees C for 12 h in a mixture of tuna oil and 1 3 molar equivalent of ethanol with 4% immobilized lipase; the second step was performed for 36 h (total reaction period, 48 h) after adding 2 3 molar equivalent of ethanol. On the other hand, the three-step reaction was conducted as follows: the first step was conducted under the same conditions as those in the two-step ethanolysis; in the second and third steps, 1 3 molar equivalent of ethanol was added after 12 and 24 h, respectively; and in the third step, the mixture was shaken for 24 h (total, 48 h). Both types of ethanolyses achieved the conversion of 95% or more of tuna oil to its corresponding E-FAs. To investigate the lipase stability, the two- and three-step ethanolyses were repeated by transferring the enzyme to a fresh substrate mixture of the first step after finishing one cycle of reaction. The two- and three-step reactions maintained over 95% of the conversion for 70 d and over 100 d, respectively.

Journal Article↗