Biomedical subjects

S Okuno

Publications and source records attributed to S Okuno.

At least 55 records · Page 3Linked to original sources

PubMed2001

Changes in body fat mass in male hemodialysis patients: a comparison between diabetics and nondiabetics.

Nutritional status is an important factor that affects morbidity and mortality of hemodialysis patients. We investigated 1-year changes in body fat mass of male patients undergoing hemodialysis (duration, 4.9 +/- 2.5 years). Fat mass of 217 male patients (age 60 +/- 13 years) was measured by dual x-ray absorptiometry twice in a 1-year interval. The patients consisted of 70 with diabetes mellitus and 147 without diabetes. At the second measurement compared with the first, a significant decrease in fat mass was observed in diabetic patients (12.1 +/- 4.4 kg versus 11.0 +/- 4.7 kg; P < 0.01); there were no significant changes in fat mass in nondiabetic patients (12.2 +/- 5.0 kg versus 11.9 +/- 4.9 kg; P = 0.15). Significant differences in percent fat mass changes per year were seen between diabetic and nondiabetic patients (P < 0.05). Protein catabolic rates of diabetic patients were significantly lower than those of nondiabetic patients (0.86 +/- 0.18 g/kg/d versus 0.93 +/- 0.19 g/kg/d; P < 0.05). In all patients, there was a significant correlation between protein catabolic rates and percent fat mass changes per year (r = 0.15; P < 0.05). These results showed that body fat mass was decreased significantly in 1 year in male diabetic patients with maintenance hemodialysis, suggesting poorer nutritional status in these patients. Poor protein intake may be one of the risk factors for the decrease in fat mass. Dual x-ray absorptiometry assessment of fat mass changes is suggested as a useful method to examine clinically the nutritional status of hemodialysis patients.

Absorptiometry, Photon↗

PubMed2001

Substrate specificity of Ca(2+)/calmodulin-dependent protein kinase phosphatase: kinetic studies using synthetic phosphopeptides as model substrates.

Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKPase) dephosphorylates and regulates multifunctional Ca(2+)/calmodulin-dependent protein kinases. In order to elucidate the mechanism of substrate recognition by CaMKPase, we chemically synthesized a variety of phosphopeptide analogs and carried out kinetic analysis using them as CaMKPase substrates. This is the first report using systematically synthesized phosphopeptides as substrates for kinetic studies on substrate specificities of protein Ser/Thr phosphatases. CaMKPase was shown to be a protein Ser/Thr phosphatase having a strong preference for a phospho-Thr residue. A Pro residue adjacent to the dephosphorylation site on the C-terminal side and acidic clusters around the dephosphorylation site had detrimental effects on dephosphorylation by CaMKPase. Deletion analysis of a model substrate peptide revealed that the minimal length of the substrate peptide was only 2 to 3 amino acid residues including the dephosphorylation site. The residues on the C-terminal side of the dephosphorylation site were not essential for dephosphorylation, whereas the residue adjacent to the dephosphorylation site on the N-terminal side was essential. Ala-scanning analysis suggested that CaMKPase did not recognize a specific motif around the dephosphorylation site. Myosin light chain phosphorylated by protein kinase C and Erk2 phosphorylated by MEK1 were poor substrates for CaMKPase, while a synthetic phosphopeptide corresponding to the sequence around the phosphorylation site of the former was not dephosphorylated by CaMKPase but that of the latter was fairly good substrate. These data suggest that substrate specificity of CaMKPase is determined by higher-order structure of the substrate protein rather than by the primary structure around its dephosphorylation site. Use of phosphopeptide substrates also revealed that poly-L-lysine, an activator for CaMKPase, activated the enzyme mainly through increase in the V(max) values.

Amino Acid Sequence↗

PubMed2001

Regulation of Ca(2+)/calmodulin-dependent protein kinase kinase alpha by cAMP-dependent protein kinase: I. Biochemical analysis.

Ca(2+)/calmodulin-dependent protein kinases (CaM-kinases) I and IV are activated upon phosphorylation of their Thr(177) and Thr(196), respectively, by the upstream Ca(2+)/calmodulin-dependent protein kinases CaM-kinase kinase alpha and beta, and deactivated upon dephosphorylation by protein phosphatases such as CaM-kinase phosphatase. Recent studies demonstrated that the activity of CaM-kinase kinase alpha is decreased upon phosphorylation by cAMP-dependent protein kinase (PKA), and the relationship between the inhibition and phosphorylation of CaM-kinase kinase alpha by PKA has been studied. In the present study, we demonstrate that the activity of CaM-kinase kinase alpha toward PKIV peptide, which contains the sequence surrounding Thr(196) of CaM-kinase IV, is increased by incubation with PKA in the presence of Ca(2+)/calmodulin but decreased in its absence, while the activity toward CaM-kinase IV is decreased by incubation with PKA in both the presence and absence of Ca(2+)/calmodulin. Six phosphorylation sites on CaM-kinase kinase alpha, Ser(24) for autophosphorylation, and Ser(52), Ser(74), Thr(108), Ser(458), and Ser(475) for phosphorylation by PKA, were identified by amino acid sequence analysis of the phosphopeptides purified from the tryptic digest of the phosphorylated enzymes. The presence of Ca(2+)/calmodulin suppresses phosphorylation on Ser(52), Ser(74), Thr(108), and Ser(458) by PKA, but accelerates phosphorylation on Ser(475). The changes in the activity of the enzyme upon phosphorylation appear to occur as a result of conformational changes induced by phosphorylation on several sites.

Adenosine Triphosphate↗

PubMed2001

Regulation of Ca(2+)/calmodulin-dependent protein kinase kinase alpha by cAMP-dependent protein kinase: II. Mutational analysis.

We previously reported that rat brain Ca(2+)/calmodulin-dependent protein kinase (CaM-kinase) IV is inactivated by cAMP-dependent protein kinase (PKA) [Kameshita, I. and Fujisawa, H. (1991) Biochem. Biophys. Res. Commun. 180, 191-196]. In the preceding paper, we demonstrated that changes in the activity of CaM-kinase IV by PKA results from the phosphorylation of CaM-kinase kinase alpha by PKA and identified six phosphorylation sites, Ser(24) for autophosphorylation, and Ser(52), Ser(74), Thr(108), Ser(458), and Ser(475) for phosphorylation by PKA. In the present study, a causal relationship between the phosphorylation and change in the activity toward PKIV peptide has been studied using mutant enzymes with amino acid substitutions at the six phosphorylation sites. The following conclusions can be drawn from the experimental results: (i) Phosphorylation of Ser74 and/or unidentified sites causes an increase in activity; (ii) phosphorylation of Thr(108) or Ser(458) causes a decrease in the activity; (iii) the inhibitory effect of the phosphorylation of Thr(108) is canceled by the stimulatory effect of the phosphorylation, but that of Ser(458) is not; and (iv) the inhibitory effects of Thr(108) and Ser(458) are synergistic. In contrast to the activity toward PKIV peptide, the activity toward CaM-kinase IV appears to be decreased by the phosphorylation of Thr(108), but not significantly affected by the phosphorylation of Ser(458).

Adenosine Triphosphate↗

PubMed2001

Identification and characterization of CaMKP-N, nuclear calmodulin-dependent protein kinase phosphatase.

Calmodulin-dependent protein kinase phosphatase (CaMKP) dephosphorylates and concomitantly deactivates multifunctional Ca(2+)/calmodulin-dependent protein kinases (CaMKs), such as CaMKI, CaMKII, and CaMKIV. In the present study, a nuclear CaMKP-related protein, CaMKP-N, was identified. This protein consisted of 757 amino acid residues with a calculated molecular weight of 84,176. Recombinant CaMKP-N dephosphorylated CaMKIV. The activity of CaMKP-N requires Mn(2+) ions and is stimulated by polycations. Transiently expressed CaMKP-N in COS-7 cells was localized in the nucleus. This finding together with previous reports regarding localization of CaMKs indicates that CaMKP-N dephosphorylates CaMKIV and nuclear CaMKII, whereas CaMKP dephosphorylates CaMKI and cytosolic CaMKII.

Amino Acid Sequence↗

PubMed2001

Effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis.

OBJECTIVE: We evaluated the effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis by use of data obtained from ophthalmic artery color Doppler flow imaging. METHODS: We examined 11 patients with ocular ischemic syndrome due to internal carotid artery stenosis (>70% stenosis) who were being treated by carotid endarterectomy. Ophthalmic artery color Doppler flow imaging indicated ophthalmic artery flow direction and peak systolic flow velocity and was performed before and at 1 week, 1 month, and 3 months after surgery. RESULTS: We assessed the ophthalmic arteries of 11 patients via color Doppler flow imaging. Before undergoing carotid endarterectomy, five patients showed reversed ophthalmic artery flow. In the other six patients who experienced antegrade ophthalmic artery flow, the average peak systolic flow velocity was 0.09 +/- 0.05 m/s (mean +/- standard deviation). Preoperative reversed flow resolved in each patient 1 week after undergoing surgery. All patients showed antegrade ophthalmic artery flow. The average peak systolic flow velocity in the patients who had preoperative antegrade flow rose significantly, to 0.21 +/- 0.14 m/s (P < 0.05). There was no significant change as compared with findings at 1 week after surgery. During the follow-up period (mean, 32.4 mo), no patients complained of recurrent visual symptoms. At the end of the study period, visual acuity had improved in five patients and had not worsened in the other six patients. CONCLUSION: Carotid endarterectomy was effective for improving or preventing the progress of chronic ocular ischemia caused by internal carotid artery stenosis.

Angiography↗

PubMed2001

Mouse chromosome 19 and distal rat chromosome 1: a chromosome segment conserved in evolution.

Through a combination of radiation hybrid mapping and studies by FISH and zoo-FISH we have made a comparative investigation of the distal portion of rat chromosome 1 (RNO1) and the entire mouse chromosome 19 (MMU19). It was found that homologous segments of RNO1 and MMU19 are similar in banding morphology and in length as determined by several different methods, and that the gene order of the 46 genes studied appears to be conserved across the homologous segments in the two species. High-resolution zoo-FISH techniques showed that MMU19 probes highlight only a continuous segment on RNO1 (1q43-qter), with no detectable signals on other rat chromosomes. We conclude that these data suggest the evolutionary conservation of a chromosomal segment from a common rodent ancestor. This segment now constitutes the entire MMU19 and a large segment distally on RNO1q in the mouse and rat, respectively.

Animals↗

PubMed2001

Correlation between peritoneal mesothelial cell cytology and peritoneal histopathology with respect to prognosis in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a serious complication seen in patients on long-term continuous ambulatory peritoneal dialysis (CAPD). We have previously reported that mesothelial cells in effluent dialysate significantly increased in size as the duration of CAPD progressed. In this study, we investigated the relationship between mesothelial cytology, histopathology of the peritoneum, and clinical outcomes of 34 CAPD patients. METHODS: When peritoneal dialysis catheters were inserted (n = 7) or removed (n = 27), a peritoneal biopsy was performed and results compared with mesothelial cytology in effluent dialysate. RESULTS: A significant positive correlation was noted between the duration of CAPD and the surface area of peritoneal mesothelial cells (r = 0.721, p < 0.0001). The surface area of mesothelial cells in peritoneal sclerosis (n = 9; 584 +/- 97 microm(2)) was significantly greater than in peritoneal fibrosis (n = 14; 389 +/- 26 microm(2), p < 0.05), pathologic acute peritonitis (n = 3; 223 +/- 10 microm(2), p < 0.005), and normal peritoneum (n = 7; 247 +/- 12 microm(2), p < 0.001). The surface area in sclerosing peritonitis (n = 1; 1,200 microm(2)) was greater than that of all the others. Giant cells were found in the 1 case with sclerosing peritonitis and in 3 of 9 cases with peritoneal sclerosis, although they were found in only 1 of 14 patients with peritoneal fibrosis and in none of those with pathologic acute peritonitis or normal peritoneum. As the surface area of mesothelial cells increased to more than 400 microm(2) and giant cells appeared in the effluent, the frequency of peritoneal sclerosis and/or clinical SEP increased. CONCLUSION: An increase in the mesothelial cell surface area and the emergence of giant cells in the effluent indicate advanced peritoneal histopathology, and may be useful indicators to determine appropriate timing of discontinuation of CAPD to prevent the development of SEP.

Adult↗

PubMed2001

Aneurysm of the posterior inferior cerebellar arteries/communicating artery.

Only 3 cases of aneurysm associated with the communicating artery between both distal posterior inferior cerebellar arteries (PICAs) have been reported in the literature. We present the 4th case of such an aneurysm arising from the communicating artery itself, which is unrelated to the arterial branches. A hypertensive 68-year-old man presented with a Hunt and Hess grade 4 subarachnoid hemorrhage. Angiographic studies revealed that the ruptured aneurysm arose from the fine communicating artery itself interconnecting both distal PICA vermian branches. The right PICA was absent and its vermian territory was supplied by the left PICA through this communicating artery. At surgery, a saccular aneurysm was noted which developed at the top of the arterial loop under the nodulus of the cerebellar vermis and was trapped. The actual prevalence and clinical significance of aneurism associated with the communicating artery interconnecting both PICAs are unknown, but defective embryonal development may lead to congenital vulnerability of the vascular wall, resulting in aneurysm formation.

Aged↗

PubMed2001

Comparative study of 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin staining for quantification of early brain ischemic injury in cats.

There are no staining methods that can reliably and unequivocally detect final infarcts in the acute stage of experimental ischemia. In most instances, 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin and eosin (HE) stainings are accepted for this purpose, but neither is perfect. We performed a comparative study of the TTC immersion method and HE staining for quantification of early brain ischemic injury in cats, focussing on the reproducibility associated with planimetry. Focal brain ischemia was produced by middle cerebral artery (MCA) occlusion via the transorbital approach in 14 cats. After 6 h of occlusion, two slices of 3 mm thickness, passing through the optic chiasma and mammillary body, were selected for pathological examination. TTC immersion and HE staining were both used for planimetric study of the surface of the same slice. The area of the injury was traced manually with the aid of computerized digital planimetry and expressed as a percentage of the area of the contralateral hemisphere. The area of hemispheric injury and the area of gray matter injury were separately calculated in the TTC specimens, and each was compared with the area of gray matter injury in the HE-stained specimens. Measurements were repeated twice on each slice to estimate errors associated with manual tracing of the boundary of the area of injury. The mean percentage values of the area of injury in the TTC-immersed gray matter specimens were lower than those detected by HE staining, although there was a very significant correlation between the two. The differences between each two measurements of TTC-determined gray matter injury were significantly less than those between each two measurements of HE-determined gray matter injury. The differences between each two measurements of TTC-determined hemispheric injury were slightly less than those between each two measurements of TTC-determined gray matter injury, although there was no significant difference between them. For quantifying ischemic injury after 6 h of MCA occlusion in cats, the TTC immersion method is more reproducible and simpler in manner than HE staining, but the results of both are significantly correlated.

Animals↗

PubMed2001

Characteristics of tissue distribution of various polysaccharides as drug carriers: influences of molecular weight and anionic charge on tumor targeting.

Using the Walker 256 model for carcinosarcoma-bearing rats, we intravenously administered 5 polysaccharide carriers with various molecular weights (MWs) and electric charges and tested for their plasma and tissue distribution. Two carriers, carboxymethylated-D-manno-D-glucan (CMMG) and CMdextran (CMDex), showed higher plasma AUC than the other carriers tested, namely, CMchitin (CMCh), N-desulfated N-acetylated heparin (DSH), and hyaluronic acid (HA). This was consistently found to be true over the range of MWs tested. For CMDex, the maximum value of plasma AUC was obtained when the MW exceeded 150 kDa. As for the anionic charge, CMDex (110-180 kDa) with a degree of substitution (DS) of the CM groups ranging from 0.2 to 0.6, showed maximum plasma AUC values. Twenty-four hours after administration, the concentration of CMDex (180-250 kDa; DS: 0.6-1.2) in tumors was more than 3% of dose/g--approximately 10-fold higher than those observed with CMCh, DSH and HA. Doxorubicin (DXR) was bound to these carriers via a peptide spacer, GlyGlyPheGly (GGFG), to give carrier-GGFG-DXR conjugates (DXR content: 4.2-7.0 (w/w)%), and the antitumor effects of these conjugates were tested with Walker 256 carcinosarcoma-bearing rats by monitoring the tumor weights after a single intravenous injection. Compared with free DXR, CMDex-GGFG-DXR and CMMG-GGFG-DXR conjugates significantly suppressed tumor growth, while the CMCh-GGFG-DXR, DSH-GGFG-DXR, and HA-GGFG-DXR conjugates in a similar comparison showed weak tumor growth inhibition. These findings suggest that the antitumor effect of the carrier-DXR conjugates was related to the extent with which the carriers accumulated in the tumors.

Animals↗

PubMed2001

Antimutagenicity of deacylated anthocyanins in purple-fleshed sweetpotato.

The antimutagenicity of the 3-sophoroside-5-glucoside of cyanidin and 3-sophoroside-5-glucoside of peonidin, the anthocyanin derivatives deacylated from the 3-(6,6'-caffeylferulylsophoroside)-5-glucoside of cyanidin (YGM-3) and 3-(6,6'-caffeylferulylsophoroside)-5-glucoside of peonidin (YGM-6) which had been purified from the sweetpotato with purple-colored flesh, was investigated by using Salmonella typhimurium TA 98. A comparison of the antimutagenicity between YGM-3 and YGM-6 and the deacylated derivatives showed that the activity of cyanidin was stronger than that of peonidin. Deacylation of the peonidin-type pigment markedly decreased this antimutagenicity. Caffeic acid showed the strongest antimutagenicity of the constituent organic acids of the anthocyanin pigments, caffeic acid, ferulic acid, and p-hydroxybenzoic acid. These results suggest that the cathecol structure plays an important role in the strong antimutagenicity of anthocyanin pigments.

Acetylation↗

PubMed2001

Pseudoxanthoma elasticum diagnosed 25 years after the onset of cardiovascular disease.

A 63-year-old man who had experienced cerebral infarction and myocardial infarction at an early age, and repeatedly underwent coronary angioplasty was admitted to our hospital for cardiac evaluation. A coronary angiography showed complex multi-vessel disease with significant stenosis in all major vessels and coronary-artery bypass grafts. A funduscopic examination to evaluate hypertensive and diabetic changes revealed angioid streaks. Therefore, a skin biopsy was performed despite the absence of characteristic skin lesions. Histopathologic examinations revealed calcification and fragmentation of elastic fibers. Therefore, he was finally diagnosed as having pseudoxanthoma elasticum 25 years after the onset of cardiovascular disease.

Cerebral Infarction↗

PubMed2001

[An autopsied case of marked cardiac hypertrophy due to multifactorial heart disease in an 85 year-old man who had been socially active].

An autopsied 85-year-old man had suffered from a mild form of diabetes mellitus since the age of 67 and had experienced the first episode of heart failure with arapid ventricular rate of atrial fibrillation at the age of 72. He had remained socially active until he died suddenly of ventricular fibrillation, although he had complications of aortic regurgitation at the age of 76 and later mitral regurgitation at the age of 80. Chest roentgenograms showed gradual increase in the cardiothoratic ratio which reached 68.1% at the final stage. Autopsy revealedmarked left ventricular hypertrophy with a heart weight of 580 g, degeneration ofaortic valves, thickening of mitralvalve cusps and moderate coronary atherosclerosis without ischemic myocardial lesions. There were no specific lesions suggestive of primary cardiomyopathies on microscopic observations and the lesions of both aortic and mitral valves were not significant enough to explain the clinical findings of aortic and mitral regurgitation. Because the pathological examination failed to identify a single disease which was responsible for the marked cardiachypertrophy, we eventually reached the conclusion that the cardiac hypertrophy developed based on a multifactorial heart disease.

Activities of Daily Living↗

PubMed2001

Peripheral ophthalmic artery aneurysm. Report of two cases.

The authors report on two patients with peripheral ophthalmic artery (OphA) aneurysms and demonstrate the mechanism by which these lesions are formed by using OphA color Doppler flow velocimetry imaging. During formation of these two aneurysms, the hemodynamic stress on the OphA was quite significant.

Adult↗

PubMed2001

[A case of glioblastoma associated with dissemination, secondary to intratumoral hemorrhage].

The occasional occurrence of dissemination and tumor-associated hemorrhage from glioblastoma is well known and widely reported in the literature. The authors present a case of cerebral glioblastoma with dissemination possibly caused by intratumoral hemorrhage. Computed tomographic (CT) scan revealed a small hemorrhagic lesion in the right frontal lobe and a sylvian fissure in a 62-year-old man who complained of sudden headache. Four months later, he again presented with neck pain followed by weakness and numbness in the extremities. Magnetic resonance images (MRI) of the cervical spine demonstrated multiple enhanced tumors. After transfer to our institution, a large cystic tumor with ring-like enhancement was found in the right frontal lobe. Progressive neurological deficits prompted an operation on the cervical tumors and a pathological diagnosis of anaplastic astrocytoma with a negative reaction for glial fibrillary acidic protein (GFAP) was made. Intraoperative findings of the second operation for the cerebral tumor disclosed that the tumor extended outside the frontal lobe, growing substantially within the sylvian subarachnoid space and involving middle cerebral artery branches. The results of a pathological study were those consistent with glioblastoma having tumor cells with little positive reaction to GFAP staining. Craniospinal radiation was undertaken as a palliative treatment of the residual tumor. On MRI, multiple nodular dissemination in the lumbo-sacral region was diagnosed. Two months later, the patient suddenly lost consciousness and suffered eye deviation. A CT scan found a large tumor-associated hemorrhage in the right frontal lobe. Emergency evacuation of the hematoma with gross total removal of the residual tumor was performed. He temporarily returned to his preoperative neurological condition but died later due to the recurrent cervical tumor. Dissemination secondary to intratumoral hemorrhage in patients with glioblastoma has not been reported. This rare case shows that hemorrhagic glioblastoma is at risk for dissemination, especially when the hemorrhage occurs in or near the subarachnoid space and tumor cells have a less positive reaction for GFAP staining.

Brain Neoplasms↗

PubMed2001

[A case of spontaneous subarachnoid hematoma of the high cervical spine presenting as Brown-Séquard's syndrome].

Spinal subarachnoid hematoma is a very rare event, occurring exclusively in the thoracic or lumbar region. We report the first recorded case of spontaneous subarachnoid hematoma in the high cervical spine presenting as Brown-Séquard's syndrome. A 57-year-old woman with no prior problems suddenly presented with Brown-Séquard's syndrome at the C1-2 disc space level following occiput neck pain. Her consciousness was clear and urinary retention was not observed. Lumbar puncture revealed no evidence of hemorrhage. Neuroradiological evaluation, including myelography, CT myelography, and MRI, demonstrated a defined hematoma in the cervical subarachnoid space at the C1-2 level. Angiographical study yielded negative findings. The patient's neurological state remained unchanged for the following 6 days. On the 7th day from the onset, a C1 and C2 laminectomy was performed. A defined clot was found after incising the intact dura matter and arachnoid membrane. This clot was easily aspirated except for a small part which was found attached to a pial vessel on the dorsal surface of the spinal cord. No underlying pathology other than coagulated blood was confirmed. Three months postoperatively, she had no neurological deficits. The clinical course of spontaneous spinal subarachnoid hematoma varies according to the rapidity and severity of hematoma formation. An immediate and precise diagnosis using multimodal neuroimagings is vital because decompressive surgery can dramatically ameliorate the neurological sequelae.

Brown-Sequard Syndrome↗

PubMed2001

[Experimental study of pharmacological hypothermia: enhanced neuroprotective effect of a novel 5-HT 1 A agonist SUN N4057 by the pharmacological hypothermia].

PURPOSE: 5-hydroxytryptamine(5-HT) 1 A receptor agonists have a potentially marked neuroprotective reaction by both neuroprotective and hypothermic effects. We previously reported (1) the neuroprotective effect against the cerebral ischemia under normothermic condition, and (2) the hypothermic effect of the novel compound of 5-HT 1 A agonist, SUN N4057. The present investigation was designed to examine the enhancement of the neuroprotective effect by its pharmacological hypothermia. METHODS: In 24 anesthetized cats(body weight 1.9-4.6 kg), the left middle cerebral artery(MCA) occlusion was performed via the transorbital approach. Just after MCA occlusion, SUN N4057(6 micrograms/kg/min) was infused. Physiological parameters were measured continuously, and arterial blood gas was analyzed hourly for 6 hours and maintained within the normal ranges. Animals were randomly allocated to the following three groups: (1) ischemic controls infused with sterile saline(Group A, n = 8), (2) SUN N4057 under normothermic condition(Group B, n = 8), (3) SUN N4057 (Group C, n = 8). Then, brain coronal sections of 3 mm in thickness were stained with 1% triphenyltetrazolium chloride(TTC) solution, and hemispheric infarct volumes were calculated by using a computerized image analysis system. RESULTS: There were no significant differences in any physiological parameters among 3 groups. In Group C, brain temperature decreased significantly starting 1 hour after MCA occlusion and dropped by 2.1 +/- 0.7 degrees C 5 hours. Infarct volumes were 35.6 +/- 6.9% (Group A), 23.3 +/- 5.8% (Group B) and 12.3 +/- 11.3% (Group C), respectively. There were significant differences among three groups(p < 0.05). CONCLUSION: On the basis of these data, we conclude that SUN N4057 provides more effective neuroprotection by the combination of hypothermic and neuroprotective effects. Chemical hypothermia may lead to a new therapeutic approaches for treatment of brain ischemia.

Animals↗