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Biomedical subjects

M Fukai

Publications and source records attributed to M Fukai.

At least 19 recordsLinked to original sources
PubMed2001

Protective effect of agiotensin II type I receptor antagonist, CV-11974, on ischemia and reperfusion injury of the liver.

BACKGROUND: Microcirculatory disturbance has been shown to play a critical role in hepatic ischemia and reperfusion (I/R) injury. Angiotensin II (AngII) is one of the most potent endogenous vasoconstrictors. Angiotensin II type I (AT1) receptor antagonist has been reported to have protective effects on I/R injury of the heart and kidney. However, effect on hepatic I/R injury has not been determined. In this study, we investigate our hypothesis that AT1 receptor antagonist, CV-11974, attenuates hepatic I/R injury. METHODS: Twelve beagle dogs underwent a 2-hr total hepatic vascular exclusion with veno-venous bypass. CV-11974 was given to animals at a dose of 0.002 mg/ kg/min for 5 min followed by 0.001 mg/kg/min for 25 min via portal vein before ischemia (group II, n=6). Nontreated animals were used as the control (group I, n=6). Animal survival, hemodynamics, hepatic tissue blood flow (HTBF), liver function, platelet count, renin activity, and AngII concentration of hepatic vein, energy metabolism, and histopathology were analyzed. RESULTS: Two-week survival was 33% in group I, in contrast, 100% in group II. Mean arterial blood pressure during early reperfusion was maintained, and HTBF after reperfusion was significantly higher in group II. Treatment attenuated liver enzyme release and decrease of platelet count, increased renin and AngII, suppressed ATP degradation during ischemia and enhanced ATP resynthesis after reperfusion. Neutrophil infiltration and histopathological damages were lessened in group II. CONCLUSIONS: Our data demonstrated that the local renin-angiotensin system might play a role in hepatic microcirculation. AT1 receptor blockade with CV-11974 attenuated hepatic microcirculatory disturbance and ameliorated I/R injury.

Angiotensin II↗
PubMed2001

Attenuation of ischemia and reperfusion injury of canine livers by inhibition of type II phospholipase A2 with LY329722.

BACKGROUND: Membrane phospholipid breakdown, caused by ischemia and reperfusion (I/R) of the liver, releases free fatty acids including arachidonic acids and lysophospholipids, which serve as precursors of various inflammatory lipid derivatives. Phospholipase A2 (PLA2) is a key enzyme that initiates this reaction. In this study, we tested our hypothesis that a type II PLA2 inhibitor, LY329722, could attenuate hepatic I/R injury caused by a 2-hr total hepatic vascular exclusion (THVE) in dogs. METHODS: Eighteen beagle dogs, subjected to a 2-hr THVE, were divided into three groups. Group 1 (n=6) was untreated and served as a control group. LY329722 was administered to animals in group 2 (n=6) intravenously (0.2 mg x kg(-1) x hr(-1)) for 60 min before ischemia, and to animals in group 3 (n=6) for 60 min starting 15 min before reperfusion (0.2 mg x kg(-1) x hr(-1)). Animal survival, systemic and splanchnic hemodynamics, hepatic tissue blood flow, liver functions, energy metabolism, hepatic venous thromboxane B2 and endothelin-1 levels, phospholipid levels and tumor necrosis factor-a mRNA expression in liver tissue, and histopathologic findings were evaluated. RESULTS: Two-week animal survival was 33% (two of six) in group 1, and 100% (six of six) in groups 2 and 3. LY329722 improved systemic and splanchnic hemodynamics, hepatic tissue blood flow, and energy metabolism, reduced liver enzyme, thromboxane B2, and endothelin-1 release, prevented hepatic phospholipid degradation and tumor necrosis factor-alpha mRNA expression, and lessened histopathologic damage and the number of neutrophil infiltrating into the liver tissue. CONCLUSION: The present study demonstrated that a type II PLA2 inhibitor, LY329722, attenuated hepatic I/R injury caused by a 2-hr THVE model in dogs.

Acetates↗
PubMed2001

Pancreatic volume in type 1 and type 2 diabetes mellitus.

We measured pancreatic volume (PV) using helical computed tomography (CT) in 26 patients with type 1 diabetes mellitus (DM), 29 patients with type 2 DM, and 22 healthy individuals. We also evaluated the relationship between PV and the body surface area (BSA), established the pancreatic volume index (PVI) by dividing PV by BSA to correct PV for the body build, and examined its relationships with the duration of illness, serum C-peptide immunoreactivity level (CPR), and serum immunoreactive trypsin level (IRT). BSA and PV were correlated significantly (p<0.0001, r=0.645) in healthy individuals, and they were correlated also in the diabetic patients (p=0.0023, r=0.563 in type 1 DM; p=0.0346, r=0.392 in type 2 DM). PV was significantly smaller in the type 1 DM group than in the healthy group and type 2 DM group (p<0.001 for both). PVI was also significantly smaller in the type 1 DM group than in the healthy group and type 2 DM group (p<0.001 for both). PVI and IRT were significantly correlated in both DM groups (p<0.0001, r=0.732 in type 1 DM; p=0.0469, r=0.371 in type 2 DM). PVI was not correlated with the duration of illness or CPR. Helical CT was useful for the measurement of the pancreatic volume, and the pancreatic volume was reduced particularly in the patients with type 1 DM. A strong correlation was observed between PV and exocrine pancreatic function in type 1 DM, but the correlation between PV and exocrine pancreatic function was weak in type 2 DM.

Adult↗
PubMed2001

Possible participation of isolated epicardial cell clusters in the formation of chick embryonic epicardium.

The embryonic epicardium is formed by the spreading of cells derived from the extracardiac proepicardial organ over the myocardial surface after transfer to the dorsal side of the myocardium via a bridge of villous projections. Using whole-heart immunostaining for keratin, we found that the chronology and pattern of epicardial formation in the chick was basically identical to that reported previously in the quail. However, discrete epicardial islands were observed on the ventrolateral surface of the atrioventricular canal as well as in two previously reported areas. Closer examination by scanning electron microscopy demonstrated the presence of isolated, sparsely distributed epicardial cell clusters on both the dorsal and ventral surfaces of the myocardium. These cells showed a surface morphology similar to that of the epicardial cells at the advancing edge of the spreading epicardial sheet and possessed numerous well-developed filopodia, suggesting active motility. These clusters are probably seeded onto the myocardium by vesicular transport from proepicardial villi, and our findings suggest that the resulting small, localised patches of epicardial cells might accelerate, supplement and tune the epicardial formation mediated by radial spreading of the epicardial sheet in the chick embryonic heart.

Animals↗
PubMed2000

Prolongation of canine liver allograft survival by a novel immunosuppressant, FTY720: effect of monotherapy and combined treatment with conventional drugs.

BACKGROUND: The immunosuppressive effect and other properties of a novel immunosuppressant, FTY720, have been studied mostly in the experimental transplantation of various extrahepatic organs. In this experiment, we evaluated the antirejection potency and adverse effects of this agent on liver grafts using a canine liver transplantation model. METHODS: Forty-eight orthotopic liver transplantations were performed by the standard technique under a veno-venous bypass. Liver recipients were divided into two studies: a single-dose study with FTY720 at various doses and a combined dose study with conventional immunosuppressants (cyclosporine or tacrolimus) alone and combined with FTY720. Survival, biochemical and hematological tests, blood levels of immunosuppressants, and postmortem histology were determined. RESULTS: The median survival of untreated control animals was 9 days, whereas treatment with FTY720 at a dose of 0.1 mg/kg/day prolonged graft survival to 49.5 days. FTY720 at 1 mg/kg/day showed a slight but insignificant prolongation to 16 days, but when the dose was increased to 5 mg/kg/day, the graft was rejected at 10 days. The combination of FTY720, 0.1 mg/kg/day, with a subtherapeutic dose of cyclosporine, 5 mg/kg/ day, prolonged median animal survival from 40 days with cyclosporine alone to 74 days. A combination of FTY720 (0.1 mg/kg/day) with tacrolimus (0.5 mg/kg/ day) compromised animal survival, reducing survival from 83.5 days with tacrolimus alone to 30.5 days due to infectious complication and emaciation by overimmunosuppression. No evident drug-induced side effects were observed. CONCLUSIONS: FTY720 has a potent immunosuppressive effect when used alone at 0.1 mg/kg/day in canine liver transplantation. FTY720 is a promising candidate for future clinical application in orthotopic liver transplantation.

Animals↗
PubMed2000

A novel hydroxyl radical scavenger, nicaraven, protects the liver from warm ischemia and reperfusion injury.

BACKGROUND: Reactive oxygen species have been considered to be involved in liver injury at the procurement, preservation, and transplantation from donors without beating hearts. A novel hydroxyl radical scavenger, nicaraven with hydrophilic and lipophilic properties, infiltrates both intracellular and extracellular spaces where it effectively scavenges reactive oxygen species. Protection by nicaraven against ischemia and reperfusion damage of the brain, heart, and kidneys has been shown. The effect of this agent on the liver remains unclear. METHODS: Two-hour total hepatic vascular exclusion was used. Eighteen beagle dogs were randomly assigned to 2 groups: 12 animals were not treated (group I) and 6 were treated with nicaraven (group II). Nicaraven was administered intravenously (2mg/kg/min) for 60 minutes before ischemia and for 3 hours, starting 30 minutes before reperfusion. RESULTS: Two-week survival rates were 25% in group I and 100% in group II (P <.01). Nicaraven inhibited lipid peroxidation in the liver, improved hepatic and systemic hemodynamics and energy metabolism, and suppressed liver enzyme release, endothelin-1 elevation in hepatic venous blood, histologic damage, and neutrophil infiltration into the liver. CONCLUSIONS: Nicaraven exerted hepatic protection against warm ischemia and reperfusion injury. This may indicate nicaraven as a potential candidate to attenuate liver injury from warm ischemia and preservation in transplantation from donors without beating hearts.

Adenine Nucleotides↗
PubMed2000

Observation of the abluminal surface of the atrioventricular endothelium which undergoes transition into cardiac cushion mesenchymal cells in the chick embryo.

In the developing chick heart, endothelial cells in the atrioventricular canal (AV) undergo a series of morphological changes and transform into cushion mesenchymal cells. In the present scanning electron microscopic study, we examined the abluminal surface features of the AV endothelium through an artificial window in the myocardial wall. The AV endothelial cell at stages 12 or earlier had a smooth, flattened basal surface with only a few blebs. In the successive stages, the abluminal surface exhibited remarkable changes; 1) the number of blebs increased, 2) elongated microvillous projections emerged, and 3) a thick filopodium, or a migratory appendage developed. It appeared, however, that these changes do not occur synchronously within the entire AV endothelium but were initially observed mostly in the proximity of the endothelial "crease" which was a limited invagination of the endothelial sheet towards the underlying acellular matrix. In addition, even in the proximity of the crease, endothelial cells with flattened basal surfaces were also observed next to endothelial cells that showed apparent morphological indications of transition into mesenchymal cells. These findings suggest that AV endothelial cells are possibly heterogeneous in the competency of transformation into mesenchymal cells and such heterogeneity would be important for maintaining the continuity of the AV endothelium.

Animals↗
PubMed2000

Angiographically demonstrated coronary collaterals predict residual viable myocardium in patients with chronic myocardial infarction: a regional metabolic study.

Angiographical demonstration of coronary collateral circulation may suggest the presence of residual viable myocardium. The development of coronary collaterals was judged according to Rentrop's classification in 37 patients with old anteroseptal myocardial infarction and 13 control patients with chest pain syndrome. The subjects with myocardial infarction were divided into 2 groups: 17 patients with the main branch of the left coronary artery clearly identified by collateral blood flow from the contralateral coronary artery [Coll(+)group, male/female 10/7, mean age 56.6 years]and 20 patients with obscure coronary trunk [Coll(-)group, male/female 16/4, mean age 54.9 years]. Thallium-201 myocardial scintigraphy and examination of local myocardial metabolism were carried out by measuring the flux of lactic acid under dipyridamole infusion load. Coronary stenosis of 99% or total occlusion was found in only 5 of 20 patients (25%)in the Coll(-)group but in 16 of 17 patients(94%)in the Coll(+)group(p < 0.001). Redistribution of myocardial scintigraphy was found in 11 of 15 patients(73%)in the Coll(+)group, but only 3 of 18 patients (17%)in the Coll(-)group(p < 0.01). The myocardial lactic acid extraction rate was--13.2 +/- 17.0% in the Coll(+)group, but 9.1 +/- 13.2% in the Coll(-)group(p < 0.001). These results suggest that coronary collateral may contribute to minimizing the infarct area and to prediction of the presence of viable myocardium.

Adult↗
PubMed1997

A chance SPECT study of ictal aphasia during simple partial seizures.

We report obtaining an ictal single photon emission computed tomographic (SPECT) scan in a right-handed 51-year-old man who had an astrocytoma in the left cerebral hemisphere and simple partial seizures characterized by aphasia. An epileptic seizure producing loss of speech and right-sided facial twitching occurred by chance during a SPECT scan. During the attack, he was unable to speak, but auditory comprehension and writing were intact. Ictal SPECT showed an area of increased perfusion in the left frontal cortex, with the area of highest perfusion involving the left frontal operculum to the inferior part of the left precentral gyrus. Interictal SPECT showed hypoperfusion in the same area. These SPECT findings suggest that the frontal operculum of the dominant hemisphere is one of the regions that can give rise to epileptic aphasia.

Astrocytoma↗
PubMed1995

Assessment of the severity of coronary artery disease by thallium-201 washout rate after dipyridamole infusion--a coronary hemodynamic and metabolic study.

This study examined the relationship between the myocardial washout rate (WR) of thallium-201 (201Tl) in dipyridamole scintigraphy and both coronary flow reserve (CFR) and myocardial lactate extraction rate (LER) after dipyridamole infusion in 31 patients with coronary artery disease (CAD) without myocardial infarction and 16 control patients. Patients with CAD demonstrated significantly lower WR (21 +/- 17 vs 43 +/- 10%, p < 0.001), lower CFR (128 +/- 82 vs 242 +/- 89%, p < 0.001) and lower LER (-2 +/- 20 vs 10 +/- 10%, p < 0.05) than did the control patients. WR was significantly correlated with CFR (r = 0.50, p < 0.001) and LER (r = 0.41, p < 0.01) in all of the patients. CAD patients with dipyridamole-induced chest pain demonstrated significantly lower WR (14 +/- 20 vs 27 +/- 12%, p < 0.05), lower CFR (97 +/- 71 vs 162 +/- 82%, p < 0.05) and lower LER (-13 +/- 21 vs 11 +/- 9%, p < 0.001) than did CAD patients without chest pain. CAD patients with dipyridamole-induced ST depression demonstrated significantly lower WR (14 +/- 20 vs 29 +/- 8%, p < 0.05), lower CFR (105 +/- 79 vs 170 +/- 73%, p < 0.05) and lower LER (-8 +/- 21 vs 11 +/- 10%, p < 0.01) than did CAD patients without ST depression. These results suggest that the myocardial washout rate of 201Tl after dipyridamole infusion reflects the severity of coronary artery disease as assessed by coronary hemodynamics, myocardial metabolism, symptoms and electrocardiography.

Aged↗
PubMed1993

A clinical study of hypergraphia in epilepsy.

Fifteen patients with epilepsy and hypergraphia were compared with 32 patients with epilepsy but without hypergraphia. The number of previous psychiatric episodes, the number of Washington Psychosocial Seizure Inventory (WPSI) items indicating emotional maladjustment, and the number of CT scan abnormalities were significantly greater in the hypergraphic patients than in the non-hypergraphic patients. Cognitive performance, EEG laterality and the scores of WPSI items related to the psychological stress of seizures did not differ significantly between the two groups. Hypergraphia reflects changes in emotional responsiveness secondary to organic temporal lobe lesions.

Adult↗
PubMed1991

Putrescine or spermidine binding site of aminopropyltransferases and competitive inhibitors.

A model of the active site of aminopropyltransferases was proposed based on the study of a number of monoamino and diamino compounds as potential inhibitors and substrates, respectively, of spermidine synthase purified from pig liver. The active site seems to have a relatively large hydrophobic cavity adjacent to a negatively charged site, to which a protonated amino group of putrescine binds, with another amino group of putrescine being situated in the hydrophobic cavity as a free form to be aminopropylated by decarboxylated S-adenosylmethionine. On the basis of the above-mentioned model, another modified one was proposed for spermine synthase, and several compounds mentioned model, another modified one was proposed for spermine synthase, and several compounds designed according to the modified model were found to potently inhibit spermine synthase, purified from rat brain, in competition with spermidine. The newly developed inhibitors were about two orders of magnitude more potent in vitro than a known inhibitor of spermine synthase, dimethyl(5'-adenosyl)sulfonium perchlorate.

Animals↗
PubMed1991

Event-related potentials in senile dementia of Alzheimer's type, multiinfarct dementia and Parkinson's disease.

We investigated event-related potentials (P300) in three types of demented patients. Fourteen patients with senile dementia of Alzheimer's type (SDAT), 15 with multiinfarct dementia (MID), 8 with Parkinson's disease with dementia and 29 normal controls participated in this study. We measured the latencies of N100 and P300 at Pz after odd-ball paradigm stimulation. N100 peaks were within the normal range in all patients. However, P300 peaks were significantly delayed in all demented patients. There were no statistical differences in the mean latencies of P300 in each demented group. P300 latencies were found to be negatively correlated with Hasegawa's dementia scale. These results suggest that regardless of its cause dementia has similar influences on the P300 latency and P300 may be a useful means to assess the degree of dementia.

Aged↗
PubMed1991

[Effect of L-carnitine in patients with ischemic heart disease].

To assess the protective effects of L-carnitine (LC) infusion on ischemic heart disease, 30 patients who had angina and ischemic ECG changes during exercise were evaluated by bicycle ergometry. They were categorized in LC and non-treatment (NT) groups. There were no significant differences in age and sex between the 2 groups. Before exercise, 15 patients (9 males and 6 females) received 60 mg/kg LC and the results including hemodynamics, coronary circulation, and cardiac metabolism at rest and during exercise were compared with those of the NT group studied in the same protocol (50 watts x to cycle, 15 min). At the end of 30 min LC drip infusion, the arterial carnitine content (LC (a)) reached 1,980 +/- 257.3 microM and then was maintained at 1,212.7 +/- 136.2 microM during exercise. There was no correlation of LC (a) with the coronary arterio-venous difference nor with myocardial uptake of LC. Although there was no significant difference in coronary blood flow (CBF: mliters/100 g/min) between the LC and NT groups at rest (LC: 92.1 +/- 29.0 vs NT: 88.0 +/- 26.5), CBF during exercise increased significantly in the LC group compared with the NT group (LC: 230.4 +/- 113.8 vs NT: 139.1 +/- 52.7; p < 0.05). In the NT group, there was no significant change in coronary arterio-venous oxygen difference ((a-cs) O2: vol %) during exercise, but in the LC group (a-cs) O2 increased significantly from 10.2 +/- 1.3 to 11.5 +/- 1.9 (p < 0.01). Furthermore, although there was no significant difference in myocardial oxygen consumption (MVO2: mliters/100 g/min) at rest between the 2 groups (LC: 9.30 +/- 2.96 vs NT: 9.71 +/- 3.09), it increased significantly in the LC group compared with the NT group during exercise (LC: 25.11 +/- 9.98 vs NT: 15.55 +/- 6.09). MVO2/LVWI (LVWI = left ventricular work index) and MVO2MT (MT = myocardial tension) did not significantly differ at rest between the 2 groups. However, these 2 indices decreased significantly during exercise (p < 0.05) in the NT group, and remained unchanged in the LC group, showing a significant difference between the 2 groups (both p < 0.05). In myocardial energy substrates, the myocardial uptake ((a-cs) x CBF) of free fatty acid (FFA: muEq/100 g/min) increased significantly in the LC group compared with that of the NT group (LC: 10.16 +/- 13.26-->31.88 +/- 27.58* vs NT: 16.02 +/- 27.92-->18.11 +/- 31.00;* = p < 0.05, LC vs NT).

Adult↗