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Biomedical subjects

S Yoshitake

Publications and source records attributed to S Yoshitake.

At least 37 records · Page 2Linked to original sources
PubMed1996

Anti-atherosclerotic effect of E5324, an inhibitor of acyl-CoA:cholesterol acyltransferase, in Watanabe heritable hyperlipidemic rabbits.

E5324, n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy]-6- methylphenyl]urea, a novel and potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), was evaluated for its anti-atherosclerotic and lipid-lowering effects in Watanabe heritable hyperlipidemic (WHHL) rabbits. At 3 months of age, 40 male WHHL rabbits were divided into 4 groups. The rabbits were fed a standard rabbit chow (control group), or standard rabbit chow containing E5324 (0.1% or 0.02%) or 1% probucol for 16 weeks. Even the high dose of E5324 did not lower the plasma total cholesterol levels throughout the experiment. Probucol slightly reduced the plasma cholesterol levels, and showed anti-atherosclerotic activity, i.e., reductions of atherosclerotic plaque formation and cholesterol content in the aorta. Although E5324 did not lower plasma cholesterol, atherosclerotic plaque formation in the aortic arch and thoracic aorta was reduced (by about 34% and 41%, respectively, at the high dose; P < 0.05). Cholesterol content in the aortic arch and thoracic aorta was also reduced (by about 59% and 62% at the high dose, respectively) compared with the control. These results suggest that E5324 acts directly on the arterial wall through ACAT inhibition, and prevents the progression of atherosclerosis in WHHL rabbits.

Analysis of Variance↗
PubMed1996

Mechanisms of satigrel (E5510), a new anti-platelet drug, in inhibiting human platelet aggregation. Selectivity and potency against prostaglandin H synthases isozyme activities and phosphodiesterase isoform activities.

Satigrel (E5510, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid) is a potent inhibitor of platelet aggregation. Like cyclooxygenase/prostaglandin H synthase (PGHS) inhibitors such as aspirin, which suppress platelet aggregation by inhibiting thromboxane A2 production, satigrel inhibits collagen- and arachidonic acid-induced aggregation of human platelets. In contrast to other PGHS inhibitors, satigrel, like cyclic nucleotide phosphodiesterase (PDE) inhibitors such as cilostazol, shows inhibitory activity against thrombin-induced platelet aggregation. To investigate the mechanism of the anti-platelet activity of satigrel, we examined the selectivity and potency of satigrel against PGHS isozyme activities and PDE isoform activities. Two isozymes of PGHS are known; constitutive enzyme (PGHS1) and inducible enzyme (PGHS2). Satigrel showed inhibitory activity against PGHS1 (IC50: 0.081 microM) and PGHS2 (IC50: 5.9 microM), suggesting the selective inhibition of PGHS1. Indomethacin, which is a selective inhibitor of PGHS1, showed similar selectivity against PGHS isozymes (IC50: 0.12 microM and 1.4 microM, respectively). These results support that satigrel suppresses thromboxane A2 production by inhibiting PGHS1. It is known that three isozymes of PDE exist in human platelets: Type V, which specifically hydrolyzes guanosine 3',5'-cyclic monophosphate (cGMP), Type III, which mainly hydrolyzes cAMP, and Type II, which hydrolyzes both cGMP and cAMP. We separated these three isozymes from human platelets and examined the inhibitory activity of satigrel against each enzyme. Of the three isozymes, the inhibitory activity of satigrel was the most potent against Type III PDE (IC50: 15.7 microM). The IC50 value for Type III corresponded with that for thrombin-induced platelet aggregation. Type V and Type II were also inhibited by satigrel (IC50: 39.8 and 62.4 microM, respectively). In human platelets, satigrel increased both cAMP and cGMP levels in a dose-dependent manner (100, 300 microM). In conclusion, satigrel inhibits collagen- and arachidonic acid-induced platelet aggregation through preventing thromboxane A2 synthesis by selective inhibition of the target enzyme, PGHS1, which exists in platelets. The anti-aggregating activity of satigrel against thrombin-induced aggregation may be due to elevation of the cyclic nucleotide levels through the inhibition of PDE isozymes.

Blood Platelets↗
PubMed1996

[Stress hormone response during midazolam/fentanyl anesthesia combined with epidural anesthesia for abdominal total hysterectomy].

Stress hormone response was investigated during midazolam/fentanyl/oxygen/air anesthesia combined with epidural anesthesia in six patients undergoing abdominal total hysterectomy (group MF). A control group of six patients received nitrous oxide/oxygen/sevoflurane anesthesia combined with epidural anesthesia (group C). We evaluated plasma concentrations of ACTH, cortisol, aldosterone and beta-endorphin during the control period, 10 min, 60 min after incision, and in the recovery room. In group C, plasma concentrations of ACTH, cortisol, aldosterone and beta-endorphin increased significantly 60 min after incision compared with control concentrations. But in group MF, they did not increase significantly during anesthesia. In the recovery room there were significant differences compared with preinduction concentrations in both groups. It is concluded that midazolam/fentanyl anesthesia combined with epidural anesthesia is more effective than nitrous oxide/oxygen/sevoflurane anesthesia combined with epidural anesthesia to control the stress response to surgery.

Adrenocorticotropic Hormone↗
PubMed1996

[IGF-1 levels in elderly patients during perioperative period].

In the present study, concentrations of serum cortisol, ACTH, IRI, growth hormone and insulin-like growth factor 1 (IGF-1) were measured in 24 surgical patients. Patients were divided into two groups, elderly group (n = 12, age > or = 60, mean age: 68.4 +/- 1.3) and younger group (n = 12, age < 60, mean age: 44.5 +/- 3.5). The samples were taken before and immediately after surgery and on days 1 and 2 postoperatively. Serum levels of cortisol, ACTH, IRI and growth hormone increased significantly after surgery compared to baseline values but they showed no significant differences between elderly group and younger group. Only serum IGF-1 levels were significantly different between them. They were at consistently lower levels in elderly group throughout this study. In contrast, they decreased significantly after surgery, but high IGF-1 levels were maintained in younger group. Catabolic condition shown by negative nitrogen balance is induced after surgery. IGF-1 has potential anabolic effect in human. The pharmacological approach using IGF-1 in the elderly surgical patients will be necessary in order to improve their overall conditions before and after surgery in the future.

Adrenocorticotropic Hormone↗
PubMed1996

[A hematologic coagulation monitoring system for bedside use].

Perioperative hemorrhage in patients undergoing surgery is a major cause of morbidity and mortality. DRIHEMATO SYSTEM COAG-1 can detect prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) easily. We combined this monitor with platelet count (PLT), activated clotting time (ACT) and thromboelastography (TEG) and devised a hematologic monitoring system for bedside use. This study of 10 adults undergoing cardiopulmonary bypass was conducted to determine the utility of this monitoring system. The specificity for lotting abnormality of this monitoring system included the following values; PT = 88%, FIB = 100% and TEG = 67%. This study suggests that this monitoring system may be useful in early diagnosis and treatment of postoperative coagulopathy.

Adult↗
PubMed1995

[The analgesic effect of iontophoresis with magnesium sulfate].

The analgesic effect of iontophoresis with magnesium sulfate was studied in fourteen healthy adult volunteers. Magnesium sulfate 0.5 mg.5 ml-1 was locally administered by the iontophoresis with 1.0 mA electric current for 10 min. The pain recognition time was measured by the pain thermometer before and after 5, 15, 30, 60 and 120 min of iontophoresis. The pain recognition time was significantly extended and lasted for 60 min. These results support the view that the iontophoresis with magnesium sulfate has analgesic effect and produces a good pain relief clinically.

Adult↗
PubMed1995

A selective type V phosphodiesterase inhibitor, E4021, dilates porcine large coronary artery.

We investigated the inhibitory effects of a newly synthesized compound, sodium 1-[6-chloro-4-(3,4-methylenedioxybenzyl)-aminoquinazolin-2-y l]piperidine-4- carboxylate sesquihydrate (E4021), on five phosphodiesterase (PDE) isozymes isolated from porcine aortic smooth muscle. E4021 specifically inhibited type V phosphodiesterase (cyclic guanosine monophosphate [cGMP]-specific PDE) in a competitive manner. A comparison of the inhibitory profiles of zaprinast and E4021 indicated that E4021 is 100 times more potent and selective as a type V PDE inhibitor. E4021 caused a significant and sustained increase in the cGMP level in endothelium-denuded porcine coronary artery, but it had no effect on the cAMP level. This compound had a relaxant effect in porcine coronary artery precontracted by prostaglandin F2 alpha in the absence of endothelial cells and relaxed it more markedly in the presence of endothelial cells. E4021 had a synergistic effect with nitroglycerin in both the increase in cGMP level and the relaxant effect in isolated porcine coronary artery. E4021 caused a dose-dependent dilation of the large epicardial coronary artery, with a reduction in mean pulmonary arterial pressure, in conscious pigs instrumented chronically with a pair of piezoelectric crystals. These results suggest that the highly selective and potent inhibitor of type V phosphodiesterase E4021 causes relaxation of the large coronary artery via an increase in the cGMP level.

Animals↗
PubMed1995

The effects of imipramine, amitriptyline and clonidine administered by iontophoresis on the pain threshold.

We performed iontophoresis of aqueous solution of imipramine and amitriptyline, tricyclic antidepressant, and clonidine, an alpha 2 agonist, in a total of 30 healthy adult volunteers. Analgesic effects were compared among the 3 drugs by measurement of the pain threshold using a thermopainmeter. No significant changes in the pain threshold were observed with imipramine or amitriptyline. On the other hand, clonidine significantly increased the pain threshold, compared with the control value before iontophoresis. Although the effects of iontophoresis of clonidine were smaller than the previously reported effects of iontophoresis with other drugs, these effects seemed to be due to the action of clonidine itself not associated with electric stimulation. More marked effects may be obtained with changes in the conditions of iontophoresis.

Adrenergic alpha-Agonists↗
PubMed1994

Possible differences in the regenerative roles played by thioltransferase and thioredoxin for oxidatively damaged proteins.

A possible involvement of thioltransferase (also known as glutaredoxin) in the regenerative reaction of proteins inactivated by oxidative stress were examined in vitro using the enzyme purified from bovine liver. Thioltransferase at physiological concentrations, together with glutathione, glutathione reductase and NADPH, regenerated the oxidatively damaged proteins with a comparable potency to that of thioredoxin. Experiments performed with protein substrates with their critical cysteine residues oxidized differently, that is, phosphofruktokinase and glyceraldehyde 3-phosphate dehydrogenase with mixed disulfide bonds and glyceraldehyde 3-phosphate dehydrogenase with sulfenyl or sulfinyl groups, indicated that thioltransferase regenerated the proteins inactivated by mixed disulfide formation more efficiently than thioredoxin, whereas thioredoxin preferentially regenerated the proteins inactivated by monothiol oxidation to sulfenic or sulfinic acid. These findings suggested that thioltransferase exerted regenerative effects on oxidatively damaged proteins like its cognate protein, thioredoxin, but with different substrate specificity, and their relative contribution to the regeneration reaction is dependent on the form of the oxidized thiols of the damaged proteins.

Glutaredoxins↗
PubMed1994

Thrombolysis of canine femoral artery thrombus by a novel modified tissue-type plasminogen activator (E6010).

The thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA) (E6010) was examined in a canine model with copper coil-induced femoral artery thrombus. This model, in which thrombolytic activity can be easily and directly quantified by determining changes in thrombus weight, should be useful for comparing the activities of various thrombolytic agents. Using this model, the present study showed that the thrombolytic activity of bolus intravenous injection of E6010 was identical to that of continuous intravenous infusion of recombinant t-PA at the same dose. This thrombolytic activity can be explained by changes in blood concentrations of the administered thrombolytic agents. On the other hand, administration of the thrombolytic agents dose-dependently caused significant changes in the levels of hemostatic and fibrinolytic factors. These changes were not so marked with administration of E6010, and therefore we concluded that E6010 is unlikely to cause bleeding complications after administration.

Animals↗
PubMed1994

[Clinical experience of extracorporeal life support with the use of centrifugal pump ECMO].

Many reports have documented the good results with the use of extracorporeal life support in severe respiratory and circulatory failure. In our institution, we have used the centrifugal pump (Bioconsol 540: Biomedicus Co. Ltd.) ECMO for extracorporeal life support, and obtained good results in three cases. We used V-V bypass ECMO in one case (idiopathic interstitial pneumonia) and V-A by-pass ECMO in other two cases (ARDS and meconium aspiration syndrome). Duration of total bypass in three cases were 34, 51 and 140 hours, respectively. Recent reports on the use of centrifugal pump have indicated that it can bring excellent results of circulatory assist for cardiogenic shock. Compared to the roller pump method, the use of centrifugal pump ECMO was very simple, and could serve as an effective method for providing improvement in a relatively short period.

Adult↗
PubMed1993

Intracoronary infusion of E6010 has more potent thrombolytic activity than tissue plasminogen activator (t-PA) in dogs: a higher plasma level of E6010 than t-PA causes potent thrombolytic activity.

We examined the thrombolytic properties of a novel modified human tissue plasminogen activator (PA) (E6010), in which cysteine 84 is replaced by serine, and which has a prolonged biologic half-life (t1/2). We compared the thrombolytic efficacy of continuous intracoronary (i.c.) infusion of E6010 with that of recombinant human tissue PA (rt-PA) in a canine model with copper coil-induced 1-h-old coronary artery thrombi and also compared the relation between thrombolytic efficacy and plasma clearance represented by pharmacokinetic parameters of i.c.-infused E6010 and rt-PA. Sixty-minute E6010 and rt-PA i.c. infusions were compared. The thrombolytic effects of i.c.-infused E6010 and rt-PA, represented by time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion rates at 60 min after reperfusion (OR) were as follows. E6010: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 25 +/- 10, 15 +/- 10, 13 +/- 5 (min); RR 100, 100, 100 (%); and OR 0, 0, 17 (%), respectively. Recombinant t-PA: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 47 +/- 12, 18 +/- 17, 14 +/- 4 (min); RR 50, 75, 100 (%); and OR 100, 33, 33 (%), respectively. These findings indicate that E6010 has more potent thrombolytic activity than rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Interleukin-6 and glucocorticosteroid responses to cardiopulmonary bypass].

The responses of interleukin-6 (IL-6), ACTH, cortisol, WBC, CRP to cardiopulmonary bypass (CPB) were studied in 5 patients who underwent elective CABG (N = 4) and AVR (N = 1). IL-6 started to increase from 3 h after the beginning of the operation at which aortic clamp was removed and reached a peak after 4 h at which CPB was withdrawn. ACTH also reached a peak after 4 h. The increase of cortisol started from 2 h when aorta was clamped, which was earlier than that of IL-6. IL-6 and ACTH fell sharply to pre-CPB levels before first postoperative day (1 POD) while cortisol remained high postoperatively. CRP level and WBC counts were maximum at 2 POD. The results suggest that the cortisol response to CPB is not only caused by IL-6, but also by other factors, such as IL-1 and TNF.

Adrenocorticotropic Hormone↗
PubMed1993

[Anesthetic consideration of a patient with congenital insensitivity to pain with anhidrosis].

Congenital insensitivity to pain with anhidrosis is a rare disorder but several clinical anesthetic experiences have been reported in Japan. We anesthetized a patient with this disorder for orthopedic operation with a low concentration of sevoflurane under monitoring of body temperature and we measured the concentrations of plasma ADH, cortisol and catecholamines levels before, during and after the operation. There were no problems during anesthesia and the patient awoke rapidly. ADH, cortisol and epinephrine concentrations showed slight elevations during and after the operation. The management of intraoperative body temperature and the necessary level of anesthesia were also discussed.

Adolescent↗
PubMed1993

[Cortisol responses to rapid ACTH test in patients with multiple organ failure].

Cortisol concentrations are usually elevated in sepsis, during major surgery and in burns. Adrenocortical response to stress seems to be essential for survival. To investigate the endogenous adrenocortical response to multiple organ failure, rapid ACTH stimulation tests were used in 15 patients. Patients were divided to nonsurvival group and survival group. Patients in both groups appeared to have increased adrenocortical activity, because basal cortisol concentrations were above normal (non-survival group: 33.8 +/- 13.7 micrograms.dl-1, survival group: 19.1 +/- 3.8). There are no significant differences between the two groups. We could not find absolutely adrenal insufficient patient. Plasma cortisol concentrations increased significantly in patients of both groups following ACTH stimulation. We found poor response to ACTH in two patients in non-survival group with very high basal cortisol concentrations. But there is no significant difference of cortisol response between the two groups. We could not determine whether the high mortality is associated with poor response to ACTH or not.

Adrenal Cortex↗
PubMed1993

[The changes of intraocular pressure during sevoflurane anesthesia in children].

We investigated the intraocular pressure (IOP) during sevoflurane anesthesia in 20 children. We measured IOP, mean blood pressure and heart rate at 7 points in each subject. IOP was measured first after induction, then after vecuronium administration, immediately after intubation, and 5, 10, 15, 30 min after intubation. There were no significant changes in IOP and hemodynamics during sevoflurane anesthesia. We consider that the optimal time for IOP measurement is 5 or 10 min after intubation and the normal range of IOP is within the mean +/- 2 standard deviation. The peak values of IOP were 19.2 and 18.8 mmHg at 5 and 10 min after intubation. The results suggest that normal range of IOP is below 20 mmHg during sevoflurane anesthesia in children.

Anesthesia, Inhalation↗
PubMed1993

[Evaluation of blood purification in perioperative acute renal failure].

The technical aspects of blood purification have made a great progress during 1980's. We reviewed our experiences of blood purification for the past six years. Between 1986 to 1991, we treated 48 perioperative patients with acute renal failure (ARF). Four were intraoperative cases and 46 were postoperative cases. Three of four intraoperative patients received major cardiovascular surgery, and hemodialysis was connected directly to ECC in these three cases, and in other one case, ARF was treated with continuous hemofiltration (CHF). There was no intraoperative complication. One patient died of septic multiple organ failure (MOF), but other three patients were discharged uneventfully. Thirty five postoperative ARF patients showed oliguric ARF, and their major causes were LOS (65%) and septic shock (29%). We treated these ARF patients with CHF combined with HD (63%), CHF only (28%) and HD only (9%). There were 21 deaths (60%) in this group and most common cause of death was septic MOF. Eleven postoperative ARF patients showed non-oliguric renal failure, and major cause of this type of ARF was thought to be aortic dissection and relative hypotension (45%). We treated these non-oliguric ARF patient with HD only (73%) and HD combined with CHF (27%). One of these non-oliguric ARF patients died from ARDS.

Acute Kidney Injury↗