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Biomedical subjects

S Satoh

Publications and source records attributed to S Satoh.

At least 217 records · Page 12Linked to original sources
PubMed1999

Role of cholinergic receptors in adrenal catecholamine secretion in spontaneously hypertensive rats.

We investigated the role of nicotinic and muscarinic receptors in secretion of catecholamines induced by transmural electrical stimulation (ES) from isolated perfused adrenal glands of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. ES (1-10 Hz) produced frequency-dependent increases in epinephrine (Epi) and norepinephrine (NE) output as measured in perfusate. The ES-induced increases in NE output, but not Epi output, were significantly greater in adrenal glands of SHRs than in those of WKY rats. Hexamethonium (10-100 microM) markedly inhibited the ES-induced increases in Epi and NE output from adrenal glands of SHRs and WKY rats. Atropine (0.3-3 microM) inhibited the ES-induced increases in Epi and NE output from adrenal glands of SHRs, but not from those of WKY rats. These results suggest that endogenous acetylcholine-induced secretion of adrenal catecholamines is predominantly mediated by nicotinic receptors in SHRs and WKY rats and that the contribution of muscarinic receptors may be different between these two strains.

Adrenal Glands↗
PubMed1999

Inhibition of neutrophil migration by a protein kinase inhibitor for the treatment of ischemic brain infarction.

This study investigated the therapeutic potential of agents that inhibited neutrophil infiltration in cerebral ischemic infarction. The migration of neutrophils elicited by N-formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor, C5a or platelet-activating factor was potently inhibited by fasudil, an inhibitor of protein kinases including rho kinase, protein kinase C and myosin light chain kinase, and hydroxy fasudil, a metabolite of fasudil, in vitro. In a microembolism model in rats, myeloperoxidase-quantified neutrophil accumulation in the ischemic brain was observed 24 hr after embolization. Intravenous administration of fasudil prevented the accumulation of neutrophils. In rats given fasudil, myeloperoxidase activity in the ipsilateral hemisphere (0.04+/-0.01 unit/g wet tissue) was significantly lower than that in ischemic rats (0.11+/-0.02 unit/g wet tissue). Fasudil also significantly reduced the size of the infarct area and improved neurological functions. These results suggest that neutrophil infiltration into the ischemic brain is involved in the pathogenesis of ischemic injury and that inhibiting neutrophil infiltration may provide an effective therapeutic intervention to reduce ischemic injury.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Promotive effects of the peptidyl plant growth factor, phytosulfokine-alpha, on the growth and chlorophyll content of Arabidopsis seedlings under high night-time temperature conditions.

In order to investigate the function of the peptidyl plant growth factor, phytosulfokine-alpha (PSK-alpha), in plants, we examined the effect of PSK-alpha on the growth and chlorophyll content of Arabidopsis seedlings under high night-time temperature conditions. Although exposure to high night-time temperatures markedly reduced the fresh weight and chlorophyll content of the seedlings, these parameters in the plants supplied with PSK-alpha remained at the same levels as those of non-treated controls. These effects were not apparent when [2-5]PSK, Tyr-SO3H and kinetin were similarly supplied. The results suggest that PSK-alpha not only promotes cell proliferation, but may aid plants in their tolerance of heat stress.

Adenine↗
PubMed1999

Glucose transporter expression in developing fetal lungs and lung neoplasms.

Glucose uptake and metabolism are essential for proliferation and survival of cells, and are supposed to be enhanced in actively proliferating cell systems such as embryonic and cancer tissues. Glucose uptake is usually carried out through glucose transporters. In the developing fetal lung, metabolism of glucose is thought to be an important process in cell proliferation, differentiation and maturation. Active glucose uptake could result in accumulation of glycogen in epithelial cells, and utilization of glycogen could be a critical phenomenon for lung epithelial development. In hamsters, although facilitative glucose transporter isoform 1 (GLUT1) and isoform 4 (GLUT4) are not detected in adult lungs, expression of them is detected with immunohistochemical and Western blot analyses in the developing fetal lungs. In human lung carcinomas, GLUT1 expression is seen in most cases of lung carcinoma, and is seen especially frequently in squamous cell carcinoma. GLUT1 expression in adenocarcinoma of the lung is correlated with reduced cell differentiation, larger tumor size and positive lymph node metastasis. A few cases of lung carcinoma show positive staining for GLUT3 and GLUT4. Thus, expression of some facilitative glucose transporter isoforms is detected in developing fetal epithelium and in lung carcinomas. Overexpression of them could enhance uptake of glucose into these cells, and the increased influx of glucose could be involved in active cell proliferation, which is a common character of the developing lung epithelium and carcinoma.

Animals↗
PubMed1999

Renal nerve stimulation induces alpha2-adrenoceptor-mediated antinatriuresis under inhibition of prostaglandin synthesis in anesthetized dogs.

The interaction between prostaglandins and alpha-adrenoceptors in neural control of tubular sodium reabsorption was examined in anesthetized dogs. Renal nerve stimulation (RNS; 0.5-1.0 Hz, 10 V, 1.0-milliseconds duration) reduced fractional excretion of Na+ (FENa) with minimal changes in hemodynamics and glomerular filtration. Intrarenal arterial infusion of prazosin (0.7 microg x kg(-1) x min(-1)), an alpha1-adrenoceptor antagonist, inhibited the RNS-induced reduction in FENa. However, the RNS-induced reduction in FENa was resistant to prazosin under pretreatment with indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor. Intrarenal arterial infusion of yohimbine (1 microg x kg(-1) x min(-1)), an alpha2-adrenoceptor antagonist, failed to inhibit the RNS-induced reduction in FENa in the absence or presence of indomethacin, but combined infusion of prazosin and yohimbine abolished the RNS-induced reduction in FENa in the presence of indomethacin. These results suggest that both alpha1- and alpha2-adrenoceptors mediate the RNS-induced antinatriuresis, but the alpha2-adrenoceptor-mediated portion is impaired by prostaglandins.

Adrenergic alpha-Antagonists↗
PubMed1999

Dehydroepiandrosterone suppresses the elevated hepatic glucose-6-phosphatase and fructose-1,6-bisphosphatase activities in C57BL/Ksj-db/db mice: comparison with troglitazone.

The effect of dehydroepiandrosterone (DHEA) on the hepatic and muscle glucose metabolizing enzymes and on blood glucose were investigated in insulin-resistant diabetic C57BL/KsJ-db/db mice and their heterozygote littermates (db/+m). The results were compared with those after troglitazone administration under the same conditions. Despite hyperinsulinemia, hepatic glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase) activities are higher in db/db than in db/+m mice. Dietary administration of DHEA and that of troglitazone for 15 days to respective groups of five mice each significantly decreased blood glucose in db/db mice and hepatic G6Pase and FBPase activities in both db/db and db/+m mice. Hepatic G6Pase and FBPase activities showed a linear relationship with blood glucose in all groups of mice, suggesting that the activities of G6Pase and FBPase are closely related to blood glucose levels. Because androstenedione, a DHEA metabolite, barely affected either of these enzyme activities or blood glucose in db/db mice, the actions of DHEA, which are similar to those of troglitazone, are presumed to be caused by DHEA itself. DHEA is considered to be a modulating agent for the activities of hepatic gluconeogenic enzymes in db/db mice.

Androstenedione↗
PubMed1999

[Morning blood glucose determination in the monitoring of metabolic control in type 2 elderly diabetic cases treated by oral hypoglycemic agents].

Daily blood glucose profiles were measured in 163 Type 2 elderly diabetic cases to evaluate whether a fasting (before breakfast) or a post-prandial (after breakfast) blood glucose concentration is able to predict blood glucose values throughout the day. In the diet-treated alone group (n = 61), the percentage of daily blood glucose profiles having plasma glucose values less than the 08:00 hours (before breakfast) value were as follows: 59.0%, 32.8%, 59.0%, and 55.7% at 18.00 (before supper), 24.00, 03.00, 06.00 hours, respectively. In group treated by oral hypoglycemic agents (OHA) (n = 102), these were as follows: 45.1%, 26.5%, 52.9%, and 67.6%, respectively. In the OHA group, the mean plasma glucose value at 08:00 hours was significantly higher in patients with the lowest plasma glucose levels between 60-79 mg/dl than in patients with these levels between 80-99 mg/dl (103.7 +/- 19.6 vs 118.7 +/- 16.9 mg/dl, p < 0.01), but that at 10:00 hours was similar in the two groups (218.8 +/- 43.9 vs 214.5 +/- 40.1 mg/dl). In patients with lowest plasma glucose levels of between 60-99 mg/dl, the 08:00 hours value correlated positively with that of 24:00 (r = 0.40), 03.00 (r = 0.53), and the 06.00 hours value (r = 0.69), but no correlation was observed with the 18.00 hours value. On the other hand, the 10:00 hours value was not associated with these time-points values. Our results reveal that before breakfast plasma glucose values are more predictive of low blood glucose values in the night during sleep than after-breakfast blood glucose values, but do not predict low blood glucose values before supper in patients on OHA.

Administration, Oral↗
PubMed1999

[Sulfonylureas and daily blood glucose profiles in elderly diabetics].

The aim of this study is to clarify the relationship between the efficacy of sulfonylureas and duration of diabetes in elderly diabetics. Daily blood glucose profiles were measured in 87 Type 2 elderly diabetic patients on sulfonylureas (tolbutamide, gliclazide or glibenclamide). Plasma glucose concentrations were determined at 08.00 (before breakfast), 10.00, 12.00 (before lunch), 14.00, 18.00 (before dinner), 20.00, 24.00, 03.00, 06.00, 08.00 hours. The subjects were divided into 4 sub-groups, according to their duration of the diabetes (< 10, 10-14, 15-19, 20 or more years). Mean plasma glucose values at 08.00, 10.00, 20.00, 03.00 and 06.00 hours were not significantly different among the four groups. However, mean plasma glucose values at 12.00, 14.00, 18.00, 00.00 hours and mean total blood glucose area under the daily profile (total BG) were significantly different among the four groups and the values in patients with a history of diabetes of 15 years or more increased. Duration of diabetes positively correlated with blood glucose values at 12.00, 14.00, 18.00, 00.00, 03.00 hours and total BG, and the dose of sulfonylureas positively correlated with blood glucose values at 12.00, 14.00, 18.00, 00.00 hours and total BG in multiple regression analysis. These results suggest that duration of diabetes and dose of sulfonylureas are important determinants of blood glucose control with sulfonylureas in elderly diabetic patients.

Aged↗
PubMed1999

[The role of ATP-receptor in controlling the urinary bladder and urethral function in rats].

BACKGROUND: The detrusor contraction involves an atropine resistant, nonadrenergic noncholinergic (NANC), component. Since adenosine triphosphate (ATP) has been proposed as a NANC transmitter, the role of ATP-receptors in the lower urinary tract was examined. MATERIALS AND METHODS: The isovolumetric bladder contractions and the urethral pressure were monitored after intra-arterial administration of ATP analogues and other drugs in 52 female SD rats under intraperitoneal urethane anesthesia. RESULTS: alpha beta metATP induced a rapid, phasic increase of the maximal bladder pressure immediately after the drug administration, which was followed by a decrease during the P 2 X-purinoceptor desensitization period, but it did not affect the resting bladder pressure. RB-2 did not affect both the maximal bladder pressure and the resting bladder pressure. As for the urethral functions, alpha beta metATP induced a decrease of the resting urethral pressure during the P 2 X-purinoceptors desensitization period, while RB-2 induced a increase of the resting urethral pressure in contrast. ATP, alpha beta metATP and RB-2 did not changed the maximal urethral relaxation. CONCLUSION: The results will indicate that ATP produces detrusor contractions through the P 2 X-purinoceptor. Although ATP dose not affect urethral relaxation during voiding phase, it controls the urethral tone during collecting phase by both the excitation of P 2 X-purinoceptor and the inhibition of P 2 Y-purinoceptor.

Animals↗
PubMed1999

[Recurrence of hepatocellular carcinoma after liver resection].

Recurrence of hepatocellular carcinoma after liver resection is usually observed in the remnant liver, and includes metachronous multicentric occurrence and intrahepatic metastasis. In stage I and II, disease-free survival rates of clinical stage I patients are significantly better than those of clinical stage II patients, although there are no differences in the disease-free survival rates of patients with advanced disease. Disease-free survival rates in long-term survivors decreased at a constant rate due to metachronous multicentric recurrence. Therefore it is important to follow postoperative patients as long as possible. In the treatment of recurrent tumors, every effort should be made to resect the tumor in the liver. Then, other regional therapies, such as percutaneous ethanol injection therapy, microwave coagulation therapy, and transcatheter arterial chemoembolization, are indicated for patients for whom re-resection is not indicated. To prevent recurrence of hepatocellular carcinoma, it is also important to suppress the hepatic necroinflammatory process due to viral hepatitis.

Carcinoma, Hepatocellular↗
PubMed1999

Effects of rolipram and cilostamide on renal functions and cyclic AMP release in anesthetized dogs.

The present study was undertaken to examine whether phosphodiesterases III and IV regulate renal cAMP level and whether inhibition of these enzymes influences renal functions in anesthetized dogs. The intrarenal arterial infusion of rolipram (0.1, 0.3, and 1 microgram/kg/min), a selective phosphodiesterase IV inhibitor, increased renal blood flow, glomerular filtration rate, urine flow rate, and urinary Na+ excretion with elevating arterial and renal venous plasma cAMP concentrations and urinary cAMP excretion. However, cilostamide (0.1, 0.3, and 1 microgram/kg/min), a selective phosphodiesterase III inhibitor, did not affect the values of these parameters. Indomethacin (3 mg/kg i.v. bolus and 1 mg/kg/min i.v. infusion), a cyclooxygenase inhibitor, reduced the basal arterial and renal venous plasma cAMP concentrations and blunted the rolipram-induced elevation of cAMP concentrations and urinary cAMP excretion. The effects of rolipram on renal hemodynamics and urine formation were attenuated in the presence of indomethacin. These results suggest that in the dog kidney in vivo, 1) phosphodiesterase IV, but not phosphodiesterase III, participates in degradation of cAMP and 2) the inhibition of phosphodiesterase IV enhances glomerular filtration and urinary Na+ excretion, the responses of which depend in part on indomethacin-susceptible (prostaglandin-mediated, probably) control of basal cAMP level.

Anesthesia, General↗
PubMed1999

[Usefulness and problems of total hepatic vascular exclusion in liver surgery].

Total hepatic vascular exclusion (THVE) is an useful method enabling safe and sure hepatic resection in patients with liver tumors adjacent to the large hepatic veins or inferior vena cava (IVC), tumor thrombi, invasion of the IVC, etc. To avoid serious hypotension during THVE, test clamping of the IVC prior to the procedure is indispensable. Hemodynamics should be carefully maintained by blood transfusion and sufficient infusion of colloidal and electrolyte solutions during THVE. The veno-venous bypass method which shunts blood from the IVC and portal vein to the superior vena cava enables prolongation of the period of THVE and is useful to avoid postoperative renal dysfunction. In situ liver perfusion with cold solution during THVE is an additional modality by which the liver is protected from warm ischemic injury and the duration of THVE can be further prolonged. However, the maximum duration of THVE is still controversial, especially in patients with chronic liver damage. The most appropriate method for THVE should be carefully chosen in each case by considering the type of lesion, liver function, and the goal of the surgery.

Constriction↗
PubMed1999

[Constriction of liver tissue herniated through a diaphragmatic defect, simulating a pulmonary tumor].

Defects in the dome of the right diaphragm are a rarity among diaphragmatic abnormalities. Here we report the case of an elderly man who presented with an intrathoracic nodular opacity adjacent to the right diaphragm on chest radiographs. A radionuclide liver scan and maximum intensity projection (MIP) images of a computed tomographic (CT) scan together yielded a diagnosis of diaphragmatic defect with herniation of liver tissue. The herniated liver was so constricted that the angle made by the nodule and diaphragm became acute, resulting in close resemblance to a pulmonary tumor. This unusual configuration of herniated liver tissue was reviewed and the cause of constriction and diagnostic procedure were discussed. To avoid unnecessary examinations, herniation of liver tissue should be included in the differential diagnosis of intrathoracic nodular opacities, particularly when they are in contact with the diaphragm.

Aged↗
PubMed1999

Clinical applications of the Doppler technique in monitoring the fetus.

The application of Doppler velocimetry in the evaluation of the normal human fetal circulation targeting organs such as the placenta, the liver, the brain, and the lungs is presented. Conditions wherein evaluation of the fetal circulation becomes important are many. These conditions include, but are not limited to, intrauterine growth retardation, fetal hydrops, and multiple gestation. The importance of combining Doppler velocimetry with M-mode echocardiography and B-mode scanning is also addressed.

Arteries↗
PubMed1998

Insulin resistance in cancer patients is associated with enhanced tumor necrosis factor-alpha expression in skeletal muscle.

The roles of tumor necrosis factor (TNF)-alpha and the facilitative glucose transporter (GLUT) 4 on the induction of insulin resistance in peripheral tissues of cancer patients was examined by quantitative competitive PCR on biopsies of abdominal rectal muscle from patients with gastrointestinal cancer. The degree of insulin resistance in these patients was measured by the euglycemic hyperinsulinemic glucose clamp using a high physiologic insulin concentration (100 microU/ml). Quantitative competitive PCR was carried out using DNA competitors constructed by deleting 20-30 bp between the two primer annealing sites. Decreased glucose uptake (M value) in peripheral tissues was accompanied by a significantly increased TNF-alpha mRNA in skeletal muscle (r=0.867, p=0.0025). GLUT4 mRNA, however, was positively correlated with M values (r=0.739, p=0.015). The amounts of mRNAs for TNF-alpha and GLUT4 in skeletal muscle were not correlated. Serum TNF-alpha concentrations remained below the limit of detection. These findings suggest that the insulin resistance in peripheral tissues of cancer patients is in part due to the induction TNF-alpha mRNA and the down regulation of GLUT4 mRNA in peripheral tissues.

Female↗
PubMed1998

A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 4. Discovery of novel frameworks mimicking the active conformation.

In recent articles we reported the identification of a series of 8-[[2, 6-dichloro-3-[N-methyl-N-[(E)-(substituted)acryloylglycyl]amino]++ +benzy l]oxy]-2-methylimidazo[1,2-a]pyridines as the first orally active non-peptide bradykinin (BK) B2 receptor antagonists. Optimization of the terminal glycine part and the imidazo[1,2-a]pyridine moiety led to the discovery of a clinical candidate (5, FR173657). With the aim of completion of the structure-activity relationship (SAR) study, we next investigated the roles of the substituents on the central phenyl ring. The results suggested that the 2,6-dichloro or 2, 6-dimethyl groups may play important roles in regulating the conformations of the 1- and 3-substituents and also may interact with hydrophobic pockets of the B2 receptors. Furthermore, according to the results of a molecular modeling study reported in part 1 of this series, we designed and synthesized a series of sterically constrained analogues by replacing the N-methylamide group with cis-amide-like rigid moieties. We discovered several bioisosteres and chemically proved that the N-methylamide moiety adopts the cis-amide form in the active conformation. Extensive chemical modification led to the identification of a novel class of highly potent and orally active non-peptide B2 antagonists represented by a pyrrole derivative (52a, FR193517). Compound 52a inhibited the specific binding of [3H]BK to recombinant human B2 receptors expressed in Chinese hamster ovary (CHO) cells and guinea pig ileum membrane preparations expressing B2 receptors with IC50s of 0.37 and 0.56 nM, respectively. This compound also displayed excellent in vivo functional antagonistic activity against BK-induced bronchoconstriction in guinea pigs at 1 mg/kg by oral administration.

Administration, Oral↗