Biomedical subjects

T Ikenoue

Publications and source records attributed to T Ikenoue.

At least 73 records · Page 4Linked to original sources

PubMed1997

Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166).

1. (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166), a novel oral hypoglycaemic agent is a non-sulphonylurea insulin secretagogue. 2. We investigated the insulin-releasing action and hypoglycaemic effect of A-4166 compared to sulphonylureas in vitro and in vivo. 3. A-4166 stimulated insulin secretion from rat freshly isolated pancreatic islets at concentrations from 3 x 10(-6) M to 3 x 10(-4) M in the presence of 2.8 mM glucose. There was no obvious difference in glucose dependency between the insulinotropic effect of A-4166 and that of glibenclamide, and no additive or synergistic effect was observed between these two drugs. 4. A-4166 displaced [3H]-glibenclamide bound to intact HIT-T15 cells in a concentration-dependent manner. The Ki value was 4.34 +/- 0.04 x 10(7) M, and the displacement potency of A-4166 was between that of glibenclamide and tolbutamide, being similar to that of gliclazide. 5. Inf fasted beagle dogs, A-4166 showed a dose-dependent hypoglycaemic effect after oral administration over the range 1 to 10 mg kg-1. The hypoglycaemic action of A-4166 showed an earlier onset and a shorter duration than that of sulphonylureas. 6. Simultaneous measurement of plasma insulin levels revealed that the hypoglycaemic effect of A-4166 was caused by a rapid-onset and brief burst of insulin secretion. 7. The pharmacokinetic profile of A-4166 was consistent with the changes of the blood glucose and plasma insulin levels. 8. Although the in vitro insulin-releasing effect of A-4166 was similar to that of sulphonylureas, its hypoglycaemic effect was more rapid and shorter-lasting, associated with rapid absorption and clearance. Thus, A-4166 may be useful in suppressing postprandial hyperglycaemia in patients with non-insulin-dependent diabetes mellitus.

Animals↗

PubMed1997

Effect of a new hypoglycemic agent, A-4166 [(-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclamide.

(-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166) is a new nonsulfonylurea hypoglycemic agent that lowers blood glucose by stimulating insulin release. In the present study, we examined the effects of A-4166, voglibose (an alpha-glucosidase inhibitor), and glibenclamide (a sulfonylurea) on the postprandial glycemic increase in rats with or without diabetes mellitus. Oral administration of A-4166 (25-100 mg/kg) dose-dependently decreased blood glucose with a rapid onset and short duration in normal rats. On the other hand, glibenclamide (1-4 mg/kg) showed a slower onset of its hypoglycemic action, and voglibose (0.2 mg/kg) had no effect. In the case of postprandial glucose excursion, the carbohydrate-induced increase in blood glucose was reduced by oral administration of either A-4166 or voglibose without causing sustained hypoglycemia in both normal and neonatal streptozotocin-induced diabetic rats. However, the efficacy of voglibose varied with the type of carbohydrate load. Glibenclamide produced a prolonged decrease in blood glucose without any appreciable effect on the initial glucose excursion. After sucrose loading, plasma insulin levels during the initial 1 h were significantly higher in A-4166-treated rats than in control rats, while voglibose completely inhibited the insulin response to sucrose. In glibenclamide-treated rats, an augmented insulin response was not seen. In conclusion, unlike other hypoglycemic agents, A-4166 suppresses postprandial glucose excursions by stimulating the early phase of insulin secretion.

Animals↗

PubMed1996

Somatostatin and insulin secretion due to common mechanisms by a new hypoglycemic agent, A-4166, in perfused rat pancreas.

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) is a nonsulfonylurea hypoglycemic agent that decreases blood glucose levels in nondiabetic and diabetic animals. In the present study, we attempted to determine the effect of A-4166 on hormone secretion from the in vitro-perfused rat pancreas and to examine the underlying secretory mechanisms. In the presence of basal glucose (3 mmol/L), A-4166 markedly stimulated insulin and somatostatin release in a concentration-dependent manner over 0.03 to 3 mmol/L. A sulfonylurea, tolbutamide, also stimulated insulin and somatostatin release. A-4166 and tolbutamide elevated the level of glucagon release; however, the change lacked a clear concentration-dependent property. A-4166 at 0.3 mmol/L and tolbutamide at 3 mmol/L exhibited maximal stimulation of insulin release to a similar extent, indicating that A-4166 is one log-order more potent than and as effective as tolbutamide. By contrast, A-4166 stimulated somatostatin release to a threefold greater extent than tolbutamide. A-4166 evoked an increase in the cytosolic free-Ca2+ concentration ([Ca2+]i) in rat pancreatic beta cells. [Ca2+]i and insulin secretory responses to A-4166 were inhibited by nitrendipine (NTD), a blocker of the L-type Ca2+ channel, and by diazoxide (DAZ), an opener of the adenosine triphosphate (ATP)-sensitive K+ channel. Furthermore, A-4166-stimulated somatostatin release was also inhibited by NTD and by DAZ. The results indicate that A-4166 and tolbutamide stimulate the release of insulin and somatostatin, and that A-4166 is much more effective than tolbutamide in releasing somatostatin, a hormone that attenuates hyperglycemia under certain circumstances. It is concluded that A-4166-induced insulin release is mediated by an increase in [Ca2+]i in beta cells. An inhibition of ATP-sensitive K+ channels and a consequent activation of L-type Ca2+ channels appear to play a key role not only in insulin secretion from beta cells, but also in somatostatin secretion from delta cells in response to A-4166.

Adenosine Triphosphate↗

PubMed1996

Maternal and fetal catecholamine responses to acute hypoxemia in Japanese Saanen goats.

Our purposes were to investigate the effects of acute hypoxemia on maternal and fetal physiological and biochemical responses in Japanese Saanen goat and to compare these responses to those obtained in other species in the previous studies. Five pregnant Japanese Saanen goats at about 120 days of gestation were operated to make fetal chronic preparation models. After a minimum of 4 days of postoperation, hypoxemia was induced by having the ewe breathe a hypoxic gas mixture (10% O2, 3% CO2, in N2) for 30 min. Maternal PO2 decreased from 84 to 40 mmHg, and fetal PO2 decreased from 22 to 16 mmHg. Only the fetal pH was significantly decreased by hypoxemia. Maternal heart rate increased with increases in arterial pressures. On the other hand, fetal heart rate showed bradycardia with a transient increase in blood pressure. During hypoxemia, maternal catecholamines minimally increased, while fetal plasma concentrations of epinephrine and norepinephrine were significantly increased. These changes in Japanese Saanen goats were first revealed by the current study and were compatible with the previous reports with sheep and monkeys. These observations suggest that the Japanese Saanen goats may be an adequate animal model for investigation of fetal physiology.

Animals↗

PubMed1996

Comparison of circulatory effects between arginine vasopressin (AVP) and dopamine in conscious newborn goats.

By using conscious chronically instrumented newborn goats, the circulatory effect of arginine vasopressin (AVP) (20 mIU/kg/ min) was studied, assuming a potential use for AVP to treat circulatory failure in the newborn, and the results were compared with those of dopamine (20 micrograms/kg/min). The AVP infusion decreased heart rate (HR) and cardiac output (CO) significantly, and increased systemic arterial pressure (SAP) and pulmonary arterial wedge pressure (PAWP) significantly, but did not change pulmonary arterial pressure (PAP) appreciably. The dopamine infusion did not change HR, SAP, and PAWP but increased CO and PAP significantly. Right atrial pressure (RAP) increased significantly in both groups. The pulmonary vascular resistance (PVR) increased significantly in both groups. The systemic vascular resistance (SVR) increased significantly in the AVP group, but did not change during experiments in the dopamine group. The calculated PVR/SVR ratios decreased significantly from the baseline value after initiation of the AVP infusion. In contrast, the dopamine infusion increased PVR/SVR ratios significantly throughout the experiments. Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome characterized by right-to-left shunting of blood at the level of the foramen ovale and ductus arteriosus. AVP may reduce the shunting of blood by elevating only SAP selectively.

Animals↗

PubMed1996

Effects of antihypertensive drugs on maternal and fetal hemodynamics and uterine blood flow in pregnant goats--comparison of nicardipine and labetalol.

This study was designed to compare the effects of nicardipine (0.02 mg/kg) and labetalol (0.5 mg/kg) on the uterine blood flow and fetal circulation after intravenous administration in unanesthetized, chronically instrumented pregnant goats. Significant decreases in maternal blood pressure and uterine blood flow were observed in both groups. The maternal heart rate increased significantly after the injection of nicardipine, whereas this change was not observed after the labetalol injection. The fetal heart rate, blood pressure and acid-base status did not change after the injection of either nicardipine or labetalol. These observations in pregnant goats suggest that both nicardipine and labetalol might be useful drugs for the treatment of acutely hypertensive crises in pregnant patients.

Animals↗

PubMed1996

[The perinatal risk factors and periventricular leukomalacia (PVL) in premature infants--relationship between fetal heart rate decelerations and PVL].

Periventricular leukomalacia (PVL) has recently been recognized as an important risk factor of neurological impairment in premature infants. We studied 29 PVL cases on perinatal risk factors comparing with a non-PVL matched control group retrospectively. Variable decelerations were more frequently observed with statistical significance in the PVL group in the intrapartum period. Then another study was conducted to evaluate the relationship between fetal heart rate (FHR) decelerations and cystic PVL prospectively. Since January 1993 through December 1994 we studied 209 low birth weight infants (31.1 +/- 3.2 weeks, 1,424 +/- 419 g) who had been subjected to intrapartum FHR monitoring and postnatal sonographic intracranial examinations sequentially every 7 days until discharge. Cystic PVL was detected in 6 of 209 cases (2.9%) and occurred only in infants who had revealed severe variable deceleration or prolonged deceleration (6/37, 16%) in intrapartum FHR monitoring. We conclude that in low birth weight infants intrapartum severe variable deceleration or prolonged deceleration might play a causal role in cystic PVL.

Bradycardia↗

PubMed1995

Endothelin-1 and big endothelin-1 increase in human endometrium during menstruation.

OBJECTIVES: Although the physiologic and pathologic roles of endothelin-1 in reproduction have been investigated, little is known about human uterine tissue levels. We studied the levels of immunoreactive endothelin-1 and immunoreactive big endothelin-1 in human endometrium and myometrium during each menstrual phase. STUDY DESIGN: Materials were obtained at hysterectomy (endometrium, n = 33; myometrium, n = 27). We measured immunoreactive endothelin-1 and immunoreactive big endothelin-1 by radioimmunoassay and performed an immunohistochemical study of the tissue. Data were analyzed by the Mann-Whitney U test. RESULTS: We detected larger amounts of immunoreactive endothelin-1 and immunoreactive big endothelin-1 in the endometrium than in the myometrium throughout the menstrual, proliferative, and secretory phases. Endometrial immunoreactive endothelin-1 and immunoreactive endothelin-1 were significantly increased in the menstrual phase (endothelin-1 68.8 +/- 23.3 pg/mg protein, n = 5, p < 0.005; big endothelin-1 45.2 +/- 5.7 pg/mg protein, n = 5, p < 0.003) compared with the other phases (endothelin-1 30.7 +/- 9.5 and 30.5 +/- 14.0 pg/mg protein; big endothelin-1 19.9 +/- 6.7 and 24.1 +/- 7.4 pg/mg protein). Immunohistochemistry demonstrated that the endometrial stromal cells were positive for antiendothelin monoclonal antibody only in the premenstrual and menstrual phases. CONCLUSION: Levels of immunoreactive endothelin-1 and immunoreactive big endothelin-1 are different in each type of uterine tissue and in each phase of the menstrual cycle. These changes may indicate some role of endothelin-1 in menstruation.

Antibodies↗

PubMed1995

Management of meconium aspiration syndrome by tracheobronchial lavage and replacement of Surfactant-TA.

Meconium aspiration syndrome creates mechanical airway obstruction with air trapping and atelectasis. Tracheobronchial saline lavage to dislodge meconium may precipitate respiratory distress, a wet lung appearance and respiratory failure. Two case studies are reported in which meconium aspiration resulted in mechanical obstruction and displacement of surfactant and in whom tracheobronchial saline lavage and artificial surfactant replacement reversed respiratory failure.

Female↗

PubMed1995

[Retinopathy and perinatal outcome in diabetic pregnancy].

Sixty patients with diabetes mellitus (DM) antedated pregnancy were enrolled; seven had proliferative retinopathy, 13 had simple retinopathy, and 40 were intact. Diet and/or insulin was prescribed to adjust their glucose control at fasting to < 100 mg/dl, as well as at 2 hours postprandial to < 120 mg/dl. Glycohemoglobin (Hemoglobin A1c) levels ranged between 5.4% and 6.4% in the third trimester in three groups. Incidences of pregnancy complications (toxemia, hydramnios, urinary tract infection and cesarean section) and neonatal complications (low Apgar score, hypoglycemia, jaundice, polycythemia, respiratory distress syndrome and anomaly) did not differ significantly with the grade of retinopathy. Compared with the intact group, the duration of DM was significantly longer in the retinopathy groups and the incidence of fetal distress was significantly higher in the proliferative retinopathy group. In ten of 60 patients (16.7%) the grade of retinopathy progressed during pregnancy. In four patients photocoagulation was performed for neovascularization, and proved to be effective. There was a tendency for those whose retinopathy progressed to the proliferative stage during pregnancy to have larger decreases in glycohemoglobin and for their retinopathy to worsen after delivery. With tight maternal glucose control and intensive fetal surveillance, we obtained good perinatal outcome in pregnancies with diabetic retinopathy, as compared to diabetic pregnancy without diabetic microangiopathy. Careful and frequent monitoring of retinal changes should be required during pregnancy and the postpartum period.

Adult↗

PubMed1995

[The perinatal risk factors of periventricular leukomalacia (PVL) in premature infants].

Periventricular leukomalacia (PVL) has recently been recognized as an important risk factor in neurological impairment of the premature infant. We studied 29 PVL cases concerning perinatal risk factors retrospectively comparing them with a non-PVL matched control group. Variable decelerations were more frequently observed with statistical significance in the PVL group in the intrapartum period. There was no significant difference between the two groups in the appearance of late deceleration. A lower incidence of RDS, a higher incidence of low Apgar score, a longer period of ventilation and oxygen inhalation and a more persistent presence of apneic spells were documented in the PVL group with statistical significance. Our study suggests the significance of variable deceleration as a risk factor in the occurrence of PVL in premature infants as well as other previously documented risk factors.

Apgar Score↗

PubMed1994

[Studies on prostaglandin production relating to the mechanism of dysmenorrhea in endometriosis].

The relationship between prostaglandins (PGs) production and the mechanism of dysmenorrhea in endometriosis is poorly understood. Consequently, we investigated the role of PGs in dysmenorrhea of endometriosis. Slices of normal endometrium, normal myometrium, adenomyosis, leiomyoma, normal ovary and affected ovary were incubated. 6-keto PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha and PGE2 concentrations of the incubation medium were measured by RIA. The results are as follows; 1) PGs production in endometriosis was significantly higher than that of other tissues, especially 6-keto PGF1 alpha, which was a dominant product in adenomyosis. 2) There were significant differences in PGs production between severe dysmenorrhea and non dysmenorrhea, especially tissue of adenomyosis with severe dysmenorrhea which produces large amounts of 6-keto PGF1 alpha. 3) There seems to be interaction between normal endometrium and normal myometrium with regard to 6-keto PGF1 alpha production. We concluded that increased PGI2 in the tissue of endometriosis seems to induce hyperalgesia during menstruation.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Concentration of interleukin-1 beta correlates with prostaglandin E2 and F2 alpha in human pre-ovulatory follicular fluid.

To investigate the role(s) of interleukin-1 beta (IL-1 beta) in human ovarian function, we measured the concentrations of IL-1 beta, prostaglandins (PGs) and steroids in follicular fluid of 90 stimulated ovaries, with reference to oocyte maturation. Concentrations of IL-1 beta were significantly higher in the follicles from which mature oocytes were recovered than in follicles from which oocytes could not be recovered (P < 0.05). IL-1 beta concentrations also increased in association with oocyte maturation. Positive significant correlations were seen between IL-1 beta and prostaglandin E2 (PGE2) (r = 0.47, P < 0.001), and between IL-1 beta and prostaglandin F2 alpha (PGF2 alpha) (r = 0.22, P < 0.05) in pre-ovulatory follicular fluid, but not between IL-1 beta and oestradiol, or between IL-1 beta and progesterone. Follicular fluid IL-1 beta might contribute to prostaglandin-induced oocyte maturation and ovulation.

Cellular Senescence↗

PubMed1994

[Influence of pregnancy on the vascular response to norepinephrine and serotonin in rat carotid artery].

Because the frequency of migrainous attacks tends to decrease in late pregnancy, we speculated that the responsiveness of the cerebral arteries to vasoactive amines which are associated with migraine changes during pregnancy. We therefore measured the effect of norepinephrine and serotonin on isometric contractions of the isolated carotid arterial rings in pregnant (n = 18) and nonpregnant rats (n = 18). The response of the arterial rings to norepinephrine was decreased significantly in the pregnant rat (p < 0.02) compared with the nonpregnant rat. This refractoriness to norepinephrine in the pregnant rat exists in both the following conditions: indomethacin (5 x 10(-7) mol/L), an inhibitor of production of prostaglandin, added to the reacting solution, and endothelium was removed. There was no difference in the maximal contraction tension in each condition. We did not observe any difference in the response to serotonin in the pregnant rat carotid artery compared with the nonpregnant one. In order to assess the activity of the endothelium-derived relaxing factor, we then measured the dilating response to acetylcholine in precontracted carotid arterial ring with 10(-7) mol/L norepinephrine. There was no difference in the dilating response. These finding indicated that the refractoriness of pregnant rat carotid artery to norepinephrine was not induced by endothelial factors, such as prostaglandin, or by an endothelium-derived relaxing factor.

Acetylcholine↗

PubMed1993

Effect of early pregnancy on maternal regional cerebral blood flow.

OBJECTIVE: The purpose of this study was to assess the effect of early pregnancy on maternal regional cerebral blood flow. STUDY DESIGN: We studied 10 pregnant women at 7 to 19 weeks' gestation by the xenon 133 washout technique by means of single-photon emission computed tomography the day before the abortion was induced and then again at a mean of 42.8 days after the abortion. RESULTS: Blood flow in the cerebral hemispheres decreased after the abortion, with a decline of 8.1% (p < 0.001). Each regional decrease was as follows: 7.6% (p < 0.01) in the frontal lobe, 9.1% (p < 0.01) in the temporal lobe, 12.9% (p < 0.001) in the parietal lobe, 9.8% (p < 0.01) in the basal ganglia, and 16.7% (p < 0.001) in the cerebellum. There was no significant difference in blood flow in the occipital lobe before versus after the abortion. CONCLUSION: Maternal regional cerebral blood flow was increased in early pregnancy compared with the nonpregnant state, except in the occipital lobe.

Adult↗

PubMed1993

Detection of human T-cell lymphotropic virus type 1 infection by the polymerase chain reaction using dried blood specimens on filter papers.

A simple method for detection of proviral DNA sequences of human T-cell lymphotropic virus type 1 (HTLV-1) was developed using dried blood specimens on filter papers. The whole blood was blotted onto the Guthrie paper. After the blood has dried, the blotted paper was punched out into small discs. The discs were then boiled to prepare the template for PCR (filter paper-PCR method). The filter paper-PCR method detected even a single HTLV-1-infected cell in three discs. The sensitivity of the filter paper-PCR method was equivalent to that of the method in which DNA was extracted with phenol and used as the template for PCR (DNA extraction-PCR method). In addition, DNA in the blotted filter paper was still utilizable as the template after the storage at 25 degrees C for at least 7 wk. A total of 53 clinical specimens from 30 seropositive and 23 seronegative individuals who were screened by particle agglutination (PA) test were analysed for HTLV-1 DNA by both PCR methods. Of 30 PA-positive specimens, 28 were also positive for HTLV-1 antibody by Western blot (WB) analysis, but two were indeterminate. The twenty eight WB-positive and one of the two indeterminate specimens were positive for HTLV-1 proviral DNA by both PCR methods. Of 23 PA-negative specimens, 22 were negative for HTLV-1 proviral DNA by both PCR methods. However, one PA-negative specimen was positive by both PCR methods. This patient was a 16-mth-old infant who was born to an HTLV-1 carrier mother and fed thereafter without her breast milk. In comparison to DNA extraction-PCR method, the sensitivity and specificity of the filter paper-PCR method was 100%, respectively.

Adult↗

PubMed1993

Interleukin-1 beta stimulates prostaglandin E2 and F2 alpha synthesis in human ovarian granulosa cells in culture.

To evaluate the roles of interleukin-1 (IL-1) in regulation of ovarian prostaglandin (PG) synthesis, we examined the effects of IL-1 beta on PGE2, PGE2 alpha, 6-keto-PGF 1 alpha and thromboxane (TX) B2 synthesis in cultures of human ovarian granulosa cells. Granulosa cells were obtained from hyperstimulated follicles in patients undergoing oocyte retrieval for in vitro fertilization-embryo transfer (IVF-ET). IL-1 beta increased immunoreactive concentrations of PGE2 and PGF2 alpha in culture medium in time- and dose-dependent manners. Concentration of PGE2 was significantly higher after 24 h incubation with 5 or more units/ml of IL-1 beta, when compared to the control value obtained without IL-1 beta (P < 0.05). Concentration of PGF2 alpha was significantly higher after 8 h incubation with more than 2 units/ml of IL-1 beta (P < 0.05). The increase in PGE2 was observed even in the presence of human chorionic gonadotropin (hCG), and blocked by indomethacin, an inhibitor of cyclooxygenase. During a 10 day incubation period, stimulatory effects of IL-1 beta on PG synthesis were observed only on the first 2 days incubations. Concentrations of 6-keto-PGF 1 alpha and TXB2 were below our measurement limits. This study demonstrated that IL-1 beta stimulates PG synthesis in human ovarian granulosa cells in vitro. IL-1 seems to play an important role in regulating ovarian functions.

Cells, Cultured↗

PubMed1993

The effect of nicardipine on maternal and fetal hemodynamics and uterine blood flow in chronically instrumented pregnant goats.

This study was designed to clarify the maternal and fetal hemodynamics of nicardipine (0.02 mg/kg) administered intravenously to unanesthetized, chronically instrumented pregnant goats. Nicardipine produced a significant increase in maternal heart rate and cardiac output, and a significant decrease in maternal mean arterial blood pressure and systemic vascular resistance. These changes persisted for about 30 minutes. There were no consistent changes in maternal pulmonary hemodynamics. Uterine arterial blood flow (UBF) decreased significantly (about 15%) after 5 minutes of the injection and returned to the control value within 30 minutes. A significant correlation between the decreases in UBF and maternal diastolic blood pressure was observed after 5 minutes of the injection. The fetal heart rate, blood pressure and acid-base status did not change after the injection of nicardipine. These observations of pregnant goats suggest that nicardipine might be a useful agent for the treatment of acutely hypertensive crises in pregnant patients.

Animals↗