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Biomedical subjects

T Takenaka

Publications and source records attributed to T Takenaka.

At least 19 recordsLinked to original sources
PubMed1997

Pharmacological profile of YM087, a novel nonpeptide dual vasopressin V1A and V2 receptor antagonist, in dogs.

The pharmacological profile of YM087 (4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin -6-yl) carbonyl]-2-phenylbenzanilide monohydrochloride) was investigated in dogs. YM087 showed high affinity for vasopressin V1A and V2 receptors in radioligand receptor binding studies with dog platelets (V1A) and kidney (V2). Intravenously injected YM087 (3-100 micrograms/kg) dose dependently inhibited the pressor response to exogenous vasopressin in anesthetized dogs. Intravenous (10-100 micrograms/kg) and oral (30-300 micrograms/kg) administration of YM087 dose dependently increased urine flow with little effect on urinary sodium and potassium excretion in normally hydrated conscious dogs. Concomitantly, the urine osmolality dropped below the plasma osmolality (300 mOsm/kg H2O). In contrast, intravenously injected furosemide (300 micrograms/kg) increased urine flow with marked increases in urinary sodium and potassium excretion. These results indicate that YM087 is the first orally effective dual vasopressin V1A and V2 receptor antagonist and that it will be a new tool in the investigation of the physiological and pathophysiological role of vasopressin in the cardiovascular system and kidney. YM087 may be useful for the treatment of patients with congestive heart failure, renal diseases and water-retaining diseases.

Animals↗
PubMed1997

Distribution of neuropeptide-containing nerve fibers in the human submandibular gland, with special reference to the difference between serous and mucous acini.

Distribution of neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)-, galanin (GAL)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the human submandibular gland was examined by the peroxidase-antiperoxidase method with attention to high-quality fixation and the condition of patients. NPY-, VIP-, and GAL-immunoreactive varicose fibers were densely distributed around the acini and ducts. Some of these fibers extended between acinar cells. The density of SP- and CGRP-immunoreactive fibers was relatively low. The number of NPY-, VIP-, and GAL-immunoreactive fibers around the mucous acini was significantly higher than around the serous acini. In the perivasculature, NPY-immunoreactive fibers were more numerous than other immunoreactive fibers. No somatostatin-, leucine-, or methionine-enkephalin-immunoreactive fibers were detected. Our findings suggest that a large number of periacinar VIP-, NPY-, and GAL-immunoreactive fibers may participate in regulating the synthesis of saliva and its secretion. Since the VIP-, NPY-, and GAL-immunoreactive fibers are more numerous around the mucous acini than around the serous ones, these fibers may take part more actively in regulating the secretory mechanisms in the mucous acini than in the serous ones. The relatively low number of CGRP- and SP-immunoreactive fibers suggests that they are less involved in the function of the human submandibular gland. Perivascular peptidergic fibers, especially NPY-immunoreactive fibers, may be involved in controlling local blood flow in this gland.

Aged↗
PubMed1997

Arginine vasopressin interacts with thromboxane in hydronephrosis.

The influence of hydronephrosis (6-10 wk) on the renal vascular response to arginine vasopressin (AVP) was assessed, using isolated perfused normal and hydronephrotic rat kidneys. In normal kidneys, AVP (0.3 nM) reduced renal perfusate flow (RPF) by 55 +/- 7% (P < 0.01). AVP-induced decrements in RPF were reversed partially by diltiazem (10 microM) and completely by 10 nM of an AVP (V1)-receptor antagonist (AVPX). In hydronephrotic kidneys, AVP reduced RPF by 81 +/- 2% (P < 0.01) and constricted afferent (AA) and efferent arterioles (EA) by 33 +/- 3 (P < 0.01) and 33 +/- 5% (P < 0.01), respectively. The addition of diltiazem altered neither RPF nor vessel diameters. Administration of AVPX recovered RPF, AA, and EA diameters. When hydronephrotic kidneys were pretreated with thromboxane (Tx) inhibitors, AVP reduced RPF by 62 +/- 5% (P < 0.01) and constricted AAs and EAs by 26 +/- 2 (P < 0.01) and 17 +/- 3% (P < 0.05), respectively. Under Tx blockade, diltiazem partially reversed the AVP-induced reduction in RPF and restored the decrements in AA diameter. Subsequent addition of AVPX returned RPF and EA diameter. Our data indicate that AVP elicits substantial renal microvascular constriction and suggest that AVP stimulates Tx production in hydronephrotic kidneys, thereby altering renal vascular responsiveness to this peptide.

Animals↗
PubMed1997

High-performance hemodiafiltration and blood pressure stability.

In the present study, we have estimated plasma nonrefilling rate and assessed its relationship to blood pressure stability during hemodialysis (HD) with normal or high sodium dialysate and during high flux hemodiafiltration (HDF). In standard HD, the greater plasma nonrefilling rate resulted in the larger decrease in blood pressure (alpha = -6.7 +/- 0.2 mm Hg/%, p < 0.01, n = 75). When compared to standard HD, high flux HDF (n = 6) altered neither plasma refilling nor blood pressure stability. Finally, the restrictive usage of high sodium dialysate reduced plasma nonrefilling rate (21 +/- 3 vs. 16 +/- 2%, p < 0.05, n = 10) and the magnitude of decrease in blood pressure (16 +/- 6 vs. 9 +/- 4 mm Hg, p < 0.05) without increase in interdialytic weight gain. Our data indicate relative safety of high performance HDF, and warrant judicious use of high sodium dialysate for the HD patients with hypotensive episodes.

Blood Pressure↗
PubMed1997

Aspirin plus either dipyridamole or ticlopidine is effective in preventing recurrent myocardial infarction. Secondary Prevention Group.

The efficacy of combining antiplatelet agents with low doses of aspirin to prevent cardiac events in patients with myocardial infarction was examined. A total of 1,083 patients with prior myocardial infarction were randomly divided into those who were (618) and were not (465) treated with antiplatelet agents, and observed for 12.5 +/- 18.5 months. Those treated with antiplatelet agents included 113 patients treated with aspirin (50 mg) plus dipyridamole (150 mg/day), 253 treated with aspirin (50 mg) plus ticlopidine (200 mg/day), and 252 treated with only 1 of the 3 antiplatelet agents. Cardiac events, including fatal or nonfatal recurrent myocardial infarction, death by congestive heart failure, and sudden death, occurred in 34 patients (7.3%) in the nontreatment group and in 19 patients (3.1%; p < 0.01) in the treatment group; odds ratio 0.40, 95% confidence interval 0.23-0.71. There were only 2 cardiac events (1.8%) in the aspirin + dipyridamole group (p < 0.05 vs nontreatment group: odds ratio 0.28: 0.08-1.03), and 5 such events (2.0%) in the aspirin + ticlopidine group (p < 0.01; odds ratio 0.28: 0.11-0.69). Subgroup analysis to exclude differences in the patients' background confirmed the efficacy of these antiplatelet agents. We conclude that combined treatment with low doses of aspirin plus either dipyridamole or ticlopidine is effective in preventing cardiac events in patients who have had prior myocardial infarction.

Aged↗
PubMed1997

Hypotensive effects of YM430, a 1,4-dihydropyridine derivative, in spontaneously hypertensive rats and renal hypertensive dogs.

The hypotensive effects of YM430 (4(((S)-2-hydroxy-3-phenoxypropyl)amino)butyl methyl 2,6-dimethyl-((S)-4-(m-nitrophenyl))-1,4-dihydropyridine-3,5-dicarboxyla te) were evaluated in hypertensive animals. In conscious spontaneously hypertensive rats (SHR), single oral administration of YM430 (10-100 mg/kg) produced a dose-dependent decrease in mean blood pressure (MBP) with slight reflex tachycardia. The hypotensive effect of YM430 reached its maximum about 2 hr after dosing and lasted for over 10 hr. Importantly, the beta 1-adrenoceptor blocking activity of YM430 had a similar time course to that of its calcium entry blocking activity. In conscious normotensive dogs (NTD: 1-10 mg/kg, p.o.), YM430 decreased MBP without reflex tachycardia, and inhibited isoproterenol (ISO)-induced tachycardia in a dose-dependent manner. In conscious renal hypertensive dogs (RHD: 0.3-3 mg/kg, p.o.), YM430 also produced a sustained hypotensive effect. Furthermore, on repeated oral administration to conscious SHR and NTD, YM430 caused a long-lasting hypotensive effect. This hypotensive activity and inhibition of ISO-induced tachycardia showed neither tolerance, augmentation nor rebound. In conclusion, YM430 has a long-lasting hypotensive effect and behaves as a hybrid compound, combining calcium entry blocking and beta 1-adrenoceptor blocking activities in vivo. In addition, the degree of the blocking activities of YM430 remains nearly constant in the long-term after oral administration.

Administration, Oral↗
PubMed1997

Pharmacological properties of YM17E, an acyl-CoA:cholesterol acyltransferase inhibitor, and diarrheal effect in beagle dogs.

YM17E (1,3-bis[[1-cycloheptyl-3-(p-dimethylaminophenyl)ureido]methyl]ben zene dihydrochloride) was found to be a potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT) in rabbit liver and intestine microsomes. Dixon plot analysis revealed that YM17E inhibited microsomal ACAT in a non-competitive manner. YM17E induced a marked decrease in serum cholesterol, especially in non-high-density lipoprotein (HDL) fractions, in cholesterol-fed rats and rats fed normal chow. Measurement of bile secretion after oral administration of YM17E in cholesterol-fed rats showed that the drug markedly accelerated the secretion of bile acids and neutral sterols. Furthermore, absorption of [3H]cholesterol from the gut of cholesterol-fed rats was significantly inhibited by YM17E. From these results, the hypocholesterolemic activity of YM17E in these animals resulted from both a decrease in cholesterol absorption from the gut and the stimulation of excretion of cholesterol from the liver into bile. However, YM17E caused secretory diarrhea in beagle dogs at near lipid lowering doses. When YM17E was administered at the same total dosage but divided into 5 daily administrations, the incidence of diarrhea was significantly reduced while its cholesterol lowering effect became stronger. These results suggest that the inhibition of intestinal and/or liver ACAT increases the risk of diarrhea development which, however, can be avoided by controlled drug administration in beagle dogs.

Animals↗
PubMed1997

[Thoracic epidural anesthesia for cholecystectomy in a patient after Fontan procedure].

A 12 year-old boy who had received modified Fontan procedure was scheduled for cholecystectomy. Anesthesia was maintained with thoracic epidural anesthesia (Th8-9) and O2-N2O-sevoflurane under mechanical ventilation through the endotracheal tube. Transeshophageal echo cardiography and mixed venous oxygen saturation (SvO2) were used for hemodynamic monitoring. The combined use of epidural anesthesia and volatile anesthetics decreased central venous pressure, left ventricular end diastolic volume, left ventricular ejection fraction and SvO2. These hemodynamic problems were easily solved by infusion therapy and a low dose of dopamine. On the other hand, there were also some hemodynamic benefits such as inhibition of tachycardia and suppression of an increase in pulmonary vascular resistance due to surgical stress. Moreover, patient returned to normal spontaneous breathing with complete analgesia during the early phase after surgery. CVP and SvO2 increased to preoperative values in the recovery room. From these results, we conclude that satisfactory results can be obtained with epidural anesthesia for upper abdominal surgery after Fontan procedure.

Anesthesia, Epidural↗
PubMed1996

Ontogeny of regulatory neuropeptides in the bullfrog taste organ.

During metamorphic stages (stages XX-XXV), the first appearance of nerve fibers containing substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), galanin (GAL), and neuropeptide Y (NPY) in the bullfrog taste organs was different for each substance. CGRP fibers appeared first in association with the immature taste organs at stage XX. Up to stage XXV, the taste organs, epithelial disks, are close to their adult form, and SP, VIP and GAL fibers appeared within them. Throughout these stages, NPY fibers were absent, and no taste cells had immunoreactivity of the five neuropeptides. The present findings and previous physiological studies suggest that the immature taste organs in metamorphic stages already function as chemical and mechanical receptors and that these sensory mechanisms are under the control of peptidergic innervation.

Animals↗
PubMed1996

Precise coexistence of regulatory peptides in the nerve fibers of the amphibian carotid labyrinth demonstrated by a combination of double immunofluorescence labelling and a multiple dye filter.

An application of double-immunolabelling in combination with a multiple dye filter system demonstrated new findings regarding the distribution pattern of peptidergic fibers in the carotid labyrinth to addition to our previous findings shown by the individual filter system. In high magnification images of about 10% of the yellowish fibers which represent the coexistence of two neuropeptides, there was a definite difference in localization between the fluorescence originating from rhodamine (substance P fibers) and from FITC (vasoactive intestinal polypeptide and neuropeptide Y fibers), but it was clear that they are intertwined within a single nerve bundle. This combination method was able to discriminate two different peptidergic fibers which run side by side. The coexistence suggested previously by the individual filter system may actually be due to the phenomenon described above. This means that it is necessary to apply the multiple dye filter system for reliable evidence of coexistence of different two substances in a single nerve fiber.

Animals↗
PubMed1996

Improved method for producing neuronal hybrids using emetine and actinomycin D.

We modified the method of somatic cell fusion for neurons to improve the efficiency of hybrid production. C1300 neuroblastoma cells were incubated with emetine and actinomycin D before fusion. After fusion between C1300 cells and adult mouse dorsal root ganglia neurons with polyethyleneglycol, we were able to select the hybrids from non-fused cells. We obtained hybrid clones at high efficiency (7.2 clones/10(4) neurons).

Animals↗
PubMed1996

Synergistic effect of aurintricarboxylic acid and triflavin in a photochemically induced thrombosis model in rats.

We report here the synergistic antithrombotic effect of aurintricarboxylic acid in combination with a snake venom-derived disintegrin, triflavin, in a photochemically induced thrombosis model in rats. The time to initiation of thrombus was prolonged by i.v. bolus injection of aurintricarboxylic acid at 10 mg/kg. In contrast, time to occlusion was dose-dependently prolonged by both agents, this prolongation being significant with aurintricarboxylic acid at 10 mg/kg i.v. and with triflavin at more than 3 mg/kg i.v. Interestingly, the combination of aurintricarboxylic acid at 3 mg/kg i.v. and triflavin at 1 mg/kg i.v. prolonged not only the initiation of thrombus, but also the time to occlusion.

Animals↗
PubMed1996

Ontogeny of the peptidergic fibers in the male mouse submandibular gland.

The first appearance of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), galanin (GAL), leucine-enkephalin (1-ENK), and methionine-enkephalin (m-ENK) in the male mouse submandibular glands were different for each. VIP immunoreactive fibers first appeared on embryonic day 15 (E15), SP on E16, and CGRP fibers on E18. GAL, 1-ENK, and m-ENK fibers appeared in the early postnatal period, and NPY fibers occurred on postnatal day 21 (P21). From P0 to P21, VIP fibers rapidly increased in number, but SP and CGRP fibers increased only slightly. After P21, VIP, SP, and CGRP fibers decreased in number. ENK fibers were found only from P0 to P14. The number of these immunoreactive fibers in the adult phase was low in comparison with that in early postnatal phase. Around the blood vessels, SP, VIP, CGRP, NPY, and GAL fibers appeared by at least P7. These findings suggested that the transient high activity of VIP, CGRP, SP, and GAL and the transient appearance of ENKs in the nerve fibers may be related to the cell proliferation and differentiation of the functionally important structures of the mouse submandibular glands, and that the peptidergic innervation around the vasculature is probably involved in controlling local glandular circulation.

Animals↗
PubMed1996

Coexistence of nitric oxide synthase and neuropeptides in the mouse vomeronasal organ demonstrated by a combination of double immunofluorescence labeling and a multiple dye filter.

Nitric oxide synthase (NOS)-immunofluorescence techniques were applied to the mouse vomeronasal organ. Immunoreactivity for NOS was found in the nerve fibers distributed in the receptor-free epithelium, and around the blood vessels and glands in the cavernous tissue. No NOS fibers were seen in the receptor area. A combination of double immunofluorescence labeling and multiple dye filter revealed that a part of the substance P (SP)-immunoreactive nerve fibers in the cavernous tissue contained NOS and that all the vasoactive intestinal polypeptide (VIP)-immunoreactive nerve fibers around the blood vessels and glands in the cavernous tissue contained NOS. A few SP-immunoreactive cell bodies in the trigeminal ganglion showed coexistence with NOS, and almost all VIP-immunoreactive cell bodies in the sphenopalatine ganglion showed coexistence with NOS. Immunoreactivity for NOS without VIP in the cell bodies in the sphenopalatine ganglion was also found. These results suggest that NOS-immunoreactive nerve fibers in the mouse vomeronasal organ originate from the trigeminal and the sphenopalatine ganglia, and may modulate the vascular tone and the glandular secretion. In addition, these functions may be controlled in part by the interaction of nitric oxide and neuropeptides.

Animals↗
PubMed1996

Two novel mutations in the alpha-galactosidase gene in Japanese classical hemizygotes with Fabry disease.

Four alpha-galactosidase gene mutations were identified in Japanese male patients with Fabry disease who had no detectable alpha-galactosidase activity. Two of them were novel mutations, an 11-bp deletion in exon 2 and a g-1 to t substitution at the 3' end of the splice acceptor site in intron 1. The former caused a frameshift and led to the creation of a new stop codon at codon 118. The latter was predicted to provoke aberrant mRNA splicing followed by accelerated degradation of the mRNA. A nonsense mutation, R301X, and a 2-bp deletion starting at nucleotide position 718, which were reported previously, were also identified in unrelated patients.

Actins↗