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Biomedical subjects

A Takahara

Publications and source records attributed to A Takahara.

At least 19 recordsLinked to original sources

Blockade of N-type Ca2+ current by cilnidipine (FRC-8653) in acutely dissociated rat sympathetic neurones.

1 The inhibitory effects of cilnidipine (FRC-8653) and various organic Ca2+ channel blockers on high voltage-activated Ba2+ currents (HVA IBa) in rat sympathetic neurones were examined by means of the conventional whole-cell patch-clamp recording mode under voltage-clamped conditions. 2 HVA IBa was classified into three different current components with subtype selective peptide Ca2+ channel blockers. No omega-Agatoxin IVA-sensitive (P-type) or omega-conotoxin MVIIC-sensitive (Q-type) current components were observed. Most (> 85%) IBa was found to consist of omega-conotoxin GVIA-sensitive N-type components. 3 The application of cilnidipine inhibited HVA 1Ba in a concentration-dependent manner. The Kd value for cilnidipine was 0.8 microM. Cilnidipine did not shift the current-voltage (I-V) relationship for HVA IBa, as regards the threshold potential and peak potential where the amplitude reached a maximum. 4 High concentration of three hypotensive Ca2+ channel blockers, nifedipine, diltiazem and verapamil, all inhibited HVA IBa in a concentration-dependent manner. The Kd values for nifedipine, diltiazem and verapamil were 131, 151 and 47 microM, respectively. A piperazine-type Ca2+ channel blocker, flunarizine, showed a relatively potent blocking action on IBa. The Kd value was about 3 microM. 5 These results thus show that cilnidipine potently inhibits the sympathetic Ca2+ channels which predominantly consist of an omega-Cg-GVIA-sensitive component. This blockade of the N-type Ca2+ channel, as well as the L-type Ca2+ channel by cilnidipine suggests that it could be used therapeutically for treatment of hypersensitive sympathetic disorders associated with hypertension.

Animals

Cilnidipine attenuates renal nerve stimulation-induced renal vasoconstriction and antinatriuresis in anesthetized dogs.

We examined the effects of cilnidipine, which is an L- and N-type Ca2+ channel blocker, on adrenergically regulated renal functions in anesthetized dogs. Renal nerve stimulation (RNS) at high frequency (3-7 Hz) decreased renal blood flow (RBF) without changes in systemic blood pressure. The RBF response was inhibited by intrarenal arterial (i.r.a.) infusion of cilnidipine at 0.1-0.3 microgram/kg/min. Low-frequency RNS (0.5-1 Hz) reduced absolute and fractional urinary sodium excretion. These responses were attenuated during i.r.a. infusion of cilnidipine at 0.3 microgram/kg/min. An increase in norepinephrine secretion rate induced by low-frequency RNS was also attenuated during cilnidipine infusion. These results suggest that cilnidipine can suppress norepinephrine release from the renal nerve endings and thereby interfere with the neural control of renal functions.

Anesthesia

Studies on the tumor-promoting activity of polyurethanes: depletion of inhibitory action of metabolic cooperation on the surface of a polyalkyleneurethane but not a polyetherurethane.

Methanol extracts prepared from three polyetherurethanes (PEUs), namely PU4, PU6, and PU8, which were synthesized using 4,4'-diphenylmethanediisocyanate, poly(tetramethylene oxide), and 1,4-butanediol, showed an inhibitory action on the gap-junctional intercellular communication in a V79 metabolic cooperation (MC) test system. However, the inhibitory potentials of methanol extracts did not correlate with the tumorigenic potential of the polyurethanes in 1-year rat implantation studies. When the MC test was carried out using glass dishes partly coated with low molecular weight PEU, the inhibitory activity was clearly detected on the surface of the polyurethane coating but not on that of the noncoated glass area. The inhibitory activity of the three PEUs investigated using polyurethane-coated dishes correlated with the values of the polyurethane's tumorigenic potential in the rat implantation study. Various polyurethanes containing polybutadiene (PBD), hydrogenated polybutadiene (HPBD), or a fluoropolyether glycol (FPEG) as the soft segment were also tested using coated dishes in the MC assay. The threshold inhibitory response of FPEG-PU was 10-fold less than that of PU4, and neither PBD-PU nor HPBD-PU showed any inhibition in the MC test system. Both the FPEG and aliphatic soft segment containing polyurethanes decreased, and had minimal influence on the gap junctional intercellular communication. Thus, the tumor-promoting potential of PBD-PU, HPBD-PU, and FPEG-PU was considered to be lower than those of the PEUs based on these in vitro test results.

Animals

[Antihypertensive effects of repeated oral administration of cilnidipine, a novel calcium antagonist, in 2K1C renal hypertensive dogs].

Antihypertensive effects of repeated oral administration of cilnidipine in 2K1C renal hypertensive dogs were compared with those of nicardipine. On the first day, oral administration of cilnidipine (3 mg/kg) or nicardipine (3 mg/kg) markedly lowered both systolic and diastolic blood pressure 1 hr after administration. The hypotensive effects of cilnidipine were longer compared with those of nicardipine. Both drugs elevated the heart rate and plasma renin activity. On the 8th and 15th days, similar responses were obtained by repeated administrations of cilnidipine and nicardipine. After withdrawal of these drugs, no rebound phenomena in blood pressure were observed. The changes in mean blood pressure were correlated with plasma cilnidipine or nicardipine concentrations that were obtained at each time of blood pressure measurement (r = -0.598; P < 0.001 and r = -0.594; P < 0.001, respectively). These results suggest that stable and long-acting antihypertensive effects of cilnidipine for 15 consecutive days in renal hypertensive dogs are related to the change in plasma drug concentrations.

Administration, Oral

Effect of polyurethane surface chemistry on its lipid sorption behavior.

The relationships among surface, bulk properties and lipid sorption behaviors of segmented polyurethanes (SPUs) with various polyol soft segments were investigated. The polyols used in this study were poly(ethylene oxide) (PEO), poly(tetramethylene oxide) (PTMO), and poly(dimethylsiloxane) (PDMS). The hard segment of these segmented polyurethanes was composed of 4,4'-diphenylmethane diisocyanate and 1,4-butanediol, present at 50 wt%. X-ray photoelectron spectroscopic (XPS) and dynamic contact angle measurements were carried out in order to analyze the surface chemical structure in the air- and water-equilibrated states. XPS revealed that in the air-equilibrated state, lower surface free energy components were enriched at the air-solid interface, whereas in the water-equilibrated state, higher surface free energy components were enriched at the water-solid interface. The change in environment from air to water induced the surface reorganization in order to minimize interfacial free energy. Lipid sorption behaviors of SPUs were investigated by means of infrared spectroscopy. Even after extensive rinsing of the surface, the amount of lipid present on the SPU surface was more than that calculated on the assumption that a monolayer covers the SPU surface. Therefore, the lipid was not only adsorbed on the surface of SPU but absorbed into SPU. The SPU with hydrophilic PEO sorbed larger amount of phospholipid compared with that with hydrophobic polyol such as PTMO and PDMS. Also, the competitive sorption behaviors of phospholipid and cholesterol from their mixed liposome solution were studied. The ratio of sorbed cholesterol to phospholipid increased with an increase in surface hydrophobicity owing to the hydrophobic nature of cholesterol.

Absorption

Effects of nifedipine, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride and atrial natriuretic peptide on endothelin-induced antinatriuresis in dogs.

Nifedipine, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) or atrial natriuretic peptide (ANP) was infused into the renal artery before and during intrarenal arterial infusion of endothelin-1 (ET) in anesthetized dogs. Before ET infusion, nifedipine (0.1 micrograms kg-1 min-1), TMB-8 (75 micrograms kg-1 min-1) or ANP (10 ng kg-1 min-1) increased the urine flow rate, urinary sodium excretion and fractional sodium excretion with little change in renal blood flow or glomerular filtration rate. ET (2 ng kg-1 min-1) reduced the basal renal blood flow, glomerular filtration rate, urine flow rate, urinary sodium excretion and fractional sodium excretion. Both nifedipine and TMB-8 induced natriuresis during ET infusion; but only TMB-8 completely reversed the ET-induced reduction in fractional sodium excretion and partially antagonized the reductions in urine flow rate and urinary sodium excretion. ANP did not induce substantial urinary responses during ET infusion. Neither nifedipine, TMB-8 nor ANP reversed the ET-induced decreases in renal blood flow and glomerular filtration rate. The present study suggests that in the dog kidney 1) the ET-induced antinatriuresis is caused in part by enhancement of tubular sodium reabsorption, 2) the tubular action of ET depends on TMB-8-sensitive calcium movements but not calcium influx through dihydropyridine-sensitive channels and 3) ANP cannot counteract the ET-induced antinatriuresis.

Animals

Effect of soft segment chemistry on the biostability of segmented polyurethanes. II. In vitro hydrolytic degradation and lipid sorption.

A series of segmented polyurethanes (SPUs) with various polyol soft segments was prepared and their hydrolytic degradation and degradation due to lipid sorption was investigated. The hydrolytic degradation of the SPUs was investigated in a papain solution, where it was shown that the SPU based on poly(ethyleneoxide) (PEO) soft segment was susceptible to hydrolytic degradation. X-ray photoelectron spectroscopic (XPS) data suggest dissociation of the urethane linkage by enzymatic degradation. Degradation by lipid sorption was observed for the SPU based on a poly(dimethylsiloxane) (PDMS) soft segment. This is ascribed to the high solubility of lipid in the PDMS segment of the SPU.

Absorption

Effect of soft segment chemistry on the biostability of segmented polyurethanes. I. In vitro oxidation.

A series of segmented polyurethanes (SPUs) containing various polyol soft segments was prepared and their resistance to oxidative degradation was investigated after aging in AgNO3 solution. The SPU with the polyether soft segment showed a large reduction in mechanical strength after exposure to the oxidative environment. Surface cracking was often observed for these specimens. XPS measurements revealed that scission of the ether linkage occurs upon oxidation. The oxidative resistance of SPUs containing aliphatic hydrocarbon soft segments was significantly improved over the poly(tetramethylene oxide) (PTMO) based polyurethane.

Calorimetry, Differential Scanning

Effect of hydrophilic soft segment side chains on the surface properties and blood compatibility of segmented poly(urethaneureas).

Segmented poly(urethaneureas) with hydrophilic side chains were prepared from poly(tetramethylene oxide) (PTMO), 4,4'-diphenylmethane diisocyanate (MDI), ethylene diamine (ED) and a diol with a long hydrophilic side chain comprised of an ethylene oxide-proplene oxide copolymer. The end groups of the hydrophilic chains were either sodium sulfonate or methoxy groups. The state of microphase separation showed a small dependence on the fraction of long-chain hydrophilic diol. Surface analysis by means of static underwater contact angle and dynamic contact angle measurements revealed that the graft chains were at the aqueous interface in the hydrated state. An ex vivo A-V shunt experiment revealed that a more thrombogenic blood-material response was correlated with an increase in the concentration of polymeric hydrophilic side chain incorporation. The polyurethane containing a long chain diol with methoxy end groups exhibited a higher level of thrombogenicity than the similar polymers possessing a sulfonate terminated side chain.

Animals

Effect of surface hydrophilicity on ex vivo blood compatibility of segmented polyurethanes.

The relationship between surface, bulk and ex vivo blood-contacting properties of segmented polyurethanes with various polyol soft segment was investigated. The polyols used in this study were poly(ethylene oxide), poly(tetramethylene oxide), hydrogenated poly(butadiene), poly(butadiene) and poly(dimethylsiloxane). The hard segment of these segmented polyurethanes was composed of 4,4' diphenylmethane diisocyanate and 1,4 butanediol, present at 50 wt%. An experimental polyurethane, Biostable PUR, which has shown excellent biostability, was used in this study. The segmented polyurethanes based on the hydrophobic polyols such as poly(dimethylsiloxane) and hydrogenated poly(butadiene) showed distinct microphase separation between hard and soft segments. X-ray photoelectron spectroscopy revealed the surface enrichment of the hydrophobic component at the air-solid interface. Dynamic contact angle measurements indicated that the poly(dimethylsiloxane)-based segmented polyurethane possessed a hydrophobic surface in water. The poly(dimethylsiloxane)-based segmented polyurethane had the lowest platelet adhesion among the segmented polyurethanes investigated in this study, whilst the platelet deposition on the poly(ethylene oxide)-based polymer increased with time.

Animals

Natriuretic effect of TMB-8 in anaesthetized dogs.

1. Effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intracellular calcium release, on renal function were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of TMB-8 (0.03 and 0.1 mg/kg per min) increased urine flow rate, urinary sodium excretion and fractional excretion of sodium without affecting blood pressure, renal blood flow or glomerular filtration rate. 3. The results suggest that TMB-8 inhibits tubular sodium reabsorption to induce natriuresis.

Animals

Surface properties and platelet reactivity of segmented poly(etherurethanes) and poly(etherurethaneureas).

Segmented poly(etherurethanes) (SPUs) and segmented poly(etherurethaneureas) (SPUUs) with various hard and soft segment components were prepared. The surface characterization of SPUs and SPUUs in the air-equilibrated state and in the hydrated-state was carried out by means of X-ray photoelectron spectroscopic (XPS) and dynamic contact angle measurements. XPS revealed that in the air-equilibrated state, lower surface free energy components were enriched at the air-solid interface, whereas in the hydrated-state higher surface free energy components were enriched at the water-solid interface. The change in environment from air to water induced the surface reorganization in order to minimize interfacial free energy. The large contact angle hysteresis was observed for SPUs and SPUUs. This hysteresis can be mainly ascribed to the surface reorganization process. Platelet adhesion tests on SPU and SPUU surfaces indicated that the existence of surface microphase separated structure played an important role in the attainment of blood compatibility.

Adsorption

[A case of left coronary ostial obstruction due to syphilitic aortitis].

Coronary ostial stenosis is a rare lesion, which is a complication of syphilitic aortitis, Takayasu's aortitis, aortic valve disease, and familial hypercholesterolemia. We present a case of left coronary ostial obstruction due to syphilitic aortitis. A 67 years old man was admitted to our hospital for evaluation of a ten year history of angina on exertion. On physical examination, the only abnormal finding was a grade 2/6 high-pitched diastolic murmur. Coronary risk factor was not detected from biochemical results, but both the TPHA and FTA-ABS test were positive. Treadmill stress test showed more than 2 mm ST segment depression associated with chest pain. Coronary angiography revealed complete obstruction of left coronary ostium with good collaterals from the right coronary artery. The coronary arterial tree was otherwise normal. Furthermore, aortagraphy showed a moderate degree of aortic regurgitation. From the examination of previous reports including our own case, we think that the angiographic features of syphilitic coronary ostial stenosis can be summarized as below. 1. Coronary artery stenosis is generally limited to the ostium. 2. The grade of stenosis almost always shows more than 90% stenosis, and sometimes bilateral coronary ostium can be affected. 3. Aortic regurgitation is frequently noted, associated with coronary ostial stenosis.

Aged

Effects of a novel Ca2+ entry blocker, CD-349, and TMB-8 on renal vasoconstriction induced by angiotensin II and vasopressin in dogs.

The effects of a Ca2+ entry blocker CD-349 and an intracellular Ca2+ release inhibitor TMB-8 on renal vasoconstriction induced by angiotensin II (ANG II) and arg-vasopressin (AVP) were examined in anesthetized dogs. Intrarenal bolus injection of ANG II (3-10 ng/kg), AVP (5-20 ng/kg) or a Ca2+ entry promotor Bay K 8644 (0.1-0.4 micrograms/kg) produced a dose-dependent decrease in renal blood flow (RBF). Intrarenal infusion of CD-349 (0.03-0.3 micrograms/kg/min) suppressed the RBF responses to ANG II, AVP, and Bay K 8644. The RBF responses to ANG II and AVP were augmented slightly by intrarenal infusion of Bay K 8644 (0.3 micrograms/kg/min). Intrarenal infusion of TMB-8 (0.03-0.1 mg/kg/min) also suppressed the RBF responses to ANG II and AVP, whereas it did not affect the RBF response to Bay K 8644. These results suggest that vasoconstriction induced by ANG II or AVP is mediated both by the influx of Ca2+ through dihydropyridine-sensitive Ca2+ channels and the release of Ca2+ from TMB-8-sensitive Ca2+ pools in the in vivo dog kidney.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Surface molecular mobility and platelet reactivity of segmented poly(etherurethaneureas) with hydrophilic and hydrophobic soft segment components.

Segmented poly(etherurethaneureas) (SPUUs) with hydrophilic and hydrophobic polyether components were prepared. The surface chemical composition of SPUUs in various environments was investigated by means of X-ray photoelectron spectroscopic and dynamic contact angle measurements. These measurements revealed that in a hydrated state, the higher surface free energy component is enriched on the surface of the SPUU in order to minimize the interfacial free energy between water and the solid surface. The surface molecular mobility showed a strong correlation with bulk molecular motion. Platelet adhesion tests and dynamic contact angle measurements after adsorption of bovine serum albumin revealed that the surface of SPUUs with hydrophilic soft segments has a non-adhesive nature. The platelet reactivity of hydrophobic SPUUs is influenced by microphase separation at the surface.

Biocompatible Materials

Effect of aggregation state of hard segment in segmented poly(urethaneureas) on their fatigue behavior after interaction with blood components.

Characterization of microphase separated structure, interaction with blood components, such as lipids, and fatigue behavior after immersion in blood components were carried out for segmented poly(urethaneureas). The materials studied were Biomer and segmented poly(urethaneurea) (TU-Mn) composed of hard segment with 4,4'-diphenylmethane diisocyanate (MDI)-ethylenediamine (EDA) or 4,4'-diaminodiphenylmethane (DAM) and soft segment with MDI-polytetramethylene glycol (PTMG) [Mn of 856, 1350, and 2000]. Small-angle x-ray scattering, wide-angle x-ray diffraction, and dynamic viscoelastic measurements revealed that these materials showed the state of microphase separation. TU-Mn with PtMG of Mn = 856 shows the partial phase mixing between hard and soft segments, and phase separation was improved with an increase of Mn of PTMG. Biomer has the characteristics of stronger aggregation of hard segment than that of TU-Mn. All the specimen showed lipid absorption, but the amount of absorption decreased remarkably after precoating on the specimen surface with serum albumin. Lipid absorption of the specimen was confirmed by dynamic viscoelastic and IR measurements. In the case of segmented poly(urethaneurea) which did not immersed in lipids solution, their fatigue strength are sufficient for application to artificial heart systems. However, fatigue strength of the TU-Mn series was decreased drastically after absorption of lipids. On the other hand, Biomer did not show a decrease of fatigue strength after lipid absorption. The reduction of fatigue strength in the TU-Mn series after lipid absorption will be attributed to the weak aggregation of hard segment domain. This reduction of fatigue strength in the TU-Mn series is characterized by formation of microcrack and mirror zone in fatigue fractured specimen. As the precoating of the specimen surface with serum albumin inhibits the absorption of lipids, the reduction of fatigue strength was not observed for the specimen precoated with serum albumin even after immersing the TU-Mn series in lipids solution for 96 days.

Absorption

Decrease of plasma sulfur amino acids in essential hypertension.

In order to evaluate the correlation between sulfur amino acids (derived mainly form animal protein in the diet) and blood pressure, free amino acids, including sulfur amino acids such as taurine and methionine, were determined in the plasma and cerebrospinal fluid (CSF) of twelve normotensive subjects and twelve patients with essential hypertension under nutritional control after at least 10 days of standard hospital diet (total calorie and protein content: 2100-2300 Cal per day and 78-83 g per day, respectively). The results obtained were as follows: plasma taurine, serine, methionine and threonine were significantly lower in patients with essential hypertension than in normotensive patients. The levels of plasma taurine, serine, methionine and total sulfur amino acids in individuals correlated inversely to systolic blood pressure. No difference was observed in the CSF levels of free amino acids in normotensive and hypertensive patients. As taurine, methionine and serine are involved in the metabolism of sulfur amino acids, these observations support the view that the decrease in plasma sulfur amino acids may be a factor contributing to elevated blood pressure.

Adult