A simple and reproducible cerebral thrombosis model in rats induced by a photochemical reaction and the effect of a plasminogen-plasminogen activator chimera in this model.

In this study a new model of cerebral ischemia, based on a middle cerebral artery (MCA) thrombosis in rats is described. Furthermore, the effect of the novel plasminogen activator (SUN9216), a plasminogen-plasminogen activator chimera, comprising the fibrin kringle 1 domain of a plasminogen, and the two kringles, and the serine protease domains of wild-type tissue plasminogen activator (t-PA), including a modification of the mannose glycosylation site on the kringle 1 of t-PA (PK1de1FE1X), was studied in this model. In the newly described model of thrombotic cerebral ischemia, an occlusive thrombus occurred usually within 8 min in the MCA as a consequence of an endothelial injury subsequent to a photochemical reaction between a systemically administered photosensitive dye (rose bengal) and a transillumination of the MCA with a high-intensity green light with a wavelength of 540 nm.

Roles of platelet-activating factor, thromboxane A2, ADP and thrombin in thrombogenesis in the guinea pig.

The mediators of photochemically induced thrombosis in the femoral artery of guinea pig were investigated. The femoral artery was occluded by a thrombus about 7 min after the initiation of photochemical reaction between rose bengal and green light. Pretreatment with a specific thromboxane (TX) A2 receptor antagonist, vapiprost, a platelet-activating factor (PAF) antagonist, WEB-2086, and ADP-induced platelet aggregation inhibitor, ticlopidine, prolonged the time to occlusion.

Effect of ibudilast on microcirculation thrombosis in rat inner ear.

The effect of ibudilast (0.1, 0.3 mg/kg), which has cerebral vasodilating and antiplatelet effects, was evaluated in two models of rat inner ear microcirculation thrombosis by using the photochemical reaction between green light (wave length: 540 nm) and intravenous injection of rose bengal.

[A new model of middle cerebral artery thrombosis in rats].

We have established a new model of middle cerebral artery (MCA) occlusion in rats due to photochemically induced thrombosis (PIT). This thrombosis is caused by photochemical reaction between green light and systemic injection of Rose Bengal (RB). Under anesthesia, the left MCA was observed without cutting the dura mater via a subtemporal craniotomy under an operation microscope.

[Statistical analysis on the cases of thyroid papillary carcinoma].

Statistical analysis was performed on the postoperative recurrence of forty four patients with thyroid papillary adenocarcinoma, who underwent radical surgery in the Department of Otolaryngology, Hamamatsu University Hospital from January 1978 to March 1991. In this study, we defined a new factor called "Operative Radicality index (OR index)" and analyzed the data with a multivariate analysis (Cox model). The result showed that the risk of postoperative recurrence was significantly affected by the age, the size of tumor and the OR index.

Role of thromboxane A2 in a microcirculation disorder of the rat inner ear.

Since thromboxane (TX) A2 causes vasoconstriction and platelet aggregation, we evaluation the effect of a TXA2 receptor antagonist (vapiprost) and a TXA2 synthetase inhibitor (Y-20811) on a microcirculation disorder in the rat inner ear that was induced by a photochemical reaction between an intravenous injection of rose bengal (RB) and green light. A gradual decrease of the cochlear action potential (CAP) to an 8 kHz sound stimulus was measured with an electrocochleogram and occurred after the RB injection. The CAP then disappeared 5 min after the injection of RB.

An animal model for hearing disturbance due to inner ear ischemia: photochemically induced thrombotic occlusion of the rat anterior inferior cerebellar artery.

A photochemical reaction between intravenous rose bengal and xenon light was used to induce a selective thrombus in the rat anterior inferior cerebellar artery (AICA). Compound action potentials (CAPs) were recorded by electrocochleography and cochlear blood flow (CBF) was monitored by laser Doppler flowmetry. Photothrombotic occlusion of the AICA caused inner ear ischemia to various degrees with or without alterations of the CAP.

Identification and characterization of aldose reductase in cultured rat mesangial cells.

Although the enhanced activity of the polyol pathway has been detected in diabetic glomeruli, the intraglomerular localization of this pathway has not yet been well defined. In this study, we attempted to identify aldose reductase, a key enzyme of the polyol pathway, in cultured rat mesangial cells and to characterize the properties of this enzyme using enzymological and immunological methods. When the aldose reductase (DL-glyceraldehyde-reducing) activity was analyzed in mesangial cell extract, the Lineweaver-Burk plot showed concave downward curvature, and the Michaelis constant was 0.

Protein images obtained by STM, AFM and TEM.

Scanning tunnelling microscopy and atomic force microscopy, one scanning the tunnelling current and the other the repulsive atomic force between same and probe, can give high-quality surface topographies of proteins, which have been difficult to obtain by more conventional methods such as transmission electron microscopy.

Effects of vapiprost, a novel thromboxane receptor antagonist, on thrombus formation and vascular patency after thrombolysis by tissue-type plasminogen activator.

1. A thrombus was induced in the rat femoral artery by endothelial damage due to the photochemical reaction between systemically-injected Rose Bengal and transillumination with green light (wavelength: 540 nm). The artery of the control rat was completely occluded in 302.

Baroreflex and beta-adrenoceptor function are diminished in rat cardiac hypertrophy due to volume overload.

We investigated whether cardiac hypertrophy induced by volume loading influences baroreflex sensitivity. Aortic insufficiency (AI) was induced in male Wistar rats by graded disruption of the aortic valve, which, after 2 weeks, resulted in a 30% increase in heart/body weight or left-ventricular/body weight ratio compared with control animals. Baroreflex sensitivity was assessed in conscious animals by measuring the heart rate (HR) responses to the changes in mean arterial pressure (MAP) induced by phenylephrine and nitroprusside sodium at 2 weeks.

Effects of isradipine on plasma renin activity in sodium-loaded and -depleted conscious rabbits.

The antihypertensive effect of calcium antagonists is altered little by high salt intake or concomitant diuretic treatment. We therefore investigated whether modest changes in the salt balance might alter the acute response of the renin-angiotensin system to the calcium antagonist isradipine in conscious rabbits. Mongrel rabbits with indwelling arterial and venous catheters were pretreated with either a single subcutaneous injection of 20 mg/kg furosemide 24 h before the experiment [sodium depletion (SD)] or the addition of 0.

Effect of spirapril on left ventricular hypertrophy due to volume overload in rats.

The effect of the angiotensin-converting enzyme (ACE) inhibitor spirapril on structural and functional parameters of volume-overloaded rat hearts was evaluated in a time-course study. Left ventricular hypertrophy (LVH) was induced by graded disruption of the aortic valve in male Wistar rats. Four weeks later, structural (LV mass and LV wall thickness) as well as functional parameters [LV end-systolic and end-diastolic volumes, stroke volume (SV), ejection fraction (EF)] were determined in anesthetized animals by magnetic resonance imaging (MRI).

A new model of equilibrium dysfunction in the rat induced by photochemical damage to the inner ear's microcirculation.

A new photochemical method was employed to damage the inner ear microcirculation in the rat. Under pentobarbital anesthesia, the middle ear was exposed by a ventral approach and the tympanic membrane and the malleus and incus were removed. The vestibule was then illuminated by a filtered xenon light (wave length: 540 nm) while rose bengal was infused intravenously.

Pharmacokinetics of caffeine and its metabolites in horses after intravenous, intramuscular or oral administration.

The pharmacokinetics of caffeine (CAF) and its metabolites, dimethylxanthines, were examined in horses administered 2.5 mg/kg of CAF intravenously (i.v.

Altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes.

The present study was undertaken to clarify the altered effect of arachidonic acid on inner ear blood flow in rats with streptozotocin-induced diabetes by use of the laser-Doppler flowmeter. Drugs were administered intraarterially via the subclavian artery in a dose range that did not affect the systemic blood pressure. Both arachidonic acid and papaverine hydrochloride increased inner ear blood flow dose-dependently.

Determination of rat heart morphology and function in vivo in two models of cardiac hypertrophy by means of magnetic resonance imaging.

Quantitative magnetic resonance imaging (MRI) was applied to assess structural and functional parameters of the rat heart in vivo. Using ECG and respiratory triggering, MR images were obtained at different time points during the cardiac cycle. This allowed accurate determinations of the left ventricular (LV) mass, wall thickness, LV end-systolic and end-diastolic volumes, stroke volume, and ejection fraction.

Mechanism of cell damage by ultrasound in combination with hematoporphyrin.

The mechanism of cell damage by ultrasound in combination with hematoporphyrin was studied. Mouse sarcoma 180 cell suspensions were exposed to ultrasound for up to 60 s in the presence and absence of hematoporphyrin, with and without active oxygen scavengers. The cell damage enhancement by hematoporphyrin was suppressed by adding histidine but not by mannitol.

Effect of arachidonic acid on the inner ear blood flow measured with a laser Doppler flowmeter.

The present study was undertaken to clarify the effect of arachidonic acid (AA) on the inner ear blood flow of rats as measured with a laser Doppler flowmeter. With the rats under anesthesia with sodium pentobarbital, the middle ear was approached ventrally and a laser Doppler probe was positioned over the lateral wall of the cochlea. Drugs were administered via the subclavicular artery.

Synergistic effect of ultrasound and hematoporphyrin on sarcoma 180.

The antitumor effects of combined use of ultrasound (US) and a photosensitizer, hematoporphyrin (Hp), were determined in mice bearing sarcoma 180. In order to find the optimum timing of the US irradiation after the administration of Hp, the Hp concentrations in the tumor and in the plasma were determined and were analyzed pharmacokinetically. Antitumor effects were evaluated by measuring the tumor size and the tumor weight.

A new model for photochemically induced thrombosis in the inner ear microcirculation and the use of hearing loss as a measure for microcirculatory disorders.

A new photochemical method was employed to cause disorders in the inner ear's microcirculation, using the rat as an animal model. Hearing loss was used as a measure for establishing the altered microcirculation. Under pentobarbital anesthesia, the middle ear was opened by a ventral approach.

The inhibitory effects of cimetidine on elimination and distribution of propranolol in rats.

We studied the effects of cimetidine on the pharmacokinetics, blood and tissue distribution and plasma protein binding of propranolol in rats. The plasma disappearance of propranolol after a 10 mg/kg intravenous injection and oral administration were fitted to a two compartment open model. In the cimetidine treated rats, the area under concentration curve after an intravenous injection (AUCiv) was increased by 64% and the plasma total body clearance (Cltot) and the rate constant at the terminal phase (beta) were decreased by 38% and 33% of those of the non-treated rats, respectively.

Intestinal absorption kinetics using a laminar flow model.

The drug concentration profile at non-steady state in the intestine was simulated using a laminar flow model. The transport equation with cylindrical coordinates was solved by a finite difference method to stimulate the concentration profile in the tube and the exit cup-mixing concentration. A drug with a various wall permeability coefficient (Pw = zero or 10(-5) to 10(-3) cm/s) and diffusion constant (D = 10(-6) to 10(-4) cm2/s) was assumed to be introduced into the tube in a pulse form.

Effects of cimetidine on quinidine distribution and tissue pH in rats.

To elucidate the mechanism(s) of the decrease of the volume of distribution at steady state (Vdss) and the tissue-to-plasma concentration ratio (Kp) of quinidine after cimetidine treatment, the following were studied; (1) the effect of cimetidine on the tissue binding of quinidine in vitro, (2) the non-linear tissue distribution of quinidine and (3) the effect of cimetidine on tissue pH. The in vitro binding of quinidine to rat tissue homogenates was not affected by cimetidine treatment. The tissue distribution of quinidine in rats was linear from 1 to 5 micrograms/ml of plasma concentration except for lung.

Involvement of thromboxane and leukotriene in arachidonate induced coronary constriction in diabetic rats.

Vascular responsiveness to sodium arachidonate was examined in isolated perfused hearts from rats with streptozotocin-induced diabetes. In diabetic rats arachidonate induced a biphasic coronary vascular response characterized by initial vasoconstriction followed by prolonged vasodilation. Non-diabetic rats showed only a vasodilator response.