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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 163 records · Page 9Linked to original sources
PubMed1998

Mechanisms of vasorelaxation induced by troglitazone, a novel antidiabetic drug, in the porcine coronary artery.

BACKGROUND: Troglitazone (TRO), a novel antidiabetic drug, has been reported to decrease blood pressure and relax vascular strips. The mechanism of relaxation induced by TRO was determined in terms of Ca2+ signaling in smooth muscle cells. METHODS AND RESULTS: Front-surface fluorometry and fura 2-loaded medial strips of porcine coronary artery were used to examine the effects of TRO on cytosolic Ca2+ concentrations ([Ca2+]i) and contractions. The sustained contraction induced by 100 nmol/L U46619 was similar to that induced by 60 mmol/L K+ depolarization (60K+). TRO concentration dependently decreased [Ca2+]i and the force of these contractions. The concentration of TRO required to induce 50% inhibition of U46619-induced force (2.9 micromol/L) was significantly lower than that required in the case of 60K+-induced force (7.3 micromol/L). Replacing extracellular Ca2+ with Mn2+ gradually quenched fluorescence at 360 nm excitation. This decline was accelerated by 100 nmol/L U46619 and 30K+ to a similar extent, indicating a similar activation of Ca2+ influx. TRO completely inhibited U46619-activated influx but partly inhibited depolarization-activated influx. Cumulative applications of extracellular Ca2+ during stimulations with U46619 or 118K+ induced stepwise increases in [Ca2+]i and force. TRO shifted the [Ca2+]i-force relation to the right during both stimulations. CONCLUSIONS: TRO relaxes coronary artery by decreasing [Ca2+]i and Ca2+ sensitivity of contractile apparatus. Inhibition of Ca2+ influx was important in decreasing [Ca2+]i. TRO more effectively inhibits receptor-operated Ca2+ influx than voltage-operated Ca2+ channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Modulation of ischemia-evoked release of excitatory and inhibitory amino acids by adenosine A1 receptor agonist.

Adenosine has been reported to have beneficial effects against ischemic brain damage, although the mechanisms are not fully clarified. To examine the role of adenosine on the ischemia-evoked release of neurotransmitters, we applied a highly selective agonist for adenosine A1 receptor, 2-chloro-N6-cyclopentyladenosine (CCPA), into the ischemic brain using in vivo brain dialysis, which directly delivered the agonist to the local brain area. Concentrations of extracellular amino acids (glutamate, aspartate, gamma-aminobutyric acid (GABA) and taurine) and regional blood flow in the striatum of spontaneously hypertensive rats (SHRs) were monitored during cerebral ischemia elicited by bilateral carotid artery occlusion for 40 min and recirculation. Striatal blood flow and basal levels of amino acids were not affected by direct perfusion of CCPA (10 microM or 100 microM). During ischemia, concentrations of glutamate, aspartate, GABA and taurine increased up to 37-, 30-, 96- and 31-fold, respectively, when vehicle alone was administered. Administration of CCPA did not affect the changes in regional blood flow during ischemia and reperfusion. Perfusion of CCPA (100 microM), however, significantly attenuated the ischemia-evoked release of aspartate (by 70%) and glutamate (by 73%). The ischemia-induced increase of GABA tended to be decreased by CCPA, although it was not statistically significant. In contrast, both low and high concentrations of CCPA had little effect on the release of taurine during ischemia. These results suggest that stimulation of adenosine A1 receptors selectively attenuated the ischemia-evoked release of excitatory amino acids, but not of inhibitory amino acids without affecting blood flow. This modulation of the release of amino acids by adenosine A1 receptor agonists may play a protective role against ischemic neuronal damage.

Adenosine↗
PubMed1998

Antihypertensive treatment improves endothelium-dependent hyperpolarization in the mesenteric artery of spontaneously hypertensive rats.

BACKGROUND: The vascular endothelium releases endothelium-derived hyperpolarizing factor (EDHF). The mesenteric arteries of 6- to 8-month-old spontaneously hypertensive rats (SHRs) exhibit an impairment of the hyperpolarization induced by acetylcholine via EDHF. METHODS AND RESULTS: We determined whether antihypertensive treatment can improve EDHF-mediated responses in SHRs. Beginning at age 8 to 9 months, the animals were treated with either enalapril (40 mg x kg(-1) x d(-1)) (SHR-Es) or a combination of hydralazine (25 mg x kg(-1) x d(-1)) and hydrochlorothiazide (7.5 mg x kg(-1) x d(-1)) (SHR-Hs) for 3 months. The control groups were age-matched SHRs (SHR-Cs) and Wistar Kyoto rats (WKYs). The two treatments lowered the blood pressure to comparable extents. The acetylcholine-induced hyperpolarization in the mesenteric artery of treated SHRs improved to a level comparable to that in WKYs (acetylcholine 10(-5) mol/L with norepinephrine 10(-5) mol/L: SHR-E, -14.4 +/- 1.8; SHR-H, -12.0 +/- 1.3; SHR-C, -7.2 +/- 1.2; and WKY, -13.3 +/- 2.3 mV). EDHF-mediated relaxation, as assessed by relaxation to acetylcholine resistant to N(G)-nitro-L-arginine in norepinephrine-contracted rings, was markedly improved in treated SHRs (maximal relaxation: SHR-E, 79.3+/-3.2%; SHR-H, 47.4+/-8.6%; SHR-C, 4.8+/-2.4%; and WKY, 45.1+/-6.0%). When the rings were contracted with 77 mmol/L KCl to eliminate EDHF response, no difference was found in relaxation to acetylcholine among the four groups. Similarly, the hyperpolarization and relaxation to levcromakalim, a K+ channel opener, were comparable among the groups. CONCLUSIONS: Antihypertensive treatment improved EDHF-mediated hyperpolarization and relaxation in the mesenteric artery in SHRs, whereas NO-mediated relaxation did not appear to be modulated by drug therapy. Thus, alterations in the EDHF system may play a pivotal role in endothelial dysfunction and its improvement with drug therapy in SHRs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Role of nitric oxide in the nucleus of the solitary tract of rats.

We have determined the role of nitric oxide (NO) in the nucleus of the solitary tract (NTS) of normotensive Wistar rats. The unilateral microinjection of Nomega-nitro-l-arginine methyl ester (10 nmol) to block the synthesis of NO into the NTS significantly decreased the arterial pressure, heart rate (HR) and renal sympathetic nerve activity (RSNA) (-19+/-2 mmHg, -23+/-5 beats/min, -30+/-2%, respectively). The microinjection of carboxy-2-phenyl-4,4,5, 5-tetramethylimidazoline-1-oxyl 3-oxide (Carboxy PTIO) (trapper of NO; 0.1 nmol) into the NTS also decreased arterial pressure and RSNA. Conversely, the microinjection of Et2N[N(O)NO]Na (NOC 18) (NO donor; 10 nmol) caused increases in arterial pressure, HR and RSNA (+14+/-2 mmHg, +11+/-2 beats/min, +38+/-7%, respectively), which was inhibited by the pre-microinjection of Carboxy PTIO (0.1 nmol). On the other hand, not only l-arginine (10 nmol) but also d-arginine (10 nmol), which is inactive to produce NO, significantly decreased the arterial pressure and RSNA. These results suggest that (1) NO acts at the NTS to increase the arterial pressure and RSNA, and (2) the microinjection of l-arginine as well as d-arginine led to decreases in arterial pressure and RSNA that were not mediated by the formation of NO in the NTS.

Animals↗
PubMed1998

Protein kinase C modulates ischemia-induced amino acids release in the striatum of hypertensive rats.

The role of protein kinase C (PKC) in mediating the ischemia-induced release of amino acids in the striatum was studied using an in vivo brain dialysis technique in the striatum of spontaneously hypertensive rats (SHRs). Using HPLC combined with fluorescence detection methods, we investigated the concentrations of amino acids in the dialysates produced by 20 min of transient forebrain ischemia. We studied the effects of an inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and another isoquinoline analog (HA1004) with less inhibitory effect on the C kinase in ischemia-induced amino acids release. Bilateral carotid artery occlusion caused a marked reduction in the striatal blood flow by 91 +/- 6%. The extent of the cerebral blood flow (CBF) reduction were essentially the same among H7-, HA1004-, and the vehicle-treated groups. Forebrain ischemia produced a marked increase in glutamate (21-fold of the basal concentration), aspartate (19-fold) and taurine (16-fold). Pretreatment with H7 markedly attenuated the ischemia-in-duced release of these three amino acids to 3, 3 and 4-fold of the basal values, respectively. Increase of gamma-aminobutyric acid (GABA) was also attenuated by H7 (vehicle; 2.46 +/- 1.26 microM, H7; 0.62 +/- 0.75 mM). HA1004 did not affect the release of glutamate, aspartate or GABA during ischemia. The ischemia-induced release of taurine was significantly inhibited by HA1004 but the effect was much smaller than that of H7. These results thus indicate that PKC plays a major role in the ischemia-induced release of amino acids in the striatum of SHR.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Effects of long-acting angiotensin-converting enzyme inhibitor, imidapril, on the lower limit of cerebral blood flow autoregulation in hypertensive rats.

The objective of the present study was to examine the effects of a long-acting angiotensin converting enzyme inhibitor, imidapril ((4S)-1-methyl-3-¿(2S)-2-[N-(1S)-1-ethoxycarbonyl-3-phenylpropyl) amino] propionyl¿-2-oxoimidazolidine-4-carboxylic acid hydrochloride), for 7 days on the cerebral blood flow autoregulatory response to hypotension in hypertensive rats. We measured the cerebral blood flow at rest and during hemorrhagic hypotension, using laser-Doppler flowmetry. At the same time, the absolute baseline cerebral blood flow values in the parietal cortex were quantified with the hydrogen clearance method. After administration of imidapril at a dose of 5 mg/kg/day for 7 days, the resting value of mean arterial blood pressure was significantly decreased by 25 mm Hg (P < 0.001), cerebral vascular resistance was lowered by 14.4% (P < 0.05) and the lower limit of cerebral blood flow autoregulation was shifted to a lower level, 106+/-11 mm Hg (mean +/- S.D.), from 137+/-8 mm Hg in the control group (P < 0.001), while resting cerebral blood flow remained unchanged. The present results demonstrated that imidapril preserves cerebral blood flow and significantly shifts the lower limit of cerebral autoregulation towards lower blood pressure levels.

Adenosine Triphosphate↗
PubMed1998

Sonographic detection of haemodynamic changes in a case of vertebrobasilar insufficiency.

We present a diagnostically challenging case of vertebrobasilar insufficiency caused by head rotation. The patient was a 58-year-old man complaining of dizziness and faintness with head rotation to the left. Vertebral arteriography with the head turned to the left revealed mechanical compression of the right vertebral artery at the occipitoatlantal joints and an occluded left vertebral artery. Duplex sonography demonstrated disappearance of the end-diastolic flow signal in the right vertebral artery on head rotation, paralleling the appearance of symptoms. Decompression of the vertebral artery by transversectomy of the atlas and hemilaminectomy of the axis completely relieved the symptoms and the Doppler flow signal pattern of the vertebral artery returned to normal: End-diastolic flow in the right vertebral artery did not disappear even when the head was rotated to the left.

Cerebrovascular Circulation↗
PubMed1998

Double-contrast radiographic assessment of lupus-associated enteropathy.

PURPOSE: To describe the double-contrast radiographic features of lupus-associated enteropathy. MATERIALS AND METHODS: Six patients with systemic lupus erythematosus involving the small bowel were assessed by double-contrast radiography of the duodenum and small intestine, with reference to clinical manifestations and jejunoscopic findings. RESULTS: Lupus-associated enteropathy could be categorized into two types: acute onset enteritis in four patients and protein-losing enteropathy with hyperlipidaemia in two patients. The former group presented with irregular thickening and spiculation in the folds of the multiple segments of the duodenum to the terminal ileum, and they were frequently accompanied by thumbprinting, suggestive of ischaemic change. The latter group was characterized by mildly thickened folds with multiple submucosal nodules in the upper portion of the jejunum. In one patient from this group, jejunal biopsy demonstrated lymphangiectasia. Both groups were successfully treated by high-dose prednisolone. Follow-up radiography in the former group showed a complete improvement within 2-7 weeks, whereas radiographic abnormalities in the latter remained even after 2 months. CONCLUSIONS: Lupus-associated enteropathy cases may be divisible into two types; an acute ischaemic enteritis type and a protein-losing enteropathy type, each presenting distinct radiographic features.

Acute Disease↗
PubMed1998

Comparative features of double-contrast barium studies in patients with isosporiasis and strongyloidiasis.

OBJECTIVE: To compare the gastrointestinal features of isosporiasis and strongyloidiasis. METHODS: Two patients with isosporiasis and three patients with strongyloidiasis were assessed by double-contrast radiography of the duodenum and small intestine, with reference to histology of the duodenal biopsy specimens. RESULTS: Both conditions affected the duodenum and the proximal jejunum, and showed similar radiographic changes as the diseases progressed. Thus, three patients with diarrhoea lasting 1 year or less showed only minimal or irregularly thickened mucosal folds, which seemed to result from mucosal inflammation. Two patients with long-standing disease periods (17 years and 30 years) presented a markedly granular mucosal appearance with effacement of the folds on radiography. These chronological differences in the radiographic features seemed to reflect the degree of villous atrophy. CONCLUSION: Isosporiasis has similar radiographic features of strongyloidiasis.

Aged↗
PubMed1998

Calcitonin gene-related peptide affords gastric mucosal protection by activating potassium channel in Wistar rat.

BACKGROUND & AIMS: Calcitonin gene-related peptide (CGRP) protects the gastric mucosa against injurious stimuli in various experimental models. The underlying mechanism could be the increase in gastric mucosal blood flow (GMBF). A number of endogenous vasodilators exert their effects through the activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels on vascular smooth muscle. The present experiments were performed to elucidate whether CGRP increases GMBF through the activation of KATP channels and whether the channels are involved in the protection by CGRP of gastric mucosa. METHODS: GMBF was determined by the hydrogen-clearance technique in male Wistar rats. Mucosal lesions were produced by intragastric superfusion with 0.15N HCland 15% ethanol for 40 minutes. Effects of an agonist (Y-26763, intra-arterially) and an inhibitor (glibenclamide, intravenously) of KATP channels were tested. RESULTS: Y-26763 increased GMBF, which was abolished by glibenclamide, and a CGRP-induced increase in GMBF was attenuated by glibenclamide. Macroscopic and microscopic lesions were exacerbated by human CGRP-(8-37) (a CGRP-1 receptor antagonist; intra-arterially) and glibenclamide but were ameliorated by exogenous CGRP (intra-arterially). CONCLUSIONS: CGRP protects the gastric mucosa against ulcerogenic stimuli, at least in part, through the activation of KATP channels in rats.

Animals↗
PubMed1998

Primary low-grade, B-cell, mucosa-associated lymphoid tissue lymphoma of the colorectum: clinical and colonoscopic features in six cases.

BACKGROUND: Unlike gastric lymphoma, the endoscopic features of low-grade, mucosa-associated lymphoid tissue (MALT) lymphoma of the colorectum have not been defined. METHODS: We analyzed colonoscopy, endoscopic ultrasonography, and histologic findings in six patients with MALT lymphoma restricted to the colorectum. Histologic confirmation of the proliferation of centrocyte-like cells with lymphoepithelial lesions formed the criteria for the selection of patients. RESULTS: Based on endoscopic findings, the patients were divided into cases of solitary (4 patients) or multifocal (2 patients) involvement. Endoscopic findings in cases of solitary involvement were uniform in that the lesions were either smooth or nodular protrusions, demonstrated by a hypoechoic mass under endoscopic ultrasonography. Multifocal involvement was endoscopically recognized as protrusions, dilated vasculature, or small ulcers. CONCLUSIONS: Protruding lesions are the main pattern of involvement in MALT lymphoma of the colorectum, although variable and multifocal involvement is also possible in this type of lymphoma.

Aged↗
PubMed1998

Advanced glycosylation end products induced tissue factor expression in human monocyte-like U937 cells and increased tissue factor expression in monocytes from diabetic patients.

Tissue factor (TF) plays a central role in the initial activation of the extrinsic coagulation pathway and is thought to be involved in the development of atherosclerosis and thrombosis. The effect of advanced glycosylation end products (AGEs) on TF expression and its mechanism were assessed by flow cytometric analysis. Human macrophage-like U937 cells, which were shown to contain mRNA encoding the receptors of advanced glycosylation end products (RAGE), expressed TF in a dose-dependent manner on incubation with AGE-albumin. AGE-albumin-induced TF expression was completely inhibited by the anti-oxidant agents, catalase and probucol. TF expression in peripheral monocytes from normal volunteers was also increased by AGE-albumin. Finally, TF expression in monocytes from individuals with diabetes mellitus, in whom the concentration of circulating AGEs is reported to be increased, was higher than that in monocytes from normal controls. These results suggest that AGE-induced TF expression in macrophages/monocytes is mediated by oxidant stress. AGEs may promote thrombosis and the development of atherosclerosis by inducing TF expression in monocytes in patients with diabetes mellitus.

Albumins↗