Biomedical subjects

Y Masuda

Publications and source records attributed to Y Masuda.

At least 325 records · Page 18Linked to original sources

PubMed1996

Endothelin-1 partially inhibits ATP-sensitive K+ current in guinea pig ventricular cells.

To clarify the pathophysiological significance of endothelin (ET) in the ischemic myocardium, we examined the effect of endothelin-1 (ET-1) on the ATP-sensitive K+ current (IK.ATP) and compared it with that of ET-3 in guinea pig ventricular cells using conventional microelectrode and patch clamp techniques. In isolated guinea pig papillary muscles, ET-1 (30 nM) markedly increased developed tension (DT), with little influence on action potential duration (APD), whereas ET-3 at the same concentration failed to affect DT or APD. Both nicorandil (1 mM) and cromakalim (30 microM) markedly shortened APD and decreased DT in papillary muscles. ET-1, but not ET-3, partially reversed the nicorandil-induced decreases in APD and DT in a concentration-dependent manner. ET-1 also attenuated the cromakalim-induced decreases in APD and DT. In single ventricular myocytes, both nicorandil and cromakalim increased a steady-state outward current, which was sensitive to 1 microM glibenclamide, suggesting that these drugs activate IK.ATP. ET-1 (30 nM) significantly inhibited the IK.ATP, whereas ET-3 failed to affect it. The ET-1 induced inhibition of IK.ATP was abolished by BQ-485 (100 nM), an ETA receptor-selective antagonist. Neither the protein kinase C (PKC) inhibitor staurosporine (20 nM) nor the calmodulin antagonist W-7 (50 microM) affected the inhibitory action of ET-1 on the nicorandil-induced IK.ATP. In pertussis toxin (PTX)-treated cells, the inhibitory action of ET-1 on IK.ATP was augmented rather than attenuated. These results suggest that ET-1 partially inhibits the IK.ATP through the activation of ETA receptors, although the precise intracellular mechanism remains to be clarified. Because activation of the ATP-sensitive K+ channels is considered to protect the ischemic myocardium, the partial inhibition of IK.ATP by ET-1 may lead to the aggravation of myocardial injury, potentially due to an increase in transmembrane Ca2+ influx.

Action Potentials↗

PubMed1996

alpha 1-Adrenoceptor stimulation partially inhibits ATP-sensitive K+ current in guinea pig ventricular cells: attenuation of the action potential shortening induced by hypoxia and K+ channel openers.

Effects of alpha 1-adrenoceptor stimulation on the action potential shortening produced by K+ channel openers (KCOs) or hypoxia and on the ATP-sensitive K+ current (IK.ATP) activated by KCOs were examined in guinea-pig ventricular cells by using conventional microelectrode and patch-clamp techniques. In papillary muscles, nicorandil (1 mM) or cromakalim (30 microM) markedly shortened the action potential duration (APD) (to 51 +/- 2% and 40 +/- 5% of each control value). Addition of 100 microM methoxamine, an alpha 1-adrenoceptor agonist, partially but significantly reversed the KCOs-induced APD shortening (to 69 +/- 3% and 50 +/- 4% of each control value). The APD-prolonging effect of methoxamine was antagonized by 1 microM prazosin (alpha 1-antagonist) and 100 nM WB4101 (alpha 1A-antagonist) but not by 10 microM chloroethylclonidine (alpha 1B-antagonist). In papillary muscles exposed to a hypoxic, glucose-free solution, APD declined gradually. In the presence of 100 microM methoxamine or 10 microM glibenclamide, the hypoxia-induced action potential shortening was significantly inhibited. In single ventricular myocytes, the KCOs increased a steady-state outward current that was abolished by glibenclamide (1 microM), thereby suggesting that these KCOs activate IK.ATP. Methoxamine (100 microM) significantly inhibited the nicorandil-induced IK.ATP by 18 +/- 5% and the cromakalim-induced IK.ATP by 16 +/- 2%. 4 beta-Phorbol 12-myristate 13-acetate (100 nM), a protein kinase C activator, failed to mimic the alpha 1-adrenoceptor-mediated inhibition of the nicorandil-induced outward current. Staurosporine (30 nM), a protein kinase C inhibitor, also failed to affect the partial inhibition of IK.ATP by methoxamine. Neither intracellular loading of heparin (100 micrograms/ml), an inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release inhibitor, nor IP3 (20 microM) plus inositol 1,3,4,5-tetrakisphosphate (IP4 5 microM) could affect the inhibitory action of methoxamine. In conclusion, alpha 1A-adrenergic stimulation partially inhibits IK.ATP in cardiac cells. Neither protein kinase C activation nor IP3 formation appears to be involved in the partial inhibition of IK.ATP. The alpha 1A-adrenoceptor-mediated inhibition of IK.ATP may be deleterious for ischemic myocardium and partly offset the cardioprotective effect of KCOs because attenuation of action potential shortening may potentially increase Ca2+ influx in ischemic cells.

Action Potentials↗

PubMed1996

Nosocomial diarrhoea in the elderly due to enterotoxigenic Clostridium perfringens.

To diagnose sporadic diarrhoea due to Clostridium perfringens infection, faecal specimens from elderly patients were examined directly for C.perfringens enterotoxin using reverse passive latex agglutination assay, and then cultured for this organism. C.perfringens isolates from those samples were grouped by slide agglutination and by pulsed-field gel electrophoresis (PFGE). Fifty of the 60 isolates agglutinated with newly raised antiserum WX2 and 38 shared the same genomic PFGE pattern. Characteristics of the epidemics and experimental data suggest that the diarrhoea was caused by a nosocomial spread of C.perfringens, and not by a food-borne outbreak.

Aged↗

PubMed1996

Epitope analysis of HLA-DR-restricted helper T-cell responses to Der p II, a major allergen molecule of Dermatophagoides pteronyssinus.

T-cell epitopes of Der p II, a major allergen of Dermatophagoides pteronyssinus, were analyzed by using human T-cell clones. We tested 38 cloned T cells from two Japanese patients with allergic rhinitis, and identified at least two peptides (K33-T47 and I58-C73) as helper T-cell epitopes. The former epitope was shown to be restricted by HLA-DRB1*1502, and the latter by HLA-DRB1*0405, both of which are typical Japanese HLA-DR alleles, suggesting that those T-cell epitopes might be important for the onset of house-dust mite allergy in the Japanese population. We prepared 15 analog peptides of the HLA- DRB1*1502-restricted 15-mer peptide. Of those 15 residues, five (F35, L37, A39, F41, and E42) were critical for the epitope activity, and three residues (F35, A39, and E42) seemed to be included in anchor motifs for HLA-DRB1*1502. The epitope peptide was also recognized by HLA-DRB1*1502-positive healthy donors; however, only allergic T cells showed Th2 functions. Antigen-presenting cells of nonallergic donors were able to activate allergic T cells to express Th2 function. This seemed to suggest that antigen recognition of T cells, as well as additional unknown factors which promote Th2, rather than Th1, responses, might be important for the onset of house-dust mite allergy.

Allergens↗

PubMed1996

Effects of class III antiarrhythmic drugs on the Na(+)-activated K+ channels in guinea-pig ventricular cells.

1. Class III antiarrhythmic drugs are known to block the outward currents through voltage-gated K+ channels. However, effects of class III antiarrhythmic drugs on the ligand-gated K+ channels have not been thoroughly examined. In this study effects of amiodarone and newer class III antiarrhythmic drugs, E-4031 and MS-551, on the Na+-activated K+ (KNa) current were examined in inside-out membrane patches and in whole cells isolated from guinea-pig ventricle. 2. The KNa channel current was activated by increasing [Na+]i from 0 mM to 30-100 mM with 150 mM [K+]o in inside-out membrane patches of ventricular myocytes. The channel current showed a larger slope conductance (210 pS), inward-going rectification and subconductance levels of various amplitudes. 3. E-4031 and MS-551 at high concentrations (300 microM) inhibited the K+ current by decreasing the open time (flickering block). On the other hand, amiodarone at relatively low concentrations (0.1-10 microM) inhibited the KNa channel current by decreasing the open probability rather than by decreasing the open time. The IC50 value of amiodarone for inhibiting the KNa channel current was 1.0 microM. 4. These drugs also inhibited the whole-cell outward current activated by intracellular loading of 50 mM [Na+]i and extracellular application of 10 microM ouabain. 5. These results indicate that class III antiarrhythmic drugs inhibit the KNa channel current in cardiac cells. However, there are sharp differences in the effective concentrations and the mode of inhibition between amiodarone and the newer class III antiarrhythmic drugs.

Amiodarone↗

PubMed1996

Glomerular capillary regeneration and endothelial cell apoptosis in both reversible and progressive models of glomerulonephritis.

In summary, angiogenetic capillary regeneration with endothelial proliferation occurred among mesangiolytic lesions in Thy-1 GN, and the damaged glomerulus recovered its normal structure with the reconstruction of the capillary network. In anti-GBM GN on WKY rats, the damaged glomerulus showed rare capillary regeneration and progressed to global sclerosis. In Thy-1 GN, endothelial cell apoptosis was found in the regenerated capillaries with endothelial cell hypercellularity. On the other hand, in anti-GBM GN on WKY rats, the number of endothelial cell apoptosis increased during the evolution of glomerular sclerosis. We have concluded that glomerular capillary regeneration plays an essential role in the recovery of damaged glomeruli. Moreover, apoptosis is indispensable in regulating the number of intrinsic endothelial cells. We also found that endothelial apoptosis is important in progression of glomerular sclerosis.

Animals↗

PubMed1996

[Research and development of zonisamide, a new type of antiepileptic drug].

Zonisamide (1,2-benzisoxazole-3-methanesulfonamide, AD-810) is a broad spectrum antiepileptic drug which has been launched in Japan and South Korea. It lacks the ureide structure included in most of the existing antiepileptic drugs. Zonisamide was synthesized by the sulfonation and the successive amination of 1,2-benzisoxazole-3-acetic acid in a very poor yield. After several efforts to optimize the compound, zonisamide was selected based on the balance of the efficacy and safety. The yield was greatly improved by the development of new synthetic routes. Zonisamide suppressed maximal electroshock seizures in mice, rats, rabbits and dogs. Its therapeutic plasma concentration range between anticonvulsant and neurotoxic effects was much wider than that of the existing antiepileptic drugs. In electroencephalographic studies on animal models of epilepsy, zonisamide, like phenytoin and carbamazepine, restricted the spread or propagation of seizures and, like sodium valproate, it suppressed the epileptogenic focus activity. Zonisamide was effective in several kindling models. In clinical studies, zonisamide exerted the efficacy against partial seizures (simple, complex, secondarily generalized seizures) and some generalized seizures (tonic-clonic, tonic, atypical absence seizures) that were comparable to that of carbamazepine and sodium valproate, respectively. Zonisamide was also effective in monotherapy. The adverse effects related with zonisamide were mainly drowsiness, ataxia, loss of appetite and gastrointestinal symptoms. Serious adverse effects which may be life-threatening have not been reported.

Animals↗

PubMed1996

Effect of the duration of fasting on myocardial fluorine-18-fluorodeoxyglucose positron emission tomography images in normal males.

To evaluate the effect of the duration of fasting on myocardial fluorine-18-fluorodeoxyglucose (FDG) uptake and distribution, 16 FDG-positron emission tomography (PET) studies were performed in 7 normal volunteers under three different conditions: glucose loading, 6 h fasting and overnight fasting. In the glucose-loaded condition, all subjects had good image quality, and myocardial metabolic rates of glucose (MRGlc) were significantly higher than those in the other two conditions. In the 6 h and overnight fasting conditions, image qualities varied according to MRGlc. Although there were visually distinct regional differences with MRGlc ranging from 0.05 to 0.15 mumol/min per g, these differences were not impressive by a quantitative analysis. The ranges of MRGlc in these two fasted conditions overlapped each other. There was a significant negative linear correlation between MRGlc and serum free fatty acid levels. Thus, MRGlc and image quality in fasted normal subjects varied with the extent of the fed-to-starved transition under clinical fasting conditions (6 h to overnight), and this transition does not depend solely on the duration of fasting. These findings may explain the heterogeneity in FDG studies under fasting conditions.

Adult↗

PubMed1996

[Effect of efonidipine hydrochloride (NZ-105), a dihydropyridine derivative with calcium antagonistic action, on myocardial oxygen tension in anesthetized dogs].

Effect of efonidipine hydrochloride (efonidipine) on myocardial oxygen tension (PO2) was investigated in open-chest anesthetized dog and compared with those of nifedipine and nisoldipine. PO2 was measured by a membrane-coated platinum wire, which was inserted into the myocardium. Intravenous administration of efonidipine (10 and 30 micrograms/kg) decreased mean blood pressure to a similar extent to that induced by nifedipine (1 and 3 micrograms/kg) or nisoldipine (1 and 3 micrograms/kg). Efonidipine increased coronary blood flow (CBF) and decreased the double product (DP) dose-dependently. Similar results were observed in nisoldipine-treated animals. Nifedipine produced a transient increase in CBF and a transient decrease in DP. The duration of action of efonidipine on CBF was longer than that of nifedipine or nisoldipine. Efonidipine increased PO2, and the effect was more pronounced in the endocardial region than in the epicardial region. Nifedipine had no significant effect on the PO2, while nisoldipine significantly increased PO2 in the endocardial region. The effect of efonidipine on the PO2 was greater than that of nisoldipine and the duration of action of efonidipine was longer than that of nisoldipine. These results suggest that efonidipine may increase PO2 by mediating, at least in part, a long-lasting increase in oxygen supply and a decrease in oxygen demand in dog heart.

Animals↗

PubMed1996

[Effect of efonidipine hydrochloride on myocardial oxygen balance in anesthetized dogs].

The aim of the present study was to investigate the effect of efonidipine hydrochloride (efonidipine) on myocardial oxygen balance in anesthetized open-chest dogs, and the results were compared to those of nifedipine or nisoldipine. Efonidipine (10 and 30 micrograms/kg) lowered the mean blood pressure, and the extent of the hypotension was similar to those induced by nifedipine (1 and 3 micrograms/kg) and nisoldipine (1 and 3 micrograms/kg). The hypotensive effect of efonidipine was very slow in onset and long-lasting as compared with that of nifedipine. Efonidipine and nisoldipine decreased the heart rate, but nifedipine increased it. Efonidipine (30 micrograms/kg) and nifedipine (1 and 3 micrograms/kg) slightly increased myocardial oxygen consumption. Nisoldipine (3 micrograms/kg) tended to increase myocardial oxygen consumption. Since efonidipine, nifedipine and nisoldipine decreased the arterio-venous oxygen difference and increased coronary sinus outflow, these drugs increased the oxygen supply to the myocardium. Furthermore, these drugs decreased myocardial oxygen demand. From these results, it is suggested that efonidipine may be useful for improving myocardial oxygen balance.

Anesthesia↗

PubMed1996

[Effects of efonidipine hydrochloride, a calcium antagonist derived from dihydropyridine, on acute myocardial ischemia in anesthetized open-chest dogs].

Effects of efonidipine hydrochloride (NZ-105), a dihydropyridine calcium antagonist, on the cardiovascular system were studied in dogs, in which the left anterior descending coronary artery (LAD) was ligated for 50 min. NZ-105 (10 or 30 micrograms/kg), nifedipine (NIF, 1 or 3 micrograms/kg) or nisoldipine (NIS, 1 or 3 micrograms/kg) was injected i.v. before LAD ligation. NZ-105, NIS or NIF decreased the total peripheral resistance (TPR) and blood pressure (BP) and increased the cardiac output (CO) and regional myocardial blood flow (RBF) dose-dependently. LAD ligation decreased RBF and produced segmental bulging in the ischemic area, decreased BP and CO, and did not change TPR. NZ-105, NIF or NIS attenuated the LAD ligation-induced regional myocardial changes. During LAD ligation, in the presence of NZ-105 (30 micrograms/kg), the values of heart rate (HR), BP, and TPR were lower, and that of CO was higher than those in the absence of the drug. Similar results were obtained with NIS (3 micrograms/kg) except that the value of HR in the presence of NIS was not lower. During ischemia, the presence of NIF (3 micrograms/kg), did not significantly change the values of the systemic circulation from those observed in the absence of NIF. In conclusion, NZ-105 may exert a cardioprotective effect by decreasing the oxygen demand of the ischemic heart.

Animals↗

PubMed1996

The metabolic and hemodynamic effects of oxethazaine in the perfused rat liver.

Alteration of hepatic microcirculation and its effects on hepatic metabolism were examined using oxethazaine (OXZ). The infusion of OXZ into isolated perfused livers rapidly increased the portal perfusion pressure (PP) and inhibited oxygen (O2) uptake, which was followed by a decrease in tissue ATP content and an increase in lactate, pyruvate and glucose release into the perfusate. P-450-dependent reductive drug metabolism was enhanced by OXZ, whereas oxidative drug metabolism was suppressed, and this was accompanied by a decrease in substrate uptake. During OXZ infusion, a time delay between the inhibition of O2 uptake and the release of cellular and xenobiotic metabolites was observed. The actions of OXZ required Ca2+. It is unlikely that the inhibition of O2 uptake is due to the inhibition of cellular respiration. The PP increase induced by OXZ was inhibited by papaverine, but not by prazosin, sodium nitroprusside and verapamil, whereas all of these vasodilators were effective against norepinephrine. Under retrograde perfusion, the PP increase by OXZ was abolished, but norepinephrine, uridine 5'-triphosphate, angiotensin II and endothelin 1 were still effective. The extrahepatic portal vein preparation contracted at high concentrations of OXZ. The results suggest that OXZ acts differently from other known vasoconstrictors and possibly narrows hepatic sinusoids to reduce the rate of substance exchange between the sinusoids and hepatocytes, including a reduction in O2 extraction.

Animals↗

PubMed1996

The use of epoxy patch grafts for the repair of experimentally-created diaphragmatic defects in dogs.

Canine pericardium which had been treated with polyepoxy compounds (Denacol EX-313) was used as a patch graft for the correction of experimentally-created diaphragmatic defects in five dogs belonging to the same litter. Clinical, macroscopic and histological examinations were conducted every month up to five months after suturing of the patch graft. Clinical examination of the patch graft showed no apparent abnormalities. Macroscopic examination conducted during autopsy showed that the patch graft maintained adequate elasticity for five months after suturing, the surface of the patch graft was covered with a thin membrane and neovascularization was observed. Histological examination showed that the surface of the patch graft was covered with a thin membrane. Inflammatory tissue reactions were observed at one month, but gradually decreased from the second month onwards. In addition, the patch graft had excellent tissue affinity.

Animals↗

PubMed1996

A quantity of stereotyped behavior of ddY mice induced by low-dose methamphetamine.

It is reported that high-dose methamphetamine (8 mg/kg) induces stereotyped behavior in ddY mice in an open field, but it is still not certain that low-dose methamphetamine (less than 2 mg/kg) can induce the stereotyped behavior in ddY mice in a narrow space. In order to investigate the problem, we evaluated the quantity of stereotyped behavior of ddY mice by using a mouse wheel-running apparatus. In this method, we have come to recognize an increase in the stereotyped behavior depending on the dose of methamphetamine and the reverse-tolerance phenomenon as a decrease in the wheel-revolution counts. The present findings indicate that low-dose methamphetamine can promote stereotyped behavior in ddY mice under conditions in which the ambulation is restricted to a narrow wheel space.

Animals↗

PubMed1996

Plant growth processes in Arabidopsis under microgravity conditions simulated by a clinostat.

The life cycle of Arabidopsis plants was examined by growing them on a horizontal clinostat. Seeds on agar media were allowed to germinate and seedlings were grown under a simulated microgravity on a horizontal clinostat. Clinorotation (3 rpm) did not appear to interfere with germination of plant seeds and development of cotyledons and leaves. Stress relaxation parameters of the cell wall, the minimum relaxation time and the relaxation rate did not appear to be affected by clinostat rotation. On the other hand, the length of inflorescences was reduced to 61-62% by clinostat rotation. Rotation was found to inhibit the polar transport of auxin, although inflorescence growth and auxin transport were not completely inhibited. From these facts, it is possible that the life cycle in Arabidopsis plants could be accomplished in space, although growth phenomena involving auxin transport and its action may be disturbed. Plants may have a capacity to grow in space and we may be able to cultivate crops in space.

Arabidopsis↗

PubMed1996

Apoptosis in progressive crescentic glomerulonephritis.

Recent studies in the experimental proliferative glomerulonephritis (GN) indicate that apoptosis is the major mechanism that mediates the resolution of glomerular hypercellularity during the repair process of experimental GN. The role of apoptosis during progressive GN, however, has not yet been well understood. We have, therefore, examined the role of apoptosis during the progression of experimental crescentic GN to end-stage renal failure. A progressive model of antiglomerular basement membrane GN was induced in Wistar-Kyoto rats with a single injection of anti-rat glomerular basement membrane antibody. Renal function and histologic studies were performed chronologically from Day 0 to Week 8 after disease induction. The incidence of apoptosis in glomeruli as well as glomerular crescents was examined during the progression of crescentic GN to end-stage kidney disease. Many leukocytes infiltrated glomeruli from the early phase of GN, and severe necrotizing and mesangiolytic glomerular damage was observed from Day 5 to Week 3. After glomerular damage, mesangial hypercellularity with mesangial cell proliferation and extracellular matrix accumulation began with crescent formation. Thereafter, glomerular inflammation continued with marked extracellular matrix accumulation until Week 4, and the renal function deteriorated. The proliferative glomerular lesions subsequently progressed to sclerotic lesions and eventually to chronic renal failure in Week 8. Although the number of proliferating cells and infiltrating leukocytes slowly decreased, glomerular inflammation resolved with scar formation as mesangial sclerosis. Significant apoptosis was present from Day 7 (mean +/- SEM, 0.53 +/- 0.12 cells/glomerular cross-section) and gradually increased in number with the proliferating lesions as glomerular inflammation continued. Moreover, apoptosis increased during the resolution of the glomerular inflammation, and many apoptotic cells were present in the sclerotic lesions in Week 8 (1.97 +/- 0.27 cells/glomerular cross-section). As glomerular inflammation subsided, cellular crescents progressed to fibrous crescents with a reduction of cellularity by Week 8, and apoptosis increased significantly within these lesions. These findings indicate that apoptosis plays an essential role in the resolution of intra- and extraglomerular inflammation and in the elimination of glomerular cells within the scarring regions for progressive crescentic GN. The regulation of the apoptotic phenomenon during crescentic GN may be important in the progression of glomerular inflammation and the development of pathologic glomerular sclerosis.

Animals↗

PubMed1996

[Comparison of cerebral vasoreactivity to acetazolamide in normal volunteer among 123I-IMP, 99mTc-ECD and 99mTc-HMPAO].

We studied the difference in the cerebral vasoreactivity to acetazolamide among three cerebral blood flow tracers, N-isopropyl-p-123I-iodoamphetamine (123I-IMP), 99mTc-ethyl cysteinate dimer (99mTc-ECD), 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO). Subjects were 4 healthy male adult volunteers at ages respectively of 30, 30, 35 and 41 years. Each subject underwent SPECT total 6 times. The three tracers were each used in the tests during rest and during acetazolamide loading, which were performed on different days. At least three days were allowed to intervene between one test and another, and all tests were completed within 2 months. The blood flow was calculated on the microsphere model with 123I-IMP, and Patlak plot method with 99mTc-ECD and 99mTc-HMPAO, to perform quantitative assessment. In the acetazolamide loading test, 1 g acetazolamide was intravenously administered, and each tracer was administered at 15 minutes after that. mCBF and BPI data on total 8 sides, one side representing the right or left side of each subject, were statistically analyzed. For rCBF, the region of interest was set up on the right and left sides of the frontal, temporal and occipital lobes on the slice passing through the third ventricle. The percent increase in mCBF with IMP was 29.3 +/- 10.5% (Mean +/- SD), significantly higher than 10.4 +/- 3.9% (p < 0.05) with ECD or 8.9 +/- 6.9% (p < 0.02) with HMPAO. The percent increase in rCBF with IMP was 30.8 +/- 13.4%, significantly higher than 14.3 +/- 13% (p < 0.001) with ECD or 8.7 +/- 14.8% (p < 0.001) with HMPAO. The percent increase in rCBF with ECD was higher than that with HMPAO, but not significantly. The percent increase in BPI calculated by Patlak plot method with ECD (26.4 +/- 14.3%) was higher than that with HMPAO (13.9 +/- 12.8%), but not significantly. It has been pointed out that 99mTc-ECD and 99mTc-HMPAO underestimate blood flow in the high blood flow area, which seemed to account for the underestimation of acetazolamide reactivity. The extent of underestimation in the high blood flow area is less with 99mTc-ECD than with 99mTc-HMPAO, while the stability of the preparation under acetazolamide is maintained, which seemed to explain difference in the reactivity.

Acetazolamide↗

PubMed1996

Protective effect of the novel cerebrovascular-selective calcium antagonist (+/-)-(E)-1-(3-fluoro-6, 11-dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate on ischemic brain damage after permanent middle cerebral artery occlusion in rats.

In this study the effect of post-ischemic treatment of AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz [b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate, CAS 143110-70-7) a cerebrovascular-selective calcium antagonist, on brain infarction and edema in a rat model of focal cerebral ischemia with permanent middle cerebral artery occlusion (MCAo) was evaluated. Brain infarct size was determined at 24 h after MCAo by measuring 2,3,5-triphenyltetrazolium chloride-negative stained area of the serial brain sections. Post-ischemic treatment of AJ-3941 (3 mg/kg p.o.), 10 min and 3 h after the insult, significantly reduced brain infarct size by 44-80%, compared to vehicle control. The reducing effect was observed both in the cortical and subcortical regions. Three days after MCAo, contents of water and Na+ in the ipsilateral hemisphere significantly increased comparing with those in control rats. Post-ischemic treatment with AJ-3941 (3 and 10 mg/kg twice daily p.o. for 2 days) markedly inhibited the increase in water content and suppressed the increase in Na+ content. In the contralateral hemisphere, these contents showed no significant differences between vehicle-treated group and either control (non-operated) or AJ-3941-treated group. AJ-3941 had only minimum effect on body temperature and physiological parameters, such as blood pressure, blood gases and glucose, even when the maximum dose used (10 mg/kg) was repeatedly administered. These results indicate that post-ischemic treatment with AJ-3941 may ameliorate the brain infarction and edema after permanent focal cerebral ischemia, and they also suggest that AJ-3941 has a beneficial effect in the treatment of ischemic cerebral damage.

Animals↗