Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 217 records · Page 12Linked to original sources

PubMed1996

Information theoretic analysis of action potential trains. II. Analysis of correlation among n neurons to deduce connection structure.

We propose a cross-correlational method based on information theory, which produces a network connection structure to account for observed patterns of action potential activity in multi-unit recordings. Firing probabilities and conditional probabilities are estimated from the action potential trains of n neurons. Two-point mutual information (2pMI) and joint conditional mutual information (JCMI) are calculated by using the estimated probabilities, and then the n-point mutual information (npMI) is calculated. A significant peak of npMI indicates that each neuron is connected to all other neurons at specified time differences, either directly or indirectly. To distinguish between direct and indirect connection, the two-point m-joint conditional mutual information (2pJCMI) is calculated over the peak region for each pair of neurons. A minimum effective connection structure among the n neurons can be deduced in this manner. The procedure for deducing the connection structure for three- and n-neuron networks is described. We apply this method to action potential trains produced by simulated neural networks. Some limitations of the method are also discussed.

Action Potentials↗

PubMed1996

Impairment of phagocytic cell respiratory burst by UVA in the presence of fluoroquinolones: an oxygen-dependent phototoxic damage to cell surface microvilli.

Fluoroquinolones are widely used clinically as broad-spectrum antimicrobial agents. One of their side effects is UVA-dependent photosensitivity, observed after the skin is exposed to sunlight. We have investigated five fluoroquinolones and have found that their phototoxicity is oxygen dependent. Human phagocytic leucocytes were stimulated with serum opsonized zymosan to produce superoxide radical (O2-) (respiratory burst) in the presence of a sensitive O2(-)-specific cypridina luciferin analogue, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazol (1,2-alpha) pyrazin-one hydrochloride (MCLA), as chemiluminescence reagent with which O2- can react to induce photon emission. The photon count was used as a measure of respiratory burst activity. When leucocytes were irradiated with UVA for 10 min in the presence of 3 micrograms ml-1 lomefloxacin, ciprofloxacin or norfloxacin, a marked decrease in respiratory burst activity was observed; in this respect, ofloxacin and tosufloxacin were weak. Scanning electron microscopy revealed that the cell surface microvilli were destroyed. The phototoxicity of fluoroquinolones could be abolished if oxygen in the tests was replaced by nitrogen or if the aminothiol DL-cysteine (1.5 mg ml-1) was added prior to irradiation. It is suggested that an oxygen species derived from UVA-excited drug molecules and oxygen mediates the phototoxicity of these fluoroquinolones.

Anti-Infective Agents↗

PubMed1996

The effect of ovariectomy on the temporomandibular joints of growing rats.

PURPOSE: This investigation studied the effects of ovariectomy, on the temporomandibular joints (TMJ) of young rats. MATERIALS AND METHODS: Four-week-old female Wistar rats were ovariectomized and killed at the intervals of 1, 2, 4, and 8 weeks postoperatively. Histomorphometric study of the TMJ was performed in a synchronous manner with an age-matched sham-operated control group. The serum levels of estrogen, calcitonin, and C-terminus parathyroid hormone were also determined. RESULTS: In the sham-operated control group, the serum levels of estrogen and calcitonin increased with age. An increase of the bone volume, with a concomitant increase of the osteoid surface, was observed at 12 weeks. Thickness of the articular soft tissue was decreased with increasing age. In the ovariectomized animals, serum estrogen was not detected during the experiment. A biphasic change in the parathyroid hormone level, with decreases at 1 and 2 weeks after the ovariectomy and increases at 4 and 8 weeks postoperatively, was observed, whereas a constant value was noted in the calcitonin level. Thickness of the articular soft tissue was increased in the anterior and central portions of the condyle at 1, 2, and 4 weeks after the ovariectomy, whereas no appreciable changes were observed in the posterior portion. The bone volume was decreased during the experiment, particularly in the posterior portion. An osteophyte in the anterior region was also observed 8 weeks postoperatively. CONCLUSIONS: Estrogen deficiency in rats during puberty predisposes to alterations of the TMJ through changes in serum calcitonin and parathyroid hormone levels.

Analysis of Variance↗

PubMed1996

Prospective study of T cell receptor utilization following the induction of murine thyroiditis.

Murine experimental autoimmune thyroiditis (EAT) is a well established model of autoimmune disease initiated by immunization with thyroglobulin. We have previously analyzed the T cell receptor (TcR) V gene families used by the intrathyroidal lymphocytic infiltrate in CBA/J mice with well established thyroiditis EAT and have implicated T cells expressing the mTcR V beta 13 gene family. We have now proceeded to examine the time course of mTcR V gene family use following immunization with mTg. We used a radiolabelled RT-PCR technique with oligonucleotides detecting 17 mouse TcR V beta gene families to examine the heterogeneity of the amplified V-D-J (CDR3) fragments. As previously, the TcR V beta 13 amplifications showed the expression of two similar homogeneous CDR3 sizes consistent with two clonally expanded T cell populations. However, such T cell clonal expansion was observed to peak at day 25 and by 90 days had markedly diminished despite the continuing presence of extensive histologic infiltration. An additional immunization with mTg at 63 days failed to maintain the mTcR V beta 13 clonal presence. Further confirmation of these observations was obtained by direct analysis of intrathyroidal T cells rescued from mice with EAT. Such intrathyroidal T cells, 25 days after mTg, demonstrated a marked increase in mTcR V13 expressing T cells to 9.4% compared to 2% of T cells in peripheral blood. It appeared, therefore, that in EAT the accumulation of V13 expressing T cells was a transient phenomenon which peaked at 25 days after immunization. The persistence of an intrathyroidal infiltration indicated that such T cells must have been accompanied by the accumulation and recruitment of additional selected bystander T cells. Such non-specific T cells may also have an integral role in the progression of autoimmune thyroiditis.

Animals↗

PubMed1996

A simple procedure for large-scale purification of 9-cis beta-carotene from Dunaliella bardawil.

For experiments designed to obtain reliable data on the metabolic pathway and biological function of 9-cis beta-carotene, sufficient quantity of this substance in pure form is needed. For this purpose, we decided to purify 9-cis beta-carotene from the dry powder of the alga Dunaliella bardawil. By use of both silica gel and ODS open column chromatography and high-performance liquid chromatography (HPLC) on an ODS column and by treatment of the sample with ethanol, we could obtain this carotenoid as fine needle-shaped orange crystals. They were found to be highly pure as judged by analytical HPLC, absorption spectrum, and nuclear magnetic resonance analysis.

Chlorophyta↗

PubMed1996

HLA-B-restricted, CD8+ cytolytic human T cell clones derived from a melanoma-invaded lymph node.

We have reported that medium containing recombinant human IL-1 (rIL-1), rIL-2, rIL-4, and rIL-6 (MB-1,2,4,6 medium) efficiently expanded autologous tumor specific CTLs in vitro. For further examination of the CTLs cultured in MB-1,2,4,6, the therapeutic activity on tumor growth inhibition in vivo and established CTL clones were studied. In vivo therapy with the CTLs in combination with rIL-2 was highly effective. To investigate CTL clones, 19 CD8+ T cell clones were obtained by limiting dilution method, each clone retained autologous-melanoma-specific, HLA-class I-restricted cytolytic activity. Four T cell clones were analyzed in detail. These T cell clones displayed a CD3+, CD4-, CD8+, CD11b-, CD16-, CD56-, CD45RA-, TcR alpha/beta + phenotype and monoclonal antibodies to HLA class I, CD3, and CD8 antigens inhibited their cytolytic activity. Moreover, these CTL clones recognize one of common melanoma antigens associated with HLA-B (B49). Analysis of the effect of different cytokines on the proliferation and cytotoxicity of cloned CTL revealed the highest growth rate in MB-1,2,4,6 but no dependence on particular cytokine combinations for autologous tumor-specific cytolytic activity. These results suggest (1) the usefulness of MB-1,2,4,6 medium in expanding autologous tumor-specific CTLs, which can be used in adoptive immunotherapy, (2) HLA-B molecules can present one of common melanoma antigens, and (3) the independence of CTLs from any cytokine combination once they become target-specific.

Antibodies, Monoclonal↗

PubMed1996

Chronic lead exposure may inhibit endothelium-dependent hyperpolarizing factor in rats.

We designed experiments to determine the effect of chronic lead exposure on endothelium-dependent responses to acetylcholine (Ach) in rat isolated blood vessels. Male Wistar rats were maintained for 1 or 3 months with or without oral lead administration. Membrane potential and isometric tension were measured in mesenteric arteries. Ach caused concentration- and endothelium-dependent relaxation in rings with endothelium contracted with phenylephrine (PE). There was no significant difference in relaxation between lead-exposed and control animals. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), both endothelium-dependent hyperpolarization and relaxation to Ach were significantly reduced in animals from the 3-month lead-exposed group. In aorta from lead-exposed groups, endothelium-dependent relaxation to Ach was not significantly different from that of age-matched controls, whereas both were completely inhibited in the presence of L-NAME. The basal levels of cyclic GMP in the aorta were not affected by lead exposure regardless of duration. These data indicate that both endothelium-dependent hyperpolarization and L-NAME-resistant relaxation decrease with chronic lead exposure in rat mesenteric arteries and suggest that lead is an inhibitor or endothelium-derived hyperpolarizing factor (EDHF).

Acetylcholine↗

PubMed1996

Pharmacokinetics and pharmacodynamics of (+/-)-sotalol in healthy male volunteers.

1. We investigated the pharmacokinetics and pharmacodynamics of (+/-)-sotalol administered orally to healthy male volunteers in single doses of 40, 80 and 160 mg and in multiple doses of 80 mg twice daily for 7 consecutive days. 2. In the single dose studies, the half-life of (-)-sotalol (7.2-8.5 h) was significantly (P < 0.01) shorter than that of (+)-sotalol (9.1-11.4 h) while the renal clearance of (-)-sotalol (110.6-126.4 ml min-1) was significantly (P < 0.01) faster than that of (+)-sotalol (102.2-110.1 ml min-1). In the multiple dose studies, similar differences in the pharmacokinetics of (+)- and (-)-sotalol were observed. In addition, the pharmacokinetics of both (+)- and (-)-sotalol on day 4 were shown to be essentially the same as those on day 7. 3. In pharmacodynamic examinations, (+/-)-sotalol prolonged QTc intervals on electrocardiograms dose-dependently after single doses of 80 and 160 mg (3.81 +/- 2.96%, 13.23 +/- 5.66%). The correlation between the plasma concentration of (+/-)-sotalol and prolongation of QTc intervals was nearly linear, and showed no hysteresis. 4. In conclusion, we demonstrated that QTc interval was prolonged with a linear correlation to the plasma concentration of (+/-)-sotalol. In addition, our study suggested that differences in the pharmacokinetics of (+)- and (-)-sotalol may be attributable to faster urinary excretion of (-)-sotalol.

Administration, Oral↗

PubMed1996

Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus.

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.

Aged↗

PubMed1996

Endothelium-dependent relaxation and hyperpolarization evoked by bradykinin in canine coronary arteries: enhancement by exercise-training.

1. Kinins, which are produced locally in arterial walls, stimulate the release of endothelium-derived vasodilator substances. Therefore, they may participate in the metabolic adaptation to chronic exercise that occurs in the coronary circulation. Experiments were designed to compare the reactivity to bradykinin in coronary arteries isolated from sedentary and exercised-trained dogs (for 8-10 weeks). 2. The organ chambers used in this study were designed for measurement of isometric tension and cell membrane potential with glass microelectrodes. Rings of canine isolated coronary arteries with endothelium were suspended in the organ chambers filled with modified Krebs-Ringer bicarbonate solution (37 degrees C, gassed with 5% CO2 in 95 O2), and were all treated with indomethacin to prevent interference from prostaglandins. 3. Bradykinin evoked concentration-dependent relaxations of the coronary arteries. However, the kinin was significantly less potent in relaxing coronary arteries from the sedentary dogs than those from the trained ones. 4. In the presence of NG-nitro-L-arginine (an inhibitor of nitric oxide synthases), concentration-relaxation curves to bradykinin were shifted to the right in both types of preparations. Nonetheless, the peptide was still significantly more potent in arteries from exercise-trained animals. 5. In the electrophysiological experiments, concentration-hyperpolarization curves to bradykinin obtained in arteries from sedentary dogs were also significantly to the right of those in vessels from exercise-trained animals. Thus, in arteries from exercised animals, bradykinin more potently evoked the release of both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). 7. The angiotensin converting enzyme (ACE)-inhibitor, perindoprilat, shifted to the left the concentration-relaxation curves to bradykinin obtained under control conditions and in the presence of NG-nitro-L-arginine. The concentration-hyperpolarization curves to bradykinin were also shifted to the left by perindoprilat. The shift induced by the ACE-inhibitor in either type of preparation was not significantly different. 8. These findings demonstrate that exercise-training augments the sensitivity of the coronary artery of the dog to the endothelium-dependent effects of bradykinin. This sensitization to bradykinin may reflect an increased role of both NO and EDHF, and is not the consequence of differences in ACE activity in the receptor compartment.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

A comparative study of the antithrombotic effect of aurintricarboxylic acid on arterial thrombosis in rats and guinea pigs.

1. The antithrombotic effect of aurintricarboxylic acid (ATA) which inhibits binding of von Willebrand factor (vWF) to platelet glycoprotein lb (GPlb) receptor was evaluated in photochemically-induced thrombosis models in the femoral artery of rats and guinea-pigs. 2. ATA at a dose of 10 mg kg-1 significantly prolonged the time required for thrombotic occlusion of the artery in rats. The antithrombotic efficacy was associated with a significant inhibition of platelet retention and ex vivo botrocetin-induced platelet aggregation. 3. On the other hand, in guinea-pigs, ATA at the same dose inhibited the platelet retention and the platelet aggregation, but did not prevent thromboocclusion. 4. ATA inhibited aggregation of washed platelets from rats or guinea-pigs in response to botrocetin and thrombin in a dose-dependent manner (1-30 microM), and to the same extent. 5. ATA moderately increased activated partial thromboplastin time and bleeding time in both species. 6. These results indicate that vWF may play a role in the development of occlusive arterial thrombosis in the rat, but not in the guinea-pig. 7. The antithrombotic activity of ATA may partly arise from its inhibitory effect on thrombin, in addition to that on the vWF-GPlb pathway

Animals↗

PubMed1996

Increase in shedding of intercellular adhesion molecule-1 in human malignant melanoma cell lines treated with hyperthermia in vitro.

Human malignant melanoma cell lines were found to increase shedding of soluble intercellular adhesion molecule-1 (sICAM-1) into the culture medium when the cells were treated with hyperthermia at 41-43 degrees C for 3-6 hr in vitro. The content of ICAM-1 in the cell lysate was also found to be increased after hyperthermia. The increased rate of ICAM-1 concentration in the cells was at maximum when they were incubated at 41 degrees C for 3 hr. Also, the melanoma cell lines heat-treated at 41 degrees C showed more intense immunofluorescence in the ICAM-1 expression on the cell surface. It remains to be investigated further whether the effects of hyperthermia on the ICAM-1 expression in melanoma cells is to augment membrane ICAM-1 expression, which in turn leads to shedding of soluble ICAM-1 or only to acceleration of shedding of sICAM-1 by unknown mechanisms.

Cytosol↗

PubMed1996

Evaluation of in-vivo transdermal absorption of cyclosporin with absorption enhancer using intradermal microdialysis in rats.

The purpose of this study was to evaluate the effect of absorption enhancer on in-vivo transdermal absorption of cyclosporin using intradermal microdialysis in rats. Cyclosporin oily solutions (0.5, 2, 8% w/v) were prepared from Sandimmun (10% w/v oily oral preparation of cyclosporin) by diluting with olive oil. 1-[2-(Decylthio)ethyl] azacyclopentan-2-one (HPE-101) and glycerin were added to the cyclosporin formulation as an absorption enhancer at various concentrations between 1 and 20%. These formulations were applied to the shaved abdomen of rats treated with intradermal microdialysis at a flow rate of 2.5 microL min-1 for 6 h. Cyclosporin was immediately detected and attained a plateau in the dermal dialysate after topical application of cyclosporin oily solution alone. Cyclosporin levels in the dialysate increased with increasing cyclosporin concentrations in the formulation from 0.5 to 8% (w/v). HPE-101 did not influence cyclosporin absorption at concentrations less than 6% (w/v). Addition of 10% (w/v) HPE-101 significantly enhanced an apparent absorption rate of cyclosporin by 4.9 times. However, 20% (w/v) HPE-101 did not show the enhancing activity. On the other hand, addition of glycerin at concentrations of 6, 10, and 20% (v/v) significantly enhanced an apparent absorption rate of cyclosporin by 3.0, 6.4, and 6.9 times, respectively. The time lag for cyclosporin absorption was less than 0.21 h in all tested cases. This microdialysis study shows that glycerin is a suitable enhancer for improving the in-vivo cyclosporin absorption from the skin.

Administration, Cutaneous↗

PubMed1996

Pharmacokinetic and pharmacodynamic properties of FK070 (KDI-792), a novel thromboxane receptor antagonist/thromboxane synthetase inhibitor, after single and multiple oral administrations to healthy volunteers.

FK070, a thromboxane A2 (TXA2) receptor antagonist/TXA2 synthetase inhibitor, was given orally to healthy male volunteers in a single- and multiple-dose study. In the single-dose study (200, 300, 400 mg), the area under the plasma concentration-time curve (AUC) and the maximum plasma concentration (Cmax) increased non-linearly with dose, while the mean elimination half-life (V0) was essentially unchanged (3.9-7.3h). Recovery of the unchanged drug in the urine was 12-25%. Cmax and AUC as determined with 200 mg of drug after a meal decreased by about 60 and 30%, respectively. Ex-vivo platelet aggregation in the plasma by a TXA2 analogue, U46619, was almost completely inhibited within 1 h, after all doses of drug, with a significant dose-dependent inhibition maintained for 8 h or more, which was much longer than was expected from drug plasma concentration. The aggregation by adenosine diphosphate (ADP) was inhibited to a lesser extent. FK070 also inhibited TXA2 synthetase as evidenced by decreased production of TXB2 and reciprocally increased production of 6-keto-prostaglandin F1 alpha in the serum during ex-vivo whole blood coagulation. These effects peaked 1 h after drug and lasted until 4 h with the higher doses. In the multiple-dose study (300 mg, twice a day, after meals for 6.5 days), drug concentrations in the plasma were well fitted to a three-compartment open model with first-order absorption. FK070 afforded extensive inhibition of platelet aggregation by U46619 throughout the administration period, with a significant inhibition lasting as long as 48 h after conclusion of administration. No clearly drug-related changes were found in routine laboratory tests, subjective and objective findings, or vital signs. FK070 was concluded to be well tolerated and to provide long-lasting blockade of TXA2 receptors, and plasma concentration-dependent inhibition of TXA2 synthetase in the platelets.

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

PubMed1996

The measurement of caffeine concentration in scalp hair as an indicator of liver function.

Caffeine concentration in plasma and scalp hair has been determined for subjects consuming normal daily amounts of caffeine and the results used as an indicator of individual hepatic metabolic capacity. Daily exposure to caffeine was assessed in six healthy Japanese volunteers by direct HPLC measurement of the concentrations of caffeine in aliquots of all caffeine-containing beverages consumed by the subjects. The measurements were repeated on three different occasions for each subject and caffeine consumption (mean +/- s.d.) was calculated as 178.0 +/- 84.3 mg day-1 with an intra-individual variability of 23.8 +/- 6.3% as coefficient of variation. A survey of daily caffeine consumption in 121 adult Japanese by means of a questionnaire revealed a similar value (231.8 +/- 177.8 mg day-1). Caffeine concentration in the plasma sampled during an overnight caffeine-free interval was measured by HPLC and a comparison made between healthy subjects and patients with liver disease (0.71 +/- 0.32, 0.77 +/- 0.45 and 3.92 +/- 1.91 micrograms mL-1 for healthy volunteers (n = 6), patients with hepatitis (n = 11) and those with liver cirrhosis (n = 4), respectively). Strands of scalp hair were collected from six healthy subjects and six patients with liver cirrhosis. Caffeine in hair was identified and measured by gas chromatography-mass spectrometry after digestion of the hair matrix with protease and extraction of the caffeine with chloroform. Caffeine concentration in hair collected from patients with liver cirrhosis (26.5 +/- 5.04 ng mg-1 hair) was significantly higher than that in hair sampled from healthy subjects (7.21 +/- 3.11 ng mg-1). These findings suggest that the determination of caffeine concentration in the plasma and hair of subjects consuming normal daily amounts of caffeine-containing beverages provides a practical assessment of individual liver metabolic capacity.

Adult↗

PubMed1996

Endogenous endotoxemia after massive hepatectomy and portal vein stenosis: beneficial effect of a prostaglandin I2 analogue on intestinal permeability.

Portal vein (PV) stenosis may contribute to operative death after extended hepatectomy combined with PV reconstruction leading to impairment of the intestinal mucosal barrier. This study was designed to investigate whether rats undergoing such surgery developed endogenous endotoxemia and increased intestinal permeability. The effect of a prostaglandin I2 (PGI2) analogue on mucosal barrier function was also studied. The rats were divided into the following five groups: sham operation, massive hepatectomy (Ht), PV stenosis (PS), combined Ht and PS (Ht+PS), and Ht+PS with subcutaneous injection of PGI2 preoperatively (PG). The 10-day survival rate, portal endotoxin level and intestinal permeability (two-sugar test) were evaluated in each group. The Ht+PS group showed a significant increase in both the portal endotoxin level and intestinal permeability (p < 0.05) and a significant worse 10-day survival (p < 0.01) than the other four groups. PGI2 pretreatment did not influence splanchnic blood flow, but decreased the endotoxin level and reduced intestinal permeability. In conclusion, the synergistic effect of massive hepatectomy and PV stenosis induced an increased intestinal permeability and consequently endotoxemia. PGI2 pretreatment significantly improved both intestinal barrier function and survival.

Animals↗

PubMed1996

Inhibitory effect of MS-153 on elevated brain glutamate level induced by rat middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: In this study we investigated the effects of a novel compound, MS-153 ([R]-[-]-5-methyl-1-nicotinoyl-2-pyrazoline), on elevated brain glutamate concentrations and cerebral infarct volume induced by middle cerebral artery (MCA) occlusion in the rat. METHODS: The rat MCA was occluded by a thrombus induced by a photochemical reaction between green light and the photosensitizer dye rose bengal, which causes endothelial injury followed by formation of a platelet- and fibrin-rich thrombus at the site of photochemical reaction; this method is routinely used in our laboratory to produce arterial occlusion in experimental animals. Extracellular glutamate concentration at the ischemic border zone was determined by a microdialysis technique. The size of cerebral infarction was measured by a histochemical technique 24 hours after MCA occlusion. MS-153 was administered at various doses as a continuous infusion for 24 hours, beginning 0 to 2 hours after MCA occlusion. RESULTS: At the ischemic border zone, the concentration of glutamate in the extracellular fluid increased by 40-fold after ischemia. At 3.13 mg/kg per hour, MS-153 reduced glutamate concentration (P < .05) and also the size of ischemic cerebral infarction (P < .05). Furthermore, the glutamate uptake inhibitor DL-threo-beta-hydroxyaspartate reversed the effect of MS-153 on glutamate concentration. CONCLUSIONS: The reduction in the size of cerebral infarction by MS-153 may be attributable to the inhibition of glutamate release or an increase in cellular glutamate uptake.

Animals↗

PubMed1996

Reversibility of compound action potential during the acute phase after transitory local ischemia.

We investigated the reversibility of compound action potential (CAP) changes induced after transitory local ischemia induced by rose bengal photochemically induced thrombosis of the rat anterior inferior cerebellar artery (AICA). Cochlear blood flow (CBF) was measured with a laser-Doppler flowmeter positioned on the lateral bony wall of the basal turn of the cochlea, and the CAP to an 8-kHz half-wave of sinusoid sound at 100 dB sound pressure level was monitored. The irradiation was started 5 minutes before the rose bengal administration and continued through the thrombosis formation. Tissue-type plasminogen activator (t-PA, 1 mg/kg) dissolved in saline was injected intravenously 2 minutes after complete photothrombotic blockade of the AICA in the rats presenting complete abolition of CAPs just after the vascular occlusions. Nineteen of the 51 rats presented complete abolition of the CAP just after the AICA occlusion, and the thrombosed AICA was successfully reperfused by t-PA administration in 11 of the 19 rats. The result showed that duration of ischemia was the more important determinant for the reversibility of CAPs during the acute phase (p = .00001), and the residual level of cochlear blood flow during ischemia was also an important factor (p = .066). It appeared that the critical time of ischemia for the complete recovery of CAPs was around 5 minutes, and that the critical limit for the irreversibility of CAPs within the acute phase was between 20 and 25 minutes.

Animals↗