Biomedical subjects

R Murata

Publications and source records attributed to R Murata.

At least 55 records · Page 3Linked to original sources

PubMed1996

Effect of hyperthermia on hippocampal synaptic transmission and CA3 kindling in developing rats.

The effect of hyperthermia on excitatory synaptic transmission in the hippocampal CA1 area in response to contralateral CA3 stimuli at 23-26 days of age and the influence of hyperthermia-induced seizures (HS) on the kindling phenomenon induced by CA3 stimulation at 27-29 days of age were investigated in developing rats. When hyperthermia (43.6 +/- 0.5 degrees C) did not induced seizures in conscious unrestrained rats, transient (< 1 h) potentiation was observed in electrically evoked synaptic responses (EPSP and population spikes). When generalized seizures were induced by hyperthermia (43.3 +/- 0.4 degrees C), long-term potentiation (LTP) was observed over 24 h. The difference in time course of the potentiation depended on whether high-voltage multispikes on the EEG, which sustained for longer than 20-30 s and associated with behavioral convulsions, appeared or not. In the following kindling session, the threshold intensity required to produce afterdischarges (ADs) in the HS rats (187 +/- 16 microA) was significantly lower than in the rats without HS (293 +/- 41 microA). However, there was no clear difference between the development of the kindling phenomenon to repeated tetanus at the threshold intensity in the rats with and without HS. It was concluded that potentiation of synaptic responses consists of two different components, transient potentiation induced by hyperthermia alone and LTP induced by HS, and that developing rats were susceptible to kindling epilepsy at the lower AD threshold intensity when experienced HS.

Analysis of Variance↗

PubMed1996

Development of an integrated radiotherapy network system.

PURPOSE: To introduce the process of developing an integrated radiotherapy network. METHODS AND MATERIALS: We developed a new radiotherapy treatment-planning system in 1987 that we named the Computer Tomography (CT) simulator. CT images were immediately transported to multiimage monitors and to a planning computer, and treatment planning could be performed with the patient lying on the CT couch. The results of planning were used to guide a laser projector, and radiation fields were projected onto the skin of the patient. Since 1991, an integrated radiotherapy network system has been developed, which consists of a picture archiving and communicating system (PACS), a radiotherapy information database, a CT simulator, and a linear accelerator with a multileaf collimator. RESULTS: Clinical experience has been accumulated in more than 1,000 patients. Based on our 7 years of experience, we have modified several components of our original CT simulator and have developed a second generation CT simulator. A standard protocol has been developed for communication between the CT scanner, treatment planning computer, and radiotherapy apparatus using the Ethernet network. As a result, treatment planning data can be transported to the linear accelerator within 1 min after completion of treatment planning. CONCLUSION: This system enables us to make optimal use of CT information and to devise accurate three-dimensional (3D) treatment-planning programs. Our network also allows for the performance of fully computer-controlled dynamic arc conformal therapy.

Computer Communication Networks↗

PubMed1996

Reoxygenation after single irradiation in rodent tumors of different types and sizes.

PURPOSE: To investigate the variation of reoxygenation patterns after single irradiation in murine tumors of different types and sizes. METHODS AND MATERIALS: Whole-body single irradiation of 13 to 15 Gy was delivered to 10 mm RIF1 tumors of C3H/He mice, 22 mm SCCVII tumors of C3H/He mice, and 16 mm EMT6 tumors of Balb/c mice. Thereafter, changes in the hypoxic fraction with time were determined by the paired survival curve method. The data were compared with the results we had ++previously obtained with 10 mm SCCVII and 10 mm EMT6 tumors. RESULTS: The hypoxic fraction at 1 h after the priming irradiation was 26% for 10 mm RIF1 tumors, 48% for 10 mm SCCVII tumors, and 100% for 10 mm EMT6 tumors. Thus, RIF1 and SCCVII tumors, both of which have few necrotic areas, showed rapid reoxygenation, whereas EMT6 tumors, which have large necrotic areas, reoxygenated slowly. Although the hypoxic fraction returned to the pretreatment level within 72 h in 10 mm SCCVII and 10 mm EMT6 tumors, it did not in 10 mm RIF1 tumors. In contrast, the patterns of reoxygenation were similar between 22 mm and 10 mm SCCVII tumors and between 16 mm and 10 mm EMT6 tumors. CONCLUSION: The three tumors showed different patterns of reoxygenation. Tumors that have a low proportion of necrosis may reoxygenate rapidly. However, tumor size appeared to have less influence on the pattern of reoxygenation.

Animals↗

PubMed1996

A case of bronchial cast.

We report a case of bronchial cast in a boy 1 year and 5 months old. Bronchial casts often obstruct the main bronchi, causing dyspnea and hypoxia. The bronchial cast was studied pathologically, with findings of eosinophilia and neutrophilic infiltration; the cast seemed to involve an allergic reaction. Such casts can be removed during bronchoscopy, but we used aspiration.

Airway Obstruction↗

PubMed1996

Combined effects of an angiogenesis inhibitor (TNP-470) and hyperthermia.

TNP-470, a synthetic analogue of fumagillin first isolated from Aspergillus fumigatus, is known to be a potent anti-angiogenic compound. The combined effects on tumour growth and tumour angiogenesis of TNP-470 and hyperthermia were investigated. The tumour used was SCCVII carcinoma of the C3H/He mouse. The tumour response was evaluated by the tumour growth (TG) time assay. The TG time is the time required for one-half of the treated tumours to reach three times the initial tumour volume. Significant delay of tumour growth was observed by TNP-470 alone (100 mg kg-1 x 2 or x 4), indicating that TNP-470 alone has antitumour effect in vivo. When TNP-470 (100 mg kg-1 x 2 or x 4) was administered after hyperthermia at 44 degrees C, the TG times of the combined treatment were significantly longer than those of heat alone (44 degrees C) or TNP-470 (100 mg kg-1 x 2 or x 4) alone. However, the TG time of combined treatment with TNP-470 and hyperthermia at 42 degrees C was quite similar to that of TNP-470 alone. This conflicting result on the combined effect of TNP-470 and hyperthermia may be related to the temperature-dependent vascular damage by hyperthermia. Dose-dependent inhibition of angiogenesis by TNP-470 was demonstrated in microangiograms obtained 4 days and 7 days after hyperthermia (44 degrees C for 30 min). It is, thus, suggested that the combined effect of TNP-470 and hyperthermia is attributable to the inhibition of angiogenesis by TNP-470 following heat-induced vascular damage.

Animals↗

PubMed1996

Combined effect of clinically relevant doses of emitefur, a new 5-fluorouracil derivative, and radiation in murine tumours.

We investigated the combined effect of radiation and clinically relevant doses of emitefur (BOF-A2), a newly developed anti-cancer agent consisting of a masked form of 5-fluorouracil (5-FU) and a potent inhibitor of 5-FU degradation, in two types of murine tumours. In preliminary pharmacokinetic studies, the area under the curve for 5-FU in plasma, after administration of 12.5 mg kg-1 and 25 mg kg-1 emitefur in mice, appeared to be similar to that obtained on the first day and that on the seventh day, respectively, after starting administration of 400-600 mg day-1 in humans. These doses (12.5 and 25 mg kg-1) of emitefur were evaluated either alone or in combination with single (15 Gy), five-fraction (4 Gy each) or ten-fraction (2.8 Gy each) irradiation using a tumour growth delay assay for SCCVII tumours and in combination with four-fraction (5 Gy each) irradiation using an in vivo-in vitro assay for EMT6 tumours. The anti-tumour and radiation-enhancing effects of 12.5 mg kg-1 emitefur were not significant in any except the ten-fraction experiment. On the other hand, multiple doses of 25 mg kg-1 emitefur given either alone or in combination with radiation produced marked effects. The mean tumour growth delay time (the time to double in volume for treated tumours minus that for untreated tumours) was 8.1 days for five administrations of 25 mg kg-1 emitefur. 10.4 days for five fractions of 4 Gy and 22.1 days for five treatments with the combination of the two. Thus, the increase in growth delay afforded by this combination was at least additive. The effect of four fractions of 5 Gy with 25 mg kg-1 emitefur in EMT6 tumours was lower than that of four fractions of 7.5 Gy, but the effect of five fractions of 4 Gy with this dose of emitefur in SCCVII tumours was similar to the effect of five fractions of 6 Gy, and the effect of ten fractions of 2.8 Gy with 25 mg kg-1 emitefur was much higher than that of ten fractions of 4.2 Gy. In conclusion, emitefur given either alone or in combination with radiation appears to have a significant anti-tumour effect even at clinically relevant dose levels, although a threshold dose exists between 12.5 and 25 mg kg-1. Further clinical studies of this compound are warranted.

Animals↗

PubMed1996

Comparison of in vivo efficacy of hypoxic cytotoxin tirapazamine and hypoxic cell radiosensitizer KU-2285 in combination with single and fractionated irradiation.

Development of strategies to eradicate radioresistant hypoxic cells would be of great benefit for clinical radiotherapy. In the present study, the in vivo effects of a promising hypoxic cytotoxin, tirapazamine (3-amino-1,2,4-benzotriazine 1,4-di-N-oxide), were examined in comparison with those of KU-2285, one of the best hypoxic cell radiosensitizers, in combination with both single and fractionated irradiation. The tumor response was assessed by the standard in vivo-in vitro clonogenic assay using SCCVII tumors in C3H mice and EMT-6/KU tumors in Balb/c mice with different characteristics of tumor hypoxia. With single-dose irradiation (18 Gy), both tirapazamine and KU-2285 showed significant enhancement of cell killing in a dose-dependent manner, but tirapazamine was more effective for SCCVII tumors with acutely hypoxic cells, while KU-2285 was more effective for EMT-6/KU tumors predominantly with chronically hypoxic cells. In fractionated irradiation regimens (4 fractions of 5 Gy at 12 h intervals), tirapazamine showed more marked combined effects at 10 and 20 mg/kg than KU2285 at 100-200 mg/kg in both SCCVII and EMT-6/KU tumors. We concluded that the effectiveness of KU-2285 and tirapazamine was correlated with the nature of tumor hypoxia with single-dose irradiation, whereas tirapazamine appeared more potent than KU-2285 with fractionated irradiation. These findings suggest the potential usefulness of tirapazamine in clinical fractionated radiotherapy.

Animals↗

PubMed1996

Changes in cell proliferative parameters of SCCVII and EMT6 murine tumors after single-dose irradiation.

To understand better the repopulation kinetics of tumor cells after radiotherapy, we investigated changes in cell proliferative parameters after single-dose irradiation of SCCVII tumors in C3H/He mice and EMT6 tumors in Balb/c mice. The following parameters were determined 0-15 days after single irradiation at 20 or 30 Gy; dividing fraction (DF), potential doubling time (Tpot), number of clonogenic cells per tumor (Ncln), and volume doubling time (Tvol). DF and Tpot were determined by in vivo-in vitro cytokinesis-block assay with cytochalasin B, Ncln was measured by in vivo-in vitro colony-forming assay, and Tvol was determined by growth delay assay. In both tumors, longer Tpot and lower DF and Ncln were obtained for 3-4 days after irradiation, but in SCCVII tumors these values returned to the pretreatment levels 9 days after irradiation. In EMT6 tumors, Tpot, DF, and Ncln did not return to the pretreatment levels even 12 days after irradiation. In the regrowth phase of both tumors following irradiation at 20 Gy, Tvol was longer than the pretreatment level, although Tpot was similar in SCCVII and only slightly longer in EMT6. Therefore, the cell loss factor in the regrowth phase was considered to be higher than the pretreatment level in both tumors. From the results, recruitment of previously quiescent cells into the proliferative pool in these tumors was suggested to contribute to repopulation after radiation.

Animals↗

PubMed1996

Adverse events associated with MMR vaccines in Japan.

The largest nationwide active surveillance of four Measles-Mumps-Rubella (MMR) vaccines was conducted in Japan. A total of 1255 pediatricians actively participated in the study, which comprised 8.6% of all members of the Japanese Pediatric Society. The total number of registered recipients of MMR vaccines was 38 203. They were arbitrarily given one of the MMR vaccines produced by three makers (Takeda, Osaka city, Kitasato Minato-ku. Tokyo and Biken Suita city, Japan) or the standard MMR vaccine made of designated strains (Kitasato's measles-AIK-C, Biken's mumps-Urabe Am9 and Takeda's rubella-To336) produced by Takeda, Kitasato and Biken and were observed for 35 days. The rates of virologically confirmed aseptic meningitis per 10,000 recipients were 16.6, 11.6, 3.2 and 0 for the standard MMR, Takeda MMR, Kitasato MMR and Biken MMR vaccines, respectively. The incidence of convulsions between 15 and 35 days was the highest with the standard MMR vaccine and the incidence of fever associated with vomiting occurring between 15 and 35 days (symptoms relevant to aseptic meningitis) were also the highest with the standard MMR vaccine. The incidence of parotid swelling was the lowest with Takeda MMR vaccine. This surveillance revealed that incidences of aseptic meningitis after administration of the standard MMR vaccine and of Biken MMR vaccine were different. This posed questions about the manufacturing consistency of the Urabe Am9 mumps virus vaccines. On the other hand, the National Institute of Health found that the biological characteristics of the Urabe Am9 mumps virus contained in the standard MMR vaccine and in the Biken MMR vaccine were different. The Biken Company reported that the mumps vaccine in the standard MMR vaccine was a mixture of two Urabe Am9 mumps vaccine bulks; one identical to that contained in the Biken MMR vaccine and the other produced by a different manufacturing process.

Child↗

PubMed1996

Development of an MR simulator: experimental verification of geometric distortion and clinical application.

PURPOSE: To evaluate the geometric distortion on magnetic resonance (MR) images obtained with a permanent magnet system and determine the usefulness of MR imaging-assisted x-ray simulation in radiation therapy treatment planning (RTTP). MATERIALS AND METHODS: The authors measured the distortion on MR images of grid-pattern phantoms. MR imaging-assisted x-ray simulation was performed with skin markers in 14 patients with bone tumors. Treatment planning had already been performed with a conventional system. RESULTS: On phantom images, most of the positional displacements within a 120-mm radius from the center of the static magnetic field were less than 2 mm; larger displacements were observed in the peripheral region of the images. MR imaging was useful in the RTTP of all patients. The original radiation field was modified after MR examination in six patients. CONCLUSION: The amount of image distortion within the practical area is acceptable for RTTP. MR imaging-assisted x-ray simulation is useful for patients with bone tumors and warrants further investigation.

Aged↗

PubMed1996

Effect of streptozotocin-induced diabetes on cyclosporin A disposition in rats.

We studied the effect of diabetes on the pharmacokinetics of cyclosporin A (CyA) after intravenous and oral administration of CyA using the plasma and lymph of streptozotocin (STZ)-induced diabetic rat. There were no significant differences in the systemic and lymphatic availabilities after intravenous administration of CyA in diabetic rats compared with those of the controls. On the other hand, systemic and lymphatic availabilities after oral administration of CyA were significantly different in diabetic rats compared to those in the controls. These results suggest that the pharmacokinetics of CyA, particularly absorption, were altered in diabetic rats. Gastrointestinal transit in diabetic rats was also studied. The gastric emptying rate in diabetic rats was enhanced compared with that of the controls, but small intestinal transit was reduced in diabetic rats, suggesting that a change in gastrointestinal transit in diabetic rats may influence the absorption of CyA. The increased absorption of CyA from the digestive tract of diabetic rats altered not only the systemic availability but also the lymphatic availability, suggesting that altered systemic availability may cause adverse effects and that altered lymphatic availability may influence the immunosuppressive effects.

Administration, Oral↗

PubMed1996

FDG-PET evaluation of therapeutic effects on VX2 liver tumor.

UNLABELLED: Transplanted VX2 liver tumor in the rabbit is an experimental liver tumor model in which 18F-2-fluoro-2-deoxy-D-glucose (FDG) accumulates to a 3.5-fold level that surrounds normal liver tissue. In this study, changes in FDG uptake were assessed in this liver tumor model after transcatheter arterial embolization (TAE) and radiotherapy. METHODS: Fifteen rabbits bearing VX2 liver tumors were treated with TAE with gelatin sponges 1 day before the FDG study, and 18 rabbits received local irradiation with electron beams at a dose of 12-36 Gy 1-10 days before the FDG study. In the FDG study, serial arterial blood sampling was performed to determine arterial input (AI), and 1 hr after tracer injection, normal liver tissue and tumor tissue were excised to measure radioactivity. The tumor FDG level per AI and the tumor-to-normal liver ratio were assessed. Dynamic PET images were obtained in 20 of the 46 rabbits. RESULTS: Tumor FDG uptake was significantly decreased 1 day after TAE (from 3.54 to 0.83 in the tumor-to-normal liver ratio) and 5 days after 30 Gy of irradiation (from 3.54 to 1.28). The decrease in tumor FDG uptake was dose-dependent, especially in the relatively low dose range (12-24 Gy). The untreated tumors could be clearly distinguished from the surrounding normal liver tissue, while the embolized tumors or the irradiated tumors were not clearly delineated. Histological analysis showed that the decrease in tumor FDG after treatment agreed well with the decrease in number of viable tumor cells. CONCLUSION: The VX2 liver tumor is an appropriate experimental tumor model for evaluating the change in FDG uptake in various therapeutic modalities. Moreover, the therapeutic effects can be assessed 1 day after TAE and 5 days after irradiation. Further clinical trials for the early evaluation of therapeutic effects on liver tumors using FDG-PET are warranted.

Animals↗

PubMed1996

Tirapazamine: hypoxic cytotoxicity and interaction with radiation as assessed by the micronucleus assay.

We investigated the cytotoxicity and the interaction with low-dose radiation (1-4Gy) of tirapazamine by the in vitro cytokinesis-block micronucleus (MN) assay. Murine SCCVII and human melanoma (G-361) cells were treated with tirapazamine under aerobic or hypoxic conditions for 1 h and the MN frequency was determined using cytochalasin-B. The cells were also treated with or without tirapazamine or KU-2285 (hypoxic cell sensitiser) under hypoxic conditions and irradiated with or without reaeration of the cell suspensions. A dose-dependent increase of MN frequency was observed by tirapazamine treatment and the hypoxic toxicity ratio was about 130 for SCCVII and 37 for G-361. The radiation dose-response curves of MN frequency suggested that the interaction of tirapazamine with irradiation appeared to be essentially additive in both cell lines. In contrast, the dose-response curve became steeper by KU-2285 treatment. Combined effects of tirapazamine and irradiation on the hypoxic cells were much higher than the radiation effect on aerobic cells at low doses, while the effects of KU-2285 did not exceed that of aerobic irradiation. In conclusion, tirapazamine appeared to be superior to hypoxic radiosensitisers at clinically relevant doses, not because of aerobic radiosensitisation but because of its potent hypoxic cytotoxicity additive to radiation effect.

Animals↗

PubMed1996

The combined antitumour effect of a new 5-fluorouracil derivative, BOF-A2, and radiation in vivo.

We examined the combined effect of radiation and BOF-A2, a newly developed anti-cancer agent consisting of a masked form of 5-fluorouracil (5-FU) and a potent inhibitor of 5-FU degradation in the liver, on murine tumors. Subcutaneous 8-mm-diameter SCCVII tumours grown in the right thigh of C3H/He mice were used. The mice were locally irradiated with single doses of 10-30 Gy or five fractions of 4 Gy for 5 days, alone or in combination with BOF-A2. BOF-A2 at doses of 30, 75 and 150 mg kg-1 was orally administered 2 h before or immediately after single doses of irradiation, while 15 or 30 mg kg-1 of BOF-A2 was given 1 h prior to each fraction of 4 Gy. The effect of BOF-A2 alone was also examined. The antitumour effect was evaluated by a tumour growth delay assay. BOF-A2 alone showed significant tumour growth delay at all doses used in this study. Combination of BOF-A2 and single or fractionated doses of radiation appeared to produce an additive tumour response, which occurred independently of sequence of the two treatments. The combined effect became greater with the dose of radiation and BOF-A2. In conclusion, BOF-A2 and radiation may be efficiently combined.

Animals↗

PubMed1995

Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series): radiosensitization efficiency and toxicity.

PURPOSE: A new 2-nitroimidazole nucleoside radiosensitizer, PR-350 (1-[1',3',4'-trihydroxy-2'-butoxy]-methyl-2-nitroimidazole), has been reported to be as efficient as and less toxic than etanidazole. This compound is racemic, and it was recently optically resolved into two isomers, PR-68 (2'R,3'S type) and PR-69 (2'S,3'R type). The other two isomers, PR-28 (2'S,3'S type) and PR-44 (2'R,3'R type), were asymmetrically synthesized. In the present study, we investigated the properties, sensitizing activity, and toxicity of PR-350 and the four optical isomers in comparison with those of other 2-nitroimidazole hypoxic cell radiosensitizers, etanidazole, KU-2285, KIN-804, and RP-170. Because PR-350 and PR-28 can be industrially synthesized, we evaluated whether either of these two drugs are suitable for further investigation. METHODS AND MATERIALS: In an in vitro study, EMT-6 cells were irradiated at a dose of 1-3 Gy under hypoxic conditions in the presence of the drugs at a concentration of 1 mM. A combined cytokinesis-block micronucleus and chromosomal aberration assay was performed. To assess the in vivo effects, colony assay and growth delay assay were performing using SCCVII tumor-bearing C3H mice. The mice received 16-24 GY 10-40 min after administration of 50-200 mg/kg of the drugs. Toxicity and pharmacokinetics in mice were also investigated. RESULTS: The sensitizer enhancement ratio (SER) in the in vitro cytokinesis-block micronucleus assay increased in the following order: PR-69 (1.27) approximately equal to PR-28 (1.31) approximately equal to PR-44 (1.38) approximately equal to PR-350 (1.41) approximately equal to PR-68 (1.47) < etanidazole (1.79) < KIN-804 (2.03) approximately equal to KU-2285 (2.30). The SER at a dose of 200 mg/kg and at an interval of 20 min (optimal interval) in the in vivo-in vitro colony assay increased as follows: PR-44 (1.26) approximately equal to PR-28 (1.29) < PR-69 (1.34) approximately equal to etanidazole (1.35) approximately equal to PR-350 (1.36) < RP-170 (1.41) approximately equal to PR-68 (1.41) < KU-2285 (1.49). The growth delay assay also showed that PR-350 was less efficient than KU-2285 and more efficient than PR-28. PR-350 and the four isomers had similar reduction potentials, but PR-28 and PR-44 were more hydrophilic than PR-68 and PR-69. The LD50 in mice were 5.8 g/kg for PR-350, approximately 7 g/kg for PR-28, 4 g/kg for PR-68, and 6 g/kg for PR-44 and PR-69. The concentration of PR-28 in the murine sciatic nerve was lower than that of PR-350. CONCLUSION: In vivo radiosensitizing activity differed among the four optical isomers, which appeared to be due, at least in part, to differences in lipophilicity. Although PR-28 was the least toxic, its low sensitization efficiency does not warrant clinical trials. Among the PR compounds, PR-68 appears to be most efficient, but optical resolution of PR-68 from PR-350 is expensive, and asymmetrical synthesis of PR-68 is not established. Therefore, PR-350 seems to be most suitable for further investigation among the PR-350 series compounds, considering its higher efficiency compared with PR-28 and PR-44, and established synthesis.

Animals↗

PubMed1995

Assessment of micronucleus induction in SCCVII cells treated with bioreductive agents, WIN 59075 (SR 4233) and mitomycin C, under aerobic and hypoxic conditions.

WIN 59075 (SR4233, tirapazamine) is a promising bioreductive antitumor agent preferentially more toxic to hypoxic cells and presently undergoing phase I clinical trials. In this investigation, we have examined the applicability of the cytokinesis-block micronucleus assay to assess the effects of bioreductive agents. SCCVII tumor cells were treated with WIN 59075 or mitomycin C at various concentrations under aerobic and hypoxic conditions. Significant induction of micronuclei in binucleate cells was demonstrated in a dose-dependent fashion and it appeared to be strongly correlated with the loss of clonogenicity in the colony assay. Both agents showed selectively higher toxicity to hypoxic cells than to aerobic cells and the ratios of the concentrations required to obtain the equivalent effects under aerobic and hypoxic conditions could be also estimated by this method as follows: the hypoxic toxicity ratios were 120-130 for WIN 59075 and 3.0-3.3 for mitomycin C. For several favorable characteristics, the cytokinesis-block micronucleus assay can provide an alternative, rapid, and reproducible means for evaluation of antitumor activities from chromosomal breakage caused by the bioreductive agents.

Dose-Response Relationship, Drug↗

PubMed1995

Relation of the enhancement of entorhinal tetanic responses by 50-Hz amygdala stimulation to the progression of kindling in the rat.

We recorded entorhinal tetanic responses to 50-Hz kindling stimulations applied at the amygdala in conscious rats, which produced facilitation and depression during the train pulses, in order to analyze the relationship of the changes in the tetanic responses to the development of both after-discharges (ADs) and behavioral seizures. Facilitation was always produced in the earlier tetanic responses and was followed by depression which reached a quasi-steady level in the later tetanic responses during each kindling stimulation. To estimate the changes in magnitude of the excitatory synaptic activation in the tetanic responses, with reference to the development of seizure stages, tetanic responses which produced the same behavioral seizure stage in each rat were averaged and the area between the negative (excitatory) potentials and the baseline of the averaged tetanic response was measured in terms of mV x ms. Magnitudes of the averaged negative components were significantly enhanced with an increase in the order of seizure stages in eight rats (P < 0.01). In addition, the mean magnitude of the averaged negative components had a linear correlation (r = 0.95, P < 0.05) with the mean AD duration with reference to the order of seizure stages in the eight rats. The magnitude of the positive (inhibitory) component in the averaged tetanic responses was also measured and found to decrease with an increase in the seizure stages (P < 0.01). The magnitude of the negative component in the test responses to single (0.3 Hz) stimuli just before kindling stimulations also increased with an increase in the order of seizure stages, indicating long term potentiation of the responses by kindling stimulations. We concluded from the results that the enhancement of facilitation of the excitatory synaptic activation and the reduction of the inhibitory synaptic activation in entorhinal tetanic responses by 50-Hz amygdala kindling stimulation is involved in the electrophysiological source of the progression of kindling epilepsy.

Amygdala↗

PubMed1995

Effects of pentobarbital on entorhinal tetanic responses and the progression of afterdischarges during the early course of amygdala kindling in rats.

We investigated the relationship between the progress of afterdischarges (AD) and the development of facilitated entorhinal tetanic responses by amygdala kindling stimulations in conscious and pentobarbital (PB)-treated rats. The entorhinal responses consisted of deep negative components and the following shallow positive components. The negative potential (mean +/- SE) reflecting excitatory synaptic activation in the test response evoked by a single stimulation (600 microA) before kindling stimulations was greater in PB-treated rats (1.3 +/- 0.21 mV, n = 6) than in conscious rats (0.5 +/- 0.08 mV, n = 9). The positive potential reflecting inhibitory synaptic activation in the test response was also greater in PB-treated rats (0.6 +/- 0.14 mV, n = 6) than in conscious rats (0.2 +/- 0.04 mV, n = 9). The magnitude of the tetanic response was estimated as the area between the excitatory negative potential and the baseline in the averaged tetanic response during each kindling stimulation (10 Hz, 100 pulses). The magnitude of the tetanic response was significantly enhanced in association with the prolongation of AD duration in the conscious rats. In the PB-treated (50 mg/kg intraperitoneally, i.p.) rats, enhancement of tetanic response was very slight and the progress of AD duration was prevented. There was a linear correlation (r = 0.9) between the magnitude of tetanic response and AD duration. These findings indicate that PB suppresses kindling-induced enhancement of excitatory synaptic activation in tetanic responses and that this enhancement is intimately related to the development of AD.

Amygdala↗