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Biomedical subjects

H Igisu

Publications and source records attributed to H Igisu.

At least 37 records · Page 2Linked to original sources
PubMed1997

Suppression of pentylenetetrazol-induced seizures by carnitine in mice.

When ddY mice were pretreated with L-carnitine (5, 10 or 20 mmol/kg), clonic as well as tonic seizures induced by pentylenetetrazol (PTZ) were dose-dependently suppressed. A time/response study (PTZ was injected 1, 5, 15 or 30 min after L-carnitine) showed that the anticonvulsive effects were apparent when the interval between L-carnitine and PTZ administration was 15-30 min. Saline containing 43% sucrose prolonged the latency to the first clonic seizure but was less effective than 20 mmol/kg L-carnitine and did not suppress clonic or tonic seizures. Alterations in brain energy metabolites caused by PTZ including increase of lactate and decrease of ATP and phosphocreatine were also suppressed by L-carnitine. L-carnitine was more potent than D-carnitine in prolonging the latency to the first clonic seizure and in decreasing the frequency of clonic as well as tonic seizures. The anticonvulsive effects of L-carnitine in PTZ-induced seizures may be unrelated to the transport of long-chain acyl CoA since they were not interfered with by D-carnitine.

Animals↗
PubMed1997

Cooperative inhibition of acetylcholinesterase activities by hexachlorophene in human erythrocytes.

Hexachlorophene (HCP), pentachlorophenol (PCP), 2,4,5-trichlorophenol (2,4,5-TCP) and 2,4,6-trichlorophenol (2,4,6-TCP) all hemolyzed washed human erythrocytes and inhibited acetylcholinesterase (AchE) activities in erythrocyte membrane. HCP was much more potent in either effect than any other compound examined. The inhibition of AchE activities by HCP was reversed on adding albumin. The dose-response curves by HCP and PCP were sigmoidal, indicating cooperative inhibition, while those by 2,4,5-TCP and 2,4,6-TCP were not. Furthermore, the cooperativity of the inhibition by HCP was greater than by PCP. Differing from that by PCP, the cooperativity of inhibition increased depending on the temperature (13, 25, 37 degrees C) and decreased when the membrane was treated with Triton X-100. The cooperativity was also decreased in the presence of albumin. On a Scatchard plot analysis, erythrocyte membranes appeared to have multiple binding sites of different affinities for HCP; binding of HCP to the low affinity site [dissociation constant (Kd) 4.7 x 10(-5) M] seemed to be responsible for the observed cooperative inhibition of AchE activities. Neither neostigmine nor fenitrothion altered the cooperativity. HCP seems to be the most potent cooperative inhibitor of AchE in human erythrocyte membranes known to date. HCP may be useful to examine AchE and milieu in human erythrocyte membranes.

Adult↗
PubMed1996

Functional and biochemical evaluation of the preserved lung in a rat model.

Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activities and total protein concentrations were examined in the postrinsing solutions from rat lungs preserved in phosphate-buffered saline (PBS), Euro-Collins (E-C) solution, or low-potassium E-C solution for 8 h at 4 degrees C, 10 degrees C, or 20 degrees C. The LDH and AST activities were higher when the organs were preserved in PBS for 8 h at 20 degrees C than at 4 degrees C or 10 degrees C, while the total protein concentration did not differ according to the temperature or solution. The activities were also higher when the lungs were preserved in Euro-Collins (E-C) solution than in PBS or the low-potassium E-C solution. On examining pulmonary functions utilizing an ex vivo reperfusion model, the lungs preserved at 20 degrees C showed poorer gas exchange than those preserved at 4 degrees C or 10 degrees C. Moreover, the organs preserved in E-C solution showed poorer function than those preserved in any other solution. These findings suggest that some enzymatic activities in the postrinsing solution could be indicators of lung viability after preservation.

Analysis of Variance↗
PubMed1996

Creatine kinase activities in brain and blood:possible neurotoxic indicator of acrylamide intoxication.

OBJECTIVES: To examine whether the activities of creatine kinase (CK) correlate with neurological disturbances caused by acrylamide. METHODS: The activities of CK and other enzymes reported to be inhibited by acrylamide in the brain and plasma, and landing foot spread (LFS) were measured in mice and rats intoxicated with acrylamide. RESULTS: Activity of CK was suppressed by acrylamide in the brain of mice in parallel with the neurological dysfunction measured by LFS. No clear alterations were found in glyceraldehyde-3-phosphate dehydrogenase, neuron-specific enolase, and lactate dehydrogenase activities over the experimental period (eight days for the exposure and 43 days for the recovery). In rats, among the plasma enzymes examined, suppression of CK activity was most notable, but thyroid activity was not affected. CONCLUSIONS: Among the enzymes so far examined, the CK activities in the brain and blood seem to be the most sensitive indicators of acrylamide intoxication.

Acrylamides↗
PubMed1995

Effects of glucose on rat lung preservation: report of a study conducted on an isolated lung reperfusion model utilizing. Another isolated lung as a "deoxygenator".

We describe herein a new experimental model in which an isolated rat lung was ventilated with a mixture of 95% nitrogen and 5% carbon dioxide to decrease the oxygen and increase the carbon dioxide in the perfused blood to create and maintain a gas composition similar to that of venous blood. By utilizing this system as a "deoxygenator," pulmonary functions, including gas exchange, could be measured for at least 60 min in isolated and preserved lungs on reperfusion. When the effects of glucose in the flushing and storage solution were examined, 5 mM glucose in the solution resulted in better preservation of the lung, as shown by a higher uptake of oxygen and a lower intratracheal pressure, than when no glucose was given. However, the presence of 50 mM glucose was not beneficial, but rather increased the wet/dry weight ratio of the tissue.

Acid-Base Equilibrium↗
PubMed1995

Protection of the brain by carnitine.

Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is widely distributed in the body including the nervous system. Its physiological function, viz. a carrier of long-chain fatty acids through the inner mitochondrial membrane, has been well established. In this review, mainly based on our experiments, we discuss the possibility that carnitine may have effects other than the "physiological" function and that it may be a potent protector of the brain. When mice were exposed to ammonia (intraperitoneal injection of ammonium acetate), they developed seizures and concentrations of brain energy metabolites were altered; ATP and phosphocreatine decreased while ADP, AMP, pyruvate and lactate increased. The seizures and changes in brain energy metabolites were clearly suppressed when the mice were pre-treated with carnitine. Furthermore, changes in energy metabolites in the brain caused by severe ischemia (decapitation) were also suppressed by carnitine. Since D-carnitine showed similar effects as those of L-carnitine, the effects seem due to function(s) of carnitine yet to be defined. Intrinsic substances including carnitine appear to deserve further studies for possible use in protecting the brain.

Ammonia↗
PubMed1994

[Acetylcholinesterase in the erythrocyte membrane].

Acetylcholinesterase (AchE) in erythrocytes is one of the typical extraneural AchEs. Its activity is high in human erythrocytes. It has been known that the enzyme is present only in the membrane in erythrocytes and that it is localized on the outer side of the membrane. Recent studies have disclosed much of the primary structure of AchE and the membrane anchor structure. However, the physiological functions of erythrocyte AchE are still totally unknown. Nevertheless, the enzyme may be regarded as a model of AchE in the nervous system. In addition, it may be used to examine the status of the erythrocyte membrane. The enzyme activity seems useful as an indicator of the effects of AchE inhibitors, such as pesticides. It should be noted, however, that the activity of AchE in erythrocytes is not always a good indicator of intoxication with AchE inhibitors.

Acetylcholinesterase↗
PubMed1994

Effects of coenzyme Q10 on lung preservation: a study with an isolated rat lung reperfusion model.

We studied the effect of Coenzyme Q10 (CoQ10) on lung preservation using an isolated rat lung reperfusion model. After the lung of a Wistar male rat was flushed with a solution consisting of 40 mM phosphate buffered saline, the heart-lung block was excised and immersed in the same solution at 10 degrees C for 6 hours. In experiment 1, CoQ10 was added to the flushing solution. In experiment 2, CoQ10 was injected i.v. 1 hour before the organ was harvested. After the preservation, both lungs were reperfused and ventilated for 30 minutes. No benefit was noted when CoQ10 was added to the flushing solution. However, when CoQ10 was pretreated one hour before harvesting, the lungs showed significantly better preservation in pulmonary artery pressure, airway pressure, gas exchange function and the wet/dry weight ratio than those of the control group. Thus, appropriate pretreatment of CoQ10 may have a beneficial effect on lung preservation.

Animals↗
PubMed1994

Effects of acrylamide and acrylic acid on creatine kinase activity in the rat brain.

In vitro, both acrylamide and acrylic acid inhibited creatine kinase (CK) activity in rat brain homogenates, and acrylic acid was more potent than acrylamide. In vivo, however, when given i.p. 50 mg/kg per day for 8 days to rats, only acrylamide inhibited CK activity in the brain and caused apparent neurological signs. 14C in the brain 24h after the injection of 14C-labelled chemicals was more than 7 times greater with acrylamide than with acrylic acid. The inhibition of CK activity by acrylamide varied in eight regions of the brain; from 54% in hypothalamus to 27% in cerebellar vermis. The regional difference of CK inhibition, however, did not agree well with either 14C distribution or with the distribution in regions which appear clinically or pathologically vulnerable to acrylamide.

Acrylamide↗
PubMed1994

Effects of pH and temperature on lung preservation: a study with an isolated rat lung reperfusion model.

After the rat lung was flushed with 40 mmol/L phosphate-buffered saline solution containing 160 mEq/L of sodium and the heart-lung block was immersed in the same solution for 6 hours, the lung was reperfused with diluted autologous blood and ventilated for 30 minutes. Pulmonary artery pressure, airway pressure, difference in oxygen tension between inflow and outflow perfusate, and wet to dry weight ratio of the tissue were determined. Lungs treated at pH 7.75 showed a significantly lower pulmonary artery pressure and wet to dry weight ratio than those treated at pH 7.26 or 7.96. Organs preserved at 10 degrees C showed a significantly lower pulmonary artery pressure than those preserved at 5 degrees or 15 degrees C. When the effect of smaller temperature variations was examined, the 12 degrees C group showed a significantly lower pulmonary artery pressure than the 10 degrees C group. Thus, the isolated rat lung reperfusion model appears to provide an efficient screening system to examine the preservation solution or other conditions for lung preservation. Under the present experimental conditions, the optimal pH and temperature for rat lung preservation seem to be 7.75 and 12 degrees C, respectively.

Airway Resistance↗
PubMed1994

Effects of hypo- and hyperglycemia on brain energy metabolites in mice exposed to carbon monoxide.

Hypoglycemia and hyperglycemia were induced in mice by fasting and by injecting with glucose, respectively. These and normally fed (normoglycemic) animals were exposed to 0.5% carbon monoxide (CO) for 10 min. This altered concentrations of energy metabolites in the brain, including decreases in phosphocreatine (PCr) and increases in creatine and lactate. The only difference between normoglycemic and hypoglycemic mice was lower lactate in the latter. In hyperglycemic mice, PCr and ATP were better preserved during CO exposure and lactate was lower than in normoglycemic mice. Blood glucose concentrations correlated well with glucose but not with lactate in the brain. Thus, moderate hypo- or hyperglycemia seems not to exacerbate CO-induced alterations of brain energy metabolism.

Animals↗
PubMed1993

[Binding of toxic substances and suppression of their toxicities by albumin--studies on psychosine and pentachlorophenol].

Psychosine (galactosylsphingosine) potently inhibits cytochrome c oxidase (COX) activity and hemolyzes washed erythrocytes in vitro. However, no hemolytic anemia is seen in patients with Krabbe disease or its animal models in which a psychosine-degrading enzyme is missing. This "discrepancy" may be caused by albumin because, 1) albumin is synthesized only in liver and it does not enter cells once it is released into the blood stream; 2) albumin can bind psychosine and suppress its effects effectively; 3) psychosine cannot exert its toxicity in the blood, should it be present there. On the other hand, an artificial substance, pentachlorophenol (PCP), which is widely used for wood preservation, causes mitochondrial dysfunction and hemolysis in vitro, both of which can be suppressed by albumin. Hence, it appears reasonable that hemolytic anemia is extremely rare, and that a dramatic improvement was seen in patients severely intoxicated with PCP. Thus, differences in the effects of these toxins seen in vitro and in vivo seem to be well explained by the effects of albumin. These also suggest that attention to the possible effects of albumin may be rewarding in monitoring and treating some intoxications.

Albumins↗
PubMed1993

Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia.

Although L-carnitine has been reported to have protective effects against ammonia toxicity, conflicting results have also been presented and the mechanisms underlying the protection, if any, are not clear. In the present study, we examined the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. Administration of ammonium acetate (15 mmol/kg) to mice caused seizures, elevation of blood ammonia and urea concentrations, and marked alterations of brain energy metabolites. Pretreatment with either L-carnitine, D-carnitine or acetyl-L-carnitine reduced the frequency of the seizures, prolonged the time until the first fit, lowered the levels of ammonia in the blood and brain, and suppressed the alterations of brain energy metabolites caused by hyperammonemia. there was no significant difference between L- and D-carnitine in the potency to inhibit the seizures. In addition, there was no difference between the two chemicals in the potency to decrease the ammonia contents in the blood and brain, or to suppress the alterations of energy metabolites in the brain. When compared with L-carnitine, however, acetyl-L-carnitine better preserved ATP in the brain, while it lowered ammonia in the blood and brain less markedly. These results show that L-carnitine and its analogues do have the potential to suppress the neurotoxicity of ammonia. Moreover, the results suggest that the protective effects of carnitine against the toxicity of ammonia are systemic, that the action of acetyl-L-carnitine may differ from that of L- or D-carnitine, and that the "classical" function of carnitine is not the sole mechanism underlying the suppression of the neurotoxicity of ammonia.

Acetates↗
PubMed1993

Highly cooperative inhibition of acetylcholinesterase by pentachlorophenol in human erythrocytes.

Pentachlorophenol (PCP) inhibited acetylcholinesterase (AchE) activity in human erythrocyte membranes with high cooperativity. The Hill coefficient for the inhibition was 4-5 in "untreated" membranes. Differences in the temperature (13, 25 and 37 degrees) or treatment with 1% Triton X-100 did not clearly affect the cooperativity which, however, increased after the erythrocyte membranes were treated with 2-mercaptoethanol and iodoacetatic acid, suggesting that higher cooperativity in the inhibition of AchE by PCP may reflect conformational changes of AchE. Thus, PCP may be useful for the study of AchE in human erythrocytes.

Acetylcholinesterase↗
PubMed1993

Effects of neurotoxins on brain creatine kinase activity.

The effects of ethylene oxide (EO), acrylamide, N,N'-methylene-bis-acrylamide (bis-acrylamide), and methyl mercury chloride (MMC) on brain creatine kinase (CK) activity were examined in vivo. EO and acrylamide, both of which cause central-peripheral distal axonopathy, inhibited CK activity in the brain and spinal cord. On the other hand, neither bis-acrylamide, a nonneurotoxic analogue, nor MMC which causes neuronopathy affected brain CK activity significantly. The inhibition of CK may play a role in the pathogenesis of distal axonal degeneration in the central and peripheral nervous systems.

Acrylamides↗
PubMed1993

Effects of L and D-carnitine on brain energy metabolites in mice given sublethal doses of ammonium acetate.

Previous studies in our laboratory have shown that L-carnitine suppresses seizures and alterations of brain energy metabolism in mice caused by hyperammonemia. The present study was done to exclude the effects of seizures on brain energy metabolism. When sublethal dose of ammonium acetate (12 mmol/kg b.wt.) was injected to mice, all mice survived without developing seizures, while clear increase of brain ammonia and alterations of brain energy metabolites were seen. In L-carnitine-treated animals, the levels of ammonia, AMP and lactate were lower and those of ATP and phosphocreatine were higher than in untreated animals. Treatment with D-carnitine also preserved the phosphocreatine level. This indicates that the improvement of brain energy metabolism by L-carnitine in hyperammonemia is not simply a result of the suppression of seizures, and that the "physiological" function of carnitine may not be the sole mechanism underlying this effect.

Acetates↗