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Biomedical subjects

K Irita

Publications and source records attributed to K Irita.

At least 55 records · Page 3Linked to original sources

[Transient tracheal obstruction during surgical correction of scoliosis in a patient with Marfan's syndrome].

A 13-yr-old male with Marfan's syndrome underwent surgical correction of severe scoliosis. He had not manifested dyspnea previously in any position. Under anesthesia with thiamylal and vecuronium, his trachea was intubated with a reinforced endotracheal tube without any difficulty. Anesthesia was maintained with nitrous oxide and fentanyl, 8 micrograms.kg-1. The patient was placed in a prone position. Thirty min after the start of operation, when orthopedists compressed the thoracic vertebrae vertically, positive pressure ventilation became impossible abruptly, even with a high airway pressure. Three min later, ventilation became possible after cessation of compression and by mouth-to-tube insufflation. SpO2 monitored with a pulse oximeter recovered immediately from 61% to 99%. A capnogram showed a lengthy retardation of an inspiratory phase. Emergency fibreoptic bronchoscopy revealed that the trachea had been compressed vertically; the compression was reduced by moving the chest supporters laterally. After the apneic episode, the operation continued uneventfully, and he was discharged a month later. A severe deformity of the thorax due to severe scoliosis and weak tracheal tissue due to connective tissue defect caused partial tracheal compression before the surgery, and made his trachea susceptible to complete obstruction by vertical external compression on the thorax. Patients with Marfan's syndrome and scoliosis should have careful preoperative airway evaluation. The selection and positioning of endotracheal tubes should be done with care. During surgery, the patient's body position and the condition of the trachea should be checked frequently. Capnography and fiberoptic bronchoscopy seem to be mandatory for early detection of tracheal stenosis and prevention of tracheal obstruction.

Adolescent↗

Carbon tetrachloride increases sinusoidal efflux of reduced and oxidized glutathione in rats.

To elucidate the significance of the changes in plasma glutathione concentrations associated with carbon tetrachloride (CCl4)-induced liver damage, the changes in the concentrations of reduced (GSH) and oxidized glutathione (GSSG) in plasma as well as in the liver were investigated in rats. In the liver, the concentration of GSH decreased, and that of GSSG increased 24 hr after the intraperitoneal administration of CCl4. In the right atrial plasma, the concentration of both GSH and GSSG increased. The GSH/GSSG ratio in the plasma decreased as did that in the liver. The net sinusoidal efflux of GSH and GSSG from the liver was calculated by subtracting their concentrations in plasma of the infrahepatic inferior vena cava from those of the suprahepatic inferior vena cava. The net efflux of GSH and GSSG started to increase as early as 3-6 hr after CCl4 administration, and reached a plateau 6 and 24 hr after CCl4 administration, respectively. On the other hand, an elongation of prothrombin time and leakage of alanine aminotransferase reached a maximum 24 and 48 hr after CCl4 administration, respectively. Vacuolization in the centri-lobular region and inflammatory infiltration started 3 and 6 hr after CCl4 administration, respectively, and progressed for 48 hr. These results suggest that CCl4 induced an increase in plasma concentrations of GSH as well as GSSG by increasing their efflux from the liver, and that the changes in plasma glutathione status might be a useful and sensitive marker for CCl4-induced liver damage.

Animals↗

The limiting effect of dichloroacetate on endotoxin-induced liver damage in starved rats.

Dichloroacetate has been shown to have therapeutic effects on sepsis and endotoxin shock and to reduce liver damage in rats intoxicated with ethanol or carbon tetrachloride. In this study, the effect of dichloroacetate on endotoxin hepatitis was investigated. Endotoxin hepatitis was induced by an intraperitoneal coadministration of 50 micrograms/kg lipopolysaccharide from Escherichia coli, and 200 mg/kg D-galactosamine in starved, male Wistar rats. This treatment induced the following changes within 24 hr: an increase in the serum aminotransferase activity, histological alterations of the liver including focal necrosis of liver cells and inflammatory infiltrates, an increase in blood pyruvate and alanine concentrations, and inhibition of starvation ketosis. The intraperitoneal administration of 250 mg/kg dichloroacetate 30 min after the administration of the toxins partially counteracted all of these changes. The administration of dichloroacetate might be useful in coping with hepatic damage as well as lacticemia and cardiovascular depression induced by endotoxins.

Alanine Transaminase↗

Endotoxin causes early changes in glutathione concentrations in rabbit plasma and liver.

The effects of endotoxin on glutathione concentrations in rabbit plasma and liver were investigated. Lipopolysaccharide (2 mg/kg) from Escherichia coli was administered intravenously to seven male Japanese rabbits. In the liver, the concentrations of reduced glutathione (GSH) started to decrease, and those of oxidized glutathione (GSSG) started to increase 1 hr after the endotoxin administration, resulting in a progressive decline in the hepatic GSH/GSSG ratio. In the arterial plasma, the concentrations of both GSH and GSSG started to increase 1 hr after the endotoxin administration. Because the increase in the concentrations of GSSG was greater than that in the concentrations of GSH, the GSH/GSSG ratio in the plasma decreased as did that in the liver. These changes in glutathione concentrations occurred simultaneously with the increase in serum osmolality, but earlier than the decrease in the arterial ketone body ratio, both of which are thought to be useful markers for liver damage. It was concluded that endotoxin induced an increase in the plasma concentrations of GSH as well as GSSG, and that the changes in plasma glutathione status might be useful markers of endotoxin-induced damage in organs, including the liver.

Animals↗

Absence of anti-trifluoroacetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage.

It has been shown that the circulating antibodies, which bind to rat hepatic microsomal proteins obtained after in vivo exposure to halothane, are detectable by immunoblotting in patients with "halothane hepatitis (HH)," and that rabbit immunized anti-sera against trifluoroacetylated rabbit serum albumin (TFA-RSA) recognizes rat microsomal distorted polypeptides in almost the same way as do sera from patients with HH. In this paper, we report first the development of a novel method of synthesizing TFA-RSA using p-nitrophenyl TFA, and second the results of tests for circulating anti-TFA antibodies in the serum of 86 patients who had received halothane anaesthesia and developed no (67 patients) or mild (19 patients, the maximum activity of serum alanine aminotransaminase 519 IU.L-1) liver damage. Serum was selected from stored sera of post-transfusion patients. The new method of synthesizing TFA-RSA was convenient and was able to be done at neutral pH. Rabbit sera obtained after immunization with the newly synthesized TFA-RSA recognized the same polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa and 59 kDa) as the established anti-sera against TFA-RSA, and these reactions were inhibited in the presence of TFA-lysine. Circulating antibodies were not detected in our patients who had developed no or mild liver damage. The present finding supports the hypothesis that the appearance of circulating antibodies against microsomal distorted proteins are specific to patients with HH. Furthermore, we have shown here that the halothane-induced mild increase in ALT activity is not associated with the appearance of those circulating antibodies, supporting the pathophysiological difference between HH and halothane-induced mild hepatic damage.

Adolescent↗

Increased sinusoidal efflux of reduced and oxidized glutathione in rats with endotoxin/D-galactosamine hepatitis.

The changes in the concentrations of reduced (GSH) and oxidized glutathione (GSSG) in the plasma as well as in the liver were investigated in rats with endotoxin hepatitis. Hepatitis was induced by intraperitoneal co-administration of small doses of Escherichia coli endotoxin and D-galactosamine. In the liver, the concentration of GSH decreased and that of GSSG increased 12 hr later. In the plasma taken from the right atrium, the concentration of both GSH and GSSG increased. The GSH/GSSG ratio in the plasma decreased, as it did in the liver. The net sinusoidal efflux of GSH and GSSG from the liver was calculated by subtracting their concentrations in plasma of the infrahepatic, suprarenal inferior vena cava from those of the suprahepatic inferior vena cava. The efflux started to increase as early as 2-4 hr after the injection of the toxins. In contrast, a leakage of alanine aminotransferase, an elongation of prothrombin time, an inhibition of starvation ketosis, and an increase in serum concentration of total bilirubin were detected as late as 6-8 hr after the injection. We conclude that endotoxin/D-galactosamine hepatitis induced an increase in plasma concentrations of GSH as well as GSSG by increasing the efflux of these peptides from the liver, and that changes in plasma glutathione status might be useful and sensitive markers for liver damage.

Animals↗

Increase in the plasma concentration of reduced glutathione observed in rats with liver damage induced by lipopolysaccharide/D-galactosamine: effects of ulinastatin, a urinary trypsin inhibitor.

The changes in plasma concentrations of reduced glutathione were investigated in rats with endotoxin hepatitis. An increase in serum alanine aminotransferase activity and in serum total bilirubin concentration was observed 12 hr after the intraperitoneal co-administration of small doses of Escherichia coli lipopolysaccharide and D-galactosamine in starved rats. At the same time, an increase in the plasma concentration of reduced glutathione was also observed. The increase in reduced glutathione from 14 +/- 2 to 20 +/- 9 microM (n = 11, P < 0.05) correlated well with that in serum alanine aminotransferase activity. Ulinastatin, a potent inhibitor of polymorphonuclear leukocyte elastase, partially counteracted all of these changes. Ulinastatin also reduced histological liver damage induced by endotoxin. We conclude that the increase in the plasma concentration of reduced glutathione reflects hepatocellular damage associated with endotoxin hepatitis. The partial reversal of the damage by ulinastatin is consistent with the proposal that the activation of polymorphonuclear leukocytes is involved in endotoxin hepatitis.

Animals↗

Substitution by fatty acids for phosphatidylserine in a reconstitution of phorbol ester binding to protein kinase C.

1. Fatty acids can be substituted or phosphatidylserine in a reconstitution of phorbol ester binding to protein kinase C. 2. Phorbol ester, however, does not seem to be effectively utilized for the activation of the enzyme. 3. It is suggested that fatty acids play a role on the activation of protein kinase C in the abnormal conditions such as ischemia, while the phospholipid-dependent activation has a physiological significance in normal conditions.

Animals↗

Difference between the calcium- and the phorbol ester-induced association of protein kinase C with phospholipid membrane.

1. Membrane association of protein kinase C is thought to be a prerequisite for the activation of the enzyme. 2. We studied the association of the enzyme with liposome. 3. We show here that the mechanisms for the calcium- and the phorbol ester-induced association of protein kinase C with liposome are different from each other. 4. Diacylglycerol is not crucial for the association of the enzyme with liposome.

Animals↗

[Effect of dibucaine on the association of protein kinase C with liposome].

The association of protein kinase C with membranes are thought to be a prerequisite for the activation of the enzyme. Dibucaine has been reported to inhibit the enzyme activity competitively with phosphatidylserine. We investigated the effect of dibucaine on the association of protein kinase C with liposome. Calcium and phorbol 12-myristate 13-acetate (PMA) independently and synergistically induced the association of rat brain protein kinase C with phosphatidylserine/phosphatidylcholine liposome. Although dibucaine inhibited the association induced by calcium alone, it did not affect the association induced by PMA alone. Dibucaine, however, inhibited the association which was induced synergistically by calcium and PMA. It was suggested that dibucaine did not always inhibit the association of protein kinase C with phospholipid membranes.

Animals↗

The effect of OP 2507, a stable analogue of prostacyclin, on Hep G2 exposed to hypoxia.

We developed a model for screening drugs to reduce ischemic liver damage using Hep G2, a hepatoblastoma cell line, and examined the effect of OP 2507, a stable analogue of prostacyclin, on hypoxic cell damage. Hypoxic exposure of the cells was done for 16 hr in an air-tight chamber which was placed inside an incubator and was purged with 5% CO2/95% N2. Adding OP 2507 (0.01-10 ng/ml) to the incubation medium during hypoxic exposure reduced mitochondrial damage estimated by MTT-reducing activity, while it failed to inhibit lactate accumulation in the medium. OP 2507 seems to be a good candidate for improving the preservation of liver allografts.

Animals↗

Protein kinase C and simulated ischemia possible aberrations of signal transduction during ischemia.

ATP depletion is always associated with prolonged ischemia. It was found that ATP affected calcium- and phospholipid-dependent activation of protein kinase C without hydrolysis of the nucleotide when the activation was monitored by an assay for [3H] 4-beta-phorbol-12, 13-dibutyrate binding activity in a reconstitution system having physiological concentrations of free calcium. When the ATP level was low, an increase in the free calcium concentration could not activate the enzyme. A decrease in pH exacerbated the depressed activation. The concentration of magnesium also affected the activation. On the other hand, free fatty acids, which increase during ischemia, were able to activate the enzyme at a low concentration of ATP in the absence of phorbol ester and phosphatidylserine. These results suggest that calcium- and phospholipid-dependent activation of protein kinase C is suppressed during ischemia, and that fatty acids in turn activate the enzyme. It is possible that ischemia interferes with normal signal transduction via the protein kinase C pathway and causes unusual protein phosphorylation.

Journal Article↗