Possible assessment for antioxidant capacity in Alzheimer's disease by measuring lymphocyte heme oxygenase-1 expression with real-time RT-PCR.
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Aged↗
Biomedical subjects
J Yoshitake
Publications and source records attributed to J Yoshitake.
Matrix metalloproteinases induction by pseudomonal virulence factors and inflammatory cytokines in vitro.
The pathogenesis of pseudomonal keratitis was investigated by focusing on induction and activation of matrix metalloproteinases (MMPs) by pseudomonal virulence factors and proinflammatory cytokines. Corneal lesions and MMP induction in vivo were evaluated in rabbit corneas infected with a clinical isolate of Pseudomonas aeruginosa. Effects of pseudomonal virulence factors [elastase, alkaline protease, exotoxin A and lipopolysaccharide (LPS)], tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta on MMP induction and activation were further examined in vitro in rabbit corneal fibroblasts (RCF) and human fibrosarcoma (HT1080) cells using reverse transcriptase-polymerase chain reaction (RT-PCR), zymography and immunoblotting. Corneal ulcers with typical ring abscesses were observed 12-24 h after infection, and MMPs, particularly MMP-9, were upregulated in infected corneas. Pseudomonal elastase caused the most extensive damage to both cell types. RCF treated with pseudomonal exoproteases or LPS expressed and secreted MMP-9. Exotoxin A had no effect on MMP expression. Both IL-1beta and TNF-alpha augmented MMP-9 expression in HT1080 cells. Pseudomonal elastase proteolytically activated MMP-2 and MMP-9 released from the cells. In conclusion, corneal destruction seen with P. aeruginosa infections may result from enhanced expression of MMPs by corneal stromal cells stimulated with pseudomonal exoproteases and proinflammatory cytokines and the proteolytic activation of MMPs by pseudomonal elastase.
ADP Ribose Transferases↗
Novel functions of human alpha(1)-protease inhibitor after S-nitrosylation: inhibition of cysteine protease and antibacterial activity.
alpha(1)-Protease inhibitor (alpha(1)PI), the most abundant serine protease inhibitor found in human plasma (at 30-60 microM), is a glycoprotein (53 kDa) having a single cysteine residue at position 232 (Cys(232)). We have found that Cys(232) of human alpha(1)PI was readily S-nitrosylated by nitric oxide (NO) without affecting inhibitory activity to trypsin or elastase. S-nitrosylated alpha(1)PI (S-NO-alpha(1)PI) not only retained inhibitory activity against these serine proteases, but also gained thiol protease inhibitory activity against a Streptococcus pyogenes protease; the parental alpha(1)PI did not have this activity. Furthermore, S-NO-alpha(1)PI exhibited bacteriostatic activity against Salmonella typhimurium at concentrations of 0.1-10 microM, which were 20- to 3000-fold stronger than those of the other NO-generating compounds or S-nitroso compounds such as S-nitrosoalbumin and S-nitrosoglutathione. NO appears to be transferred into the bacterial cells from S-NO-alpha(1)PI via transnitrosylation, as evidenced by electron spin resonance spectroscopy with an NO spin trap. Thus, we conclude that S-NO-alpha(1)PI may be generated from the reaction between alpha(1)PI and NO under inflammatory conditions, in which production of both is known to increase. As a result, new functions, i.e., antibacterial and thiol protease inhibitory activities of alpha(1)PI, were generated.
Animals↗
Intravascular ultrasound imaging of the pulmonary arteries in primary pulmonary hypertension.
OBJECTIVE: Intravascular ultrasound has the unique ability to provide cross-sectional images of the arterial wall. This study examined intravascular ultrasound (IVUS) images of the proximal pulmonary arteries in primary pulmonary hypertension (PPH). METHODOLOGY: Study 1: Specimens from four patients who had died of PPH (in vitro PPH group) were compared with those of three patients who had died of subarachnoid haemorrhage but had no evidence of cardiopulmonary disease (in vitro control group). Three-centimetre segments of the following levels were examined by IVUS: pulmonary trunk, eight secondary branch arteries of the upper, middle, and lower lobes of both lungs, and the thoracic descending aorta. Study 2: Four patients with PPH (in vivo PPH group) and five patients without pulmonary hypertension and no evidence of cardiopulmonary disease (in vivo control group) were examined. The IVUS images of the apical segmental artery of the right upper lobe and the descending branch of the right pulmonary artery were studied. RESULTS: Echographic examination of formalin-fixed preparations of secondary branch sections of the pulmonary artery failed to show a clear three-layer structure in the in vitro control group (24 preparations), but a distinct three-layer structure and increased vessel wall thickness were observed in the in vitro PPH group (32 preparations). Similar findings were obtained in the in vivo study. The mean echo density of the proximal pulmonary arterial wall correlated well with the mean pulmonary arterial pressure (mPA) in the in vitro PPH, and also correlated with the mPA in the in vivo study (r = 0.960, P < 0.0001). The echo intensity of secondary branch sections of the pulmonary artery was higher in the in vitro PPH group than in the in vitro control group (180.5 +/- 27.0 vs 132.5 +/- 26.7 counts, P < 0.001); similar results were obtained in the in vivo study (144.7 +/- 23.4 vs 85.0 +/- 14.3 counts, P < 0.01). CONCLUSIONS: These results suggest that the histological changes detected in the pulmonary artery walls in the PPH group were responsible for the increased echo intensity.
Adult↗
Viral mutation accelerated by nitric oxide production during infection in vivo.
Nitric oxide (NO), superoxide (O(2)(-)), and their reaction product peroxynitrite (ONOO(-)) are generated in excess during a host's response against viral infection, and contribute to viral pathogenesis by promoting oxidative stress and tissue injury. Here we demonstrate that NO and peroxynitrite greatly accelerates the mutation of Sendai virus (SeV), a nonsegmented negative-strand RNA virus, by using green fluorescent protein (GFP) inserted into and expressed by a recombinant SeV (GFP-SeV) as an indicator for mutation. GFP-SeV mutation frequencies were much higher in the wild-type mice than in those lacking inducible NO synthase, suggesting that mutation of the virus in vivo is NO dependent. High levels of NO and NO-mediated oxidative stress were induced by GFP-SeV infection in the lung of the wild-type mice, but not in the iNOS-deficient mice, as evidenced by electron spin resonance spectroscopy and immunohistochemical analysis for nitrotyrosine formation as well as histopathological examination. Furthermore, peroxynitrite, an NO-derived reactive nitrogen intermediate, enhanced viral mutation in vitro. These results indicate that the oxidative stress induced by NO produced during the natural course of viral infection increases mutation, expands the quasispecies spectrum, and facilitates evolution of RNA viruses.
Animals↗
Protective effect of S-nitrosylated alpha(1)-protease inhibitor on hepatic ischemia-reperfusion injury.
S-Nitrosylated compounds (nitrosothiols; RS-NOs) function as nitric oxide (NO) reservoirs and preserve the antioxidant activities of NO. We found remarkable cytoprotection by an S-nitrosylated protease inhibitor from human plasma, S-nitroso-alpha(1)-protease inhibitor (S-NO-alpha(1)-PI) that possesses a completely nitrosylated SH group, in hepatic ischemia-reperfusion injuries in rats. Liver ischemia was induced in rats by occluding both the portal vein and hepatic artery for 30 min and was followed by reperfusion. S-NO-alpha(1)-PI and control compounds such as native alpha(1)-PI, an NO synthase (NOS) inhibitor, and standard RS-NOs were given via the portal vein just after reperfusion was initiated. Liver injury was evaluated by measuring the extracellular release of liver enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase). Infiltration of neutrophils and induction of apoptosis and heme oxygenase-1 (HO-1) in the liver were also examined. Maximal liver injury occurred at 3 h after reperfusion and then decreased gradually. Not only did S-NO-alpha(1)-PI treatment (0.1 micromol; 5.3 mg/rat) greatly reduce elevation of liver enzymes in plasma, as well as neutrophil accumulation and apoptotic change in liver, it also improved the impaired hepatic blood flow as assessed by laser Doppler flowmetry and potentiated the induction of HO-1 in the liver. Although native alpha(1)-PI moderately reduced liver injury, low molecular weight RS-NOs such as S-nitrosoglutathione and S-nitroso-N-acetyl penicillamine produced no obvious protective effect. An NOS inhibitor exacerbated the hepatic ischemia-reperfusion injuries. These results suggest that S-NO-alpha(1)-PI exerts a potent cytoprotective effect on ischemia-reperfusion liver injury by maintaining tissue blood flow, inducing HO-1, and suppressing neutrophil-induced liver damage and apoptosis.
Animals↗
Potentiation of carbon tetrachloride-induced liver damage by dibutylyl-3',5'-cyclic AMP in unstarved rats.
It has been reported that carbon tetrachloride-induced liver damage is potentiated by starvation partly due to fat accumulation in the liver and a decrease in hepatic reduced glutathione concentration and that dibutylyl-3',5'-cyclic AMP (DBcAMP) affects fuel metabolism and decreases hepatic reduced glutathione. We investigated the effects of DBcAMP on carbon tetrachloride-induced liver damage both in unstarved and starved rats. In unstarved rats, intraperitoneal administration of DBcAMP potentiated an increase in serum alanine aminotransferase activity and fatty vacuolization in the liver, both of which were induced by carbon tetrachloride. Hepatic reduced glutathione concentration was also reduced by DBcAMP, although the change was not significant. In contrast, the administration of DBcAMP in starved rats did not affect carbon tetrachloride-induced changes in serum alanine aminotransferase activity, histological alterations and hepatic reduced glutathione concentration. Administration of DBcAMP to control rats induced different responses in unstarved control rats compared with starved control rats: in unstarved rats, blood glucose concentration decreased but serum free fatty acid concentration increased, whereas in starved rats, blood glucose concentration increased and serum free fatty acid concentration decreased. It was suggested that DBcAMP potentiated carbon tetrachloride-induced liver damage in unstarved rats, probably due to hepatic fat accumulation and a decreased hepatic reduced glutathione concentration. The former could increase the affinity of the liver for carbon tetrachloride and the latter could accelerate carbon tetrachloride-induced lipid peroxidation. It was also suggested that DBcAMP failed to affect carbon tetrachloride-induced liver damage in starved rats, probably because starvation had already decreased hepatic glutathione concentration and DBcAMP had different effects on fuel metabolism compared with effects observed in unstarved rats.
Alanine Transaminase↗
Effects of OP 2507, a stable analogue of prostaglandin I2, on carbon tetrachloride-induced liver damage in starved rats.
It has been reported that vasodilatory prostaglandins have cytoprotective effects against various types of liver damage. We investigated the effects OP 2507, a stable analogue of prostaglandin I2, on carbon tetrachloride-induced liver damage in starved rats. Intraperitoneal administration of OP 2507 at 1,500 micrograms/kg lessened both an increase in serum alanine aminotransferase activity and an inhibition of starvation ketosis, both of which were induced by carbon tetrachloride. At lower doses, however, OP 2507 not only failed to ameliorate the carbon tetrachloride-induced changes, but it actually exaggerated them. Although the deterioration of carbon tetrachloride-induced liver damage by lower doses of OP 2507 was not statistically significant, it seems possible that OP 2507 has dual effects on carbon tetrachloride-induced liver damage. While none of the three agents cimetidine, reduced glutathione and deferoxamine, prevented increase in serum alanine aminotransferase activity induced with lower dose OP 2507, allopurinol had a tendency to prevent the increase, indicating that lower doses of OP 2507 may promote a reaction catalyzed by xanthine oxidase. We propose that both the co-administration of prostaglandins and other potentially hepatotoxic drugs, and the administration of prostaglandins to patients with drug-induced liver damage should be done carefully.
Alanine Transaminase↗
[Mycoplasma pneumonia found by the occurrence of atelectasis during the induction of anesthesia in a child with tetralogy of Fallot].
A 3-yr-old girl was scheduled to undergo surgical repair of tetralogy of Fallot. She had no sign or data indicating an infectious disease, other than a slight dry cough for a few days prior to the proposed operation. During the induction of anesthesia with nitrous oxide, oxygen and sevoflurane, transient moist rale was noticed with a precordial stethoscope. Her trachea was intubated without any difficulty after the administration of pancuronium, followed by a chest auscultation, which revealed vesicular sound bilaterally but no rale. However, a chest X-ray taken after the right subclavian vein catheterization showed a massive hypoaeration in the upper left pulmonary region. The presence of the right-to-left intracardiac shunt made it impossible to detect the occurrence of atelectasis by a decrease in SpO2. Fiberoptic bronchoscopy showed no obstruction of the bronchus and no hypersecretion initially, but physical therapy and humidification made it possible to aspirate intratracheal sputum. Because there seemed to be an imbalance between the relatively uneventful induction of anesthesia and the relative resistance of atelectasis to authentic therapies, the operation was postponed, and the antibody to mycoplasma pneumoniae was titrated. The titer in the serum was 1:80, and increased to 1:560 6 days later. Chest X-rays revealed normal lung condition 3 days later, and she was given erythromycin, 800 mg.day-1 for 2 weeks. We conclude that we should be alert to possible asymptomatic mycoplasma infection, which potentially makes patients susceptible to atelectasis during the perioperative period.
Anesthesia, Inhalation↗
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↗
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↗
Rationale for preoperative screening of anti-HCV antibody.
We investigated the incidence of the anti-HCV antibody and associated factors in 1,031 surgical patients who had received blood transfusion during or after operation from October 1988 to April 1991, at Kyushu University Hospital. One hundred fifteen patients (11.2%) were anti-HCV positive. Sixty of the 219 patients (27.%) with a history of transfusion were positive, as were 55 of 812 (6.8%) without it. Patients aged under 40 showed a 0.6% positive rate (1 of 175) as did 8.5% (54 of 637) of those 40 and over in the no transfusion history group. Among the 637 patients without transfusion histories and aged over 40, patients with preoperative maximum ALT value over 36 IU. l(-1) had significantly higher positivity (16.0%, 29/181) than those with ALT values less than 35 IU. l(-1) (5.5%, 25/456, P < 0.01). The incidence of anti-HCV antibody in preoperative surgical patients in our hospital is ten times higher than that of donors. Anti-HCV are associated with transfusion, age, and liver dysfunction. Operating room personnel are at high risk because of contact with many HCV carrier patients.
Journal Article↗
Intra-operative blood pressure control by prostaglandin E1 in patients with hypertension and ischemic heart disease--a multi-center study.
The purpose of this multi-center study was to evaluate the efficacy and safety of prostaglandin E1 (PGE1) administration in achieving deliberate hypotension and in treating intraoperative hypertension for patients with a history of hypertension and ischemic heart disease. PGE1 (0.08 microg.kg(-1).min(-1)) decreased systolic blood pressure from 125 +/- 29 to 106 +/- 22 mmHg (mean +/- SD) in the deliberate hypotension group (n = 158) and from 155 +/- 34 to 125 +/- 32 mmHg in the antihypertension group (n = 55). The heart rate significantly increased from 80 +/- 15 to 85 +/- 18 beats.min(-1) in the deliberate hypotension group, but was not significantly altered in the antihypertension group. The time required to obtain the desired level of blood pressure was approximately 20 min in the deliberate hypotension group. When the infusion was stopped, blood pressure returned approximately to the preinfusion level within about 20 min. No rebound hypertension was observed. PGE1 significantly increased the urine flow in patients who had a low urine flow before PGE1 infusion. Thirteen out of 213 patients (5.6%) had side effects such as excessive hypotension (1%), phlebitis (3%), and unexpected tachycardia (1%), which were alleviated gradually after discontinuation of PGE1 infusion. No dysarrhythmia and further ST segment changes in the electrocardiograms were observed. These findings suggest that PGE1 can be safely used to control arterial blood pressure during surgery in patients having preoperative hypertension and ischemic heart disease.
Journal Article↗
Changes in venous capacitance during prostaglandin E1-induced hypotension; comparisons with trinitroglycerin.
The purpose of this study was to examine the effects of prostaglandin E1 (PGE1) on venous capacitance during controlled hypotension. Trinitroglycerin (TNG) was used as a control agent. In rats anesthetized with ketamine, mean arterial pressure was lowered to 70 mmHg and subsequently 50 mmHg by intravenous infusion of PGE1 or TNG. Venous capacitance was assessed before and during induced hypotension by measuring the mean circulatory filling pressure (MCFP). MCFP was measured after briefly arresting the circulation by inflating an indwelling balloon in the right atrium. MCFP was significantly decreased by PGE1 from 7.9 +/- 0.3 to 6.9 +/- 0.3 mmHg at mean arterial pressure of 70 mmHg and to 6.9 +/- 0.2 mmHg at mean arterial pressure of 50 mmHg. The decrease in MCFP by PGE1 at mean arterial pressure of 70 mmHg was not significantly different from TNG. However, the decrease in MCFP by PGE1 at mean arterial pressure of 50 mmHg was significantly less than that by TNG. The results suggest that the venous capacitance may be increased by PGE1 to a similar degree with TNG at doses to produce a comparable level of moderate hypotension, but the increase in venous capacitance may be less in PGE1 than TNG at doses to produce deep hypotension.
Journal Article↗
Cardiopulmonary bypass and plasma taurine.
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Journal Article↗
An increase in plasma concentrations of granulocyte elastase during and after bench surgery of the liver.
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Journal Article↗