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Biomedical subjects

Kiyoshi Morita

Publications and source records attributed to Kiyoshi Morita.

At least 19 recordsLinked to original sources

A neutrophil elastase inhibitor, sivelestat, ameliorates lung injury after hemorrhagic shock in rats.

Hemorrhagic shock followed by resuscitation (HSR) causes neutrophil sequestration in the lung which leads to acute lung injury (ALI). Neutrophil elastase (NE) is thought to play a pivotal role in the pathogenesis of ALI. This study investigated whether sivelestat, a specific NE inhibitor, can attenuate ALI induced by HSR in rats. Male Sprague-Dawley rats were subjected to hemorrhagic shock by withdrawing blood so as to maintain a mean arterial blood pressure of 30+/-5 mm Hg for 60 min followed by resuscitation with the shed blood. HSR-treated animals received a bolus injection of sivelestat (10 mg/kg) intravenously at the start of resuscitation followed by continuous infusion for 60 min (10 mg/kg/h) during the resuscitation phase, or the vehicle. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, myeloperoxidase (MPO) activity, gene expression of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS), DNA binding activity of nuclear factor (NF)-kappaB, and immunohistochemical analysis of intercellular adhesion molecule (ICAM)-1. HSR treatment induced lung injury, as demonstrated by pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio, MPO activity, gene expression of TNF-alpha and iNOS, and DNA-binding activity of NF-kappaB, and enhanced expression of ICAM-1. In contrast, sivelestat treatment significantly ameliorated the HSR-induced lung injury, as judged by the marked improvement in all these indices. These results indicate that sivelestat attenuated HSR-induced lung injury at least in part through an inhibition of the inflammatory signaling pathway, in addition to the direct inhibitory effect on NE.

Animals↗

Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts.

Carbon monoxide (CO), a byproduct of heme catabolism by heme oxygenase (HO), confers potent antiinflammatory effects. Here we demonstrate that CO derived from HO-1 inhibited Toll-like receptor (TLR) 2, 4, 5, and 9 signaling, but not TLR3-dependent signaling, in macrophages. Ligand-mediated receptor trafficking to lipid rafts represents an early event in signal initiation of immune cells. Trafficking of TLR4 to lipid rafts in response to LPS was reactive oxygen species (ROS) dependent because it was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase, and in gp91(phox)-deficient macrophages. CO selectively inhibited ligand-induced recruitment of TLR4 to lipid rafts, which was also associated with the inhibition of ligand-induced ROS production in macrophages. TLR3 did not translocate to lipid rafts by polyinosine-polycytidylic acid (poly(I:C)). CO had no effect on poly(I:C)-induced ROS production and TLR3 signaling. The inhibitory effect of CO on TLR-induced cytokine production was abolished in gp91(phox)-deficient macrophages, also indicating a role for NADPH oxidase. CO attenuated LPS-induced NADPH oxidase activity in vitro, potentially by binding to gp91(phox). Thus, CO negatively controlled TLR signaling pathways by inhibiting translocation of TLR to lipid rafts through suppression of NADPH oxidase-dependent ROS generation.

Animals↗

Colonic interposition and supercharge for esophageal reconstruction.

AIMS: We evaluated the techniques of colonic interposition and supercharge for esophageal reconstruction and discussed the main considerations related to these procedures. PATIENTS AND METHODS: In this study, we performed 51 esophageal reconstructions using colonic interposition. Twenty-eight of the 51 patients had synchronous or allochronic gastric malignancy. We selected colonic interposition for high anastomosis in 11 patients and also for esophageal bypass in 3 patients. This procedure was also selected to preserve gastric function in 5 patients. We recently performed the supercharge technique for colonic interposition in 41 patients. RESULTS: Despite the long duration and multistep nature of the operation procedure, no perioperative complications were noted. The patients returned to a good quality of life. The incidence of postoperative weight loss did not differ significantly between the colonic reconstruction group and the gastric reconstruction group. In terms of heartburn and dumping syndrome, the outcome was markedly better in the colonic reconstruction group (no cases of heartburn or dumping syndrome) than that in the gastric reconstruction group. CONCLUSION: For reconstruction of the esophagus, the colonic interposition and supercharge technique is advantageous and contributes to the patient's quality of life.

Adult↗

Clinical significance of T1-weighted MR images following transient cerebral ischemia.

To try to determine the cause of hyperintensity of T1-weighted MR images that occurred on and after day 7 following transient cerebral ischemia, dynamic changes in T1-weighted images and histology of rats subjected to 20 min of 4-vessel occlusion were observed. T1-weighted images showed no remarkable alteration on days 1 and 3, although high signal intensity in the striatal region, in which the T1 value was significantly lower than the values on days 1 and 3, was observed on day 7. High signal intensity in T1-weighted images indicates low T1 values. Histological observation revealed accumulation of microglia in the striatal region on day 7 by lectin staining. There was a tight correlation between T1 values and number of lectin-positive cells. Microglia had stout processes and hypertrophic cell bodies on day 7, resembling lipid-laden phagocytes. Sudan black B staining showed the presence of many fatty droplets in the striatal region on day 7. Furthermore, double staining with lectin and Sudan black B revealed the presence of fatty droplets in bodies of lectin-positive cells on day 7. These results suggest that hyperintensity of T1-weighted images on day 7 following transient ischemia and reperfusion indicates accumulation and phagocytic activation of microglia. T1-weighted images seem to represent the progression of non-reversible tissue injury after transient ischemia and reperfusion.

Animals↗

General anesthesia in a patient with dystrophic epidermolysis bullosa.

A 13-year-old boy with epidermolysis bullosa underwent a repair of pseudosyndactyly. He had a long history of bullae formation in the oral cavity and on the pharynx and body surface, and some were active at the time of surgery. We chose inhalational general anesthesia with tracheal intubation using sevoflurane and nitrous oxide. The trachea was successfully extubated after the surgery, and no major bulla formation was observed. General anesthesia with tracheal intubation may be chosen as anesthesia for patients with epidermolysis bullosa.

Adolescent↗

Relief of bronchial obstruction using a Fogarty catheter in a patient with bronchomalacia.

Tracheobronchomalacia can be latent without showing any clinical manifestations and may be incidentally found during anesthesia. In such cases, hypoxia may occur during anesthesia. We experienced obstruction of the left main bronchus caused by bronchomalacia that was incidentally found during open-heart surgery in a 4-yr-old patient. We could not reopen the airway by routine techniques, such as positive pressure, and had great difficulty in weaning the patient from cardiopulmonary bypass. The use of a Fogarty catheter allowed the relief of airway obstruction and weaning from cardiopulmonary bypass.

Airway Obstruction↗

[Anesthetic management in a child with epidermolysis bullosa undergoing esophageal dilatation].

We experienced the anesthetic management of a child with epidermolysis bullosa undergoing esophageal dilatation. Anesthesia was induced with oxygen/nitrous oxide mixture and sevoflurane. Oral tracheal intubation was with a lubricated laryngoscope blade using vecuronium 0.1 mg x kg(-1) and fentanyl 0.1 microg x kg(-1). To avoid friction and shearing forces on the skin, endotracheal tube was tied with a tape without adhesion and fixed around the neck. We removed adhesive parts of pulse-oximetry probe and electrocardiogram electrodes, then attached to the patient's skin covered with Vaseline. Peripheral venous access was secured in the left ankle and sutured. These methods were effective to avoid new blisters and to keep patient safe.

Anesthesia, General↗

[A case of recrudescent groove pancreatitis, which was in remission by proximal gastrectomy with vagotomy for gastric cancer].

This report describes our experience with a 60 year old male who suffered from a recrudescence of groove pancreatitis. He had been treated by conservative medication therapy by proton pump inhibitor used for therapy of duodenal ulcer, and was in remission. During a follow-up one year later, endoscopy revealed gastric cancer, for which a proximal gastrectomy and vagotomy were performed. The patient continues to remain in remission for the groove pancreatitis. Our experience with the clinical course of this disease, in which treatment for duodenal ulcer was used effectively, offers new insights into the progression and therapy of groove pancreatitis.

Gastrectomy↗

Highly liver-specific heme oxygenase-1 induction by interleukin-11 prevents carbon tetrachloride-induced hepatotoxicity.

Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, can be induced in response to various oxidative stimuli, and its induction is thought to be critical in the cellular defense against oxidative tissue injuries. Carbon tetrachloride (CCl(4)) treatment of rats causes lipid peroxidation of cell membranes and produces massive hepatic injury. We previously demonstrated that HO-1 induction following CCl(4) treatment is an essential part of the cellular defense against the CCl(4)-inducible toxic changes. As recombinant human interleukin-11 (rhIL-11) has been shown to induce HO-1 in cultured hepatoma cells, we examined the effect of rhIL-11 in vivo in rats on the CCl(4)-induced tissue injury. rhIL-11 treatment of animals by itself markedly induced HO-1 mRNA and its functional protein principally in the liver. rhIL-11 treatment (150 microg/kg) of the CCl(4)-administered (1 ml/kg) animals led to a further increase in HO-1 mRNA, while it markedly suppressed CCl(4)-induced serum alanine transaminase, hepatic malondialdehyde formation, tumor necrosis factor-alpha mRNA, nitric oxide synthase mRNA, nuclear factor-kappaB DNA-binding activity, as well as inflammatory changes of hepatocytes. In contrast, inhibition of HO activity by tin-mesoporphyrin, a competitive specific inhibitor of HO, entirely abolished the cytoprotective effect of rhIL-11. These findings thus demonstrate that rhIL-11 confers significant protection against CCl(4)-induced hepatic injury by virtue of its liver-specific HO-1 induction.

Animals↗

[Neuromuscular blocking effects of Org 9426 (rocuronium bromide); a comparative study with vecuronium bromide in Japanese patients].

BACKGROUND: Efficacy and safety of Org 9426 were compared with those of vecuronium bromide in Japanese patients. METHODS: We studied 88 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of 0.6 mg x kg(-1), 0.9 mg x kg(-1) of Org 9426 or 0.1mg x kg(-1) of vecuronium. Following an intubation dose, patients received maintenance doses of 0.1, 0.15 or 0.2 mg x kg(-1) of Org 9426 or 0.025 mg x kg(-1) of vecuronium. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: The onset times of the 0.6 and 0.9 mg x kg(-1) of Org 9426 groups were 84.6 and 77.1 sec respectively, which showed statistical difference between the onset time of 0.1 mg x kg(-1) of vecuronium, 125.7 sec. The intubation condition was similar among three treatment groups. The clinical durations of 0.6 and 0.9 mg x kg(-1) of Org 9426 and 0.1 mg x kg(-1) of vecuronium were 53.4, 73.4 and 59.9 min, respectively. Clinical duration and spontaneous recovery time of maintenance dose of 0.15 mg x kg(-1) of Org 9426 were similar to those of 0.025 mg x kg(-1) of vecuronium. CONCLUSIONS: Org 9426 showed more rapid onset time than that of vecuronium and similar clinical duration and recovery times to those of vecuronium in Japanese patients.

Androstanols↗

Radiofrequency ablation of metastatic mediastinal lymph nodes during cooling and temperature monitoring of the tracheal mucosa to prevent thermal tracheal damage: initial experience.

Institutional review board approval and patient informed consent were obtained. Radiofrequency ablation in a total of 10 sessions was performed for each mediastinal lymph node metastasis from esophageal cancer that had a mean largest diameter of 2.2 cm +/- 0.6 (standard deviation) in seven male patients (mean age, 59 years). During ablation, cooling and temperature of the tracheal mucosa were monitored in the proper position in eight of the 10 sessions; in the other two sessions, monitoring was not done because of tracheal stenosis (perforation resulted). Three of the four lymph nodes that were 2.0 cm or smaller in largest diameter showed no evidence of local progression for at least 1 year since ablation; all three of the nodes greater than 2.0 cm in largest diameter progressed within 6 months. The 1-year survival rate was 60%; the median survival time was 13 months. Radiofrequency ablation may be effective for local control of small metastatic mediastinal lymph nodes, and cooling and temperature monitoring of the tracheal mucosa in the proper position may prevent thermal tracheal damage.

Adult↗

Increased heme catabolism in critically ill patients: correlation among exhaled carbon monoxide, arterial carboxyhemoglobin, and serum bilirubin IXalpha concentrations.

It has been reported that exhaled carbon monoxide (CO) concentrations and arterial carboxyhemoglobin (CO-Hb) concentration in blood may be increased in critically ill patients. However, there was no study that examined correlation among amount of CO in exhaled air, CO-Hb concentrations in erythrocytes, and bilirubin IXalpha (BR) in serum, i.e., the three major indexes of heme catabolism, within the same subject. Here, we examined CO concentrations in exhaled air, CO-Hb concentrations in arterial blood, and BR levels in serum in 29 critically ill patients. Measurements of exhaled CO, arterial CO-Hb, and serum total BR have been done in the intensive care unit. As control, exhaled CO concentration was also measured in eight healthy volunteers. A median exhaled CO concentration was significantly higher in critically ill patients compared with control. There was significant correlation between CO and CO-Hb and CO and total BR level. We also found CO concentrations correlated with indirect BR but not direct BR. Multivariate linear regression analysis for amount of exhaled CO concentrations also showed significant correlation with CO-Hb and total BR, despite the fact that respiratory variables of study subjects were markedly heterogeneous. We found no correlation among exhaled CO, patients' severity, and degree of inflammation, but we found a strong trend of a higher exhaled CO concentration in survivors than in nonsurvivors. These findings suggest there is an increased heme breakdown in critically ill patients and that exhaled CO concentration, arterial CO-Hb, and serum total BR concentrations may be useful markers in critically ill conditions.

Aged↗

Effects of 7-nitroindazole and N-nitro-l-arginine methyl ester on changes in cerebral blood flow and nitric oxide production preceding development of hyperbaric oxygen-induced seizures in rats.

Hyperbaric oxygen (HBO(2)) exposure induces increases in cerebral blood flow (CBF) and extracellular concentrations of nitric oxide (NO) that precede the appearance of central nervous system toxicity, which may manifest as convulsions. To elucidate the origins of NO production during HBO(2) exposure, we examined the effects of the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole (7-NI), and the non-selective NOS inhibitor, N-nitro-l-arginine methyl ester (l-NAME), on changes in CBF and NO metabolites (NO(x), nitrite and nitrate) using a laser Doppler flow probe and in vivo microdialysis techniques, respectively. Rats were anesthetized, artificially ventilated, and pressurized to 5 atmosphere absolute (ATA) with pure oxygen for 60 min. In rats treated with vehicle, CBF and NO(x) levels in the cortex increased to 201% and 239% of basal levels, respectively, before the onset of electrical discharges, measured by electroencephalogram. The increase in CBF and NO(x) was completely inhibited by 7-NI and l-NAME. Both drugs also inhibited the appearance of electrical discharges for 60 min. Dynamic changes in CBF and NO(x) were not significantly different between 7-NI and l-NAME. These findings suggest that neuronal NOS is the main mediator of NO production associated with increase in CBF leading to the appearance of electrical discharge during HBO(2) exposure.

Animals↗

Prevention of hemorrhagic shock-induced lung injury by heme arginate treatment in rats.

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress, which leads to acute lung injury. Heme oxygenase (HO)-1 (EC 1.14.99.3), the rate-limiting enzyme in heme catabolism, is inducible by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. In this study, we examined expression of HO-1 as well as tissue injuries in the lung, liver, and kidney after HSR in rats. We also pretreated animals with heme arginate (HA), a strong inducer of HO-1, and examined its effect on the HSR-induced lung injury. HO-1 expression significantly increased in the liver and kidney following HSR, while its expression in the lung was very low and unchanged after HSR. In contrast to HO-1 expression, tissue injury and tumor necrosis factor-alpha (TNF-alpha) gene expression was more prominent in the lung compared with those in the liver and kidney. HA pretreatment markedly induced HO-1 in pulmonary epithelial cells, and ameliorated the lung injury induced by HSR as judged by the improvement of histological changes, while it decreased TNF-alpha and inducible nitric oxide synthase gene expression, lung wet weight to dry weight ratio, and myeloperoxidase activity. In contrast, inhibition of HO-1 by tin-mesoporphyrin administration abolished the beneficial effect of HA pretreatment. These findings suggest that tissues with higher HO-1 may be better protected than those with lower HO-1 from oxidative tissue injury induced by HSR. Our findings also indicate that HA pretreatment can significantly suppress the HSR-induced lung injury by virtue of its ability to induce HO-1.

Animals↗

Anesthetic management of a patient with severe dilated cardiomyopathy and an automatic implantable cardioverter-defibrillator (AICD) during total gastrectomy.

We report a case of severe dilated cardiomyopathy with an automatic implantable cardioverter-defibrillator (ICD) undergoing total gastrectomy. During the operation, the defibrillation function of the ICD was suspended and its pacing function was used solely in VOO mode. Electrodes of an external defibrillator were attached on the chest wall, and a pulmonary arterial (PA) catheter with a ventricle pacing port was inserted into the pulmonary artery. Proper perioperative management, including measures that the patient underwent the surgery uneventfully and could attain a rapid and successful discharge from the intensive care unit.

Anesthesia, General↗

Measurement of GABA and glutamate in vivo levels with high sensitivity and frequency.

In the present protocol, we demonstrate a high-performance liquid chromatography (HPLC) system that enables detection of very low amounts of gamma-aminobutyric acid (GABA) (0.03 pmol) and glutamate (0.8 pmol). The HPLC system consists of two pumps, an electrochemical detector, a high-pressure six-way switching valve, a guard column, a microbore column, and a column oven. A microdialysis probe was implanted in the right parietal cortex in rats. Dialysates were collected every 5 min and were split into two equal aliquots for separate analysis of GABA and glutamate. After derivatization with o-phthalaldehyde (OPA), samples were isocratically separated and purified by the guard column. To make the peak of GABA or glutamate appear in an opportune place in a chromatogram, a six-way switching valve was used to control the eluate containing GABA or glutamate to be led to the microbore column and electrochemical detector. By the use of this system, decrease in extracellular concentration of GABA, which precedes the appearance of electrical discharge initiated by hyperbaric oxygen (HBO2) exposure, was detected by microdialysis at the time resolution of 5 min.

Animals↗

The lower intestinal tract-specific induction of heme oxygenase-1 by glutamine protects against endotoxemic intestinal injury.

OBJECTIVE: The aim of the present study was to investigate whether glutamine pretreatment improves intestinal injury in rats with endotoxemia by its heme oxygenase-1 induction in the lower intestinal tract. DESIGN: Randomized, blinded, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Sprague-Dawley male rats, weighing 220-250 g (n = 201). INTERVENTIONS: Rats were treated with glutamine (0.75 g/kg) dissolved in lactated Ringer's solution via the tail vein. Endotoxemia was induced in rats by intraperitoneal injection of lipopolysaccharide (10 mg/kg or 20 mg/kg for survival study). Lipopolysaccharide-treated animals were pretreated with glutamine or lactated Ringer's solution 9 hrs before lipopolysaccharide treatment. Some of the glutamine-pretreated animals further received tin mesoporphyrin (1 micromol/kg), a specific inhibitor of heme oxygenase activity, 1 hr before lipopolysaccharide treatment. MEASUREMENTS AND MAIN RESULTS: Glutamine treatment markedly induced heme oxygenase-1 messenger RNA and protein in the mucosal epithelial cells as well as in the lamina propria cells in the ileum and the colon, whereas its expression in the duodenum and the jejunum was not influenced by the treatment. Glutamine treatment before lipopolysaccharide administration significantly ameliorated lipopolysaccharide-induced mucosal injury, inflammation, and apoptotic cell death in the ileum and the colon, as judged by significant decreases in tumor necrosis factor-alpha gene expression, histologic damage scores, and expression of activated caspase-3 and by an increase in gene expression of Bcl-2. In addition, glutamine treatment markedly decreased lipopolysaccharide-induced mortality. In contrast, treatment with tin mesoporphyrin abolished the beneficial effect of glutamine pretreatment. CONCLUSIONS: Glutamine pretreatment significantly ameliorated intestinal tissue injury of rats following lipopolysaccharide treatment. The same treatment also improved the survival of animals from endotoxemia. The protective effect of glutamine is mediated by its lower intestine-specific induction of heme oxygenase-1, since its inhibition by tin mesoporphyrin completely abolished the beneficial effect of glutamine.

Animals↗