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Biomedical subjects

Naoko Hitosugi

Publications and source records attributed to Naoko Hitosugi.

10 recordsLinked to original sources
PubMed2006

Morphine modulates monocyte-macrophage conversion phase.

Monocyte migration and their activation into the macrophage phenotype play a role in the modulation of tissue injury. We studied the effect of morphine on the monocyte-macrophage conversion phase (MMCP). Phorbol 12-myristate 13-acetate (PMA) activated THP-1 cells and promoted their adhesion to the substrate. Morphine inhibited PMA-induced MMCP. However, opiate receptor antagonists attenuated this effect of morphine. Interestingly, PMA as well as morphine-stimulated superoxide production by monocytes. Superoxide dismutase (SOD) not only inhibited PMA-mediated MMCP but also attenuated the inhibitory effect of morphine. PMA not only enhanced adhesion of monocytes to a filter but also promoted their migration. These findings suggest that the PMA-induced macrophage phenotype conversion may be accelerating their migration; whereas, morphine may be preventing the migration of monocytes by inhibiting MMCP.

Cell Adhesion↗
PubMed2006

[A case of craniofacial injury by javelin].

We report a case of 16-year-old woman with craniofacial impalement injury by javelin (used by athletic sports) thrown from a distance of 30 meters. When the patient was admitted to the emergency department, the javelin had been in the orbita, and the patient was assessed by trauma team including an anesthesiologist. The patient was alert and complained of severe pain. Head CT and X-ray indicated the javelin had entered though the orbita into the maxillary sinus. Sphenoidal sinus was also partly destroyed by the impact. Anesthesia was soon induced in the emergency room to release the patient from the unbearable pain. To avoid tension cephalus, awake fiberscopic endtracheal intubation was performed. Anesthesia was maintained with propofol, vecuronium and fentanyl before transporting the patient to an operating room. The javelin and her head were strongly fixed with fiber cast to prevent from moving while she was transported to the operating room. The javelin was successfully removed during the operation. The fractures were fixed, and lacerations were sutured. The most important principle of management with craniofacial impalement injury is that the impaling object should remain in situ while patient is rapidly transported to an operating room, since it could extend tissue injury, and have a tamponade-like effect on damaged vascular structure.

Adolescent↗
PubMed2004

Morphine-induced macrophage apoptosis: oxidative stress and strategies for modulation.

Occurrence of macrophage apoptosis has been implicated for the altered immune function found in an opiate milieu. In the present study, we evaluated the role of oxidative stress in morphine-induced macrophage apoptosis. Morphine promoted the apoptosis of macrophages. This effect of morphine was associated with the production of superoxide and nitric oxide (NO). Antioxidants provided protection against morphine-induced macrophage injury. In addition, diphenyleneiodonium chloride, an inhibitor of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, attenuated the proapoptotic effect of morphine. Antitransforming growth factor-beta (anti-TGF-beta) antibody and propranolol (an inhibitor of the phospholipase D pathway) inhibited morphine-induced superoxide generation as well as apoptosis. N'-Tetraacetic acid tetra (acetoxymethyl) ester, a calcium-chelating agent, inhibited morphine-induced apoptosis, whereas thapsigargin (a calcium agonist) stimulated macrophage apoptosis under basal as well as morphine-stimulated states. These studies suggest that morphine-induced macrophage apoptosis is mediated through downstream signaling involving TGF-beta and NO production. Moreover, there is NADPH oxidation activation involving phospholipase D and Ca(2+), leading to the generation of superoxide. In in vivo studies, administration of N-acetyl cysteine and preinduction of heme oxygenase activity and epoetin alpha prevented morphine-induced peritoneal macrophage apoptosis, thus further confirming the role of oxidative stress in morphine-induced macrophage apoptosis.

Animals↗
PubMed2003

Comparative analysis of apoptosis-inducing activity of codeine and codeinone.

BACKGROUND: There are relatively few studies about the antiproliferative effects of codeine-related compounds on human cancer cell lines, compared with those of morphine-related compounds. The authors previously found that codeinone, an oxidation metabolite of codeine, among 10 opioids, showed the highest cytotoxic activity (DNA fragmentation-inducing activity) against human promyelocytic leukemic cell lines (HL-60). This was counteracted by an antioxidant, N-acetyl-L-cysteine (NAC). These findings prompted us to perform a more detailed study of apoptosis induction after codeinone treatment. METHODS: Apoptosis was induced by treating HL-60 cells for 1-6 h with codeine or codeinone. DNA fragmentation was assessed by both agarose gel electrophoresis and fluorometric determination of the fragmented DNA after staining with diamidinophenylindole (DAPI). The appearance of apoptotic cells was monitored by microscopic observation after staining with Hoechst (H)-33342, and fluorescence activated cell sorter (FACS) after staining with Annexin. The release of cytochrome c and cytochrome oxidase from mitochondria and activation of caspase 3 were monitored by Western blot analysis. Intracellular caspase 3-like activity was confirmed by FACS, using cell permeable substrate. Mitochondrial manganese-containing superoxide dismutase (MnSOD) activity and mRNA expression were assayed by activity staining after separation on the polyacrylamide gel electrophoresis, and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: Codeinone induced internucleosomal DNA fragmentation and production of Annexin-positive apoptotic cells more potently than codeine in HL-60 cells. Codeinone stimulated the release of both cytochrome c and cytochrome oxidase, and cleavage of procaspase 3 without significant changes in both the activity and expression of MnSOD. CONCLUSIONS: Codeinone was found to possess both apoptosis and necrosis-inducing activity, in addition to the reported antinociceptive activity, further substantiating its antitumor potential.

Analgesics, Opioid↗
PubMed2003

[Propofol depresses the activity of hypoglossal nerve more than that of phrenic nerve in rabbits].

BACKGROUND: Respiratory depression, such as obstruction of upper airway and inadequate ventilation, often appears during sedation and anesthesia. We studied the effect of propofol on the upper airway patency and the inspiratory drives. METHODS: Experiments were performed on the adult rabbits vagotomized, paralyzed and ventilated with nitrous oxide-oxygen-sevoflurane. We evaluated and compared depressant effect of propofol on the peak amplitude of both hypoglossal nerve (AMP-HG) and phrenic nerve (AMP-PH) activities, inspiratory time (Ti), expiratory time (Te) and respiratory cycle (Tc). RESULTS: Bolus injections of propofol transiently reduced AMP-HG more than AMP-PH (18 and 70% of control, respectively). But AMPs returned to the control levels about 10-15 min after the injection. For 0.5 mg.kg-1.min-1 continuous infusion, propofol soon began to reduce both AMPs. AMP-HG was reduced to about 20% and AMP-PH to 60% of control. Administration of propofol with 1.0 mg.kg-1.min-1 caused more reduction in AMPs with respiratory slowing and AMP-HG disappeared in some animals. CONCLUSION: During the sedation with low dose of propofol, we need to pay attention to potential upper airway obstruction. In addition to the above, high doses of propofol could reduce spontaneous inspiratory drive, and we need to keep both upper airway patency and sufficient ventilation.

Anesthetics, Intravenous↗
PubMedDate not supplied

Induction of cell death by pro-oxidant action of Moxa smoke.

Moxa smoke induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in other cell lines. The cytotoxic activity of Moxa smoke was significantly reduced by a popular antioxidant, N-acetyl-L-cysteine (NAC). Moxa smoke showed oxidation potential (measured by NO monitor) and produced carbon radical (measured by ESR spectroscopy). The addition of NAC significantly reduced both the oxidation potential and carbon radical intensity of Moxa smoke. Activity staining of polyacryamide gel electrophoresis of MnSOD revealed the possible modification of the conformation and/or activity of this enzyme at an early stage of HL-60 cell death. These data suggest that Moxa smoke induces cytotoxicity by its pro-oxidant action.

Acetylcysteine↗
PubMedDate not supplied

Partial purification of cytotoxic substances from moxa extract.

The major cytotoxic activity of Moxa was extracted with CH2Cl2 and partially purified by three cycles of silica gel column chromatography. The active fractions showed higher cytotoxicity against six human tumor cell lines (two oral squamous cell carcinoma, one salivary gland tumor, one melanoma, two leukemia) than three normal oral human cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell). All fractions failed to protect the cells from the cytopathic effect induced by HIV infection. ESR spectroscopy showed that all fractions produced little or no radical under alkaline conditions, while showing much lower O2- scavenging activity, generated by hypoxanthine-xanthine oxidase reaction, than antioxidants and polyphenols. Active fractions induced DNA fragmentation in HL-60 cells, but failed to modify the mobility and activity of mitochondrial Mn-containing superoxide dismutase (MnSOD), in contrast to Moxa smoke. These data suggest that the active principles in the Moxa extract might be different from that in Moxa smoke, which produced carbon radical and modified MnSOD mobility and activity.

Anti-HIV Agents↗
PubMedDate not supplied

Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines.

We have investigated whether morphine and codeine, potent analgesic compounds most commonly used as cancer pain relievers, show tumor-specific cytotoxic activity and whether they can induce apoptosis or necrosis by monitoring the stainability with Annexin V and propidium iodide with fluorescence-activated cell sorter. Both opioids showed higher cytotoxic activity against three human tumor cell lines (lung carcinoma A549, mammary gland carcinoma MCF7, promyelocytic leukemia HL-60) than against three normal human cells (periodontal ligament fibroblast HPLF, gingival fibroblast HGF, pulp cell HPC). Morphine produced the major part of the apoptotic cell populations and the minor part of the necrotic cell populations in A549 and MCF7 cells, more effectively than codeine. In addition, morphine increased the activity of mitochondrial Mn-containing superoxide dismutase (MnSOD) in HL-60 cells, but decreased the MnSOD activity in A549 and MCF7 cells. The apoptosis-inducing activity of opioids may provide new strategies for the treatment and prevention of cancer.

Analgesics, Opioid↗
PubMedDate not supplied

Analysis of apoptosis signaling pathway in human cancer cells by codeinone, a synthetic derivative of codeine.

We have recently found that codeinone, an oxidation metabolite of codeine, induced apoptosis, characterized by internucleosomal DNA fragmentation and mitochondrial cytochrome c release in HL-60 human promyelocytic leukemic cell lines, most effectively among 10 opioids. These findings prompted us to investigate whether codeinone induces apoptosis in other human cancer cells and possible changes in mitochondrial enzyme. FACS analysis demonstrated that codeinone induced the production of ANNEXIN-positive apoptotic cells in three different human cancer cells (HL-60, MCF7, A549). The apoptotic cells were visualized by microscopical observation after staining with Hoechst (H)-33342. Fluorometric assay showed that codeinone time-dependently activated caspase 3 and caspase 9, but not caspase 8, suggesting the activation of intrinsic apoptotic signaling pathway via mitochondria. Western blot analysis demonstrated that codeinone enhanced the Pro-apoptotic Bax protein expression, but reduced the anti-apoptotic Bcl-2 protein expression. Codeinone did not significantly change the manganese superoxide dismutase (MnSOD) activity nor its mRNA expression. This apoptosis-inducing activity, in conjunction with antinociceptive activity, further substantiated the antitumor potential of codeinone.

Apoptosis↗