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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 1,387 records · Page 77Linked to original sources

Radical intensity and carcinogenic activity of benz[c]acridines.

Among 13 benz[c]acridines, six 7-methyl-substituted compounds (7-methylbenz[c]acridine, 7,9-dimethylbenz[c]acridine, 7,10-dimethylbenz[c]acridine, 7,11-dimethylbenz[c]acridine, 7,9,10-trimethylbenz[c]acridine, 7,9,11-trimethylbenz[c]acridine) were carcinogenic, while the other seven compounds (benz[c] acridine, 8-methylbenz[c]acridine, 9-methylbenz[c]acridine, 10-methylbenz[c]acridine, 11-methylbenz[c]acridine, 5,7-dimethylbenz[c]acridine, cis-5,6-dihydroxy-5,6-dihydrobenz[c]acridine) were inactive. Using both McLachlan-Hückel molecular orbital (McLachlan-HMO) and HMO methods, all the carcinogenic compounds were shown to have the elevated pi-spin density at 12th nitrogen atom of their molecules, as compared with noncarcinogenic compounds. Electron spin resonance (ESR) spectroscopy, however, revealed that both carcinogenic and noncarcinogenic compounds produced no detectable amounts of radical. This is in contrast to ascorbates, gallates and benzo[a]phenothiazines, which induced apoptosis by radical mediated mechanism(s). Amino acid analysis demonstrated that methionine oxidation is not involved in the induction of carcinogenic activity by benz[c]acridines.

Acridines↗

A clinical comparison between Technegas SPECT, CT, and pulmonary function tests in patients with emphysema.

Pulmonary emphysema can be easily diagnosed by X-ray CT (CT) as low attenuation areas. Recently 99mTc Technegas has been used for ventilation scintigraphy. The present study was undertaken to assess the usefulness of SPECT images using Technegas scintigraphy and CT, as compared with pulmonary function tests in patients with pulmonary emphysema. Fifteen patients were examined. We classified and defined the score according to the findings of Technegas scintigraphy (Technegas) images into four grades, from Score 0 to Score 3, and those of CT into five grades, from Score 0 to Score 4, both from normal to severe. The right lung was divided into nine segments, and the left into eight. To obtain the average of the entire lung, the total score from both lungs was divided by 17. These average scores in for SPECT and CT were compared with the results of pulmonary function tests. The average score of Technegas correlated well with % forced expiratory volume in one second (%FEV1.0) (r = 0.87), and forced expiratory volume in one second % (FEV1.0%) (r = 0.83). These results were better than those provided by CT. The average scores of the upper and lower lung fields were also calculated. The score in the upper lung field was higher than that in the lower field. Technegas can assess ventilation impairment in pulmonary emphysema more easily than CT, especially in the upper lung field.

Administration, Inhalation↗

Chelating effect of human serum proteins on metal-catalyzed ascorbate radical generation.

Purified human serum albumin and immunoglobulin G (IgG) were investigated for their metal-chelating activity, using ESR spectroscopy. Both copper (Cu2+) and iron ions (Fe3+) enhanced the radical intensity of both sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA). Albumin significantly reduced the stimulation effect of copper, but not that of iron. On the other hand, IgG effectively reduced the radical intensity of iron, without affecting that of copper. The present study demonstrates the specific chelating action of these serum proteins, suggesting their possible preventive effects on metal-catalyzed pathogenic diseases.

Adult↗

Correlation between structure and diverse biological activities of "half-mustard type" phenothiazines.

The structure and activity relationship of fifteen "half-mustard type" phenothiazines and related compounds were investigated. These compounds did not show any direct bactericidal activity, possibly due to the lack of radical generation activity. Pretreatment with phenothiazines significantly reduced the lethality of Escherichia coli GN2411 infection, possibly due to activation of the host defense mechanism. Higher concentrations of these compounds showed cytotoxic activity against several cultured tumor cell lines. However, no clear-cut relationship was established between biological activity and two dipole moments (mu g, mu e).

Anti-Bacterial Agents↗

Comparative study of the antitumor action between sodium 5,6-benzylidene-L-ascorbate and sodium ascorbate (minireview).

This review summarizes our comparative study of the antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA) and sodium ascorbate. Both SBA and ascorbate produced ascorbate radicals during decomposition, elevated oxidation potential and oxidized methionine to methionine sulfoxide, in the regular culture medium. They induced apoptotic cell death (characterized by internucleosomal DNA fragmentation) in human myelogenous leukemic cell lines, but killed most of other tumor cell lines by necrosis without induction of internucleosomal DNA fragmentation. The cytotoxic activity of SBA and ascorbate was significantly enhanced in the presence of copper and the stimulation effect of copper was reduced by a heavy metal antagonist. However, the cytotoxic activity of SBA was only slightly modified by iron, cysteine analog or catalase, in contrast to ascorbate, which was highly sensitive to all these agents. Furthermore, intravenous administration of SBA induced degeneration in chemically-induced hepatocellular carcinoma whereas ascorbate was inactive. These data suggest the differential mode of antitumor action between these two compounds.

Animals↗

Effect of physiological fluids on radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate.

The effect of various physiological fluids on the radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA) was investigated using ESR spectroscopy. Blood from various animals did not significantly affect the radical intensity of both ascorbates, whereas the corresponding plasma fractions significantly enhanced the radical intensity. This suggests that some populations of blood cells might modify the interaction between plasma components and ascorbates. Saliva contained labile substance(s) which effectively reduced the ascorbate radical intensity. HPLC demonstrated the presence of endogenous ascorbate in rat liver and brain homogenates. When sodium ascorbate or SBA was incubated with any of these homogenates, their radical intensity was synergistically enhanced, but abruptly declined without any apparent ascorbate degradation. Incubation with homogenates elevated the radical intensity of SBA up to the level significantly higher than that of sodium ascorbate. The present data suggest that antitumor action of SBA might be mediated via the accelerated production of ascorbate radical in the target organ.

Animals↗

Effect of chemotherapy on Tl-201 tumor uptake: experimental study.

The purpose of this study was to investigate the correlation between histopathological changes and 201Tl accumulation in tumor following chemotherapy in the evaluation of chemotherapeutic effect. Walker 256 carcinoma implanted in the right thighs of Wistar rats was treated by the intravenous injection of adriamycin (ADR). 201Tl scintigraphy was performed before and 12, 24, 72, and 96 hours after chemotherapy. The count ratio of tumor to normal muscle (T/N ratio) was measured by gamma camera. Tumor growth rate was measured and histopathological examination of the tumor after 201Tl scintigraphy was performed. The tumors of all rats disappeared within 2 weeks after chemotherapy, but the T/N ratio did not change. Histopathological findings showed a decrement of tumor cells, small necrotic regions, and remarkable lymphocyte infiltration in the tumor bed in the healing stage. After 201Tl injection, lymphocytes isolated from tumor tissue showed noted 201Tl accumulation. These results suggest that the T/N ratio did not decrease after ADR chemotherapy because of the accumulation of 201Tl in lymphocytes. We concluded that the use of 201Tl may underestimate the therapeutic effect of ADR.

Animals↗

Biological activity of 6,12-dihydro-1-benzopyrano[3,4-b][1,4]benzothiazin-6-ones.

Ten 6,12-dihydro-1-benzopyrano[3,4-b][1,4]benzothiazin-6-ones (Coumarins)[1-7] and related coumarins [8-10] were compared for their cytotoxic activity and radical intensity. Among these compounds, compound 7 showed highest cytotoxic activity against human promyelocytic leukemic HL-60 cells. Compound 7 produced radicals under alkaline conditions, and showed the lowest pi-spin density at S-atom of the molecule, suggesting the delocalization of pi-spin density. These data suggest the possible relation between radical intensity and biological activity.

Antineoplastic Agents↗

Interaction between eugenol-related compounds and radicals.

The radical modulating activity of 2-methoxy-4-(2-propenyl)phenol (eugenol), 2-t-butyl-4-methoxy-phenol (BHA), and their dimers (bis-eugenol, bis-BHA) was investigated, using ESR spectroscopy. Eugenol produced radicals in alkaline solutions, and enhanced the radical intensity of both sodium-L-ascorbate and sodium 5,6-benzylidene-L-ascorbate. BHA has similar, but slightly lower activity, and their dimers were inactive. Their ability to scavenge the superoxide anion (O2-), generated by hypoxanthine and xanthine oxidase reaction, was in the order of eugenol > bis-eugenol > BHA > bis-BHA. The relative radical intensity among these compounds was paralleled by their cytotoxic activity. The present study demonstrates that eugenol and BHA were very reactive with radicals and their reactivity was considerably reduced by dimerization. The applicability of the dimerized eugenol in dentistry was discussed.

Ascorbic Acid↗

Development of a 3D CT-scanner using a cone beam and video-fluoroscopic system.

We describe the design and implementation of a system that acquires three-dimensional (3D) data of high-contrast objects such as bone, lung, and blood vessels (enhanced by contrast agent). This 3D computed tomography (CT) system is based on a cone beam and video-fluoroscopic system and yields data that is amenable to 3D image processing. An X-ray tube and a large area two-dimensional detector were mounted on a single frame and rotated around objects in 12 seconds. The large area detector consisted of a fluorescent plate and a charge coupled device (CCD) video camera. While the X-ray tube was rotated around the object, a pulsed X-ray was generated (30 pulses per second) and 360 projected images were collected in a 12-second scan. A 256 x 256 x 256 matrix image was reconstructed using a high-speed parallel processor. Reconstruction required approximately 6 minutes. Two volunteers underwent scans of the head or chest. High-contrast objects such as bronchial, vascular, and mediastinal structures in the thorax, or bones and air cavities in the head were delineated in a "real" 3D format. Our 3D CT-scanner appears to produce data useful for clinical imaging and 3D image processing.

Equipment Design↗

Radical scavenging activity of Acer nikoense Maxim. extract.

The effect of hot water and alkaline extracts of Acer nikoense Maxim. on the radical intensity of sodium ascorbate, superoxide anion (O2-)(produced by hypoxanthine-xanthine oxidase reaction) and hydroxyl radical (-OH)(generated by Fenton reaction) was investigated using ESR spectroscopy. All these extracts produced radical(s) under alkaline conditions and enhanced the radical intensity of sodium ascorbate. Among these fractions, Fr. I showed the highest stimulation effect, which coincided with its higher degradation rate and capacity to enhance the cytotoxic activity of ascorbate. These fractions also dose-dependently reduced the radical intensity of O2- and -OH. The present study demonstrates that Acer nikoense Maxim. extracts potentiate both radical intensity and apoptosis-inducing activity of ascorbate.

Dose-Response Relationship, Drug↗

Relationship between radical intensity and cytotoxic activity of dopamine-related compounds.

Millimolar concentrations of dopamine (DA), norepinephrine (NE), and 3,4-dihydroxyphenylacetic acid (DOPAC) were cytotoxic to human promyelocytic leukemiC HL-60 cells. However, their metabolites (3,4-dihydroxymandelic acid (DOMA), 3-methoxytyramine (MT), normetanephrine (NMN)) and six synthetic derivatives (which have two OCH3 groups replacing two OH groups on catechol backbone) displayed much lower cytotoxic activity. Three active compounds, but not other less potent compounds, produced radicals under alkaline conditions. All active compounds significantly enhanced the decay of ascorbic acid endogenously present in rat brain homogenate, whereas all synthetic derivatives were inactive. Ascorbic acid induced apoptotic cell death in HL-60 cells and the apoptosis induction was significantly reduced by simultaneous addition of (DA). The cytotoxic activity of (DA) was also neutralized by ascorbic acid. These data suggest the possible interaction between (DA) and ascorbic acid.

Animals↗

Effect of antioxidants on radical intensity and cytotoxic activity of eugenol.

The effect of antioxidants on the radical intensity of 2-methoxy-4-(2-propenyl)phenol (eugenol) was investigated, using ESR spectroscopy. Eugenol produced radicals in alkaline solutions, with an optimum pH of 9.5. The intensity of eugenol radical was a positive function of its concentration, reaching a plateau level at 100 mM. The eugenol radical was rapidly diminished under alkaline conditions. Water-soluble antioxidants, such as cysteine, N-acetyl-L-cysteine, glutathione and sodium ascorbate, completely scavenged the eugenol radical. Gallic acid at lower doses significantly, but not completely, scavenged the eugenol radical. Among water-insoluble antioxidants, terpenes (beta-carotene, retinol, lycopene) effectively scavenged the eugenol radical, whereas phenolic compounds (alpha-tocopherol, Trolox) were inactive. Millimolar concentrations of eugenol were cytotoxic against human salivary gland and oral squamous carcinoma cell lines. Addition of sodium ascorbate or beta-carotene reproducibly reduced the cytotoxic activity of eugenol. The applicability of the antioxidants in dentistry was discussed.

Acetylcysteine↗

Role of hydrogen peroxide for cell death induction by sodium 5,6-benzylidene-L-ascorbate.

The role of hydrogen peroxide in the induction of cell death in human promyelocytic leukemic HL-60 cells by sodium 5,6-benzylidene-L-ascorbate (SBA) and its degradation product, ascorbic acid, was investigated. Millimolar concentrations of these compounds induced cell death, characterized by cell shrinkage, nuclear and internucleosomal DNA fragmentation, disappearance of microvilli and condensation of chromatin near the nuclear membrane. Catalase significantly reduced the cytotoxic activity of these compounds, whereas superoxide dismutase, nitric oxide (NO) generator, NO scavenger and NO synthase inhibitor were inactive, suggesting the possible role of H2O2. Determination of H2O2 with the peroxyoxalate chemiluminescence demonstrated that sodium ascorbate and SBA produced H2O2 in amounts necessary for cell death induction.

Antineoplastic Agents↗

Role of hydrogen peroxide in antitumor activity induction by sodium 5,6-benzylidene-L-ascorbate.

Role of hydrogen peroxide (H2O2) in the induction of antitumor activity against chemically-induced rat hepatocellular carcinoma by sodium 5,6-benzylidene-L-ascorbate (SBA) was investigated. ESR spectroscopy demonstrated that rat liver homogenate of cancerous tissue significantly enhanced the radical intensity of SBA more potently than that of precancerous or normal tissue. The peroxyoxalate chemiluminescence method demonstrated that SBA significantly enhanced the production of H2O2-derived chemiluminescence intensity in the liver homogenates, and the effect of SBA was greater in cancerous tissue than in precancerous or normal tissue. Addition of ascorbic acid, a degradation product of SBA, showed similar but slightly weaker stimulation effects. These data suggest that antitumor activity of SBA in vivo might, at least in part, be due to H2O2 production.

Animals↗

Enhancement of radical intensity and cytotoxic activity of ascorbate by Crataegus cuneata Sieb et. Zucc. extracts.

The radical modulation activity of hot water and NaOH extracts of the thorn apple of Crataegus Cuneata Sieb. et. Zucc. was investigated, using ESR spectroscopy. The radical intensity of sodium ascorbate was slightly reduced at lower concentrations of the extracts, but it was synergistically enhanced at higher concentrations. Higher concentrations of the extracts also synergistically stimulated the cytotoxic action of sodium ascorbate against human oral squamous carcinoma and salivary gland tumor cell lines. All these extracts effectively scavenged superoxide anion and hydroxyl radical, produced by hypoxanthine-xanthine oxidase and Fenton reaction, respectively, and their activity was comparable with that of lignins prepared by the same procedure from other plants. These data further supports the medicinal efficacy of plant extracts.

Antineoplastic Agents↗

Radical modulation activity of lignins from a mangrove plant, Ceriops decandra (Griff.) Ding Hou.

The radical modulation activity of hot water and alkaline extracts from leaf of Ceriops decandra, a mangrove plant, was investigated using ESR spectroscopy. IR and NMR analyses demonstrate that the leaf extracts have a lignin-like polyphenolic structure. All these extracts produced radical(s) under alkaline conditions. The radical intensity of sodium ascorbate was slightly reduced at lower concentrations of the extracts, but it was synergistically enhanced at higher concentrations. All the extracts effectively scavenged superoxide anion, produced by hypoxanthine-xanthine oxidase reaction. Pretreatment of mice with the extracts significantly protected them from the lethal infection by E. coli. Similar activity was found in lignins from pine seed shell of Pinus parviflora Sieb. et Zucc. These data further support the medicinal efficacy of plant extracts.

Animals↗

Radical intensity and cytotoxic activity of curcumin and gallic acid.

Natural phenolic compounds, curcumin and gallic acid, were compared for their cytotoxic activity in relation to their radical modulating activity. These two compounds induced apoptotic cell death in human promyelocytic leukemic HL-60 cells and human oral squamous carcinoma HSC-4 cells. Curcumin was more cytotoxic than gallic acid. Catalase reduced significantly the cytotoxic activity of gallic acid, but not that of curcumin. ESR spectroscopy demonstrated that curcumin produced radicals under alkaline conditions, scavenged the superoxide anion radical, and enhanced the radical intensity of sodium ascorbate at higher concentrations. As compared with curcumin, gallic acid produced higher amounts of radicals and more efficiently scavenged the superoxide anion radical. Gallic acid reduced the radical intensity of sodium ascorbate, suggesting a possible interaction between these two compounds. These data suggest that curcumin and gallic acid induce apoptosis by different mechanisms.

Antineoplastic Agents↗