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1.
Int J Sports Med ; 35(10): 871-3, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24604353

ABSTRACT

The influence of sports drinks and mouthguards on the pH level of tooth surface was examined. A custom-made mouthguard was fabricated for each subject. The pH level was measured by electric pH meter with sensitivity of 0.01 up to 30 min. Sports drinks (pH=3.75) containing 9.4% sugar were used in this study. Measurements were performed on a cohort of 23 female subjects without a mouthguard (control), wearing a mouthguard only (MG), wearing a mouthguard after 30 ml sports drink intake (SD+MG), wearing a mouthguard during a 5-min jogging exercise (MG+EX) and wearing a mouthguard during jogging after sports drink intake (SD+MG+EX). For 7 male subjects, the same measurements were performed while a sports drink was taken over the mouthguard (MG+SD, MD+EX+SD). MG showed statistically higher pH level than control (p<0.05). SD+MG exhibited a significant decrease in pH level, and SD+MG+EX exhibited even below the critical level of pH 5.5 in some subjects. When sports drinks were taken over the mouthguard, no significant differences in pH level were observed among the different conditions.Within the limitations of this study, it was suggested that wearing a mouthguard during exercise is in itself not a possible risk factor for dental caries, while wearing a mouthguard after consuming sports drinks is.


Subject(s)
Beverages , Mouth Protectors , Sports Equipment , Tooth/chemistry , Beverages/adverse effects , Dental Caries/etiology , Equipment Design , Exercise , Female , Humans , Hydrogen-Ion Concentration , Male , Mouth Protectors/adverse effects , Risk Factors , Surface Properties
2.
Cell Death Dis ; 4: e679, 2013 Jun 20.
Article in English | MEDLINE | ID: mdl-23788036

ABSTRACT

Cytokines such as interleukins are known to be involved in the development of neuropathic pain through activation of neuroglia. However, the role of chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, in the nociceptive transmission remains unclear. We found that CCL-1 was upregulated in the spinal dorsal horn after partial sciatic nerve ligation. Therefore, we examined actions of recombinant CCL-1 on behavioural pain score, synaptic transmission, glial cell function and cytokine production in the spinal dorsal horn. Here we show that CCL-1 is one of the key mediators involved in the development of neuropathic pain. Expression of CCL-1 mRNA was mainly detected in the ipsilateral dorsal root ganglion, and the expression of specific CCL-1 receptor CCR-8 was upregulated in the superficial dorsal horn. Increased expression of CCR-8 was observed not only in neurons but also in microglia and astrocytes in the ipsilateral side. Recombinant CCL-1 injected intrathecally (i.t.) to naive mice induced allodynia, which was prevented by the supplemental addition of N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. Patch-clamp recordings from spinal cord slices revealed that application of CCL-1 transiently enhanced excitatory synaptic transmission in the substantia gelatinosa (lamina II). In the long term, i.t. injection of CCL-1 induced phosphorylation of NMDA receptor subunit, NR1 and NR2B, in the spinal cord. Injection of CCL-1 also upregulated mRNA level of glial cell markers and proinflammatory cytokines (IL-1ß, TNF-α and IL-6). The tactile allodynia induced by nerve ligation was attenuated by prophylactic and chronic administration of neutralizing antibody against CCL-1 and by knocking down of CCR-8. Our results indicate that CCL-1 is one of the key molecules in pathogenesis, and CCL-1/CCR-8 signaling system can be a potential target for drug development in the treatment for neuropathic pain.


Subject(s)
Chemokine CCL1/physiology , Neuralgia/metabolism , Spinal Cord/physiopathology , Analgesics/administration & dosage , Animals , Cells, Cultured , Chemokine CCL1/antagonists & inhibitors , Dizocilpine Maleate/administration & dosage , Ganglia, Spinal/metabolism , Gene Expression , Gene Knockdown Techniques , Glutamic Acid , Hyperalgesia/drug therapy , Injections, Spinal , Male , Mice , Mice, Transgenic , Neuralgia/drug therapy , Neuroglia/metabolism , Nociception , Peripheral Nerve Injuries/drug therapy , Peripheral Nerve Injuries/metabolism , Phosphorylation , Protein Processing, Post-Translational , RNA, Small Interfering/genetics , Receptors, CCR8/genetics , Receptors, CCR8/metabolism , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Spinal Cord/metabolism
3.
Dermatology ; 204(2): 118-23, 2002.
Article in English | MEDLINE | ID: mdl-11937736

ABSTRACT

BACKGROUND: The development of sebocytes and lipogenesis are known to be dependent on androgens. However, it is not fully understood whether growth factors are involved in the regulation of cell proliferation and lipid formation in sebaceous glands. OBJECTIVE: This study was designed to evaluate the effect of growth factors such as epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), basic fibroblast growth factor (bFGF) and keratinocyte growth factor (KGF) on cell proliferation and lipogenesis in cultured hamster sebocytes. METHODS: Cell proliferation and intracellular lipid accumulation in these hamster sebocytes treated with growth factors were examined. RESULTS: EGF, TGF-alpha and bFGF augmented the proliferation of hamster sebocytes for 8 days in a time- and dose-dependent manner. However, KGF had no effect on their proliferation. Moreover, the accumulation of intracellular lipids consisting mainly of triglycerides was suppressed in EGF-, TGF-alpha-, bFGF- and KGF-treated hamster sebocytes. CONCLUSION: EGF, TGF-alpha and bFGF, but not KGF, have mitogenic activity on hamster sebocytes, and all these growth factors act as antilipogenic factors. Moreover, it is likely that the formation of intracellular lipid droplets is independent of cell proliferation in hamster sebocytes.


Subject(s)
Growth Substances/pharmacology , Lipid Metabolism , Sebaceous Glands/drug effects , Animals , Cell Culture Techniques , Cell Physiological Phenomena , Cricetinae , Epidermal Growth Factor/pharmacology , Fibroblast Growth Factor 2/pharmacology , Fibroblast Growth Factor 7 , Fibroblast Growth Factors/pharmacology , Male , Sebaceous Glands/cytology , Sebaceous Glands/metabolism , Transforming Growth Factor alpha/pharmacology
4.
Phytother Res ; 15(8): 681-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11746860

ABSTRACT

In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Immunosuppressive Agents/pharmacology , Intercellular Adhesion Molecule-1/drug effects , Medicine, Traditional , Phytotherapy , Plant Extracts/pharmacology , Vascular Cell Adhesion Molecule-1/drug effects , Animals , Antibodies, Monoclonal , Endothelium/drug effects , Humans , Malaysia , Pyrones/pharmacology , Rats , Tumor Cells, Cultured/drug effects
5.
J Invest Dermatol ; 117(4): 965-70, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11676839

ABSTRACT

We have previously reported the establishment of a culture system of hamster auricular sebocytes. Although their morphologic and biochemical properties are very similar to those of human sebocytes, the regulation of lipogenesis is not clear. Therefore, we investigated the effect of epidermal growth factor, all-trans retinoic acid, 1alpha,25-dihydroxyvitamin D3, and androgens such as testosterone and 5alpha-dihydrotestosterone on lipogenesis in cultured hamster sebocytes. Intracellular lipid droplets detected with Oil-Red-O staining were observed in 5 d cultures and increased in a time-dependent manner; 40.7% +/- 1.11% of 2 wk cultured cells tested lipid-positive by flow cytometric analysis. When the hamster sebocytes were cultured in the presence of epidermal growth factor, all-trans retinoic acid, or 1alpha,25-dihydroxyvitamin D3, the intracellular lipid droplets were diminished by all-trans retinoic acid and epidermal growth factor, and slightly by 1alpha,25-dihydroxyvitamin D3. The intracellular lipid droplets consisted mainly of triglycerides (71.8%) and, as minor components, cholesterol (18.0%), wax esters (3.6%), and free fatty acids (6.6%). Epidermal growth factor and all-trans retinoic acid decreased the intracellular accumulation of triglycerides (92.6% and 96.1% inhibition, respectively) and free fatty acids (54.3% and 62.6% inhibition, respectively) in the sebocytes. In addition, 1alpha,25-dihydroxyvitamin D3 decreased the triglyceride level (34.3% inhibition), but augmented the accumulation of wax esters (30% increase). There was no difference in the level of cholesterol as a result of these treatments, however. In contrast, 5alpha-dihydrotestosterone augmented the formation of intracellular lipid droplets along with an increase in the accumulation of triglycerides in hamster sebocytes. Our findings that regulation of lipogenesis by all-trans retinoic acid and androgen in hamster sebocytes is identical to regulation in humans suggest that hamster sebocytes are useful for the elucidation of sebaceous function at the cellular level. Furthermore, this is the first evidence that epidermal growth factor and 1alpha,25-dihydroxyvitamin D3 may act as suppressors in the regulation of lipogenesis in hamster sebocytes in vitro.


Subject(s)
Calcitriol/pharmacology , Epidermal Growth Factor/pharmacology , Lipids/antagonists & inhibitors , Sebaceous Glands/drug effects , Sebaceous Glands/metabolism , Animals , Cells, Cultured , Cricetinae , Dihydrotestosterone , Lipids/biosynthesis , Lipids/chemistry , Male , Mesocricetus , Sebaceous Glands/cytology , Tretinoin/pharmacology
6.
J Agric Food Chem ; 49(8): 3965-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11513696

ABSTRACT

The structure of a new carotenoid, isolated from the fruits of the red tomato-shaped paprika Capsicum annuum L., was elucidated to be (3S,5R,6S,5'R)-3,6-epoxy-5,6-dihydro-5-hydroxy-beta,kappa-carotene-3',6'-dione by spectroscopic analyses, including fast atom bombardment collision-induced dissociation-mass spectrometry/mass spectrometry (FAB CID-MS/MS) and was designated capsanthone 3,6-epoxide. Capsanthone 3,6-epoxide is assumed to be an oxidative metabolite of capsanthin 3,6-epoxide in paprika.


Subject(s)
Capsicum/chemistry , Carotenoids/chemistry , Plants, Medicinal , Carotenoids/analysis , Carotenoids/isolation & purification , Gas Chromatography-Mass Spectrometry , Spectrometry, Mass, Fast Atom Bombardment
7.
Quintessence Int ; 32(7): 561-70, 2001.
Article in English | MEDLINE | ID: mdl-11495568

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the in vivo remineralization of the possible non-resin infiltrated hybridoid layer between the hybrid layer and the subjacent dentin substrate using nanoindentation, energy dispersive x-ray spectroscopy microanalyses (EDS), and scanning electron microscopy (SEM) technologies. METHOD AND MATERIALS: Twenty Class V cavities were placed in healthy adult monkey teeth. Each cavity was total etched with 37% phosphoric acid for 60 seconds, rinsed, and air dispersed, and SA-Primer was applied to the collagen layer. Cavities were divided into two groups: In group 1, Protect Liner (low-viscosity resin) and Clearfil AP-X (resin composite) were placed per manufacturer's directions, and no bonding agent was placed on the acid-etched interface. In group 2, Clearfil Photobond (bonding agent) was applied, and Protect Liner and Clearfil AP-X were placed as in group 1. Teeth were observed at 7 days (control) and 6 months by nanoindentation, EDS, and SEM. RESULTS: Six-month data showed an increased nanohardness in areas 5 pm adjacent to the demineralized or partially demineralized dentin interface. Following treatment with a conventional adhesive system on the acid-etched interface (group 2), there were increased nanohardness and calcium EDS measurements in the substrate just below the resin-dentin impregnated layer. CONCLUSION: Our 6-month in vivo nanoindentation and EDS data demonstrate that the non-resin infiltrated zone becomes remineralized following adhesive resin treatment.


Subject(s)
Dental Bonding , Dentin/physiology , Resin Cements , Tooth Remineralization , Acid Etching, Dental , Analysis of Variance , Animals , Calcium/analysis , Chi-Square Distribution , Dentin/chemistry , Dentin Permeability , Electron Probe Microanalysis , Hardness , Macaca mulatta , Methacrylates , Microscopy, Electron, Scanning , Surface Properties
8.
J Nat Prod ; 64(5): 578-81, 2001 May.
Article in English | MEDLINE | ID: mdl-11374947

ABSTRACT

Five new minor carotenoids, 1-5, were isolated from the oyster Crassostrea gigas. The structure of 1 was determined to be (3S,5R,6R,6'S)-3,5,6'-trihydroxy-3'-oxo-6,7-didehydro-5,6-dihydro-10,11,20-trinor-beta,epsilon-caroten-19',11'-olide 3-acetate by detailed analyses of NMR and CD data. The structures of the other carotenoids, 2-5, were also determined in a similar manner. In the FAB-MS/MS of 2-4, having the 5-hydroxy-3,6-epoxy-5,6-dihydro-beta-carotene moiety, the characteristic product ions resulting from the sequential cleavage of C-C bonds in the polyene chain were observed.


Subject(s)
Carotenoids/chemistry , Ostreidae/chemistry , Animals , Circular Dichroism , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, Ultraviolet
9.
J Agric Food Chem ; 49(3): 1601-6, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11312902

ABSTRACT

Eleven apocarotenoids (1-11) including five new compounds, 4, 6, 9, 10 and 11, were isolated from the fruits of the red paprika Capsicum annuum L. The structures of new apocarotenoids were determined to be apo-14'-zeaxanthinal (4), apo-13-zeaxanthinone (6), apo-12'-capsorubinal (9), apo-8'-capsorubinal (10), and 9,9'-diapo-10,9'-retro-carotene-9,9'-dione (11) by spectroscopic analysis. The other six known apocarotenoids were identified to be apo-8'-zeaxanthinal (1), apo-10'-zeaxanthinal (2), apo-12'-zeaxanthinal (3), apo-15-zeaxanthinal (5), apo-11-zeaxanthinal (7), and apo-9-zeaxanthinone (8) which have not been previously found in paprika. These apocarotenoids were assumed to be oxidative cleavage products of C(40) carotenoid such as capsanthin in paprika.


Subject(s)
Capsicum/chemistry , Carotenoids/chemistry , Plants, Medicinal , Carotenoids/isolation & purification , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Molecular Structure , Plant Stems/chemistry
10.
Bioorg Med Chem ; 8(8): 2027-35, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11003147

ABSTRACT

6-Nitro-5-deazaflavin derivatives bearing O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha- and beta-D-galacto-non-2-ulopyranosylonate)alkyl group (sialosylalkyl group) at N(3) or N(10) and 8-amino-5-deazaflavin substituted with the sialosylalkyl group at the amino group were synthesized and their physicochemical properties as well as antitumor effects on KB and L1210 cells have been investigated. The configurations of the glycosides were determined by 1H NMR and rate of hydrolysis of the glycosidic bond. It has been found that these conjugate molecules show significant antitumor activities. Combination of an 8-amino-5-deazaflavin with the sialosylalkyl group have been found to give rise to significant increase in antitumor activities of the compound. Antitumor effects of 6-nitro-5-deazaflavin-sialic acid conjugate molecules were similar or rather weak in comparison with those of the 6-nitro-5-deazaflavin derivatives without sialosylalkyl group.


Subject(s)
Antineoplastic Agents/chemical synthesis , Flavins/chemical synthesis , Flavins/pharmacology , Sialic Acids/chemical synthesis , Sialic Acids/pharmacology , Animals , Antineoplastic Agents/pharmacology , Circular Dichroism , Drug Screening Assays, Antitumor , Flavins/chemistry , Humans , KB Cells , Leukemia L1210 , Mice , Molecular Structure , Sialic Acids/chemistry
11.
Kaku Igaku ; 37(4): 291-301, 2000 Jul.
Article in Japanese | MEDLINE | ID: mdl-10965649

ABSTRACT

The relationship between myocardial perfusion, fatty acid metabolism, and cardiac functional recovery were investigated by using single photon emission computed tomography (SPECT) with 99mTc-1,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin: TF) and lodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) in patients with myocardial infarction. We examined myocardial SPECT in 18 patients with acute myocardial infarction (AMI) underwent successful reperfusion therapy within 24 hours from onset. TF myocardial SPECT (early and delayed images) and BMIPP (early image) SPECT were performed 2 weeks after onset of AMI, and regional TF and BMIPP defect scores of the infarct area were scored visually by a 4-point system. There was a significant correlation between the defect score of the TF delayed image, BMIPP image and SD/chord (indicator of regional wall motion abnormalities on left ventriculograms) at subacute phase (TF: r = -0.592, p = 0.011, BMIPP: r = -0.643, p = 0.004). Good correlations were also found between the defect score of the TF delayed image, the BMIPP image and the SD/chord at chronic phase (TF: r = -0.491, p = 0.037, BMIPP: r = -0.599, p = 0.007). Furthermore, there was a significant correlation between the improvement of SD/chord (acute to chronic phase) and the degree of reverse redistribution score of TF (r = 0.735, p = 0.022), and discordance score between TF and BMIPP (r = 0.691, p = 0.037). In conclusion, resting BMIPP and TF myocardial SPECT performed in patients with subacute phase AMI were shown to be useful in predicting improvement of left ventricular function at chronic phase.


Subject(s)
Fatty Acids , Iodine Radioisotopes , Iodobenzenes , Myocardial Infarction/diagnostic imaging , Organophosphorus Compounds , Organotechnetium Compounds , Radiopharmaceuticals , Tomography, Emission-Computed, Single-Photon/methods , Ventricular Function, Left/physiology , Aged , Female , Humans , Male , Middle Aged , Myocardial Infarction/physiopathology
12.
Chem Pharm Bull (Tokyo) ; 47(8): 1068-72, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10478461

ABSTRACT

A copoly (DL-lactic/glycolic acid) (PLGA), with a weight-average molecular weight of about 8400, has been characterized using fast atom bombardment (FAB)-tandem mass spectrometry in order to determine the sequence. Because of the large molecular size, PLGA was partially hydrolyzed and the terminal hydroxyl groups in the resulting oligomer mixture acetylated as the indicator. The FAB spectrum of this sample showed a complex ion signal pattern containing monomer to octamer. Diagnostic product ions containing useful information for sequence determination were observed in collision-induced dissociation-MS/MS and MS/MS/MS of these oligomer ions. The results of analysis for dimers through pentamers showed that they have random sequences of lactic and glycolic acid, suggesting that the whole structure of PLGA also has a random sequence.


Subject(s)
Excipients/chemistry , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Polymers/chemistry , Acetylation , Delayed-Action Preparations , Hydrolysis , Indicators and Reagents , Polylactic Acid-Polyglycolic Acid Copolymer , Spectrometry, Mass, Fast Atom Bombardment
13.
Pract Periodontics Aesthet Dent ; 11(7): 819-26; quiz 827, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10853583

ABSTRACT

This article provides biological and technological information that strengthens clinicians' understanding of cohesive hybridization and pulp therapy in order to support their routine use of bonding and resin systems. Utilizing cohesive systems, clinicians should experience several advantages over traditional water-soluble base and liner systems. When properly applied, cohesive hybridization of vital dentin prevents immediate postoperative hypersensitivity under all restorations and completely seals the entire tooth-restoration interface, which provides a reduction in recurrent caries.


Subject(s)
Dental Bonding , Dental Leakage/prevention & control , Dental Pulp Capping , Dental Pulp Exposure/prevention & control , Dental Restoration, Permanent/methods , Animals , Calcium Hydroxide , Dental Cavity Lining , Dental Leakage/complications , Dental Pulp Exposure/etiology , Dentin Sensitivity/prevention & control , Dentin, Secondary/growth & development , Dentin-Bonding Agents , Humans , Resin Cements
14.
Am J Dent ; 11 Spec No: S55-63, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9760881

ABSTRACT

PURPOSE: To evaluate the histologic response of 332 non-exposed and 127 exposed monkey pulps applying nine adhesive systems. MATERIALS AND METHODS: Class V and Class I cavities were used in non-exposed and exposed monkey pulps at the three ISO usage time intervals. RESULTS: There were no histologic differences in pulp responses among the nine adhesive systems used in either Class V and/or Class I cavities when compared to pulp responses of Ca(OH)2 controls at the ISO time intervals. The nine adhesive systems and resin composites are non-toxic to either non-exposed or exposed pulps, being biologically compatible to pulp tissues when placed on mechanical pulp exposures following hemorrhage control with a 2.5% NaOCl and per manufacturers' directions. It is imperative that clinicians understand the biological importance of hemorrhage control as well as the technique sensitivity of hydrophilic primers in order to optimize the efficacy of adhesives for clinical success against microleakage of bacterial factors.


Subject(s)
Dental Pulp Capping/adverse effects , Dental Pulp/drug effects , Dentin-Bonding Agents/adverse effects , Animals , Biocompatible Materials/adverse effects , Calcium Hydroxide/pharmacology , Composite Resins/adverse effects , Dental Pulp Capping/methods , Dental Pulp Necrosis/chemically induced , Dentin, Secondary/drug effects , Dentin, Secondary/growth & development , Hemostasis/drug effects , Macaca mulatta , Materials Testing , Methacrylates/adverse effects , Oral Hemorrhage/prevention & control , Pulpitis/chemically induced
15.
Quintessence Int ; 29(3): 177-88, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9643253

ABSTRACT

OBJECTIVE: Recent studies have demonstrated that acid etching of vital dentin and pulpal tissue does not retard pulpal healing, odontoblastoid cell differentiation, or dentinal bridge formation when the pulp is capped with adhesive resins. The purpose of this study was to evaluate the pulpal response in nonexposed and exposed monkey pulps to treatment with the Clearfil Liner Bond 2 and Clearfil AP-X system. METHOD AND MATERIALS: Class V and Class I cavities in nonexposed and exposed pulps were observed at 7 or 8, 27, and 97 days. RESULTS: There were no differences in pulpal inflammation between the Clearfil Liner Bond 2/Clearfil AP-X specimens and calcium hydroxide controls in either Class V or Class I cavities at the various time periods. CONCLUSION: Clearfil Liner Bond 2 and Clearfil AP-X system is not toxic to either nonexposed or exposed pulpal tissues when placed according to manufacturer's directions.


Subject(s)
Biocompatible Materials/toxicity , Dental Pulp Capping/methods , Dental Pulp/drug effects , Methacrylates/toxicity , Animals , Dental Cavity Lining , Dental Pulp/microbiology , Dental Pulp Capping/adverse effects , Dental Pulp Necrosis/chemically induced , Dentin, Secondary , Macaca mulatta , Odontoblasts/drug effects , Pulpitis/chemically induced , Sodium Hypochlorite/pharmacology , Wound Healing
16.
Bioorg Med Chem ; 6(3): 301-14, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9568284

ABSTRACT

A series of 6-nitro-5-deazaflavins bearing at N(3) or N(10) position the pyrrolecarboxamide(s) group as DNA minor groove binder has been synthesized. These hybrid molecules show similar redox properties to those of 6-nitro-5-deazaflavins with no pyrrolecarboxamide(s) group, suggesting that they generate stable one- and two-electron reduction product(s). Electrolytic reductions of the hybrid molecules were carried out at a controlled potential under anaerobic conditions in the presence of plasmid pBR322 DNA. Significant conversions of the supercoiled circular pBR322 DNA (form I) to the open circular DNA (form II) have been found by treatment with the reductively activated 6-nitro-5-deazaflavin derivatives. Their DNA damaging effects have been found to be enhanced as the number of pyrrolecarboxamide group as the DNA binder increases. Antitumor activities of the hybrid molecules towards KB and L1210 cells were evaluated in vitro. It has been found that the antitumor effects of the compounds on KB cells slightly change and those on L1210 cells decrease as the number of the pyrrolecarboxamide group increases. These results reveal that the combination of 6-nitro-5-deazaflavin molecule with the pyrrolecarboxamide(s) group increase the DNA binding properties of the compounds, giving rise to promoted DNA damaging effects, and also suggest that the combination would affect the capacity of the compounds to act as the substrate for intracellular reductases and/or the cellular uptake of the compounds.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , DNA/drug effects , Flavins/chemical synthesis , Flavins/pharmacology , Pyrroles/chemical synthesis , Pyrroles/pharmacology , Animals , DNA/metabolism , DNA Damage , Drug Screening Assays, Antitumor , Humans , KB Cells , Leukemia L1210/drug therapy , Mice , Oxidation-Reduction , Structure-Activity Relationship
17.
Gan To Kagaku Ryoho ; 23 Suppl 2: 143-7, 1996 Jun.
Article in Japanese | MEDLINE | ID: mdl-8678557

ABSTRACT

During the process of invasion, tumor cells must detach from the primary neoplasm and degrade host stroma. E-cadherin is responsible for the cell-cell adhesion and collagenase IV is the one of the matrix metalloproteinases. We determined whether the levels of mRNA for E-cadherin and collagenase IV were differently expressed within 12 cases of early and 13 cases of advanced gastric cancers using a rapid calorimetric in situ hybridization assay for mRNA. In 6 of 12 early cancers, we found a decreased expression of E-cadherin mRNA in the invasion edge compared to the main tumor. In advanced gastric cancers, 3 out of 13 cancers also exhibited this finding. Higher expression of the collagenase IV at the invasion edge of the tumor compared to the main tumor was observed in half of the early and advanced gastric cancer cases. Inverse expression levels of E-cadherin and collagenase IV mRNA were observed in 6 of 12 early cancers. However, only one of 13 advanced cancer cases expressed the same finding.


Subject(s)
Adenocarcinoma/genetics , Cadherins/genetics , Collagenases/genetics , Gene Expression Regulation, Neoplastic , RNA, Messenger/analysis , Stomach Neoplasms/genetics , Adenocarcinoma/pathology , Gene Expression Regulation, Enzymologic , Humans , In Situ Hybridization , Neoplasm Staging , Stomach Neoplasms/pathology
19.
Transpl Int ; 9 Suppl 1: S25-7, 1996.
Article in English | MEDLINE | ID: mdl-8959783

ABSTRACT

Much attention has been paid to only natural antibody titer of the recipients in ABO-incompatible kidney transplantation. In this study, we looked at the distribution of blood type antigens in the kidney tissue. Thirty-seven biopsy specimens from patients with nephritis or transplanted kidneys were recruited. Fifteen were type A, 14 were type B, and 8 were type AB. Kidney tissues were stained with anti-A or anti-B antibody using immunohistological staining. The stained dots in each section were regarded as the area and were measured by image analyzer. B antigen was expressed very weakly both in the glomeruli and in interstitium as compared with A antigen. In type AB, B antigen was less expressed than A antigen. Based on these results, we performed B-incompatible kidney transplantation. No rejection was seen without preoperative depletion of natural antibody and splenectomy. These results may suggest that type B-incompatible kidney transplantation might possibly be performed without preoperative depletion of natural antibodies.


Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility/immunology , Kidney Transplantation/immunology , ABO Blood-Group System/analysis , Adult , Humans , Male
20.
Transpl Int ; 9 Suppl 1: S226-9, 1996.
Article in English | MEDLINE | ID: mdl-8959834

ABSTRACT

This study was designed to investigate the effects of pravastatin (Pr) on accelerated coronary arteriosclerosis in transplanted hearts. The rabbit hearts were transplanted to the recipients' neck heterotopically, and received FK506. The rabbits in group 1 were fed a normal diet (ND), and cholesterol-rich diet (CD) in group 2 and 3. Pr (10 mg/kg) was given to group 3. They were sacrificed at 4 weeks and the severity of myocardial rejection and arterio-sclerosis was assessed and scored histologically. The serum lipid levels were significantly elevated by a CD. However, addition of Pr had no effect on the levels of LDL and total cholesterol (TC). There was no significant difference in myocardial rejection in each group. Transplanted hearts in group 2 showed more severe arteriosclerotic lesions than those in group 1. Pr treatment in group 3 diminished the severity of coronary arteriosclerosis. Pr may prevent the accelerated coronary arteriosclerosis after heart transplantation without significant changes in TC and LDL.


Subject(s)
Anticholesteremic Agents/therapeutic use , Coronary Artery Disease/prevention & control , Liver Transplantation/adverse effects , Pravastatin/therapeutic use , Animals , Graft Rejection , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Lipids/blood , Male , Rabbits
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