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Electrocardiographic effects of diagnostic imaging agents

ACADEMIC RADIOLOGY 2002年第2-Sup期9卷 S444-S446页

作者： Wiggins, J Beckmann, R Weinmann, HJ Lehr, R Berlex Labs Inc Wayne NJ 07470 USA Schering AG D-1000 Berlin Germany

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Protection by metal complexes with SOD-mimetic activity against oxidative gastric injury induced by indometacin and ethanol in rats

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ANNALS OF CLINICAL BIOCHEMISTRY 2001年第6期38卷 694-700页

作者： El-Missiry, MA El-Sayed, IH Othman, AI Mansoura Univ Fac Sci Dept Zool Mansoura 35516 Egypt

We have investigated the protective effect or oral administration of copper and manganese complexes with superoxide dismutase (SOD)-mimetic activity against oxidative gastric mucosal injury induced by the non-steroidal antiinflammatory drug indometacin with ethanol in the rat. The total area of the gastric lesions and lipid peroxidation were significantly increased 1 h after oral administration of indometacin (15 mg/kg) and ethanol, indicating in acute oxidative injury. The activities of SOD, catalase (CAT), glutathione-S-transferase (GST) and glutathione content were significantly decreased in the gastric mucosa by indometacin plus ethanol. Manganese or copper complexes showed SOD-mimetic activity. Pretreatment with these complexes protected against gastric mucosal lesions and decreased lipid peroxides, as well as attenuating the decrease in the activities or SOD, CAT and GST in gastric mucosa. These findings suggest that active oxygen species and lipid peroxidation play an important role in the pathogenesis of gastric mucosal injury induced by indometacin. In addition, we have shown that Mn and Cu complexes have gastroprotective properties against ulceration induced by indometacin plus ethanol. The present results suggest that appropriate copper or manganese complex supplementation may potentially provide prophylaxis or therapy for some pathologies associated with excessive free radical production and inhibited SOD activity.

关键词：消炎药非甾类/毒性铜/药理学乙醇/毒性自由基/代谢胃黏膜/药物作用胃黏膜/损伤胃黏膜/代谢吲哚美辛/毒性脂质过氧化作用/药物作用锰/药理学分子模拟有机金属化合物/药理学氧化还原超氧化物歧化酶/药理学动物男(雄)性大鼠

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Light-induced apoptosis involves a defined sequence of cytoplasmic and nuclear calcium release in AlPcS₄-photosensitized rat bladder RR 1022 epithelial cells

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PHOTOCHEMISTRY AND PHOTOBIOLOGY 2000年第2期72卷 210-216页

作者： Rück, A Heckelsmiller, K Kaufmann, R Grossman, N Haseroth, E Akgün, N Inst Laser Technol Med & Metrol D-89081 Ulm Germany Univ Frankfurt Clin Dermatol & Venereol D-6000 Frankfurt Germany Ben Gurion Univ Negev Fac Hlth Sci IL-84105 Beer Sheva Israel Soroka Univ Med Ctr Skin Bank & Investigat Dermatol Lab Beer Sheva Israel

Oxidative stress induced by light activation of photosensitizers is regarded to have a role in triggering cell death pathways during photodynamic therapy (PDT). Reactive oxygen species have been proposed to act as signal transduction molecules activating downstream reactions that lead to apoptosis, Mainly debated is the cooperating role of other signaling systems like calcium or pH. The present work contributes to this discussion by studying PDT effects in cell cultures of rat bladder epithelial cells for the hydrophilic tetrasulfonated aluminum phthalocyanine (AlPcS4), Cells were coincubated with the photosensitizer and the calcium-sensitive probe Fluo-3, The light-induced reactions were analyzed with a confocal laser scanning microscope. The dynamics of the process during light activation was observed with subcellular resolution. A transient calcium elevation during the irradiation process was detected, especially in the cell's nuclei, followed by a more sustained increase. The evaluation of the energy-dose-dependent phototoxicity after an incubation time with the photosensitizer of I and 24 h, showed enhanced phototoxicity when the drug was present for 24 h, Surprisingly, stimulation of cell proliferation was observed at very low light doses (at 0.2 J/cm(2)) when the drug was incubated for 24 h (cell viability 160%), Induction of apoptosis could be observed after irradiation with fluences between 1 and 3 J/cm(2). Apoptotic cells were identified with fluorescein isothiocyanate-labeled Annexin V, which binds to phosphatidylserine after its translocation to the outer plasma membrane. In the presence of the antioxidant pyrrolidinedithiocarbamate the transient calcium elevation was totally inhibited, as was the subsequent translocation of PS, In contrast, N-acetyl-L-cysteine did not suppress the transient calcium increase. Our data might be consistent with calcium regulated processes during AlFcS(4)-PDT and the involvement of oxygen radicals.

关键词：细胞凋亡/生理学细胞凋亡/辐射效应钙信号/辐射效应细胞系细胞核/代谢细胞质/代谢上皮细胞/药物作用上皮细胞/代谢上皮细胞/辐射效应吲哚类/药理学光有机金属化合物/药理学光化学疗法光敏感药/药理学膀胱/药物作用膀胱/代谢膀胱/辐射效应动物大鼠

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Monoselenolipoic acid may be an outstanding pharmaceutical antioxidant with direct thioredoxin-like activity

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MEDICAL HYPOTHESES 2000年第3期55卷 185-186页

作者： McCarty, MF Pantox Labs San Diego CA 92109 USA

Owing to the low pKa of its selenohydryl group, reduced monoselenolipoic acid (MSL) can be expected to be a very versatile antioxidant with direct thioredoxin-like activity. Since MSL supports the growth of lipoate-dependent bacteria, it can be anticipated that MSL will be susceptible to reversible reduction by one or more of the enzymes that reduces lipoic acid - thus greatly potentiating MSLs utility as an antioxidant. If it is not metabolized to release toxic free selenide, MSL may have interesting pharmaceutical potential. (C) 2000 Harcourt Publishers Ltd.

关键词：抗氧化剂/药理学有机金属化合物/药理学硒硫辛酸/化学

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Synthesis, characterization, and cytotoxicity of trifunctional dinuclear platinum complexes: Comparison of effects of geometry and polyfunctionality on biological activity

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JOURNAL OF MEDICINAL CHEMISTRY 2000年第16期43卷 3189-3192页

作者： Qu, Y Rauter, H Fontes, APS Bandarage, R Kelland, LR Farrell, N Virginia Commonwealth Univ Dept Chem Richmond VA 23284 USA Inst Canc Res CRC Ctr Canc Therapeut Sutton SM2 5NG Surrey England

The synthesis of two new isomeric trifunctional dinuclear platinum complexes of formula [{PtCl(NH3)(2)}mu-NH2(CH2)(6)NH2-{PtCl2(NH3)}](+) (1,2/c,c and 1,2/t,c) is reported. Their biological activity in selected human tumor cell lines sensitive and resistant to CDDP (cisplatin, cis-[Pt(NH3)(2)Cl-2]) is described and compared with the profile for their bifunctional analogues, [{cis/trans-PtCl(NH3)(2)}(2)mu-NH2(CH2)(6)NH2](2+). The trifunctional dinuclear platinum complexes showed a unique profile of cytotoxicity against human cancer cell lines, with low resistance factors in A2780, CH1, and 41M cell. lines. The resistance factor is dependent on the geometry of the Pt coordination spheres - suggesting that these may be associated with DNA-binding modes. Retention of activity against CDDP-resistant cell lines and a different spectrum of activity compared to CDDP and also within different classes of polynuclear platinum complexes suggest that not only are they mechanistically different from mononuclear platinum complexes but also each individual class of polynuclear platinum structure may have its own unique character.

关键词：胺类/化学抗肿瘤药/化学合成抗肿瘤药/化学抗肿瘤药/药理学 DNA 肿瘤/代谢抗药性肿瘤药物筛选试验抗肿瘤有机金属化合物/化学合成有机金属化合物/化学有机金属化合物/药理学铂构效关系肿瘤细胞培养的人类

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Effect of fluorine substitution on the interaction of lipophilic ions with the plasma membrane of mammalian cells

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BIOPHYSICAL JOURNAL 2000年第3期79卷 1490-1497页

作者： Kürschner, M Nielsen, K von Langen, JRG Schenk, WA Zimmermann, U Sukhorukov, VL Univ Wurzburg Lehrstuhl Biotechnol Biozentrum D-97074 Wurzburg Germany Univ Wurzburg Inst Anorgan Chem D-97074 Wurzburg Germany

The effects of the anionic tungsten carbonyl complex [W(CO)(5)SC6H5](-) and its fluorinated analog [W(CO)(5)SC6F5](-) on the electrical properties of the plasma membrane of mouse myeloma cells were studied by the single-cell electrorotation technique. At micromolar concentrations, both compounds gave rise to an additional antifield peak in the rotational spectra of cells, indicating that the plasma membrane displayed a strong dielectric dispersion. This means that both tungsten derivatives act as lipophilic ions that are able to introduce large amounts of mobile charges into the plasma membrane. The analysis of the rotational spectra allowed the evaluation not only of the passive electric properties of the plasma membrane and cytoplasm, but also of the ion transport parameters, such as the surface concentration, partition coefficient, and translocation rate constant of the lipophilic anions dissolved in the plasma membrane. Comparison of the membrane transport parameters for the two anions showed that the fluorine-substituted analog was more lipophilic, but its translocation across the plasma membrane was slower by at least one order of magnitude than that of the parent hydrogenated anion.

关键词：生物转运细胞膜/药物作用细胞膜/生理学电化学膜脂质类/生理学模型生物学多发性骨髓瘤有机金属化合物/药理学肿瘤细胞培养的动物小鼠

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Synthesis, structural characterization and antitumor activity evaluations of copper complex with tetraazamacrocyclic ligand

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 1999年第8期9卷 1087-1092页

作者： Kong, DY Qin, C Meng, LH Xie, YY Chinese Acad Sci Shanghai Inst Mat Med Shanghai 200031 Peoples R China

Cu (II) complex with 1,4,7,10-tetrakis(2-cyanoethyl-)-1,4,7,10 tetraazacyclododecane was prepared and characterized by X-ray diffraction. Four nitrogen atoms of macrocyclic ligand and oxygen atom of water molecule defined a tetragonal pyramidal polyhedron surrounding the central copper atom. Preliminary pharmacological tests showed that it had antitumor activity against P388 and BEL-7404 cell lines in vitro. Also it exhibited perturbation effects to K562 tumor cell lines at G(0)-G(1) stage and further studies showed that it can cleave supercoiled DNA( pBR 322) to nicked and linear DNA in aerobic condition. (C) 1999 Elsevier Science Ltd. All rights reserved.

关键词：抗肿瘤药/化学合成抗肿瘤药/化学抗肿瘤药/药理学铜/化学铜/药理学 DNA 超螺旋剂量效应关系药物流式细胞术 K562细胞模型分子核酸构象有机金属化合物/化学合成有机金属化合物/化学有机金属化合物/药理学肿瘤细胞培养的人类

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Oxidized low-density lipoprotein as a delivery system for photosensitizers: Implications for photodynamic therapy of atherosclerosis

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1999年第1期289卷 528-534页

作者： de Vries, HE Moor, ACE Dubbelman, TMAR van Berkel, TC Kuiper, J Leiden Univ Sylvius Lab Leiden Amsterdam Ctr Drug Res Div Biopharmaceut NL-2300 RA Leiden Netherlands Leiden Univ Dept Mol Cell Biol NL-2300 RA Leiden Netherlands

Photodynamic therapy is a promising new strategy in the treatment of cardiovascular diseases. Photodynamic therapy for vascular diseases may be improved by the specific delivery of photosensitizers to the atherosclerotic lesion. In this study, we studied whether oxidatively modified low-density lipoprotein (OxLDL) could be used as a specific carrier for photosensitizers, thereby using the scavenger receptor expressed on macrophages as a target. The photosensitizer aluminum phthalocyanine chloride (AlPc) was incorporated into OxLDL, and its photodynamic effects were studied. Macrophages (RAW 264.7) were incubated with various concentrations of OxLDL-AlPc for different periods. After illumination of the cells with red right, cytotoxicity was observed that was dependent on the time of illumination and incubation. Macrophages incubated with OxLDL-AlPc that were not illuminated revealed no cytotoxicity;The uptake of the OxLDL-AlPc complexes was mediated by scavenger receptors expressed on macrophages. In the presence of the polyanion polyinosinic acid, a specific ligand for scavenger receptors,no cytotoxicity could be observed. Serum incubations of the OxLDL-AlPc complexes revealed that these complexes stay intact after incubation. No redistribution of AlPc to other plasma (lipo-) proteins could: be detected, and 80-90% of the AlPc remained associated with the OxLDL particle. These results indicate that OxLDL may function as a specific delivery system for photosensitizers to the scavenger receptors expressed on the macrophages in the atherosclerotic lesion, increasing the beneficial effects of photodynamic therapy for cardiovascular diseases.

关键词：动脉硬化/治疗细胞培养的色谱法液相药物释放系统乳状剂吲哚类/投药和剂量吲哚类/药理学脂蛋白类 LDL/代谢巨噬细胞/药物作用巨噬细胞/代谢有机金属化合物/投药和剂量有机金属化合物/药理学氧化还原光化学疗法光敏感药/投药和剂量光敏感药/药理学受体 LDL/药物作用受体 LDL/代谢受体氧化LDL 清道夫受体 E类甘油三酯类/化学甘油三酯类/分离和提纯动物小鼠

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A comparative study of the cellular uptake and photodynamic efficacy of three novel zinc phthalocyanines of differing charge

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PHOTOCHEMISTRY AND PHOTOBIOLOGY 1999年第3期69卷 390-396页

作者： Ball, DJ Mayhew, S Wood, SR Griffiths, J Vernon, DI Brown, SB Univ Leeds Sch Biochem & Mol Biol Ctr Photobiol & Photodynam Therapy Leeds LS2 9JT W Yorkshire England Univ Leeds Dept Colour Chem & Dyeing Leeds LS2 9JT W Yorkshire England

Three novel substituted zinc phthalocyanines (one anionic, one cationic and one neutral) were compared to two clinically used photosensitizers, 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) and polyhematoporphyrin (PHP), as potential agents for photodynamic therapy (PDT). Using the RIF-1 cell line,photodynamic efficacy was shown to be related to cellular uptake. The cationic phthalocyanine (PPC, pyridinium zinc [II] phthalocyanine) had improved activity over the other two phthalocyanines and slightly improved activity over PHP and m-THC. The initial subcellular localization of each photosensitizer was dependent upon the hydrophobicity and plasma protein binding. The phthalocyanines had a punctate distribution indicative of lysosomes, whereas m-THPC and PW had a more diffuse cytoplasmic localization, A relocalization of phthalocyanine fluorescence was observed in some cases following low-level light exposure, and this was charge dependent. The anionic phthalocyanine (TGly, tetraglycine zinc Cn] phthalocyanine) relocalized to the nuclear area, the localization of the hydrophobic phthalocyanine (TDOPc, tetradioctylamine zinc [II] phthalocyanine) was unchanged, whereas the distribution of the cationic phthalocyanine (PPC) became more cytoplasmic, This suggests that relocalization following low-level irradiation is a critical factor governing efficacy, and a diffuse cytoplasmic distribution may be a determinant of good photodynamic activity.

关键词：细胞系电化学吲哚类/化学吲哚类/药代动力学吲哚类/药理学有机金属化合物/药代动力学有机金属化合物/药理学光化学疗法光敏感药/化学光敏感药/药代动力学光敏感药/药理学亚细胞部分/代谢动物小鼠

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Effects of acid suppression and bismuth medications on the performance of diagnostic tests for Helicobacter pylori infection

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AMERICAN JOURNAL OF GASTROENTEROLOGY 1999年第9期94卷 2380-2383页

作者： Bravo, LE Realpe, JL Campo, C Mera, R Correa, P Louisiana State Univ Med Ctr Dept Pathol New Orleans LA 70112 USA Univ Valle Dept Pathol Cali Colombia Hosp Dept Gastroenterol Serv Pasto Colombia

OBJECTIVE: This study was designed to investigate whether acid suppression and bismuth medications interfere with the performance of diagnostic tests for Helicobacter pylori (H. pylori) infection. METHODS: Sixty patients with previous diagnoses of atrophic gastritis and H. pylori infection made in gastric biopsies taken at Hospital Departmental, Paste, Colombia, were enrolled in the study. C-13 breath urea test (UBT) and stool antigen test (HpSA) were performed simultaneously. Two baseline tests were performed: one 7 days before and another the day before starting medications. A total of 20 patients received for 2 wk one of the following treatments: a) ranitidine;b) lansoprazole;or c) bismuth subsalicylate. The tests were repeated while the patients were on the prescribed medication on days 7 and 14 and then 2 wk after finishing the medication. RESULTS AND CONCLUSIONS: Utilizing standard cut-off values for the tests, our results indicate that in the case of the C-13 UBT test, ranitidine does not interfere with the results, whereas lansoprazole and bismuth may be expected to yield a significant proportion of false negative results (30-40% for lansoprazole and 45-55% for bismuth). In the case of the HpSA test, ranitidine does not interfere, whereas lansoprazole and bismuth may be expected to yield a nonsignificant proportion of false negative results (15-25% for lansoprazole and 10-15% for bismuth). Absolute values for both tests may be used to study the effects of the pharmacological agents on the characteristics of the infection. (Am J Gastroenterol 1999;94:2380-2383. (C) 1999 by Am. Coll. of Gastroenterology).

关键词： 2-吡啶甲基亚硫酰苯咪唑类抗溃疡病药/药理学抗溃疡病药/治疗应用抗原细菌/分析铋/药理学铋/治疗应用呼吸试验粪便/化学螺杆菌感染/诊断螺杆菌感染/药物疗法螺杆菌幽门/免疫学奥美拉唑/类似物和衍生物奥美拉唑/药理学奥美拉唑/治疗应用有机金属化合物/药理学有机金属化合物/治疗应用雷尼替丁/药理学雷尼替丁/治疗应用水杨酸盐类/药理学水杨酸盐类/治疗应用敏感性与特异性尿素/代谢人类

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