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Serum selenium response to maximal anaerobic exercise among sportsmen trained at various levels 不同训练水平运动员血清硒对最大无氧运动的反应
Pub Date : 2004-01-01 DOI: 10.1002/jtra.20000
M. Hanifi Emre, Halil Düzova, Banu Sancak, Alaadin Polat, Hasan Erdoğan, Saim Yologlu
Serum selenium (Se) is a constitutional part of both major plasma selenoprotein P and glutathione peroxidase (GSH-Px), a cytoprotective enzyme against the oxidative damage. It is an accepted fact that any case related to oxidative stress increased by physical exercise changes serum Se levels. In this study serum Se levels were examined in high physical activity (group I), moderate physical activity (group II), and low physical activity (group III) males undertaking a soccer-training regimen. In addition, Se changes before and after the acute intensive maximal exercise in an anaerobic-loading coordination tests among groups I, II, and III soccer players were investigated. For a minimum of 3 months, the players in group I (n = 12), exercising more than 5 h a week, group II (n =9 ), exercising less than 5 h but more than 2 h a week, and group III (n = 11), exercising regularly or irregularly less than 2 h were examined. Heart rate monitor 220 (heart rate)-age formula was used to evaluate the maximal exercising test during the procedure. Serum Se was analyzed by atomic absorption spectrophotometry. The difference between groups before and after the exercise was tested by Wilcoxon test, and the difference varying in the groups was tested by Kruskal–Wallis variance analyse. The relation between heart rate and serum Se was tested by Sperman's rank correlation analyses. After maximal physical exercise, the serum selenium level decreased significantly compared with pre-exercise values (P < 0.05) in group I only. In group I, maximal and pre-exercise heart rates as opposed to pre- and postexercise serum Se level were negative correlated (P < 0.05). In conclusion, a nutrition regime rich in selenium may be beneficial for both athletes who exercise regularly and in patients with increasing oxidative stress. J. Trace Elem. Exp. Med. 17:93–100, 2004. © 2004 Wiley-Liss, Inc.
血清硒(Se)是血浆主要硒蛋白P和谷胱甘肽过氧化物酶(GSH-Px)的组成部分,谷胱甘肽过氧化物酶是一种抗氧化损伤的细胞保护酶。一个公认的事实是,任何与体育锻炼增加的氧化应激有关的病例都会改变血清硒水平。在本研究中,对参加足球训练方案的高体力活动(第一组)、中等体力活动(第二组)和低体力活动(三组)男性的血清硒水平进行了检测。此外,在无氧负荷协调试验中,研究了I、II和III组足球运动员在急性高强度最大运动前后硒的变化。在至少3个月的时间里,对每周锻炼超过5小时的第一组(n=12)、每周锻炼少于5小时但超过2小时的第二组(n=9)和定期或不定期锻炼少于2小时的三组(n=11)的球员进行了检查。心率监测器220(心率)-年龄公式用于评估手术期间的最大运动测试。采用原子吸收分光光度法测定血清硒含量。运动前后各组之间的差异通过Wilcoxon检验进行检验,组间差异通过Kruskal–Wallis方差分析进行检验。用Sperman秩相关分析法检测心率与血清硒的关系。在最大限度的体育锻炼后,仅在组I中,血清硒水平与运动前的值相比显著降低(P<;0.05)。在I组中,最大心率和运动前心率与运动前和运动后血清硒水平呈负相关(P<;0.05)。总之,富含硒的营养方案可能对经常运动的运动员和氧化应激增加的患者都有益。J.Trace Elem。Exp.Med.17:93–1002004。©2004 Wiley-Liss,股份有限公司。
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引用次数: 12
Zinc status in autistic children 自闭症儿童的锌状况
Pub Date : 2004-01-01 DOI: 10.1002/jtra.20002
Özgür Yorbik, Cemal Akay, Ahmet Sayal, Adnan Cansever, Teoman Söhmen, Ayhan O. Çavdar
The transition metal zinc is an essential element for normal development and function of biological systems including the central nervous system (CNS). Zinc may be an important trace element for the etiology and symptoms of subgroups of autistic children because it is an essential catalytic or structural element of many proteins and important for neural activity and the control of neuronal death. The aim of this study was to evaluate zinc status in children with autistic disorder. Plasma, erythrocyte, and hair zinc levels were measured by atomic absorption spectrophotometry in the 45 and 39 autistic children, respectively. Forty-one healthy children in the same age group were selected as controls. Plasma and erythrocyte zinc levels in the autistic children were found to be significantly lower than normal (P < 0.05). The mean hair zinc level of the patients was also low when compared with that obtained from normal Turkish children. These results may indicate chronic zinc deficiency or metabolic abnormality of zinc in autistic children. Further studies are required to clarify underlying mechanisms. J. Trace. Elem. Exp. Med. 17:101–107, 2004. © 2004 Wiley-Liss, Inc.
过渡金属锌是包括中枢神经系统(CNS)在内的生物系统正常发育和功能的必需元素。锌可能是自闭症儿童亚组病因和症状的重要微量元素,因为它是许多蛋白质的重要催化或结构元素,对神经活动和控制神经元死亡很重要。本研究的目的是评估自闭症儿童的锌状况。分别用原子吸收分光光度法测定了45名和39名自闭症儿童的血浆、红细胞和头发锌水平。选择41名同年龄组的健康儿童作为对照。发现自闭症儿童的血浆和红细胞锌水平显著低于正常水平(P<;0.05)。与正常土耳其儿童相比,患者的平均头发锌水平也较低。这些结果可能表明自闭症儿童长期缺锌或锌代谢异常。需要进一步的研究来阐明潜在的机制。J.追踪。Elem。Exp.Med.17:101–1072004。©2004 Wiley-Liss,股份有限公司。
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引用次数: 34
Gastrointestinal nematodes, trace elements, and immunity 胃肠道线虫、微量元素和免疫力
Pub Date : 2003-10-22 DOI: 10.1002/jtra.10043
Kristine G. Koski, Marilyn E. Scott

The exploration of the scientific literature on the interrelationship among trace elements, gastrointestinal nematodes, and their requisite Th2 immunity demonstrates extensive literature but regrettably, research remains inadequate and sparse, with far fewer studies having investigated the interrelationship among trace elements and host immunity in infected hosts. Gastrointestinal nematodes, such as hookworms, Ascaris lumbricoides, and Trichuris trichiura, require activation of the Th2 arm of the immune cascade and the expression of the Th2 cytokines (interleukin-4, interleukin-5, and interleukin-10) and their effectors for worm expulsion. However, parasites have evolved a series of strategies to invade the host and to evade host defense mechanisms. Many of these mechanisms involve metalloproteinases for tissue invasion and enzymes, such as catalase and superoxide dismutase, to minimize free radical damage to the parasitic tissues from the host's immune system. Deficiencies of iron, molybdenum, copper, and zinc, have been associated with higher worm burdens, as have excessive intakes of molybdenum, iron, and copper. The possibility is emerging that there may be an optimum trace element level in the diet above which and below which the parasite is advantaged. Moreover, there is some data to suggest that specific trace elements may be directly toxic to the parasite. J. Trace Elem. Exp. Med. 16: 237–251, 2003. © 2003 Wiley-Liss, Inc.

对微量元素、胃肠道线虫及其必要的Th2免疫之间相互关系的科学文献的探索表明了大量的文献,但令人遗憾的是,研究仍然不够充分和稀少,研究感染宿主中微量元素与宿主免疫之间相互关系的研究要少得多。胃肠道线虫,如钩虫、蛔虫和鞭虫,需要激活免疫级联的Th2臂,并表达Th2细胞因子(白细胞介素-4、白细胞介素-5和白细胞介质-10)及其驱逐蠕虫的效应物。然而,寄生虫已经进化出一系列入侵宿主和躲避宿主防御机制的策略。其中许多机制涉及组织侵袭的金属蛋白酶和过氧化氢酶和超氧化物歧化酶,以最大限度地减少宿主免疫系统对寄生组织的自由基损伤。铁、钼、铜和锌的缺乏与较高的蠕虫负担有关,钼、铁和铜的摄入过多也是如此。饮食中可能存在最佳微量元素水平,高于或低于该水平,寄生虫都有优势。此外,有一些数据表明,特定的微量元素可能对寄生虫直接有毒。J.Trace Elem。《实验医学》16:237-2512003。©2003 Wiley-Liss,股份有限公司。
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引用次数: 62
Late-breaking abstracts VIth conference of the International Society for Trace Element Research in Humans (ISTERH), Québec City, Canada, September 7–12, 2002 国际人类微量元素研究学会(ISTERH)第六次会议,加拿大魁北克市,2002年9月7日至12日
Pub Date : 2003-07-14 DOI: 10.1002/jtra.10028
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引用次数: 0
Effects of vitamin E and selenium on thyroid status, adrenocorticotropin hormone, and blood serum metabolite and mineral concentrations of Japanese quails reared under heat stress (34°C) 维生素E和硒对热应激(34°C)下饲养的日本鹌鹑甲状腺状态、促肾上腺皮质激素、血清代谢产物和矿物质浓度的影响
Pub Date : 2003-01-01 DOI: 10.1002/jtra.10029
M. Ferit Gursu, N. Sahin, O. Kucuk
This study was conducted to determine the effects of vitamin E and selenium (Se) on triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), adrenocorticotropin hormone (ACTH), and serum glucose, urea, triglyceride, cholesterol, Ca, P, Na, and K concentrations of Japanese quails reared under heat stress (34°C). One-hundred twenty 10-day-old Japanese quails were randomly assigned to four treatment groups with three replicates of 10 birds each. The birds with a 2 × 2 factorial design received either two levels of vitamin E (125 and 250 mg/kg of diet) or two levels of selenium (0.1 and 0.2 mg/kg of diet). Greater dietary vitamin E and selenium inclusions resulted in a greater (P = 0.001) serum T3, T4, and TSH, but lower (P = 0.001) ACTH concentrations. No interactions between vitamin E and selenium were detected (P ≥ 0.11) for serum concentrations of T3, T4, TSH, and ACTH. Serum glucose, urea, triglyceride, and cholesterol concentrations decreased (P = 0.001), whereas protein concentrations increased (P = 0.001) when both dietary vitamin E and selenium increased. Serum albumin concentrations increased (P = 0.001) with greater dietary vitamin E but did not change with dietary selenium (P = 0.16). No interactions on any blood metabolites were detected (P ≥ 0.11). Serum activities of serum glutamic oxalate transaminase and serum glutamic pyruvate transaminase were not influenced by dietary vitamin E or selenium (P ≥ 0.42). However, serum activity of alkaline phosphatase increased (P = 0.001) with both increasing dietary vitamin E and selenium. There were no interactions detected for the serum enzyme activities (P ≥ 0.09). Increasing both dietary vitamin E and selenium caused an increase in serum concentrations of Ca, P, and K (P = 0.001), but a decrease in serum concentrations of Na (P = 0.001). No interactions were detected for serum mineral concentrations (P ≥ 0.07) except for P (P = 0.001). Results of the present study showed that dietary vitamin E and selenium have synergistic effects, and that supplementing a combination of dietary vitamin E (250 mg) and selenium (0.2 mg) positively influences some blood parameters that may positively influence the performance of Japanese quails under heat stress. J. Trace Elem. Exp. Med. 16:95–104, 2003. © 2003 Wiley-Liss, Inc.
本研究旨在测定维生素E和硒(Se)对热应激(34°C)下饲养的日本鹌鹑的三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺激素(TSH)、促肾上腺皮质激素(ACTH)以及血糖、尿素、甘油三酯、胆固醇、钙、磷、钠和钾浓度的影响。将120只10日龄日本鹌鹑随机分为四个处理组,每组10只,重复三次。采用2×2因子设计的鸟类接受两个水平的维生素E(125和250 mg/kg饮食)或两个水平(0.1和0.2 mg/kg饮食)的硒。膳食中维生素E和硒含量越高,血清T3、T4和TSH含量越高(P=0.001),ACTH浓度越低(P=0.000)。血清T3、T4、TSH和ACTH浓度未检测到维生素E和硒之间的相互作用(P≥0.11)。当膳食维生素E和硒都增加时,血清葡萄糖、尿素、甘油三酯和胆固醇浓度降低(P=0.001),而蛋白质浓度增加(P=0.000)。血清白蛋白浓度随膳食维生素E的增加而增加(P=0.001),但不随膳食硒的增加而改变(P=0.016)。未检测到任何血液代谢产物的相互作用(P≥0.11)。血清谷氨酸草酸盐转氨酶和血清谷氨酸丙酮酸转氨酶的活性不受膳食维生素E或硒的影响(P≥0.42)。然而,血清碱性磷酸酶活性随着膳食维生素E和硒的增加而增加(P=0.001)。血清酶活性没有检测到相互作用(P≥0.09)。增加膳食维生素E和硒会导致血清Ca、P和K浓度增加(P=0.001),但血清Na浓度下降(P=0.001)。血清矿物质浓度(P≥0.07)除P外未检测到相互作用。本研究结果表明,膳食维生素E和硒具有协同作用,补充膳食维生素E(250 mg)和硒(0.2 mg)的组合对一些血液参数产生积极影响,这些参数可能对日本鹌鹑在热应激下的表现产生积极影响。J.Trace Elem。Exp.Med.16:95–1042003。©2003 Wiley-Liss,股份有限公司。
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引用次数: 19
Copper retention in intestinal mucosal cells of young men at normal and high copper intakes† 正常和高铜摄入量下年轻男性肠粘膜细胞中的铜滞留†
Pub Date : 2003-01-01 DOI: 10.1002/jtra.10031
Judith R. Turnlund, Joseph M. Domek, Padmanabhan P. Nair, Sam J. Bhathena
The role of intestinal cells in copper homeostasis and storage has not been studied. Homeostasis is regulated by absorption, excretion, and storage. Copper is excreted via the bile, and it has been assumed that the increased excretion into the gastrointestinal tract when diets are high in copper was due to biliary copper. It seemed possible that some of the absorbed copper is sequestered in the intestinal cells. To test this hypothesis we measured the copper content of mucosal epithelial cells isolated from stool samples of 8 young men when consuming their usual diets and after 129 days of supplementation with 7 mg/day copper. The mean copper content of the cells, expressed as mg copper per gram of cell protein, was 0.78 versus 1.65 mg/g (SEM 0.19) (P < 0.02) when the usual and copper-supplemented diets, respectively, were consumed. In contrast to the copper content of plasma and urine, copper in intestinal cells increased significantly when intake was high. It is likely that copper was sequestered by these cells following absorption and did not get into systemic circulation. Thus, the amount of endogenous copper in stools is probably a combination of biliary copper excretion and copper sequestered in exfoliated intestinal epithelial cells. This suggests that retention of copper by the intestinal cells increases when dietary copper is high and plays a role in copper homeostasis. J. Trace Elem. Exp. Med. 16:105–108, 2003. Published 2003 Wiley–Liss, Inc.
肠道细胞在铜稳态和储存中的作用尚未得到研究。稳态受吸收、排泄和储存的调节。铜通过胆汁排出,人们认为,当饮食中铜含量高时,胃肠道的排泄量增加是由于胆汁中的铜。一些被吸收的铜似乎被隔离在肠道细胞中。为了验证这一假设,我们测量了从8名年轻男性的粪便样本中分离的粘膜上皮细胞的铜含量,这些年轻男性在食用日常饮食时以及在补充7mg/天铜129天后。当分别食用普通日粮和补充铜的日粮时,细胞的平均铜含量(以毫克铜/克细胞蛋白表示)分别为0.78和1.65mg/g(SEM 0.19)(P<;0.02)。与血浆和尿液中的铜含量相反,当摄入量高时,肠细胞中的铜显著增加。铜很可能在吸收后被这些细胞隔离,没有进入系统循环。因此,粪便中内源性铜的含量可能是胆汁中铜排泄和脱落肠上皮细胞中铜螯合的组合。这表明,当膳食铜含量高时,肠道细胞对铜的保留会增加,并在铜稳态中发挥作用。J.Trace Elem。Exp.Med.16:105-1082003。出版于2003年,Wiley–Liss,股份有限公司。
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引用次数: 10
Gastrointestinal nematodes, trace elements, and immunity 胃肠道线虫,微量元素和免疫力
Pub Date : 2003-01-01 DOI: 10.1002/JTRA.10043
K. Koski, M. Scott
The exploration of the scientific literature on the interrelationship among trace elements, gastrointestinal nematodes, and their requisite Th2 immunity demonstrates extensive literature but regrettably, research remains inadequate and sparse, with far fewer studies having investigated the interrelationship among trace elements and host immunity in infected hosts. Gastrointestinal nematodes, such as hookworms, Ascaris lumbricoides, and Trichuris trichiura, require activation of the Th2 arm of the immune cascade and the expression of the Th2 cytokines (interleukin-4, interleukin-5, and interleukin-10) and their effectors for worm expulsion. However, parasites have evolved a series of strategies to invade the host and to evade host defense mechanisms. Many of these mechanisms involve metalloproteinases for tissue invasion and enzymes, such as catalase and superoxide dismutase, to minimize free radical damage to the parasitic tissues from the host's immune system. Deficiencies of iron, molybdenum, copper, and zinc, have been associated with higher worm burdens, as have excessive intakes of molybdenum, iron, and copper. The possibility is emerging that there may be an optimum trace element level in the diet above which and below which the parasite is advantaged. Moreover, there is some data to suggest that specific trace elements may be directly toxic to the parasite. J. Trace Elem. Exp. Med. 16: 237–251, 2003. © 2003 Wiley-Liss, Inc.
关于微量元素与胃肠道线虫及其必需的Th2免疫之间相互关系的科学文献的探索显示了广泛的文献,但令人遗憾的是,研究仍然不足和稀少,在感染宿主中调查微量元素与宿主免疫之间相互关系的研究远远少于。胃肠道线虫,如钩虫、蛔虫和毛线虫,需要激活免疫级联的Th2臂,并表达Th2细胞因子(白细胞介素-4、白细胞介素-5和白细胞介素-10)及其效应物来驱逐蠕虫。然而,寄生虫已经进化出一系列入侵宿主和逃避宿主防御机制的策略。其中许多机制涉及组织入侵的金属蛋白酶和酶,如过氧化氢酶和超氧化物歧化酶,以尽量减少宿主免疫系统对寄生组织的自由基损伤。铁、钼、铜和锌的缺乏与较高的蠕虫负担有关,钼、铁和铜的过量摄入也是如此。有一种可能性正在出现,即饮食中可能存在一个最佳微量元素水平,高于这个水平和低于这个水平对寄生虫有利。此外,有一些数据表明,特定的微量元素可能直接对寄生虫有毒。J. Trace Elem。中华医学杂志,16(6):391 - 391,2003。©2003 Wiley-Liss, Inc
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引用次数: 62
Arsenic essentiality: A role affecting methionine metabolism†‡ 砷的重要性:影响蛋氨酸代谢的作用††
Pub Date : 2003-01-01 DOI: 10.1002/jtra.10044
Eric O. Uthus
Although there is no known biological function of arsenic, considerable evidence suggests that arsenic has a physiological role related to methionine metabolism. In early studies using amino acid-based diets, it was found that arsenic deprivation had little effect on growth in rats fed adequate methionine. However, in rats fed suboptimal methionine, arsenic deprivation resulted in a significant reduction in body weight. Other studies showed that feeding methyl depletors caused severe signs of arsenic deprivation. Because it was found that alteration in methionine status or methyl metabolism affected signs of arsenic deprivation, and that many of these signs were related to methionine or methyl metabolism, it was hypothesized that arsenic has a physiological role affecting methionine metabolism. In animal studies testing this hypothesis, it was shown that arsenic deprivation reduces the hepatic concentration of S-adenosylmethionine. Additionally, arsenic status affects DNA methylation in animal and cell culture models; very low or high doses of arsenic, compared with control amounts, result in an apparent hypomethylation of DNA. Because global DNA hypomethylation is associated with an increased incidence of cancer, we tested whether dietary arsenic (deficient, adequate, or excess; 0, 0.5 or 50 μg arsenic/g diet, respectively) would affect the formation of aberrant crypts in rats treated with the carcinogen dimethylhydrazine. Aberrant crypts are preneoplastic lesions that have been associated with colon carcinomas. More aberrant crypts were observed in rats fed the high amount of dietary arsenic compared to those fed adequate arsenic. The number of aberrant crypts in the arsenic-deprived group also tended to be higher than those found in rats fed adequate arsenic. Thus, many findings indicate that arsenic plays a role in methionine/methyl metabolism; however, the site of action of arsenic remains unknown. Possibly, arsenic is instrumental in maintaining the metabolic pool of S-adenosylmethionine. These results show that compared to controlled amounts, having too little or too much arsenic in the diet is harmful. That is, there is an amount of dietary arsenic that is not only not harmful, but beneficial. J. Trace Elem. Exp. Med. 16:345–355, 2003. Published 2003 Wiley-Liss, Inc.
尽管目前还没有已知的砷的生物学功能,但有相当多的证据表明,砷具有与蛋氨酸代谢有关的生理作用。在使用氨基酸饮食的早期研究中,发现缺砷对喂食充足蛋氨酸的大鼠的生长几乎没有影响。然而,在喂食次优甲硫氨酸的大鼠中,缺砷可显著降低体重。其他研究表明,喂食甲基消耗物会导致砷缺乏的严重迹象。由于发现甲硫氨酸状态或甲基代谢的改变会影响砷缺乏的迹象,并且其中许多迹象与甲硫氨酸或甲基代谢有关,因此假设砷在影响甲硫氨酸代谢方面具有生理作用。在验证这一假设的动物研究中,研究表明,缺砷会降低肝脏中S-腺苷甲硫氨酸的浓度。此外,砷状态影响动物和细胞培养模型中的DNA甲基化;与对照量相比,非常低或高剂量的砷会导致DNA明显的低甲基化。由于整体DNA低甲基化与癌症发病率的增加有关,我们测试了饮食中的砷(不足、充足或过量;分别为0、0.5或50μg砷/g饮食)是否会影响接受致癌物二甲基肼治疗的大鼠异常隐窝的形成。异常隐窝是与结肠癌相关的癌前病变。与喂食足量砷的大鼠相比,喂食大量砷的大白鼠中观察到更多的异常隐窝。缺砷组异常隐窝的数量也往往高于喂食充足砷的大鼠。因此,许多研究结果表明,砷在甲硫氨酸/甲基代谢中发挥作用;然而,砷的作用部位仍然未知。砷可能有助于维持S-腺苷甲硫氨酸的代谢库。这些结果表明,与控制量相比,饮食中砷含量过少或过多是有害的。也就是说,饮食中有一定量的砷不仅无害,而且有益。J.Trace Elem。《实验医学》,16:345–3552003。出版于2003年,Wiley-Liss,股份有限公司。
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引用次数: 45
Copper-lowering therapy with tetrathiomolybdate for cancer and diseases of fibrosis and inflammation† 四硫代钼酸盐降铜治疗癌症及纤维化和炎症疾病†
Pub Date : 2003-01-01 DOI: 10.1002/jtra.10045
George J. Brewer
Angiogenesis is required for tumor growth and is a likely Achilles heel for cancer. However, antiangiogenic agents have been somewhat disappointing in cancer therapy, perhaps because they target a single angiogenic factor, and there is much redundancy in angiogenic systems. Copper is required for high levels of angiogenesis, and many angiogenic factors have a requirement for copper. Thus, anticopper drugs offer the possibility of more global inhibition. Our group has developed tetrathiomolybdate (TM) for the initial treatment of neurologic Wilson's disease. Penicillamine makes about 50% of these patients neurologically worse, and many never recover. Only 2 of 55 (3.6%) patients worsened when treated with TM. Because TM exhibited desirable properties of potency, speed, and safety, we studied it as an antiangiogenic agent. We hypothesize that if copper is lowered to midrange, the cellular requirements for copper are met, but angiogenic cytokine signaling is inhibited. TM has shown strong inhibition of cancer growth in five rodent models, encouraging results in a canine study of advanced and metastatic cancer, and encouraging results in a phase 1/2 study of advanced and metastatic cancer in 42 patients. Finally, we have hypothesized that the pathway of fibrosis involving transforming growth factor beta (TGF-β) and connective tissue growth factor is inhibitable by copper-lowering therapy with TM. This pathway is overactive and dysregulated in many diseases of fibrosis. In animal studies, TM has completely inhibited the pulmonary fibrosis induced by bleomycin, the hepatitis induced by concanavalin A, and the cirrhosis induced by carbon tetrachloride. We find that TM inhibits transforming growth factor beta and inflammatory cytokines tumor necrosis factor alpha and interleukin-1-beta. J. Trace Elem. Exp. Med. 16:191–199, 2003. © 2003 Wiley-Liss, Inc.
血管生成是肿瘤生长所必需的,可能是癌症的致命弱点。然而,抗血管生成药物在癌症治疗中有些令人失望,可能是因为它们靶向单一的血管生成因子,并且在血管生成系统中有很多冗余。高水平的血管生成需要铜,许多血管生成因子都需要铜。因此,抗铜药物提供了更全面抑制的可能性。我们小组已经开发出四硫代钼酸盐(TM),用于神经系统Wilson病的初步治疗。青霉胺使这些患者中约50%的神经系统恶化,许多患者永远无法康复。55名患者中只有2名(3.6%)在接受TM治疗时病情恶化。由于TM具有良好的效力、速度和安全性,我们将其作为一种抗血管生成剂进行了研究。我们假设,如果铜降低到中等水平,细胞对铜的需求就会得到满足,但血管生成细胞因子信号传导会受到抑制。TM在五种啮齿类动物模型中显示出对癌症生长的强烈抑制作用,在犬对晚期和转移性癌症的研究中取得了令人鼓舞的结果,在42名患者中对晚期和迁移性癌症的1/2期研究中取得令人鼓舞的成果。最后,我们假设TM降铜治疗可抑制转化生长因子β(TGF-β)和结缔组织生长因子的纤维化途径。该途径在许多纤维化疾病中过度活跃和失调。在动物研究中,TM完全抑制了博来霉素诱导的肺纤维化、刀豆球蛋白A诱导的肝炎和四氯化碳诱导的肝硬化。我们发现TM抑制转化生长因子-β和炎性细胞因子-肿瘤坏死因子-α和白细胞介素-β。J.Trace Elem。《实验医学》,16:191–1992003。©2003 Wiley-Liss,股份有限公司。
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引用次数: 14
Changes of zinc, copper, and iron levels in the lung of male rats after subacute (4-week) and subchronic (13-week) exposure to formaldehyde 亚急性(4周)和亚慢性(13周)暴露于甲醛后雄性大鼠肺中锌、铜和铁水平的变化
Pub Date : 2003-01-01 DOI: 10.1002/jtra.10026
Og̊uz Aslan Özen, Ahmet Songur, Mustafa Sarsılmaz, Mehmet Yaman, İlter Kuş
The medical use of formaldehyde has focused especially on laboratory use. Harmful effects of formaldehyde inhalation, such as nasal squamous cell carcinoma, are quite well documented. However, detailed studies of the mechanisms of the damaging effects of formaldehyde on lung tissue are quite limited. Amounts of such elements as zinc, copper, and iron within lung tissue indicate whether or not they function physiologically. In this study, 36 adult albino Wistar male rats (6 animals per group) were exposed to 0 (Control), 5, and 10 ppm (1 ppm ≊ 1.2 mg/m3) of formaldehyde gas for subacute (4-week) and subchronic (13-week) periods. Whole-body exposure was continuously carried out for 8 h/day, 5 days/week. Body weights were recorded weekly. Levels of metals mentioned above were measured in lung tissue by atomic absorption spectrometry using wet ashing and were then compared with levels in the control groups. At the end of the study, a gradual decrease in weight gain, a decrease in zinc levels, and an increase in iron levels were observed in both subacute and subchronic groups compared to control groups. Statistically significant increases in tissue Fe levels were seen in the 10 ppm subacute (P < 0.001), 5 ppm subchronic (P < 0.001), and 10 ppm subchronic (P < 0.001) groups. We conclude that subacute or subchronic exposure to cytotoxic concentrations of formaldehyde may cause growth retardation and alter the trace element levels of zinc and iron in the lung tissue. J. Trace Elem. Exp. Med. 16:67–74, 2003. © 2003 Wiley-Liss, Inc.
甲醛的医学用途尤其集中在实验室使用上。吸入甲醛的有害影响,如鼻鳞状细胞癌,已经有了很好的记录。然而,对甲醛对肺组织损伤作用机制的详细研究相当有限。肺组织中锌、铜和铁等元素的量表明它们是否具有生理功能。在这项研究中,36只成年白化Wistar雄性大鼠(每组6只)暴露于0(对照)、5和10ppm(1ppm≊1.2 mg/m3)的甲醛气体中,持续亚急性(4周)和亚慢性(13周)。全身暴露持续进行8小时/天,5天/周。每周记录体重。通过使用湿灰化的原子吸收光谱法测量肺组织中上述金属的水平,然后将其与对照组中的水平进行比较。研究结束时,与对照组相比,亚急性组和亚慢性组的体重增加逐渐减少,锌水平下降,铁水平增加。在亚急性10ppm(P<;0.001)、亚慢性5ppm(P>;0.001)和亚慢性10ppm(P/lt;0.001。我们得出的结论是,亚急性或亚慢性暴露于细胞毒性浓度的甲醛可能会导致生长迟缓,并改变肺组织中锌和铁的微量元素水平。J.Trace Elem。Exp.Med.16:67-742003。©2003 Wiley-Liss,股份有限公司。
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引用次数: 5
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The Journal of Trace Elements in Experimental Medicine
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