免疫功能与血清锌、硒浓度的相关性

免疫系统是机体识别、清除内源和外源异型抗原,防御疾病功能的重要系统,微量元素缺乏可导致免疫功能降低.微量元素（锌、硒）通过多方面对免疫系统产生影响,它们参与了体内许多重要代谢途径,锌、硒元素缺乏会导致体内多种蛋白、酶失活,影响免疫相关因子转录、合成,从而影响免疫系统发挥正常生理功能,导致免疫功能低下,免疫功能缺陷等疾病.关键词：固有免疫;适应免疫;锌;硒分类号：R392.12 文献标识码：A     

硒与自身免疫性甲状腺疾病

硒是人体必需的一种微量元素,以硒蛋白的形式发挥其生物学功能.自身免疫性甲状腺疾病(AITD)患者中,血清硒及硒蛋白水平存在异常.研究表明,硒缺乏可能通过降低多种硒蛋白酶的抗氧化活性、影响辅助性T细胞(Th) 1/Th2平衡、减弱巨噬细胞抗原识别和提呈作用等途径参与AITD的发生.补硒治疗对AITD患者病情缓解可能有一定的作用,但其安全性有待进一步的临床研究提供证据.     

硒与甲状腺

硒是生命必需的一种微量元素.硒在体内最主要的生物活性形式是硒代半胱氨酸,以硒代半胱氨酸为活性中心的蛋白质,称为含硒蛋白.硒主要的生物学作用是抗氧化和抗炎症反应.甲状腺内含有多种含硒蛋白,其中最重要的2种为谷胱甘肽过氧化物酶和脱碘酶,前者是甲状腺组织中重要的抗氧化剂,保护甲状腺细胞免受氧化应激损伤;后者是一组与甲状腺激素代谢相关的酶.硒缺乏与多种甲状腺疾病的发生发展有关.研究表明,低硒可加重自身免疫性甲状腺疾病、增加甲状腺癌发病风险以及促进甲状腺肿的发生发展等.补硒可能具有一定治疗作用,但补硒治疗目前尚不成熟,其有效性、安全性等尚需更多的临床药物研究提供理论依据.     

硒预防心血管病的研究进展

<正>硒是人体必需的微量元素之一,是人体重要的含硒蛋白质的必要组成部分,硒具有抗炎、抗氧化应激、促进免疫调节等作用〔1〕,硒缺乏与癌症、病毒感染及多种心血管疾病等〔2〕相关。饮食补充硒等营养物质常用于保持健康和疾病预防,特别是各种慢性疾病患者。硒发挥心血管疾病保护作用的实验证据充分。本文就硒对心血管疾病的预防及作用机制作一综述。1硒的生物学特征与功能目前,人蛋白质组中已发现25种硒蛋白,常见的如谷胱甘     

硒缺乏与甲状腺疾病

硒在甲状腺激素的合成、活化、代谢过程及甲状腺抗氧化系统和免疫系统中发挥重要作用。甲状腺滤泡上皮细胞表达众多功能性硒蛋白(含硒基半胱氨酸的酶),如:谷胱甘肽过氧化物酶、脱碘酶、硫氧还原蛋白还原酶(TR)及硒蛋白P。硒缺乏与许多甲状腺疾病如甲状腺肿、亚临床克汀病、自身免疫性甲状腺炎、低T4综合征、甲状腺癌等密切相关。补硒可能会给这些疾病的治疗开辟一条新的途径。     

硒与自身免疫性甲状腺疾病

自身免疫性甲状腺疾病(AITD)的发病机制十分复杂,可能与自由基诱发的氧化应激和凋亡有关.硒是哺乳动物维持正常功能必需的微量元素之一,其在甲状腺激素的合成、活化、代谢过程及甲状腺抗氧化系统和免疫系统中发挥重要作用.血清硒水平低可以引起或加重甲状腺组织的免疫紊乱与慢性炎性反应,引起AITD.补充一定剂量的硒可能改善AITD患者的炎性反应,为AITD的治疗开辟一条新的途径.     

硒缺乏与甲状腺疾病

硒在甲状腺激素的合成、活化、代谢过程及甲状腺抗氧化系统和免疫系统中发挥重要作用。甲状腺滤泡上皮细胞表达众多功能性硒蛋白(含硒基半胱氨酸的酶)，如：谷胱甘肽过氧化物酶、脱碘酶、硫氧还原蛋白还原酶(TR)及硒蛋白P。硒缺乏与许多甲状腺疾病如甲状腺肿、亚临床克汀病、自身免疫性甲状腺炎、低T3综合征、甲状腺癌等密切相关。补硒可能会给这些疾病的治疗开辟一条新的途径。     

碘与硒对甲状腺功能影响的研究进展

碘与硒是人体必需的两种微量元素,是构成人体甲状腺激素、蛋白和酶类的重要组成成分,对甲状腺功能的正常发挥有着重要的影响。研究二者在甲状腺系统中的关系以及对甲状腺功能的影响,对预防和治疗甲状腺疾病具有重要的理论意义和实用价值。     

克山病区硒与免疫功能的调查与分析

一般认为，硒在防病、抗病机理中，增强机体免疫功能是重要一环，硒防治克山病也可能与此有关。笔采用Ｅ花环和ＥＡ花环为主要手段，对补硒和不补硒的地区以及非病区的抽样人群作为对照研究。结果发现硒似科与免疫功能的增强无关。无论是在细胞免疫还是体液免疫方面均未发现其增强免疫功能的证据。     

大鼠睾丸组织中的含硒蛋白

目的　探讨雄性大鼠睾丸组织中的含硒蛋白。方法　采用 75 Se活体标记、SDS- PAGE和γ射线探测等技术研究睾丸组织中含硒蛋白的分布。结果　在睾丸组织中检测到 9种含硒蛋白质或亚单位 ,其分子量分别为 117.0 ,78.0 ,6 6 .6 ,5 7.2 ,43.0 ,38.1,2 5 .0 ,2 0 .1和 18.0 k Da。结论　其中有些是已知的硒蛋白 ,有些则可能是先前未被认识的新硒蛋白 ,它们对雄性大鼠性腺的发育和分泌功能可能具有一定影响     

The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health.

Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.     

Selenium and the control of thyroid hormone metabolism.

Thyroid hormone synthesis, metabolism and action require adequate availability of the essential trace elements iodine and selenium, which affect homeostasis of thyroid hormone-dependent metabolic pathways. The three selenocysteine-containing iodothyronine deiodinases constitute a novel gene family. Selenium is retained and deiodinase expression is maintained at almost normal levels in the thyroid gland, the brain and several other endocrine tissues during selenium deficiency, thus guaranteeing adequate local and systemic levels of the active thyroid hormone T(3). Due to their low tissue concentrations and their mRNA SECIS elements deiodinases rank high in the cellular and tissue-specific hierarchy of selenium distribution among various selenoproteins. While systemic selenium status and expression of abundant selenoproteins (glutathione peroxidase or selenoprotein P) is already impaired in patients with cancer, disturbed gastrointestinal resorption, unbalanced nutrition or patients requiring intensive care treatment, selenium-dependent deiodinase function might still be adequate. However, disease-associated alterations in proinflammatory cytokines, growth factors, hormones and pharmaceuticals modulate deiodinase isoenzyme expression independent from altered selenium status and might thus pretend causal relationships between systemic selenium status and altered thyroid hormone metabolism. Limited or inadequate supply of both trace elements, iodine and selenium, leads to complex rearrangements of thyroid hormone metabolism enabling adaptation to unfavorable conditions.     

Selenium and the thyroid gland: more good news for clinicians

The thyroid is the organ with the highest selenium content per gram of tissue because it expresses specific selenoproteins. Since the discovery of myxoedematous cretinism and thyroid destruction following selenium repletion in iodine‐ and selenium‐deficient children, data on links between thyroid metabolism and selenium have multiplied. Although very minor amounts of selenium appear sufficient for adequate activity of deiodinases, thus limiting the impact of its potential deficiency on synthesis of thyroid hormones, selenium status appears to have an impact on the development of thyroid pathologies. The value of selenium supplementation in autoimmune thyroid disorders has been emphasized. Most authors attribute the effect of supplementation on the immune system to the regulation of the production of reactive oxygen species and their metabolites. In patients with Hashimoto's disease and in pregnant women with anti‐TPO antibodies, selenium supplementation decreases anti‐thyroid antibody levels and improves the ultrasound structure of the thyroid gland. Although clinical applications still need to be defined for Hashimoto's disease, they are very interesting for pregnant women given that supplementation significantly decreases the percentage of postpartum thyroiditis and definitive hypothyroidism. In Graves' disease, selenium supplementation results in euthyroidism being achieved more rapidly and appears to have a beneficial effect on mild inflammatory orbitopathy. A risk of diabetes has been reported following long‐term selenium supplementation, but few data are available on the side effects associated with such supplementation and further studies are required.     

Thyroid cancer yield in patients with Graves' disease

The management of thyroid nodules in patients with Graves' disease remains an issue both of concern and controversy for those who care for these patients. At one time, thyroid cancer in patients with thyrotoxicosis was considered to be extremely rare, but this perception has proven to be incorrect. Several studies have demonstrated both an increased incidence of nodules and of thyroid cancer in patients with Graves' disease, with cancer rates varying from as low as 1% to as high as 9% of cases. These divergent estimates of malignancy rates in Graves' disease have predictably led to variability in management recommendations. Considerable controversy also exists as to whether or not thyroid cancer behaves more aggressively in patients with Graves' disease. Anecdotal experience and a number of studies have suggested an increased aggressiveness of papillary and follicular thyroid cancer in patients with Graves' disease, but these findings are not universal. Underlying both issues of the incidence and aggressiveness of thyroid cancer is the role of thyrotropin (thyroid stimulating hormone, TSH) in the development and stimulation of thyroid cancer. The association between TSH and thyroid cancer has long been known. TSH has a central role in thyroid growth and normal functioning and appears to play a similar part in the growth and development of thyroid cancer. The close relationship of TSH to the stimulating TSH-R antibodies (TSH-R AB) seen in Graves' disease has led to the perception that thyroid cancer occurring in the setting of Graves' disease may become more aggressive as a result of stimulation by these autoantibodies. This article will summarize the existing literature pertaining to thyroid cancer in Graves' disease, and suggest an evidence-based approach to the management of these patients.     

Selenium, selenoproteins and the thyroid gland: interactions in health and disease

The trace element selenium is an essential micronutrient that is required for the biosynthesis of selenocysteine-containing selenoproteins. Most of the known selenoproteins are expressed in the thyroid gland, including some with still unknown functions. Among the well-characterized selenoproteins are the iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases, enzymes involved in thyroid hormone metabolism, regulation of redox state and protection from oxidative damage. Selenium content in selenium-sensitive tissues such as the liver, kidney or muscle and expression of nonessential selenoproteins, such as the glutathione peroxidases GPx1 and GPx3, is controlled by nutritional supply. The thyroid gland is, however, largely independent from dietary selenium intake and thyroid selenoproteins are preferentially expressed. As a consequence, no explicit effects on thyroid hormone profiles are observed in healthy individuals undergoing selenium supplementation. However, low selenium status correlates with risk of goiter and multiple nodules in European women. Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined. The baseline selenium status of an individual could constitute the most important parameter modifying the outcome of selenium supplementation, which might primarily disrupt self-amplifying cycles of the endocrine-immune system interface rectifying the interaction of lymphocytes with thyroid autoantigens. Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction.     

Studies on suppressor cell function in thyroid diseases.

Suppressor cell function of peripheral mononuclear cells has been examined in patients with Graves' disease, Hashimoto's thyroiditis, and thyroid cancer, as well as in healthy subjects. Suppressor cell function was assessed through two methods: 1) measurement of enhanced blastogenesis after 24-h preculture and 2) concanavalin A-inducible suppressor activity. The results from the two tests were coincident and indicate that suppressor cell function was significantly decreased in the Graves' disease population but not changed in either the Hashimoto's thyroiditis or the thyroid cancer groups compared to healthy controls. The impairment of suppressor cell function in the Graves' disease population was still observed when patients became euthyroid by treatment with antithyroid drugs, although the treated patients had improved suppressor cell function compared to untreated patients (P = NS). Low activity of suppressor cell function in the Graves' disease population might be a constitutional character based on an inherited abnormality specific for the disease population.     

The importance of selenium to human health

The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.     

Selenium and human health

Selenium is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant and anti-inflammatory effects to the production of active thyroid hormone. In the past 10 years, the discovery of disease-associated polymorphisms in selenoprotein genes has drawn attention to the relevance of selenoproteins to health. Low selenium status has been associated with increased risk of mortality, poor immune function, and cognitive decline. Higher selenium status or selenium supplementation has antiviral effects, is essential for successful male and female reproduction, and reduces the risk of autoimmune thyroid disease. Prospective studies have generally shown some benefit of higher selenium status on the risk of prostate, lung, colorectal, and bladder cancers, but findings from trials have been mixed, which probably emphasises the fact that supplementation will confer benefit only if intake of a nutrient is inadequate. Supplementation of people who already have adequate intake with additional selenium might increase their risk of type-2 diabetes. The crucial factor that needs to be emphasised with regard to the health effects of selenium is the inextricable U-shaped link with status; whereas additional selenium intake may benefit people with low status, those with adequate-to-high status might be affected adversely and should not take selenium supplements.     

Increased aggressiveness of thyroid cancer in patients with Graves' disease

To evaluate whether coexistence of Graves' disease affects the prognosis of thyroid cancer we examined the clinical and pathological characteristics of 22 differentiated thyroid carcinomas concomitant with hyperthyroidism; 13 were associated with Graves' disease, and 9 with autonomous thyroid nodules. Carcinomas were identified in a consecutive series of 359 hyperthyroid patients (132 with Graves' disease and 227 with autonomous thyroid nodules) who underwent surgery during a 6-yr period. One hundred and thirty-seven thyroid carcinomas were found in the 582 euthyroid patients operated on in the same period. In Graves' patients, carcinomas were more often multifocal (46.1% vs. 0%), locally invasive (61.5% vs. 11.1%), and metastatic to lymph nodes (61.5% vs. 11.1%) or to distant sites (23.0% vs. 0%) than in patients with autonomous thyroid nodules. In addition, carcinomas concomitant with Graves' disease were larger (3.3 +/- 1.8 vs. 1.0 +/- 0.7 cm) than the ones associated with autonomous thyroid nodules and showed a high recurrence rate. In euthyroid patients, aggressiveness of thyroid cancer was intermediate. Serum TSH levels were suppressed in all hyperthyroid patients with thyroid cancer. However, circulating thyroid-stimulating antibodies were present in 12 of 13 cancer patients with Graves' disease, but were absent in patients with autonomous thyroid nodules. Our study suggests, therefore, that TSAb may play a role in determining the high aggressiveness of thyroid cancer in Graves' disease patients and indicates that a vigorous treatment should be pursued in this subgroup of patients.     

Clinicopathological characteristics of thyroid cancer in patients on dialysis for end-stage renal disease.

BACKGROUND: The prevalence rate of thyroid cancers in patients with renal failure is variable in different studies. Our aim was to determine the prevalence and clinicopathological characteristics of thyroid cancers in the dialysis population and to evaluate the potential risk factors. METHODS: We performed a retrospective analysis on end-stage renal disease (ESRD) patients on dialysis and thyroidectomized patients without ESRD (2000-2006). Then we compared the data of thyroid cancer patients on dialysis (n = 9) with the data of patients who had histopathologically verified benign thyroid disease on dialysis (n = 23) and with the histopathological data of thyroid cancer patients without ESRD. RESULTS: Papillary thyroid cancer (PTC) was the only histotype that was found in 9 of 420 (2.1%) ESRD patients on dialysis. Multifocal PTC was found in eight of nine patients; of them, four had follicular variant of PTC (FVPTC). Two patients had lymphatic metastasis at diagnosis. Eight PTCs were classified as tumor-node-metastasis (TNM) stage I and one as stage II. Among the analyzed factors, age (r = 0.374, p = 0.01) and duration of dialysis (r = 0.436, p = 0.007) showed a significant positive correlation with the occurrence of thyroid cancer. CONCLUSIONS: We conclude that the prevalence of thyroid cancer in patients undergoing dialysis was not higher than that in the background population. Age and duration of dialysis showed a significant positive correlation with the occurrence of thyroid cancer in patients on dialysis. Among the histotypes, there may be higher percentage of PTC, FVPTC, and multifocality in dialysis patients. The effect of these characteristics on prognosis of thyroid cancer in dialysis patients is needed to be further evaluated.