EIA定量检测T_3、T_4的方法学评价和临床应用

目的 :了解酶免疫法定量检测血清中三碘甲状腺原氨酸 (T3 )和甲状腺素 (T4 )的可行性。方法 :采用酶免疫法和放射免疫法检测 31份血清的T3 和T4 含量 ,其结果与放射免疫法的检测结果作对照 ,同时对一定数量的血清标本作重复试验、回收试验和干扰试验。结果 :酶免疫法灵敏度T3 :0 3nmoL/L ,T4 :5 2nmoL/L ;血清标本批内CV值和批间CV值 :T3 为7 5 %和 9 3% ,T4 为 5 6 %和 8 4% ;T3 平均回收率为 10 3% ;T4 平均回收率 10 4%。应用EIA及RIA共测定临床标本 31例 ,同时进行相关性检验 ,两法结果无显著性差异 (P >0 0 5 )。结论 :酶免疫法用于血清T3 和T4 定量测定具有灵敏度高和准确性强 ,实验干扰因素较易控制等特点。     

Thyroid hormone modulates membrane currents in guinea-pig ventricular myocytes

Summary Thyroid hormones have been previously shown to alter cardiac electrophysiological and mechanical properties in humans and in experimental animals. To investigate electrophysiological mechanisms responsible for some of these alterations, we recorded action potentials and membrane currents from isolated ventricular myocytes obtained from euthyroid, hypothyroid and hyperthyroid guinea-pigs. Hyperthyroidism was induced by injecting 150 g/kg triiodothyronine for 8–11 days, and hypothyroidism was induced by propylthiouracil treatment for 35–45 days. We found that the slow inward current, was increased by hyperthyroidism and decreased by hypothyroidism: in euthyroid, hyperthyroid and hypothyroid myocytes peak slow inward current was (mean ± SEM) : –1.08 ± 0.06 nA, –1.83 ±0.18^a nA and –0.64 ± 0.07^a nA, respectively (a,p < 0.005). In addition, the membrane potential at which peak slow inward current occurred was modified by the thyroid state and in euthyroid, hyperthyroid and hypothyroid myocytes it was (mean ± SEM): 4.8 ± 0.7 mV, –1.8 ± 1.6^a mV and 11.0 ± 1.4^a mV, respectively.The outward rectifying current, was also affected by the thyroid state, and in euthyroid, hyperthyroid and hypothyroid myocytes, the amplitude atV _M = + 60 mV was (mean ± SEM): 0.51 ± 0.09 nA, 1.15 ± 0.08^a nA and 0.49 ± 0.05 nA,respectively. a,p < 0.001 compared to euthyroid myocytes. Intraperitoneal administration of a single dose of triiodothyronine to guinea-pigs, 2 h prior to the electrophysiological experiment, increased the slow inward current amplitude, as was seen with chronic hyperthyroidism, but had no significant effect on the outward current and on the action potential. Finally, action potential and membrane currents were not altered by superfusing euthyroid myocytes with 10^–6 mol/l triiodothyronine for 30 min, or by introducing 10^–7 mol/l triiodothyronine into the cell through the recording pipette.From these findings we conclude that cardiac mechanical performance may be modulated by thyroid hormones through their effect on the slow inward current, while shortening of action potential duration is brought about, at least in part, by increasing the amplitude of the outward rectifying current. Send offprint requests to O. Binah at the above address     

三碘甲状腺原氨酸对双侧颈总动脉闭塞成年大鼠室下区神经发生的影响

目的 探讨三碘甲状腺原氨酸（triiodothyronine,T3）对双侧颈总动脉闭塞成年大鼠室下区（subventricular zone,SVZ）神经发生的影响。方法 成年雄性Sprague-Dawly大鼠15只,随机分为假手术组、双侧颈总动脉结扎（2-vessel occlusion,2VO）组和T3干预组,每组5只。双侧颈总动脉永久性结扎术制作慢性脑缺血模型。模型制作后7d腹腔注射5-溴脱氧尿嘧啶核苷（5-bromo-2’-deoxyuridine,BrdU）标记新增殖细胞,采用免疫荧光染色法观察SVZ BrdU阳性细胞。结果 假手术组、2VO组和T3 干预组BrdU阳性细胞数量分别为174.8±18.5、325.0±51.0和499.4±30.8个,各组间比较均有显著差异(F= 101.68,P＜0.001),T3干预组BrdU阳性细胞数显著多于2VO组和假手术组（P均＜0.001）,2VO组亦显著多于假手术组(P＜0.001)。结论 甲状腺激素可促进成年2VO大鼠SVZ神经祖细胞增殖。     

Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease

Abstract. Carrero JJ, Qureshi AR, Axelsson J, Yilmaz MI, Rehnmark S, Witt MR, Bárány P, Heimbürger O, Suliman ME, Alvestrand A, Lindholm B, Stenvinkel P (Karolinska Institutet, Stockholm; and Karo Bio AB, Novum, Huddinge; Sweden). Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J Intern Med 2007; 262 : 690–701. Objectives. In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end‐stage renal disease (ESRD). Design. After exclusion of 23 patients with thyroid‐stimulating hormone (TSH) values outside the normal range (0.1–4.5 mIU L^?1), 187 clinically and biochemically euthyroid incident ESRD stage 5 patients starting dialysis were followed for a median of 20 (range 1–60) months. Measurements of total and free forms of thyroid hormones, s‐albumin, hs‐CRP, interleukin (IL)‐6, vascular adhesion molecule (VCAM)‐1 and insulin‐like growth factor 1 (IGF‐1) were performed at baseline. Results. In this population, 17 out of 210 patients (8%) were defined as subclinically hypothyroid. Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3). When using the cut‐off levels derived from ROC, low T3 levels were associated with increased inflammation (higher hs‐CRP, IL‐6 and VCAM‐1) and lower concentration of both s‐albumin and IGF‐1. Finally, low T3 but not low free triiodothyronine was associated with worse all‐cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors. Conclusion. This study showed that low T3 levels are independent predictors of all‐cause and also cardiovascular disease mortality in biochemically euthyroid patients, perhaps due to an intimate association with inflammation. Based on these results, the use of T3 levels in studies assessing the relationship between thyroid dysfunction and mortality risk is recommended.     

甲状腺激素在心脏移植手术中的应用

心脏移植供心的严重缺乏以及供心质量问题是困扰心脏移植术后疗效进一步提高及心脏移植广泛开展的主要原因。随着甲状腺激素(thyroid hormone,TH)与心脏功能关系研究的进一步深入,在心脏移植手术中应用TH的研究取得了可喜的进展,它不但可提高供心的质量、心脏移植的成功率、降低死亡率,同时可使原本不适宜移植的供心得到利用,从而大大扩大了供心的数量。目前有许多心脏中心将TH作为常规治疗手段应用于心脏移植。现对TH在心脏移植中的应用作一综述。     

Thyroid hormones in human tumoral and normal nervous tissues

We have studied T4 and T3 concentrations, DNA and protein concentrations and 5′ and 5 deiodinases in samples of brain tumors obtained at surgery from 49 patients, and, in most cases, also from surrounding normal tissue. T4 concentrations in normal cortical tissue (6.19±0.45 ng/g) were lower than in white matter, but the difference disappeared when referred to the DNA content (2.26±0.27 ng/mg DNA). No other differences were found between cortical and white matter, or among cortical lobes. T4 in normal tissue was higher than previously reported, mostly from autopsy samples, whereas T3 (0.99±0.07 ng/g) was similar. 5′D-I activity was negligible as compared to 5′D-II (8.11±1.09 fmol/h/mg protein). When expressed in relation to the different DNA contents of normal vs. tumoral tissue, 5′D-II activities were the same for both. 5D activity was highly variable in the tumoral tissue, with negligible activities in meningiomas and pituitary adenomas. When referred to the DNA content, T4 and 5′D-II were the same, but T3 concentrations were lower in the tumor (0.24±0.03 ng/mg DNA) as compared to normal (0.35±0.04 ng/mg DNA) tissue samples. Whether or not this decrease of T3 affects the expression of T3-sensitive processes remains to be studied.     

T3 对 MG63 细胞株 TRAIL，QPG，QPGL 表达的影响

目的观察在不同浓度T3环境下人成骨肉瘤MG63细胞株肿瘤坏死因子相关凋亡诱导配体(TRAIL)及其护骨素(OPG)、护骨素配体(OPGL)的表达,探讨甲亢性骨质疏松症的发病机制。方法用不同浓度T3(对照组,10-12、10-10、10-8mol/L组)分别刺激培养的MG63细胞24h,RT-PCR法检测TRAIL,OPG,OPGLmRNA的表达。结果T3对MG63细胞中TRAIL,OPGLmRNA的表达,均按照对照组、10-12mol/L组、10-10mol/L组、10-8mol/L组顺序递增(P<0.05),OPGmRNA的表达按照此顺序递减(P<0.05),10-8mol/L组TRAILmRNA的水平明显高于对照组(P<0.05)。同时,OPG/OPGL比率按照对照组、10-12mol/L组、10-10mol/L组、10-8mol/L组顺序递减。结论T3可能导致成骨细胞中TRAIL和OPGL表达增多,OPG的表达减少。这可能是甲亢性骨质疏松症的重要发病机制之一。     

Toxicological effects of clofibric acid and diclofenac on plasma thyroid hormones of an Indian major carp,Cirrhinus mrigala during short and long-term exposures

In the present investigation, the toxicity of most commonly detected pharmaceuticals in the aquatic environment namely clofibric acid (CA) and diclofenac (DCF) was investigated in an Indian major carp Cirrhinus mrigala. Fingerlings of C. mrigala were exposed to different concentrations (1, 10 and 100 μg L⁻¹) of CA and DCF for a period of 96 h (short term) and 35 days (long term). The toxic effects of CA and DCF on thyroid hormones (THs) such as thyroid stimulating hormone (TSH), thyroxine (T₄) and triiodothyronine (T₃) levels were evaluated. During the short and long-term exposure period TSH level was found to be decreased at all concentrations of CA (except at the end of 14^th day in 1 and 10 μg L^−l and 21^st day in 1 μg L^−l) whereas in DCF exposed fish TSH level was found to be increased when compared to control groups. T₄ level was found to be decreased at 1 and 100 μg L^−l of CA exposure at the end of 96 h. However, T₄ level was decreased at all concentrations of CA and DCF during long-term (35 days) exposure period. Fish exposed to all concentrations of CA and DCF had lower level of T₃ in both the treatments. These results suggest that both CA and DCF drugs induced significant changes (P < 0.01 and P < 0.05) on thyroid hormonal levels of C. mrigala. The alterations of these hormonal levels can be used as potential biomarkers in monitoring of pharmaceutical drugs in aquatic organisms.     

High free triiodothyronine and free-triiodothyronine-to-free-thyroxine ratio levels are associated with metabolic syndrome in a euthyroid population

Aims

To determine the association between free triiodothyronine (FT3), free thyroxine (FT4) and free-triiodothyronine-to-free-thyroxine ratio (FT3/FT4) levels and Metabolic Syndrome (MetS).