Effect of Hypo- and Hyperthyroidism on Hexokinase in the Developing Cerebellum of the Rat

Abstract: Total hexokinase levels (units/g tissue) have been measured during postnatal development of the cerebellum in control, hypothyroid, and hyperthyroid rats. In addition, distribution of hexokinase in the developing cerebellum has been observed with an immunofluorescence method. Hypothyroidism delays the normally observed postnatal increase in total hexokinase activity, whereas hyperthyroidism accelerates the increase. In normal animals, hexokinase levels in maturing Purkinje cells pass through a transient increase, with maximal levels at approximately 8 days postnatally followed by rapid decline to relatively low levels by 12 days; hypothyroidism delays this transient increase and subsequent decline, but hyperthyroidism does not appear to affect markedly the timing of this phenomenon. Cerebellar glomeruli are relatively enriched in hexokinase content, as judged by their intense fluorescence. Hypothyroidism delays the development of intensely stained glomeruli. Hyperthyroidism did not appear to cause precocious increase in numbers of glomeruli but may have increased the rate at which the hexokinase was assimilated by newly formed glomeruli. The effects of hypo- and hyperthyroidism on total cerebellar hexokinase levels are interpreted in terms of the effect of thyroid hormone on the biochemical maturation of synaptic structures rich in hexokinase.     

Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium

Atrial fibrillation is one of the common arrhythmias associated with hyperthyroidism. This study examined the effects of thyroid hormone (T3) on mRNA expression and currents of major ionic channels determining the action potential duration (APD) in the rat atrium using the RNase protection assay and the whole-cell patch-clamp technique, respectively. T3 increased the Kv1.5 mRNA expression and decreased the L-type calcium channel mRNA expression, while the Kv4.2 mRNA expression did not change. APD was shorter in hyperthyroid than in euthyroid myocytes. The ultrarapid delayed rectifier potassium currents were remarkably increased in hyperthyroid than in euthyroid myocytes, whereas the transient outward potassium currents were unchanged. L-type calcium currents were decreased in hyperthyroid than in euthyroid myocytes. T3 shifted the current-voltage relationship for calcium currents negatively. In conclusion, T3 increased the outward currents and decreased the inward currents. The resultant changes of ionic currents shortened APD, providing a substrate for atrial fibrillation.     

妊娠合并甲状腺功能亢进症对妊娠及围生儿结局的影响

目的:研究妊娠合并甲状腺功能亢进症(甲亢)对妊娠及围生儿结局的影响。方法:收集从2011年1月到2014年2月我院收治的110例妊娠合并甲亢的患者的临床资料作(40例未治疗,70例接受治疗)和90例正常健康孕妇的临床资料,记录三组孕产妇的妊娠结局及新生儿结局,比较其结果有无统计学差异。结果:未治疗组妊娠不良结局及围生儿不良结局的发生率均高于治疗组,差别有统计学意义(P0.05);而治疗组与对照组相比,差异均无统计学意义(P0.05)。结论:妊娠合并甲亢可给母婴带来严重危害,早期进行规律化治疗可减少不良事件的发生。     

Oxidative stress activates insulin-like growth factor I receptor protein expression, mediating cardiac hypertrophy induced by thyroxine

Thyroxine can cause cardiac hypertrophy by activating growth factors, such as IGF-I (insulin-like growth factor-I). Since oxidative stress is enhanced in the hyperthyroidism, it would control protein expression involved in this hypertrophy. Male Wistar rats were divided into four groups: (I) control, (II) vitamin E-supplemented (20 mg/kg/day subcutaneous), (III) hyperthyroid (thyroxine 12 mg/l, in drinking water), and (IV) hyperthyroid + vitamin E. After 4 weeks, the contractility and relaxation indexes of left ventricle (LV), and cardiac mass were increased by 54%, 60%, and 60%, respectively, in hyperthyroid group. An increase in lipid peroxidation (around 40%), and a decrease in total glutathione (by 20%) was induced by thyroxine and avoided by vitamin E administration. Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were increased (by 83% and 54%, respectively) in hyperthyroid, and vitamin E avoided changes in SOD. Protein expression of SOD, GST, and IGF-I receptor (IGF-IR) were increased (by 87%, 84%, and 60%, respectively) by thyroxine, and vitamin E promoted a significant reduction in SOD and IGF-IR expression (by 36% and 17%, respectively). These results indicate that oxidative stress is involved in cardiac hypertrophy, and suggest a role for IGF-IR as a mediator of this adaptive response in experimental hyperthyroidism.     

Annona squamosa seed extract in the regulation of hyperthyroidism and lipid-peroxidation in mice: Possible involvement of quercetin

Annona squamosa (Custard apple) seeds are generally thrown away as waste materials. The extract of these seeds was evaluated for its possible ameliorative effect in the regulation of hyperthyroidism in mouse model. Serum triiodothyronine (T₃), thyroxine (T₄) concentrations, hepatic glucose-6-phospatase (G-6-Pase) and 5′-mono-deiodinase (5′DI) activity were considered as the end parameters of thyroid function. Simultaneously hepatic lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activities were investigated to observe its hepatotoxic effect, if any.

L-T₄ administration (0.5 mg/kg/d for 12 days, i.p.) increased the levels of serum T₃ and T₄, activity of hepatic G-6-Pase, 5′DI and LPO with a parallel decrease in SOD and CAT activities. However, simultaneous administration of the Annona seed extract (200 mg/kg) or quercetin (10 mg/kg) to T₄-induced hyperthyroid animals for 10 days, reversed all these effects indicating their potential in the regulation of hyperthyroidism. Further, the seed extract did not increase, but decreased the hepatic LPO suggesting its safe and antiperoxidative nature. Quercetin also decreased hepatic LPO. When relative efficacy was compared with that of propyl thiouracil (PTU), a standard antithyroidic drug, experimental seed extract appeared to be more effective. Phytochemical analyses including HPLC revealed the presence of quercetin in the seed extract and the results on the effects of quercetin suggested the involvement of this phytochemical in the mediation of antithyroidal activity of Annona squamosa seed extract.     

两种甲状腺功能亢进症动物模型的对比研究

目的：复制两种甲状腺功能亢进症动物模型,对比研究它们成型性及可持续性的异同,为研究治疗甲亢的药物提供良好的评价载体。方法优甲乐模型：大鼠灌胃给予优甲乐50μg/100 g鼠重共21 d,于末次给药后第1、7、14天分别于眼底取血和接取尿液,检测相关指标;小肠结肠炎耶尔森氏菌模型：大鼠尾静脉注射小肠结肠炎耶尔森氏菌,于第0、5、10、15、20天共注射5次,并于末次注射后第5、15、25天大鼠眼底取血和接取尿液,检测相关指标。结果优甲乐模型：造模后T3、T4、FT3、FT4显著升高,但造模型后1周即恢复正常,尿液代谢的PCA图中显示模型组整体代谢网络偏离空白组,2周后恢复正常;小肠结肠炎耶尔森氏菌模型：造模后第15天和25天时T3和T4升高,第25天时TSH显著升高,尿液代谢的PCA图中模型组偏离空白组,而第15天和25天时未回到空白组位置。结论优甲乐甲亢模型成型性好但恢复迅速,作为药效评价时适合预防给药;而小肠结肠炎耶尔森氏菌甲亢模型成型性好并且持续性较好,作为药效评价时可采取治疗给药方式。     

从"诸躁狂越，皆属于火"谈甲亢的中医药治疗

"诸躁狂越,皆属于火"是《黄帝内经》中病机十九条其中的一条,至今仍是分析疾病病机的重要依据。甲状腺功能亢进症(甲亢)是临床上常见的甲状腺疾病,其病机与脏腑之火密切相关,使用"诸躁狂越,皆属于火"的理论指导辩证论治甲亢在临床上广泛使用。脏腑气机不疏、情志不遂,内火遂生,可导致狂、躁等症状,火热日久可耗伤气阴,并可产生痰热、瘀血,但贯穿疾病始终的仍为火热,是疾病的起始因素,临床上从火论治甲亢,使用清热法、清热药治疗甲亢,在临床及动物实验方面均取得了明显的效果,再次证明了从"诸躁狂越,皆属于火"治疗甲亢的有效性。     

滋水清肝饮联合甲巯咪唑治疗甲状腺功能亢进症患者疗效观察和血清IGF-1、APN的影响

摘要 目的：评价滋水清肝饮联合甲巯咪唑治疗甲状腺功能亢进症（甲亢）患者临床疗效以及对血清IGF-1、APN水平的影响。方法：选入我院2021年3月~2023年2月收治的甲亢患者80例,随机分为对照组和观察组,各40例,其中对照组予以甲巯咪唑治疗,观察组采用滋水清肝饮+甲巯咪唑治疗。评价并比较两组的临床疗效、血清IGF-1和APN水平变化等。结果：与治疗前相比,两组治疗后主要中医证候积分、心率、FT3和FT4显著降低, TSH明显升高（P＜0.05）,而观察组降低/升高幅度更大,与对照组差异显著（P＜0.05）;观察组治疗总有效率92.50%,显著高于对照组的72.50%（P＜0.05）;与两组治疗前相比,治疗后血清IGF-1和APN水平下降,且观察组下降幅度较对照组大（P＜0.05）;观察组不良反应发生率较对照组低（5.00% vs 25.00%,P＜0.05）。结论：滋水清肝饮联合甲巯咪唑疗效确切,改善临床症状、甲状腺功能,下调血清IGF-1、APN水平,减少不良反应。     

甲亢孕妇血清25-羟维生素D水平对42天婴儿骨密度影响的研究

目的：探讨甲状腺功能亢进（甲亢）孕妇经治疗后,其体内25-羟维生素D（25-（OH）D3）水平对42天婴儿胫骨声波的传导速度（speed of sound,SOS）值、骨代谢生化指标的影响。方法：选取我院门诊及住院确诊的甲亢孕妇40例为甲亢组（T组）,随机抽取健康孕妇40例作为对照组（C组）,甲亢组给予丙硫氧嘧啶治疗后,监测两组孕妇25-（OH）D3水平与生后42天婴儿的胫骨SOS值、骨代谢生化指标,并进行对比观察、统计分析。结果：甲亢组孕妇在产后42天体内25-（OH）D3的水平比其在产后第1天升高（P〈0.05）,甲亢组孕妇在产后42天体内25-（OH）D3水平接近对照组（P〉0.05）,在产后42天婴儿的胫骨SOS值接近对照组（P〉0.05）,甲亢组产后42天婴儿的血清钙（Ca）及血清碱性磷酸酶（AKP）接近对照组（P〉0.05）。结论：甲亢组孕妇给予丙硫氧嘧啶治疗后,甲状腺功能恢复正常,其体内25-（OH）D3水平升高,所产42天婴儿的骨密度也随着升高。     

Expression of new human inorganic pyrophosphatase in thyroid diseases: its intimate association with hyperthyroidism

Inorganic pyrophosphatase (PPase) controls the level of inorganic pyrophosphate produced by biosynthesis of protein, RNA, and DNA. Thus, PPase is essential for life. PPase expression is unclear in the thyroid. We cloned a new human PPase, phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPPase), and established a rabbit polyclonal anti-LHPPase antibody. This is the first study to determine the PPase expression by immunohistochemistry and Western blot. Intranuclear LHPPase expression of thyrocytes was enhanced most prominently in Graves' disease and autonomously functional thyroid nodule. To estimate a regulating factor of subcellular localization of LHPPase, we examined its expression of Graves' disease-derived thyrocytes in vitro with the disease-originated serum. Nuclear expression of LHPPase was lost in cultured thyrocytes even with the serum, while its cytoplasmic expression was retained. The data suggest that increased expression of LHPPase is associated with hyperthyroidism. Intranuclear expression of LHPPase may not be regulated by Graves' disease-derived serum factors.