Pentylenetetrazole-induced convulsions affect cellular and molecular parameters of the mechanism of action of triiodothyronine in adult rat brain

The aim of the current study was to elucidate whether the response of the adult rat brain to thyroid hormones is affected by the intensity of neuronal activity. For this purpose, the kinetic characteristics of nuclear T3 binding, the relative expression of thyroid hormone receptor (TR) isoforms and the synaptosomal content of thyroid hormones in adult rat brain were examined after administration of a single convulsion dose of pentylenetetrazole (PTZ). Experiments in adult Wistar rats revealed an increase (33%) of the density of specific T3 nuclear receptors in cerebral hemispheres 4h after PTZ-induced seizures while no changes were observed in the dissociation constant. The relative expression of the T3-binding isoforms of TRs was not affected, while there was a gradual decrease of the relative expression of the TR alpha2 variant (non-T3 binding isoform). The above changes were coupled with an increase of the synaptosomal T3 levels during the epileptic seizures. Our study revealed inversely proportional changes between the nuclear T3 binding sites and the TR alpha2 mRNA levels 4 h after PTZ-induced seizures, suggesting that the regulation of the expression of the non-T3 binding variant of TRs determines the nuclear T3 binding sites in adult rat brain, while the synaptosomal T3 levels could play a novel functional role in the signaling from the synapse to the nucleus.     

Thyroid hormones in the rat amygdala as common targets for antidepressant drugs, mood stabilizers, and sleep deprivation.

BACKGROUND: There have been repeated reports of antidepressant effects of thyroid hormones. In this study, we investigated whether antidepressant treatments enhance the concentrations of thyroid hormones in rat brain. METHODS: Each of the groups of rats was treated for 14 days with one of the following: an antidepressant drug (desipramine, paroxetine, venlafaxine, or tianeptine); a mood stabilizer (lithium or carbamazepine); or 8 hours' partial sleep deprivation. Thyroid hormone concentrations were quantified in homogenates, nuclei, mitochondria, synaptosomes, myelin, and microsomes in 11 rat brain areas. RESULTS: No drug effects were seen on nuclear triiodothyronine (T(3)) concentrations in any brain area. In the amygdala, all antidepressant drugs enhanced the levels of T(3) in the myelin fraction. Triiodothyronine molecules were identified in the myelin by immunogold labeling. Quantification of the major lipid components showed a selective decrease in cholesterol in the myelin of the amygdala after desipramine treatment. Desipramine induced an increase in protein concentrations, 3,5-diiodothyronine levels, and the activity of the mitochondrial enzyme succinate dehydrogenase in the mitochondria of the amygdala. Lithium, carbamazepine, and partial sleep deprivation raised the levels of T(3) in synaptosomes of the amygdala. CONCLUSIONS: These results demonstrate that thyroid hormones in the amygdala are a common target of different antidepressant and mood-stabilizing therapies.     

糖尿病合并甲状腺功能亢进症的临床分析

目的：探讨糖尿病合并甲状腺功能亢进症（甲亢）患者的治疗方法及疗效。方法：回顾性分析本院近年来收治的糖尿病合并甲状腺功能亢进症患者68例,对其临床表现、治疗方法、临床疗效进行分析。结果：68例患者中,空腹血糖均恢复至5.4~6.9mmol/L,餐后2h血糖（2hPG）维持在7.8~11.2mmol/L,患者甲状腺功能检测64例恢复或接近正常。39例患者于甲亢症状控制后胰岛素用量减少15%~25%。结论：糖尿病与甲状腺功能亢进症可相互影响,经联合治疗可取得满意疗效。     

T_3对人神经干细胞分化过程中甲状腺激素受体表达的影响

目的　探讨三碘甲状腺原氨酸 (T3)在神经干细胞 (NSC)分化中的作用以及甲状腺激素受体(TR)mRNA在NSC分化过程中的表达变化。方法　在体外成功诱导扩增NSC ,用T3 对NSC进行诱导分化 ,半定量RT PCR法检测NSC在分化前后TRsmRNA的表达变化 ,免疫细胞化学方法鉴定分化后的细胞类型。结果　T3 可诱导NSC分化为神经元、少突和星形胶质细胞 ,其中髓鞘碱性蛋白 (MBP)阳性细胞约占 80 %。当NSC分化时存在不同的TRsmRNA的时间顺序表达。结论　T3 能诱导NSC向胶质细胞分化 ,是少突胶质细胞分化的重要调控因子 ,并通过TRs的时间顺序表达来发挥其重要生理作用     

Low free triiodothyronine levels are related to symptomatic intracranial hemorrhage and poor functional outcomes after intravenous thrombolysis in acute ischemic stroke patients

Background and Objective: Low free triiodothyronine (fT3) levels have been associated with increased mortality and poor functional outcomes in patients with stroke. However, the research of relationship between fT3 levels and acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT) is scarce. We aimed to investigate the association of fT3 levels with symptomatic intracranial hemorrhage (sICH) and functional outcomes at discharge in AIS patients with IVT.

Methods: Patients with AIS admitted to West China hospital, Sichuan University, who had underwent IVT treatment, were consecutively and retrospectively included. Demographic and clinical information were collected and analyzed according to the levels of fT3. We used logistic regression analysis to estimate the multivariable adjusted association of fT3 levels and post-IVT sICH, and functional outcomes at discharge.

Results: Among the 46 patients (26 males; mean age, 63.6 years) in the final analysis, 17 patients (37.0%) had fT3 levels lower than the reference range. After adjustment for age, gender, and statistically important variables (NIHSS on admission, urea levels and creatinine levels), low fT3 levels were significantly associated with post-IVT sICH (p = 0.01, OR = 0.27, 95% CI 0.10–0.77) and poor functional outcomes at discharge (p = 0.04 OR = 2.58, 95% CI 1.05–6.35).

Conclusion: We found that lower free T3 levels are independently related to post-IVT sICH and poor functional outcomes at discharge in AIS patients with IVT, which should be verified and extended in large cohorts in the future.     

冠心病患者甲状腺功能及FT3与冠状动脉病变关系的研究

目的：探讨冠心病患者甲状腺功能情况及游离甲状腺素（FT3）水平与冠脉病变的关系。方法：选择2012年至2014年期间入住我院,经冠脉造影证实的238名冠心病患者,分析其甲状腺功能情况;在排除甲亢、亚临床甲亢,甲状腺功能（甲减）、亚临床甲减后,其余217例患者根据FT3水平被分为正常FT3组（192例）和低FT3组（25例）,比较两组患者一般临床情况和冠脉造影结果。结果：（1）238名患者中甲亢2例（0.84％）,甲减11例（4.62％）,亚临床甲亢3例（1.26％）,亚临床甲减5例（2.10％）,低T3综合征25例（10.50％）;（2）与正常FT3组比较,低FT3组患者总胆固醇[TC ,（4.14±1.59） mmol/L比（7.33±1.72） mmol/L]、载脂蛋白 E [ApoE ,（3.91±0.98） mmol/L比（4.55±1.52） mmol/L]、肌酐[Cr ,（97.99±30.85）μmol/L比（116.64±43.20）μmol/L]、N末端B型利钠肽原[NT-proBNP ,140（62-462） pg/ml比739（304-4922） pg/ml]水平显著升高（P均＜0.01）;（3）冠心病患者中FT3降低的患者合并三支病变的比例显著高于正常 FT3组（76.0％比40.1％, P＜0.01）。结论：低游离甲状腺素综合征是冠心病患者最常见的甲状腺功能异常,游离甲状腺素水平降低的患者更容易多支血管受累。     

Hormone and somatic changes in rats pair-fed to growth retarded dorsomedial hypothalamic nuclei-lesioned rats

Rats with dorsomedial hypothalamic nuclei lesions (DMNL) are hypophagic and have reduced linear and ponderal growth, but have normal body composition and anabolic hormone concentrations. Previous studies have shown rats pair-fed to levels consumed (70–80% of ad lib) by DMNL rats, using a meal-feeding paradigm, have abnormal body composition and hormone concentrations. Whether the noted changes were due to restriction per se or method of food presentation was uncertain. In the present study, one group of shamoperated rats was pair fed (SHPF) by a computer-operated system that presented 45 mg food pellets in the exact amount and pattern as their DMNL yoked partner; another sham-operated group was ad lib fed (SHAD). At the end of Experiment 1 (11 days) and Experiment 2 (3 weeks) blood was collected for hormone and metabolite analyses; body compositions were also determined. Unlike an earlier report, the DMNL and SHPF groups had normal percentage body fat. Percentage carcass protein was similar in all groups at 11 days, but slightly elevated in DMNL rats at 3 weeks. Also, in contrast to an earlier study, plasma-free fatty acid levels were comparable in DMNL and SHPF rats. Plasma insulin was normal in the DMNL and SHPF rats at 11 days, but was lowered (p < 0.05) in the SHPF group at 3 weeks. Plasma thyroxine was reduced (p < 0.01) in the SHPF group at 11 days but returned to normal by 3 weeks. Thyroxine and triiodothyronine levels were normal in the DMNL groups. Plasma corticosterone levels were similar in all groups. The hormonal data suggests that hypophagic DMNL rats do not show the physiological changes that are observed in SHPF rats and that the DMNL rats' lower food consumption may be normal for their lesioned-induced lowered body weight. These data also show that not only food restriction per se, but the pattern of intake during food restriction can have an important influence on resultant hormonal and body composition data.     

Effect of a Selenium-Deficient Diet on Blood Values of T3 and T4 in Cows

Pastures in the south of Chile have been shown to be selenium deficient, and as selenium is a component of deiodinase type 1, which is necessary for the synthesis of triiodothyronine (T3) at peripheral levels, the effect of selenium deficiency on the blood concentration of theses hormones in cows was studied. Twelve pregnant Friesian cows were randomly allocated into two homogeneous groups of six animals each - selenium supplemented and selenium deficient. The selenium deficient diet consisted of 11.5 kg of hay, 500 g of soya bran, 150 g of mineral mix (without selenium), 500 g of fat for animal feeding, and was given from day 15 of lactation until the end of the study. A commercial concentrate (Cosetan) and urea was also given according to lactation requirements (up to 5 kg and up to 120 g, respectively). The selenium content was 0.05 ppm of dry matter (equivalent to 18% of the daily requirements). The supplemented group was injected subcutaneously with 1 mg Se/kg, using the commercial product Deposel (1 ml/50kg). Blood samples were obtained by coccygeous vein venepuncture before supplementation (prepartum basal values) and thereafter every 15 days. GSH-Px activity in plasma was measured using a HITACHI 4020 spectrophotometer. Serum T3 and thyroxine (T4) concentrations were measured by electrochemiluminiscence. ANOVA, Tuckey test and Student’s t-test were used to establish the significance of the intra group differences, with p=<0.05 being considered significant. There were no significant differences in blood values of T4 in either the supplemented or non-supplemented groups during pregnancy and lactation. However the blood values of T4 decreased significantly (p=<0.05) during days 30–60 of lactation to values below the reference range. The T3 serum concentrations in the supplemented group of cows were significantly lower (p=<0.05) at 60, 90 and 150 days of lactation than cows that had been supplemented with selenium.