131I联合促甲状腺激素抑制治疗对分化型甲状腺癌血生化及骨密度的影响

目的  观察术后131I联合促甲状腺激素（TSH）抑制治疗的分化型甲状腺癌（DTC）患者,研究TSH抑制治疗对血生化及骨密度（BMD）的影响。方法  选择DTC术后患者44例,均在术后使用131I清除残余甲状腺,“清甲”治疗后及时给予甲状腺素片行TSH抑制治疗,TSH抑制至<0.1 mU/L。“清甲”治疗6个月左右,进行“清甲”是否成功的“评估”或“清灶”治疗。患者2次入院均空腹测定血生化全套,包括谷丙转氨酶（GPT）、谷草转氨酶（GOT）、碱性磷酸酶（AKP）、血糖（GLU）、尿素氮（BUN）、肌酐（Cr）、钙（Ca）、磷（P）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、降钙素（CT）、骨钙素（BGP）、甲状旁腺激素（PTH）、25羟维生素D3（VD3）;2次入院均测定腰椎（L1~4）、左股骨颈（Neck）、左大转子（Troch）、左沃氏三角区（Ward’s）的BMD（g/cm2）。2次入院数据的差值以Δ表示,如ΔGPT=GPT1-GPT2。结果  ①年龄和Ward1呈负相关,而且年龄和Neck2、Ward2负相关更明显,多元回归方程也有一致结果（Ward2=1.001~0.008）;年龄与ΔWard呈正相关。②术后时间间隔平均60.5 d,与ΔBGP呈负相关,与4个部位BMD无显著相关性。③TSH抑制时间与BGP2呈负相关,与Neck2呈正相关。结论  短期内（6个月左右）131I联合TSH抑制治疗对BMD的影响较小,仅表现为年龄和Ward呈负相关,且越是高龄患者治疗后Ward更低、ΔWard越大;术后时间间隔及TSH抑制时间对BMD的影响不显著。

     

促甲状腺激素抑制疗法对分化型甲状腺癌患者骨代谢、CD44V6、sIL-2R水平的影响

目的 研究促甲状腺激素（TSH）抑制疗法对分化型甲状腺癌（DTC）患者骨代谢、白细胞分化抗原44变异型6（CD44V6）及可溶性白细胞介素-2受体（sIL-2R）水平的影响。方法 选取2019年3月—2022年1月内蒙古医科大学附属医院收治的100例DTC患者,按照随机数字表法分为对照组和TSH组,每组50例。对照组术后给予甲状腺素替代疗法,TSH组术后给予TSH抑制疗法。比较两组治疗前后甲状腺功能［TSH、游离三碘甲状腺原氨酸（FT₃）、游离甲状腺激素（FT₄）］、骨代谢［总I型胶原氨基酸延长肽（PINP）、β-胶原特殊序列（β-Crosslaps）］、免疫功能［T淋巴细胞亚群（CD3⁺、CD4⁺、CD8⁺）］、血清CD44V6、sIL-2R水平的变化情况,并评价两组用药的安全性。结果 治疗后3个月,TSH组血清TSH水平较对照组低（P <0.05）,而血清FT₃、FT₄水平较对照组高（P <0.05）;两组治疗前后血清PINP、β-Crosslaps水平比较,差异无统计学意义（P >0.05）;治疗后3个月,TSH组CD3⁺、CD4⁺水平较对照组高（P <0.05）,而CD8⁺水平较对照组低（P <0.05）;治疗后3个月,TSH组CD44V6、sIL-2R水平较对照组低（P <0.05）;两组不良反应发生率比较,差异无统计学意义（P >0.05）。结论 TSH抑制疗法可有效改善DTC患者甲状腺功能,增强免疫功能,降低血清CD44V6、sIL-2R水平,对骨代谢影响较小,且用药安全性良好。     

Thyrotropin internalization is directed by a highly conserved motif in the seventh transmembrane region of its receptor

The thyrotropin (TSH) receptor is a member of G protein-coupled seven-transmembrane-segment receptors. It is characterized by a large extracellular domain linked to the seven transmembrane segments and ending with a cytoplasmic tail. Sequence alignment shows that a highly conserved motif, NPXXY where X is any amino acid, exists at the boundary between the seventh transmembrane domain and proximal part of the cytoplasmic tail of virtually all G protein-coupled receptors. This motif has been implicated as an internalization signal for several cell surface receptors, such as the low density lipoprotein (LDL), insulin and insulin-like growth factor-1 (IGF-1) receptors. The potential effects of this motif on the TSH receptor signal transduction and receptor-mediated TSH internalization was analysed by replacement of the tyrosine⁶⁷⁸ residue with an alanine residue. This mutation does not impair high affinity TSH binding, but completely abolishes the ability of cAMP response upon TSH stimulation. It also significantly reduces TSH internalization. The role of the cytoplasmic tail of the TSH receptor in receptor-mediated internalization was also assessed. Deletion of up to 56 amino acids from the C-terminus of the cytoplasmic tail enhances TSH internalization as compared to the wild-type receptor. We conclude that tyrosine⁶⁷⁸ in the NPXXY motif is required for efficient receptor-mediated TSH internalization and G protein coupling. The cytoplasmic tail of the TSH receptor may contain sequence domains which could modulate the effects of the NPXXY internalization signal.     

Testing a novel pictorial medication sheet to improve adherence in veterans with heart failure and cognitive impairment

Objectives(a) To evaluate efficacy of a pictorial medication sheet to improve adherence in veterans with heart failure (HF) and cognitive impairment (CI); (b) to describe acceptance of the intervention.BackgroundCI is prevalent in HF and is associated with worsened medication adherence. The Veteran's Administration has developed a medication image library; however, use of images to improve adherence has not been tested.MethodsThirty-six veterans with HF and CI were enrolled and provided pictorial medication sheets and an optional alarmed pillbox. Adherence pre-and post-intervention was determined by 30-day pill counts. Acceptance was assessed from interviews.ResultsTwenty-seven veterans (75%) completed the study. Overall medication adherence was poor, however there was significant improvement from pre-intervention (M = 79.74, SD = ±16.98) to post-intervention (M = 84.74, SD = ±10.00) adherence (t(26) = 2.16, p < .05, Cohen's d = .42).ConclusionsThis pilot study provides preliminary evidence that medication images improve adherence with complex medication regimens. The intervention was well received by patients.     

Recovery of insulin sensitivity and Slc2a4 mRNA expression depend on T3 hormone during refeeding

Objective

GLUT4 protein, encoded by the Slc2a4 gene, plays a key role in muscle glucose uptake, and its expression decreases in muscles under insulin resistance. Slc2a4/GLUT4 decreases with fasting and rapidly increases with refeeding and the same occurs to plasma glucose, amino acids, insulin and T3. Thus, they might be potential regulators of the Slc2a4 gene, which makes them promising targets for strategies to improve GLUT4 expression. Herein, we investigate the role of metabolic–hormonal parameters triggered by refeeding upon the Slc2a4 expression.

Materials/Methods

Plasma glucose/insulin/T3, and gastrocnemius Slc2a4 mRNA contents were measured in rats studied at the end of 48-h fasting, and subsequently at: i) 2–4 h after spontaneous refeeding; ii) 2–4 h after T3 injection, without refeeding; and iii) 0.5–2 h after intravenous infusion of insulin, insulin + glucose and insulin + amino acids, without refeeding.

Results

Refeeding increased plasma glucose/insulin/T3 and muscle Slc2a4 mRNA, reverting insulin resistance. Post-fasting infusions surprisingly induced a further Slc2a4 mRNA decrease (~ 20%, P < 0.05 vs. fasting), but T3 injection induced a ~ 2-fold increase in Slc2a4 mRNA, 2–4 h later (P < 0.001). Moreover, T3 increased glycemia and insulinemia to the 2 h-refed rats levels, suggesting that T3 elevation is a key factor to the mechanisms of metabolic balance during refeeding.

Conclusions

Refeeding induces a rapid increase in muscle Slc2a4 expression, not associated with increased plasma glucose, insulin or amino acids, but highly correlated to increased plasma T3 concentration. This result points out T3 hormone as a powerful Slc2a4 enhancer, an effect that may be acutely explored in situations of insulin resistance.