Ex vivo stimulation of renal tubular p-aminohippurate transport by dexamethasone and triiodothyronine in human renal cell carcinoma

This paper is the third of a long-term planned series of papers dealing with ex vivo investigations of drug transport in human kidney. The aims of this study are (a) to investigate whether or not human renal cell carcinoma (RCC) can actively accumulate p-aminohippurate (PAH) and (b) to test the response of RCC on dexamethasone or triiodothyronine (T3) using tissue slices ex vivo. By this approach, the accumulation capacity of RCC should be stimulated as a prerequisite for an increased uptake of anti-tumour drugs. Tissue slices of RCC samples of 30 patients were incubated for 24 h in Williams medium E containing 0.01–50 μM dexamethasone or T3. Thereafter, slices were placed in PAH-containing Cross–Taggart medium, and PAH uptake into kidney tissue was measured for 2h under standardised conditions as described previously. In intact human renal cortical slices, PAH uptake capacity, expressed as slice to medium ratio (Q _S/M), was about 2.8 ± 0.16 after 24 h of incubation and increased significantly in dexamethasone-containing medium in a concentration-dependent manner, up to ∼150%, whereas T3 did not influence PAH accumulation. On the other hand, in RCC the PAH accumulation capacity was completely abolished (Q _S/M∼1). However, after administration of dexamethasone, the accumulated amount of PAH increased significantly in RCC tissue in a concentration-dependent manner, up to ∼190%. T3 was without effect in RCC, too. Surprisingly, the dexamethasone-mediated stimulation could be differentiated into responders and non-responders, with maximal effects at different concentrations for each patient. Nevertheless, the maximal transport rates remained low in RCC, even under hormone influence. In conclusion, a moderate stimulation of tubular transport capacity can be shown ex vivo in human RCC. This phenomenon is only of a relatively low degree compared with intact renal tissue. However, in principle, the response of RCC on dexamethasone could form a basis for further therapeutic strategies to overcome multi-drug resistance in RCC patients. For this purpose, additional experiments analysing the expression of transporters of the ABC cassette-type are in progress. Received: 25 April 2000 / Accepted: 27 July 2000     

三碘甲状腺原氨酸提高肿瘤细胞化疗敏感性的实验研究

目的：研究三碘甲状腺原氨酸(T3)对肿瘤细胞化疗的增敏作用。方法：MTT比色法；结果：(1)T3的作用对人肺巨细胞癌细胞株(PLA-801D)的生长无明显影响，与PLA-801D作用后T3的浓度无明显变化。(2)经T3作用后能提高鬼臼乙叉甙(Vp-16)对PLA-801D的抑制率，而且这种增敏作用在T3持续存在时更明显。T3对Vp-16)的增敏作用与T3作用的时间和浓度无明显相关性。(3)T3对顺铂(DDP)无增敏作用。结论：三碘甲状腺原氨酸对Vp-16有一定增敏作用。     

The influences of thermal stress on serum biochemical parameters of Iranian fat-tailed sheep and their correlation with triiodothyronine (T3), thyroxine (T4) and cortisol concentrations

In order to study the influences of thermal stress on serum biochemical parameters of Iranian fat-tailed sheep and their correlation with triiodothyronine (T₃), thyroxine (T₄) and cortisol concentrations, an experiment was conducted using 45 clinically healthy Iranian fat-tailed sheep. These animals were divided into three experimental groups: group I, 15 sheep at 4 °C, group II 15 sheep at 21 °C and group III 15 sheep at 40 °C. Blood samples were taken from the jugular vein of all animals after 7 days exposure to the appropriate environmental temperature. The concentrations of total protein, glucose, cholesterol, total lipid, calcium, inorganic phosphorus, magnesium, creatine kinase, lactate dehydrogenase, triiodothyronine and thyroxine in cold stress conditions were higher than in heat stress; in contrast, the activities of aspartate aminotransferase and alanine aminotransferase were higher in heat stress conditions than in cold (p = <0.05). Although there were no significant differences in the concentrations of blood urea nitrogen, triglyceride, alkaline phosphatase and cortisol at either heat stress or cold stress, the first three assays were significantly lower than in animals kept at optimum temperatures, with cortisol having significantly higher values. These results revealed that very hot and very cold conditions had a profound effect on serum biochemical parameters.Abbreviations ALT alanine aminotransferase - AST aspartate aminotransferase - BUN blood urea nitrogen - LD lactate dehydrogenase - CK creatine kinase - ALP alkaline phosphatase     

三碘甲状腺原氨酸在脑外伤预后模型中的研究价值

目的探究三碘甲状腺原氨酸纳入脑外伤预后模型中的可行性。方法回顾性分析 2018年 6月至 2021年 5月徐州医科大学附属连云港医院收治 319例神经外科脑外伤病人临床资料,建立预后模型,检测模型性能。结果模型组中,预后良好组共 187人,预后不良组共 132人。预后良好组年龄( 53.18±14.81)岁,预后不良组年龄( 59.54±13.69)岁。预后良好组格拉斯哥昏迷量表(GCS)评分( 10.44±2.43)分,预后不良组 GCS评分( 5.96±2.78)分。预后良好组瞳孔对光反射双侧阳性 83.96%(157/ 187例)一侧阴性 10.70%(20/187例)双侧阴性 5.35%(10/187例)预后不良组瞳孔对光反射双侧阳性 29.55%(39/132例),一侧阴性 17.,42%(23/132例),双侧阴性53.,03%(70/132例)。预后良好组,赫尔辛基 CT(HCT)评分(3.17±2.48)分,预后不良组 HCT评分( 7.08±3.11)分。预后良好组抗凝、抗血小板药物服用史 5.88%(11/187例),预后不良组抗凝、抗血小板药物服用史 13.64%(14/132例)。预后良好组白细胞( 13.58±5.76)×109/L,预后不良组白细胞( 16.92±6.45)×109/L。预后良好组 T3水平( 1.20±0.32) mmol/L,预后不良组 T3水平( 0.91±0.03)mmol/L。逐步回归及多因素分析后,年龄, GCS评分,瞳孔对光反射双侧阴性, HCT评分,抗凝、抗血小板药物服用史,白细胞计数及 T3水平均与预后不良相关。模型 A包括年龄, GCS评分,瞳孔对光反射;模型 B在模型 A的基础上添加 HCT评分及抗凝、抗血小板药物服用史;模型 C在模型 B的基础上添加白细胞计数及 T3水平。随着纳入因素的增多,模型的性能逐渐增强。模型 C是最佳预测模型,经内部验证及外部验证依然有较强性能。结论 T3水平与预后不良成负相关,做为实验室指标与白细胞计数共同纳入脑外伤预后模型可以提高模型的性能。     

Drive for thinness score is a proxy indicator of energy deficiency in exercising women

The purpose of this study was to determine the association between drive for thinness (DT) and adaptations to energy deficiency in exercising women. This observational study evaluated psychometric and metabolic factors in sedentary (n=9, 27.9+/-2.0 yr) and exercising women (n=43, 24.0+/-1.1 yr). Volunteers were retrospectively grouped according to exercise status (sedentary or exercising) and a DT score of normal (sedentary or exercising) or high (exercising only). Resting energy expenditure (REE) and metabolic hormones (triiodothyronine, (TT3), ghrelin, leptin, insulin) were measured repeatedly over a 2-3 month period. The DT subscale successfully discriminated the groups based on energy status. Although the groups did not differ in body weight, the high DT group exhibited adaptations to chronic energy deficiency, including a REE below 90% of their predicted REE (86+/-3.0%), significantly lower TT3 levels and significantly higher ghrelin levels than the normal DT groups. Since energy deficiency plays a causal role in the Female Athlete Triad, DT may serve as a proxy indicator of underlying energy deficiency and may be useful for identifying individuals at risk for Triad disorders prior to the development of serious clinical sequelae.     

化学发光酶免疫分析法测定血清三碘甲状腺原氨酸的建立与研究

目的建立化学发光酶免疫分析法测定血清三碘甲腺原氨酸(T3)及临床甲状腺疾病病情的监测和预后。方法化学发光酶免疫分析法(CLEIA)采用辣根过氧化酶(HRP)-鲁米诺竞争法。结果该方法的灵敏度为0.19nmol/L,在0.52~10.28nmol/L的范围内线性良好。CLEIA测定血清T3的批内与日间变异系数分别为4.96%和4.935%。在血红蛋白浓度<2.4g/L、总胆红素浓度<342μmol/L、甘油三酯<9.9mmol/L时的干扰率无临床意义。与放射免疫分析法有较好的相关性(r=0.9264)。结论CLEIA法测定血清T3能及时有效地满足甲状腺疾病患者的临床需要,有助于进一步对检测试剂盒的研制。     

甲状腺功能正常的高血压患者血清甲状腺激素水平与高尿酸血症的相关性研究

背景 血尿酸（SUA）与高血压的发生、发展密切相关,高血压患者常伴随甲状腺功能改变。但目前在甲状腺功能正常的高血压患者中,甲状腺激素水平与高尿酸血症（HUA）患病风险的相关研究鲜有报道。 目的 探讨甲状腺功能正常的原发性高血压（EH）患者血清甲状腺激素水平与HUA的相关性。 方法 回顾性选取2019年1月至2020年12月延安大学咸阳医院心血管内科收治的甲状腺功能正常的EH患者267例为研究对象,根据是否合并HUA分为非HUA组（166例）与合并HUA组（101例）。比较两组患者的一般资料及实验室检查指标,包括性别、年龄、体质指数（BMI）、收缩压（SBP）、舒张压（DBP）、吸烟史、饮酒史、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、血肌酐（Scr）、SUA、促甲状腺激素（TSH）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）。采用多因素Logistic回归分析探讨EH患者发生HUA的影响因素;采用Pearson相关分析探讨甲状腺激素水平与SUA水平的相关性。 结果 两组患者性别、年龄、BMI、DBP、吸烟史、饮酒史比较,差异均有统计学意义（P<0.05）;两组患者TC、TG、LDL-C、Scr、SUA水平比较,差异均有统计学意义（P<0.05）;合并HUA组EH患者FT3水平高于非HUA组（t=-5.066,P<0.05）。多因素Logistic回归分析结果显示,男性〔OR=2.843,95%CI（1.121,7.215）,P=0.028〕,BMI值高〔OR=1.126,95%CI（1.020,1.234）,P=0.018〕,TG〔OR=1.824,95%CI（1.300,2.560）,P=0.001〕、LDL-C〔OR=2.804,95%CI（1.157,6.795）,P=0.022〕、Scr〔OR=1.071,95%CI（1.041,1.102）,P<0.001〕、FT3〔OR=2.297,95%CI（1.326,3.977）,P=0.003〕水平升高为EH患者发生HUA的危险因素;高龄〔OR=0.959,95%CI（0.931,0.989）,P=0.007〕为EH患者发生HUA的保护因素。Pearson相关分析结果显示,EH患者FT3水平与SUA水平呈正相关（r=0.327,P<0.001）。 结论 男性,BMI值高,TG、LDL-C、Scr、FT3水平升高可能是EH患者发生HUA的危险因素,高龄可能是EH患者发生HUA的保护因素,且甲状腺功能正常的EH患者FT3水平与SUA水平呈正相关;血清FT3水平升高的EH患者更易发生HUA,应引起临床医生重视。     

甲巯咪唑联合糖皮质激素对甲状腺功能亢进合并症患者的临床疗效及安全性观察

目的 研究甲巯咪唑联合地塞米松治疗甲状腺功能亢进合并症的临床疗效及安全性。 方法 选取2015年2月至2016年2月间,在咸阳市第一人民医院内分泌科接受治疗的甲状腺功能亢进合并症患者94例。根据简单随机数字表法分为观察组和对照组各47例。两组均给予常规的甲状腺功能亢进对症药物及护肝等治疗,其中对照组给予口服比索洛尔治疗,观察组则给予口服甲巯咪唑联合地塞米松治疗。分别对比两组临床疗效、治疗前后甲状腺素水平与肝功能变化、不良反应发生情况。 结果 观察组治疗总有效率为91.49%(43/47),显著高于对照组的72.34%(34/47),差异有统计学意义(P＜0.05)。治疗后观察组血清游离三碘甲状腺原氨酸(FT3)、血清游离甲状腺素(FT4)水平均显著低于对照组,均差异有统计学意义(均P＜0.05)。治疗后观察组谷丙转氨酶(ALT)、谷草转氨酶(AST)水平均显著低于对照组,均差异有统计学意义(均P＜0.05)。治疗后两组头痛、头晕、白细胞减少以及皮疹发生率均差异无统计学意义(均P＞0.05)。 结论 甲巯咪唑联合地塞米松治疗甲状腺功能亢进合并症的临床疗效显著,可显著改善患者甲状腺素水平以及肝功能,具有较好的安全性。     

慢阻肺急性加重期患者血清CRP、FT3、TNF-α测定在病情严重程度评估中的意义

[目的]通过检测慢性阻塞性肺疾病急性加重期(AECOPD)患者血清C-反应蛋白(CRP)、游离三碘甲腺原氨酸(FT3)、肿瘤坏死因子-α(TNF-α)水平变化,探讨血清生化指标在判断病情严重程度中的作用.[方法]选取2012年10月至2015年10月医院收治的106例AECOPD患者为研究对象,其中合并呼吸衰竭48例(A组),不合并呼吸衰竭58例(B组),另外选择同期非AECOPD患者30例(C组),免疫比浊法测定血清CRP,化学发光法测定FT3,酶联免疫吸附法测定TNF-α,分析其与病情严重程度的相关性.[结果]受试者血清CRP、TNF-α水平A组>B组>C组,FT3水平A组白细胞(WBC)异常率,CRP异常率>嗜中性粒细胞(N%)异常率(P<0.05).[结论]血清CRP、TNF-α、FT3水平与AECOPD患者病情严重程度有一定相关性,可作为病情严重程度评估的参考指标.     

Eficiency of triiodothyronine treatment on organ donor hemodynamic management and adenine nucleotide concentration

Objective We compared hemodynamic values, oxygen utilization, and adenine nucleotide concentration in the extracted organs of brain-dead donors treated with triiodothyronine vs. standard support treatment.Design Prospective, randomized, double-blind controlled study.Patients We recruited 52 consecutive adult cadaveric organ donors. Inclusion criteria were diagnosis of brain-death, transplantation suitability [1], and family consent for donation; exclusion criterion was preexisting thyroid disease.Interventions The treatment group (n=29) received an intravenous bolus of 1 µg/kg triiodothyronine followed by continuous perfusion at 0.06 µg/kg per hour, and controls (n=23) received 0.9% ClNa delivered over 270 min. Hemodynamics, tonometry, thyroid hormones, and serum lactate were measured every 90 min from brain death to extraction procedure. Biopsies were processed to determine adenine nucleotides concentration.Results Hemodynamic measurements did not differ significantly in the two groups, and the inotrope dose could not be diminished after treatment. Thyrotropin levels increased from brain death to extraction procedure in controls. Thyrotropin measured 90 and 180 min after the beginning of the perfusion was significantly lower in the treatment group than controls. The Pco₂ gap increased in both groups from brain death to the extraction procedure. The lactate level of the treatment group was lower than in controls. Biopsy specimens were obtained in 19 controls and in 20 donors of the treatment group; the adenine nucleotides concentration did not show any significant difference.Conclusions Triiodothyronine did not add any benefit over the standard management of the organ donor nor did it affect the adenine nucleotides concentration of any biopsied organs.This study has been supported by a grant from FIS (Health Ministery, Spain)