Anti-myeloperoxidase IgG subclass distribution and avidity in sera from patients with propylthiouracil-induced antineutrophil cytoplasmic antibodies associated vasculitis

OBJECTIVE: Propylthiouracil (PTU) could induce MPO-ANCA-positive vasculitis. The aim of this study was to compare the IgG subclass distribution and avidity of MPO-ANCA in sera from patients with primary ANCA-associated vasculitis (AASV) and PTU-induced vasculitis. METHODS: Nineteen patients with primary AASV with MPO-ANCA and thirteen patients with PTU-induced vasculitis were enrolled in the current study. Sera in both active phase and remission were collected. Anti-MPO IgG subclasses were detected by antigen specific ELISAs using specific monoclonal antibodies as second antibodies, and MPO-ANCA avidity was assessed by antigen-inhibition ELISAs. RESULTS: In primary AASV, all four anti-MPO IgG subclasses could be detected in active phase with IgG1 (100%), IgG2 (73.7%), IgG3 (63.2%) and IgG4 (94.7%), and in remission, IgG1 and IgG4 subclasses in most patients remained positive. However, in PTU-induced vasculitis, anti-MPO IgG3 subclass could not be detected, the anti-MPO IgG subclasses in active phase were IgG1 (100%), IgG2 (61.5%) and IgG4 (46.2%). Furthermore, five out of the six patients (88.8%) with PTU-induced vasculitis with positive IgG4 subclass in active phase turned to negative in remission, however, only eight out of the fourteen patients (57.1%) with primary AASV turned to negative. The median avidity constant of MPO-ANCA was 56 (8.96 to >140) x 10(7) mol/l for patients with primary AASV and 0.7 (<0.28 to >140) x 10(7) mol/l for patients with PTU-induced vasculitis respectively. Furthermore, the relative levels of MPO-ANCA avidity were associated with elevation of ESR in primary AASV and were associated with BVAS scores in patients with PTU-induced vasculitis, respectively. CONCLUSION: MPO-ANCA IgG subclass distribution and avidity were different between patients with primary AASV and PTU-induced vasculitis. It was suggested that the mechanism of ANCA production in PTU-induced vasculitis was different from that in primary AASV, and the avidity of MPO-ANCA might be associated with disease activity.     

Ornithine decarboxylase and polyamines in developing rat brain and heart: Effects of perinatal hypothyroidism

Hypothyroidism induced by perinatal administration of propylthiouracil (PTU) had profound effects on growth of the heart, with major organ weight deficits persisting well beyond the termination of drug treatment. These effects were preceded by disruption of the developmental patterns of cardiac ornithine decarboxylase (ODC) and the polyamines, which are thought to be intracellular modulators of cellular maturation. Activity of cardiac ODC was depressed in the PTU-treated group and putrescine and spermidine levels were markedly subnormal. PTU administration also affected brain growth, but much less so than in the heart. The disruption of the brain ODC/polyamine system was also less pronounced, with relatively small degrees of spermidine depletion and a slight elevation of ODC. For both tissues, the biochemical effects of perinatal hypothyroidism were opposite to those found previously for administration of exogenous thyroid hormones. These results support the views that:

1. (1) endogenous thyroid hormones contribute to the maintenance of normal developmental patterns of ODC and the polyamines, and

2. (2) the ODC/polyamine system participates in events modulating subsequent tissue growth.

应用丙基硫氧嘧啶复制动脉粥样硬化模型中对大鼠心脏损伤的影响

目的通过高脂饲料结合免疫损伤方法复制大鼠动脉粥样硬化模型,并观察丙基硫氧嘧啶在动脉粥样硬化模型复制中对大鼠心脏损伤的影响。方法选择36只雄性Wistar大鼠,随机分为正常组、高脂饲料组和高脂饲料+丙基硫氧嘧啶组,后两组同时辅以免疫损伤和腹腔注射VD3,饲养90 d后,测定和观察血液生化指标、病理变化、免疫组化情况。结果 (1)高脂+丙基硫氧嘧啶组与高脂组和正常组相比较,心肌损伤指标肌酸激酶、肌酸激酶同工酶差异均有显著性(P<0.05);(2)HE染色发现高脂+丙基硫氧嘧啶组心肌细胞排列紊乱、水肿,血管内壁增厚,泡沫细胞和少量炎性细胞浸润;(3)免疫组化法方法测定心肌细胞中Bcl-2和Bax的表达,高脂+丙基硫氧嘧啶组表达显著升高(P<0.05),心肌细胞凋亡加速。结论丙基硫氧嘧啶在应用于大鼠动脉粥样硬化模型复制中,对大鼠心肌病理学及Bcl-2、Bax蛋白表达产生影响。     

丙基硫氧嘧啶诱发抗中性粒细胞胞质抗体阳性小血管炎2例并文献复习

目的 研究丙基硫氧嘧啶(PTU)诱发的抗中性粒细胞胞质抗体(ANCA)阳性小血管炎的临床病理表现及诊治方法.方法 对我院近2年诊治的2例PTU引起的ANCA阳性小血管炎进行临床病理分析并复习相关文献.结果 2例病人均为女性,年龄43、50岁,平均46.5岁.分别服PTU时间6月、17年.2例均出现发热、关节痛,并累及肾脏及肺等重要脏器,出现咯血和肾功能不全.2例均出现核周型ANCA(p-ANCA)阳性,胞质型ANCA(c-ANCA)阴性,抗甲状腺球蛋白抗体升高,1例抗核抗体(ANA)阳性.肾脏活检病理均有新月体性肾炎改变,确诊后2例患者均立刻停用PTU,并应用糖皮质激素(0.5～1g/d×3 d)冲击,后期使用糖皮质激素维持治疗,1例联合应用CTX(1g/次,1次/4周)冲击,临床症状缓解.结论 PTU可诱发ANCA阳性小血管炎,应及时诊断和停药,并使用糖皮质激素或联合应用免疫抑制剂治疗.     

甲巯咪唑与丙基硫氧嘧啶对甲亢继发骨质疏松患者骨密度的影响

目的观察甲巯咪唑与丙基硫氧嘧啶对甲亢继发骨质疏松患者骨密度的影响,为临床甲亢继发骨质疏松的治疗提供参考。方法选取2012年12月至2013年12月来我科住院治疗的46例甲亢继发骨质疏松患者,采用随机数字法平均分为观察组和对照组。在常规治疗基础上,观察组采用甲巯咪唑进行治疗,对照组使用丙基硫氧嘧啶进行治疗。比较两组治疗前后的血钙(Ca)、血镁(Mg)、血磷(P)、血碱性磷酸酶(ALP)、24 h尿钙(UCa)变化;于治疗前后测量患者腰椎、股骨颈骨密度(BMD),分析甲巯咪唑与丙基硫氧嘧啶对甲亢继发骨质疏松患者骨密度的影响;并比较两组药物不良反应的发生情况。结果观察组治疗后24 h UCa水平明显低于对照组,差异有统计学意义(P<0.05);观察组治疗后Mg水平明显高于对照组,差异有统计学意义(P<0.05)。观察组治疗后Ca、P、ALP水平与对照组比较差异无统计学意义(P>0.05)。观察组治疗后腰椎、股骨颈骨密度均略高于对照组,但差异无统计学意义(P>0.05)。对照组肝功能损害的发生率明显高于观察组,差异有统计学意义(P<0.05)。结论甲巯咪唑和丙基硫氧嘧啶均可以改善甲亢继发骨质疏松患者的骨代谢状态,但甲巯咪唑升高患者骨密度的作用更明显,且不良反应相对较轻,值得临床借鉴使用。     

Purpura chez une jeune femme hyperthyroïdienne

IntroductionPropylthiouracil (PTU) is a synthetic antithyroid drug that can induce ANCA-associated vasculitis.ObservationA 27-year-old woman diagnosed with Graves’ disease was on PTU for the past 10 years. She developed purpuric lesions of the legs and on the tip of the nose diagnosed as vasculitis. ANCAs were positive, with anti-MPO and anti-PR3 on blood ELISA. After discontinuation of PTU, she was able to fully recover.ConclusionAll synthetic antithyroid drugs can induce ANCA-associated vasculitis, more often PTU. In most cases, antibodies are directed against MPO. Dual anti-MPO and anti-PR3 positivity is possible, but rare. The mechanism could be through an accumulation of PTU in neutrophils, altering the structure of MPO and making it immunogenic. PTU can also induce ANCA-free or lupus vasculitis, maculopapular rashes or urticaria. Many other drugs can induce ANCA-associated vasculitis.     

早期治疗妊娠期甲状腺功能亢进对母婴的身体健康影响分析

目的 探讨妊娠期甲状腺功能亢进妇女早期治疗对母婴健康的影响.方法 回顾性分析我院2011年至2013年收治的88例妊娠期合并轻中度甲亢患者的临床资料,根据患者治疗方案分为甲硫咪唑组(28例)、丙硫氧嘧啶组(28例)和对照组(32例),比较三组妊娠妇女妊娠期间的疾病变化情况及母婴情况.结果 ①治疗后三组患者FT3、FT4、TSH水平差异具有统计学意义(P＜0.05),并且甲硫咪唑治疗组和丙硫氧嘧啶治疗组患者的FT3、FT4、TSH水平差异具有统计学意义(P＜0.05);②三组新生儿FT3、FT4、TSH水平差异具有统计学意义(P＜0.05),并且甲硫咪唑治疗组和丙硫氧嘧啶治疗组新生儿FT3、FT4、TSH水平差异具有统计学意义(P＜0.05);③两治疗组患者妊高症发生率、早产发生率和平均分娩孕周与对照组比较差异均具有统计学意义(P＜0.05),并且甲硫咪唑治疗组和丙硫氧嘧啶治疗组患者的平均分娩孕周差异具有统计学意义(P＜0.05);④甲硫咪唑治疗组和丙硫氧嘧啶治疗组新生儿低体重出生率、胎儿窘迫率和出生体重与对照组比较差异也具有统计学意义(P＜0.05),甲硫咪唑治疗组和丙硫氧嘧啶治疗组新生儿出生体重差异均具有统计学意义(P＜0.05).结论 早期采取甲硫咪唑或丙硫氧嘧啶对妊娠期甲状腺功能亢进妇女进行治疗对母婴健康、提高新生儿出生质量均有积极作用,并且甲硫咪唑作用更佳,可作为妊娠期甲状腺功能亢进的首选治疗.     

丙基硫氧嘧啶导致的抗中性粒细胞胞质抗体阳性小血管炎及其靶抗原研究

目的 研究丙基硫氧嘧啶（PTU）引起的抗中性粒细胞胞质抗体（ANCA）阳性小血管炎的临床病理表现及其靶抗原。方法 对我院近年诊治的4例PTU引起的ANCA阳性小血管炎患者进行临床病理分析。以纯化的7种已知的ANCA靶抗原蛋白酶3（PR3）、髓过氧化物酶（MPO）、人白细胞弹力蛋白酶（HLE）、乳铁蛋白（LF）、组蛋白酶G（CG）、杀菌／通透性增高蛋白（BPI）和天青杀素（AZU）为固相抗原,采用ELISA法检测患者血清的靶抗原及治疗前后抗体滴度的变化。结果 4例病人中男女各2例,平均年龄30（11－57）岁,服PTU时间7－60个月。4例均有肾脏、肺脏、皮肤、关节肌肉和血液系统等受累,均为p-ANCA阳性,患者血清均识别MPO、LF和CG;3例识别HLE、AZU,2例识别PR3;无1例识别BPI。多数抗体滴度高,可大于1：25600;而服PTU无小血管炎临床表现的甲状腺功能亢进（甲亢）病人的30份血清均为阴性。肾活检2例为新月体性肾炎,2例为轻微病变,免疫荧光检查均为阴性。4例患者均立即停用PTU,3例应用免疫抑制剂,1例行血浆置换。4例小血管炎的临床症状均得以缓解,但1例晚期新月体肾炎患者发展为慢性肾衰竭而依赖透析。停药和治疗后各种抗体滴度均有所下降,但多未能短期阴转。结论 PTU可引起ANCA阳性小血管炎,其自身抗体可识别中性粒细胞胞质中多种已知的靶抗原;及时诊治,预后较好。     

Intermittent polyarthritis due to propylthiouracil

Summary A case of intermittent polyarthritis developing as a result of long term propylthiouracil (PTU) uptake is described together with successful treatment based on drug replacement.     

抑亢丸联合丙硫氧嘧啶治疗甲状腺功能亢进症的疗效观察

目的探讨抑亢丸联合丙硫氧嘧啶治疗甲状腺功能亢进症的临床疗效。方法选取2018年1月—2020年1月在驻马店市中心医院治疗的甲状腺功能亢进症患者86例,随机分为对照组(43例)和治疗组(43例)。对照组口服丙硫氧嘧啶片,初始剂量100 mg/次,3次/d,服用半个月后,根据甲状腺功能指标调整剂量为50 mg/次,3次/d。治疗组在对照组基础上口服抑亢丸,6g/次,2次/d。两组均连续治疗2个月。观察两组患者临床疗效,同时比较治疗前后两组患者血清游离三碘甲腺原氨酸(FT3)、血清游离甲状腺素(FT4)、三碘甲状腺原氨酸(T3)和甲状腺素(T4)水平,及不良反应情况。结果治疗后,对照组和治疗组临床有效率分别为76.74%和93.02%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者FT3、FT4、T3、T4水平均显著降低(P0.05),且治疗组显著低于对照组(P0.05)。治疗期间,对照组患者药物不良反应发生率为46.51%,显著高于治疗组的16.28%,两组比较差异具有统计学意义(P0.05)。结论抑亢丸联合丙硫氧嘧啶治疗甲状腺功能亢进可明显改善临床症状,促进甲状腺功能指标的恢复,且不良反应低。