丙硫氧嘧啶缓释片与普通片的犬体内药动学及生物利用度比较

目的:研究丙硫氧嘧啶缓释片在beagle犬体内的药动学过程,测定其药动学参数、相对于普通片的生物利用度和生物等效性。方法:采用双交叉试验设计法,取6条健康beagle犬随机分成2组,分别服用丙硫氧嘧啶缓释片和普通片,用高效液相色谱法测定丙硫氧嘧啶的血药浓度,利用3P97软件包计算主要的药动学参数以及相对生物利用度,并判断生物等效性。结果:犬口服丙硫氧嘧啶后符合二房室模型特征,缓释片和普通片的MRT分别为(5.3±s0.6)h和(3.0±0.6)h,tmax分别为(2.4±0.5)h和(1.1±0.3)h,cmax分别为(15.6±2.0)和(23.3±2.9)mg·L-1,缓释片的相对生物利用度为(114±4)%。结论:丙硫氧嘧啶缓释片和普通片具有生物等效,且缓释片具有12h缓释效果。     

PROP test: prediction of caries risk by genetic taste perception among the visually impaired children

The study sample consisted of 100 children with visual impairment aged 6–14 years. 6‐n‐propylthiouracil (PROP) sensitivity test was carried out. The Caries experience was recorded, estimation of Streptococcus mutans done and their taste likes and dislikes assessed through a food preference questionnaire. The Caries experience and S. mutans levels were highest in the non‐tasters, comparatively low in medium tasters and the least in the supertasters. Dietary preferences indicated tasters were sweet dislikers and non‐tasters, sweet likers. PROP test can be a useful tool in determining genetic taste sensitivity levels amongst the visually impaired children and thus used as a screening tool in those children who are at a high risk of developing dental caries.     

Propylthiouracil-induced autoimmune disease

Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU) is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day) since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality.     

Meta‐analysis of propylthiouracil for alcoholic liver disease – a Cochrane Hepato‐Biliary Group Review

Abstract: Aims/Background: The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease. Methods: Systematic Cochrane Review of randomised clinical trials. The Cochrane Hepato‐Biliary Controlled Clinical Trials Register, The Cochrane Library, MEDLINE, and full text searches were combined. All analyses were performed according to the intention‐to‐treat method. Only randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis and/or alcoholic cirrhosis were included. Interventions encompassed propylthiouracil at any dose versus placebo or no intervention. The trials could be double‐blind, single‐blind or unblinded. Results: Six randomised clinical trials randomising 710 patients demonstrated no significant effects of propylthiouracil versus placebo on mortality (Peto odds ratio (OR) 0.91, 95% confidence interval (CI) 0.59 to 1.40), liver‐related mortality (OR 0.78, CI 0.45 to 1.33), complications to the liver disease (OR 1.14, CI 0.58 to 2.24), and liver histology. Propylthiouracil was associated with a nonsignificant trend toward an increased risk of nonserious adverse events (OR 1.49, CI 0.74 to 2.99) and with the rare occurrence of serious adverse events (leukopenia). Conclusions: This systematic review could not demonstrate any significant effect of propylthiouracil on any clinically important outcomes (mortality, liver‐related mortality, liver complications and liver histology) of patients with alcoholic liver disease.     

甲巯咪唑与丙硫氧嘧啶对甲状腺功能亢进患者肝功能影响的临床对照研究

目的探讨甲巯咪唑和丙硫氧嘧啶对甲状腺功能亢进患者肝功能影响的疗效。方法选取80例甲状腺功能亢进患者,随机分为两组,甲组（41例）口服甲巯咪唑,乙组（39例）口服丙硫氧嘧啶片。观察并记录两组患者治疗前后甲状腺功能指标,肝功能指标,肝功能受损情况及治疗期间不良反应情况,评价甲巯咪唑和丙硫氧嘧啶对甲状腺功能亢进患者肝功能的影响。结果治疗前,两组患者由于甲状腺功能亢进,三碘甲腺原氨酸（FT₃）、四碘甲腺原氨酸（FT₄）均处于高水平状态,且差异无统计学意义。促甲状腺激素（TSH）分泌受到抑制,处于较低水平。治疗后,患者甲状腺功能亢进症状有所改善,患者FT₃、FT₄较治疗前降低,TSH较治疗前升高（P<0.05）,但组间比较差异无统计学意义。治疗前,两组丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷氨酰转肽酶（GGT）水平相比,差异无统计学意义。治疗后乙组ALT、AST、GGT水平均有所升高,并明显高于甲组（P<0.05）,其中,以ALT变化最为明显;甲组治疗前后无明显变化。治疗期间,甲组患者出血5例肝损伤,乙组14例肝损伤,乙组患者肝损伤比例明显高于甲组（P<0.05）,乙组患者肝脏损伤发生时间明显晚于甲组（P<0.05）。治疗期间,两组不良反应发生率无统计学差异。结论甲巯咪唑与丙硫氧嘧啶对甲状腺功能亢进的疗效相当。与丙硫氧嘧啶相比,甲巯咪唑对肝脏损伤程度较小,但服药后较早引起肝脏损伤,建议在甲状腺功能亢进治疗期间,应定期复查患者肝功能。     

Possible association of medications during pregnancy with low estriol level of the triple antenatal screening test

Objective: Our purpose was to reach the reasons of isolated low levels of maternal serum unconjugated estriol (uE3) levels (≤0.3 multiples of the median (MoM)) in the triple-marker screen with special emphasis on maternal diseases and medications used for them. Methods: Single center retrospective cross-sectional analysis. Of 13,367 non-smoking women with identified singleton pregnancies screened for triple test, during 3-year period (2007–2009), a group of women with isolated low serum uE3 levels (≤0.3 MoM) (n?=?14) were selected as the study group. Results: Of these 14 women, no one gave birth with ichthyosis. Five patients had, isolated very low uE3 levels (<0.01 MoM). Of these women, one had umbilical cord knot, one was on corticosteroid and three were on propylthiouracil treatment. So, there was history of maternal drug intake in 28.5% of cases with isolated low uE3 (≤0.3 MoM). This rate increases to 80% in cases with very low uE3 levels (<0.01 MoM). Conclusions: Maternal diseases and medications used during pregnancy can affect fetus and antenatal screening test results. This is important during counseling of patients and to perform the appropriate antenatal and postnatal evaluation of the mother and fetus with multidisciplinary approach.     

丙硫氧嘧啶致严重粒细胞缺乏及急性肝损害

1名34岁女性,因患甲状腺功能亢进,口服丙硫氧嘧啶(PTU)100mg,3次/d,地西泮10mg,3次/d。服药19d后出现发热(T38.3℃)、皮疹、咽痛、恶心等症状。实验室检查示:WBC1.18×109/L,中性粒细胞计数0.50×109/L,ALT457U/L,AST120U/L,Glu8.49mmol/L。停用丙硫氧嘧啶,给予还原型谷胱甘肽、水飞蓟宾葡甲胺、氯雷他定、地西泮、非格司亭治疗。4周后患者血常规恢复正常,肝功能明显好转。     

反相高效液相色谱法测定人血浆中丙基硫氧嘧啶浓度

本文报道用反相高效液相色谱法测定人血浆中丙基硫氧嘧啶浓度。用Ultrasphere-ODS柱,甲醇:水(30:70)为流动相,茶碱作内标,于254nm检测。萃取回收率为89.1%,方法回收率为98.1%,日内变异系数为5.9%,日间变异系数为7.2%。本法灵敏,准确,重现性好,已用于临床甲亢病人药代动力学研究的血药浓度测定,取得良好结果。     

NADPH-d/NOS reactivity in the lumbar dorsal horn of congenitally hypothyroid pups before and after formalin pain induction

We have previously demonstrated that congenitally hypothyroid rat pups exhibit altered behavioral response to formalin pain induction during postnatal period. In the present study, using NADPH-diaphorase histochemistry and NOS immunostaining, we investigated the effect of congenital hypothyroidism on the NOS expression in spinal cord of intact neonates at postnatal days of 15 and 21. We also examined the effect of thyroid dysfunction on the NADPH-d/NOS expression in response to formalin nociception. Congenital hypothyroidism induced by propylthiouracil (PTU) treatment started from gestational day 16 and continued to postnatal day 15 or 21. Congenitally hypothyroid pups exhibited marked reduction in NADPH-d reactive cells (84% and 66% in P15 and P21, respectively; P < 0.001) and NOS-ir cells (52% and 91% in P15 and P21, respectively; P < 0.001) in superficial lumbar dorsal horn laminae (I–II) as compared to that of normal pups. Moreover, in congenitally hypothyroid pups the NADPH-d/NOS expression following hindpaw formalin injection did not change significantly. Our results demonstrate that congenital hypothyroidism affect developmental expression of NOS in spinal dorsal horn, which may in part explain the altered behavioral pain response as we previously reported in hypothyroid pups.     

丙基硫氧嘧啶改善甲亢患者心脏及内分泌功能的疗效及意义

１３例初诊甲亢患者于应用丙基硫氧嘧啶治疗前、治疗３个月及６个月时超声心动图检测心功能并用放射免疫分析法检测血浆心钠素（ＡＮＰ）、肾素活性（ＰＲＡ）、血管紧张素Ⅱ（ＡｎｇⅡ）及血清甲状腺激素（ＴＴ＿３、ＴＴ＿４）水平。治疗后心率下降（Ｐ＜０．００１），体重增加（Ｐ＜０．００１），心输出量及心指数下降（Ｐ＜０．０５）。各瓣膜区流速减慢（Ｐ＜０．０５），ＴＴ＿３、ＴＴ＿４恢复正常。随高动力性循环状态改善，血浆ＡＮＰ水平明显下降（Ｐ＜０．０１）．ＡｎｇⅡ及ＰＲＡ明显升高（Ｐ＜０．０１及０．００１）。提示丙基硫氧嘧啶能有效改善甲亢患者的心脏功能及内分泌功能。