Switching from conventional antipsychotics to ziprasidone: A randomized,open-label comparison of regimen strategies

In clinical psychopharmacology, the optimal method of switching from treatment A to treatment B with regard to efficacy and tolerability is an important area of study. We investigated the effects on efficacy and tolerability of switching patients from conventional antipsychotics to ziprasidone. This was a 6-week open-label, randomized study of 54 patients with persistent schizophrenia or schizoaffective disorder. Patients received ziprasidone 40 mg BID for 2 days, with titration up to 80 mg BID thereafter. The switch from conventional antipsychotics to ziprasidone was achieved using one of three discrete schedules: (1) abrupt discontinuation of conventional antipsychotics on day 1; (2) fast taper—50% of conventional antipsychotic dosage on days 1 through 7, followed by discontinuation and (3) slow taper—100% of conventional antipsychotic dosage on days 1 and 2, followed by 50% on days 3 through 7, then discontinuation. We found some evidence that the slow-taper strategy was associated with greater reductions in BPRS total scores early in the study compared to the other two strategies. However, these differences did not remain significant at endpoint, suggesting that there was no overall difference between the strategies.     

Characterization of skin abnormalities in a mouse model of osteogenesis imperfecta using high resolution magnetic resonance imaging and Fourier transform infrared imaging spectroscopy

Evaluation of the skin phenotype in osteogenesis imperfecta (OI) typically involves biochemical measurements, such as histologic or biochemical assessment of the collagen produced from biopsy-derived dermal fibroblasts. As an alternative, the current study utilized non-invasive magnetic resonance imaging (MRI) microscopy and optical spectroscopy to define biophysical characteristics of skin in an animal model of OI. MRI of skin harvested from control, homozygous oim/oim and heterozygous oim/+ mice demonstrated several differences in anatomic and biophysical properties. Fourier transform infrared imaging spectroscopy (FT-IRIS) was used to interpret observed MRI signal characteristics in terms of chemical composition. Differences between wild-type and OI mouse skin included the appearance of a collagen-depleted lower dermal layer containing prominent hair follicles in the oim/oim mice, accounting for 55% of skin thickness in these. The MRI magnetization transfer rate was lower by 50% in this layer as compared to the upper dermis, consistent with lower collagen content. The MRI transverse relaxation time, T2, was greater by 30% in the dermis of the oim/oim mice compared to controls, consistent with a more highly hydrated collagen network. Similarly, an FT-IRIS-defined measure of collagen integrity was 30% lower in the oim/oim mice. We conclude that characterization of phenotypic differences between the skin of OI and wild-type mice by MRI and FT-IRIS is feasible, and that these techniques provide powerful complementary approaches for the analysis of the skin phenotype in animal models of disease.     

FT_3、FT_4及sTSH测定对伴睡眠障碍甲减症的临床应用价值

目的：探讨甲状腺激素及sTSH测定对有睡眠障碍的甲状腺机能减退症临床价值,以减少误诊,提高医疗质量。方法：通过分析本病患者睡眠障碍表现与sTSH、FT3、FT4水平的关系。结果：甲减症睡眠障碍不同表现组甲状腺激素水平各异,思睡、嗜睡组和鼾眠或睡眠呼吸暂停组的sTSH、FT3、FT4浓度显著异常于倦怠、多梦、梦魇或梦惊组（P〈0.01）和健康对照组（P〈0.01）。结论：甲状腺激素及sTSH测定对有睡眠障碍症状的甲减症确诊及疗效监测、评估具有重要临床价值。     

稳定表达MACC1的胃癌BGC-823/pBaBb-puro-MACC1细胞株的建立及其肿瘤相关基因的研究基因

目的构建含有全长肠癌转移相关基因(MACC1)的表达载体,建立稳定表达MACC1的胃癌BGC-823/pBaBb-puro-MACC1细胞系,通过基因芯片技术筛选出转染MACC1后胃癌细胞株的差异表达基因,探讨MACC1基因与差异基因之间可能的调节机制或信号通路。方法以人胚肾293FT细胞为模板,经PCR扩增获全长MACC1 cDNA序列,将目的基因序列克隆入带有绿色荧光蛋白报告基因的pBaBb-puro表达载体,建立pBaBb-puro-MACC1表达载体。经限制性内切酶酶切鉴定、测序并转染293FT细胞观察报告基因表达情况判断是否构建成功。构建成功后的pBaBb-puro-MACC1表达载体转染人胃癌BGC-823细胞,建立稳定表达MACC1的BGC-823/pBaBb-puro-MACC1细胞。qRT-PCR及western blot检测转染细胞的MACC1基因表达,应用基因芯片技术筛选出转染MACC1基因后胃癌细胞株的差异表达基因并对其探讨研究。结果成功扩增全长MACC1cDNA,经测序鉴定序列完全正确;转染293FT细胞可见清晰的绿色荧光表达。BGC-823/pBaBb-puro-MACC1细胞能够稳定表达MACC1。基因芯片筛选出差异基因发现上调基因33个,下调基因24个,这些差异表达基因的功能涉及多个方面。结论成功构建了含有全长MACC1cDNA的表达载体系统,建立了稳定表达MACC1的BGC-823/pBaBb-puro-MACC1细胞,通过对差异基因的分析发现MACC1可能引起胃癌细胞株BGC-823基因表达谱中一些非常重要的分子的改变,为MACC1基因进一步研究奠定了良好基础。     

海带有机碘与无机碘对甲亢大鼠血清FT_3和FT_4及尿碘的影响

目的研究海带有机碘(3,5-二碘酪氨酸,DIT)与无机碘(碘化钾,KI)对甲亢形成中的Wistar大鼠血清游离三碘甲状腺原氨酸(FT_3)、血清游离甲状腺素(FT_4)和尿碘水平的影响。方法将72只SPF级Wistar雄性大鼠随机分成8组,分别为正常对照组、甲亢模型组、DIT组(低、中、高剂量)和KI组(低、中、高剂量),其中低、中、高剂量(以碘计)分别为25.0、166.7、500.1μg/kg。正常对照组灌胃生理盐水,甲亢模型组灌胃甲状腺片悬浊液,其余组同时灌胃甲状腺片悬浊液及其相应的碘剂量。自由摄食饮水,连续喂养30 d,检测各组大鼠血清FT_3、FT_4和尿碘水平。结果与正常对照组比较,甲亢模型组大鼠末期体重下降,血清FT_3和FT_4、尿碘升高(P0.05)。与甲亢模型组比较,DIT各组末期体重较甲亢模型组高,血清FT_3、FT_4水平降低,尿碘水平明显上升(P0.05),KI各组末期体重、血清FT_3、FT_4水平无明显差异,尿碘水平明显上升(P0.05);DIT各组末期体重较对应的KI剂量组高,其中低、中剂量组有统计学意义(P0.05),DIT各组与对应的KI剂量组比较,血清FT_3、FT_4水平都显著降低(P0.05),尿碘水平明显上升,其中中、高剂量组有统计学意义(P0.05)。结论 DIT在甲状腺片诱导大鼠甲亢过程中,一定程度上可降低血清FT_3、FT_4水平,对甲状腺片所致甲亢产生一定的拮抗作用;而无机碘组仅有尿碘排出增加,KI对血清FT_3、FT_4水平无影响。     

截短型小鼠成纤维细胞生长因子受体-1基因慢病毒载体构建及在真核细胞中的表达

本研究旨在克隆小鼠成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,fgfr1)基因,构建携带增强型绿色荧光蛋白(EGFP)的截短型fgfr1(△fgfr1)重组慢病毒载体并在真核细胞中表达。采用逆转录-聚合酶链反应(RT-PCR)以BALB/c胎鼠脑组织为模板克隆全长型fgfr1基因,连接至克隆载体pCR-Blunt,通过反向PCR技术删除胞内磷酸化区域获得△fgfr1,限制性内切酶酶切后亚克隆至慢病毒转移质粒,构建携带EGFP及△fgfr1双顺反子自身失活型重组慢病毒表达质粒,通过脂质体转染法与包装质粒及包膜蛋白质粒共转染包装细胞293FT,超速离心浓缩病毒颗粒后转染293FT细胞,用荧光显微镜及流式细胞术(FCM)检测EGFP的表达,免疫印迹法(Western blot)鉴定截短型FGFR1蛋白表达。结果表明,成功克隆小鼠fgfr1基因,构建重组慢病毒转移载体LV-IRES-EGFP-△fgfr1及对照载体LV-IRES-EGFP,三质粒系统共转染293FT细胞后获得病毒滴度达到108 TU/ml。以重组病毒载体转染293FT细胞后第4天在荧光显微镜下观察到较强绿色荧光表达,FCM检测转染效率可达95%,Western blot检测显示,转染后293FT细胞表达截短型FGFR1蛋白。结论:成功构建了自身失活型慢病毒载体LV-IRES-EGFP-△fgfr1,并在真核细胞中获得表达。     

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.     

Evaluation of catch-up growth in severe pediatric Hashimoto's hypothyroidism

BackgroundWe aimed to evaluate catch-up growth in children with severe Hashimoto's hypothyroidism (HH) after thyroid hormone replacement therapy (HRT).MethodsA multicenter retrospective study was conducted including children referred for growth slowdown that led to the diagnosis of HH between 1998 and 2017.ResultsA total of 29 patients were included, with a median age of 9.7 years (13–172 months). Median height at diagnosis was -2.7 [-4.6; -0.1] standard deviation score (SDS), with a height loss of 2.5 [0.7; 5.4] SDS compared to height before growth deflection (p<0.0001). At diagnosis, the median TSH level was 819.5 mIU/L [100; 1844], the median FT4 level was 0 pmol/L [undetectable; 5.4], and the median anti-thyroperoxidase antibody level was 1601 UI/L [47; 25,500].In the 20 patients treated only with HRT, there were significant differences between height at diagnosis and height at 1 year (n = 19, p<0.0001), 2 years (n = 13, p = 0.0005), 3 years (n = 9, p = 0.0039), 4 years (n = 10, p = 0.0078), and 5 years (n = 10, p = 0.0018) of treatment but not in the case of final height (n = 6, p = 0.0625). Median final height was -1.4 [-2.7; 1,5] SDS (n = 6), with a significant difference between height loss at diagnosis and total catch-up growth (p = 0.003).The other nine patients were also given growth hormone (GH). They were smaller at diagnosis (p = 0.01); however, there was no difference in final height between those two groups (p = 0.68).ConclusionSevere HH can lead to a major height deficit, and catch-up growth seems to be insufficient after treatment with HRT alone. In the most severe cases, administration of GH may enhance this catch-up.