Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Erythema induratum of Bazin in a 10‐year‐old boy

Erythema induratum of Bazin (EIB) is a form of tuberculid resulting from hypersensitivity to tuberculosis antigen. EIB occurs most commonly in middle‐aged women and is not typically seen in children. Here, we present a rare case of EIB, presenting as a chronic nodular panniculitis, in a 10‐year‐old Korean boy.     

Sample size re-estimation for clinical trials with longitudinal negative binomial counts including time trends

In some diseases, such as multiple sclerosis, lesion counts obtained from magnetic resonance imaging (MRI) are used as markers of disease progression. This leads to longitudinal, and typically overdispersed, count data outcomes in clinical trials. Models for such data invariably include a number of nuisance parameters, which can be difficult to specify at the planning stage, leading to considerable uncertainty in sample size specification. Consequently, blinded sample size re-estimation procedures are used, allowing for an adjustment of the sample size within an ongoing trial by estimating relevant nuisance parameters at an interim point, without compromising trial integrity. To date, the methods available for re-estimation have required an assumption that the mean count is time-constant within patients. We propose a new modeling approach that maintains the advantages of established procedures but allows for general underlying and treatment-specific time trends in the mean response. A simulation study is conducted to assess the effectiveness of blinded sample size re-estimation methods over fixed designs. Sample sizes attained through blinded sample size re-estimation procedures are shown to maintain the desired study power without inflating the Type I error rate and the procedure is demonstrated on MRI data from a recent study in multiple sclerosis.     

3-(3-吡啶基)-6-芳基-7H-1,2,4-三唑并[3,4-b][1,3,4]噻二嗪的合成与波谱表征

目的：研究分子中含吡啶基的有多个杂环的化合物系列的波谱表征，方法：由烟酸出发，经多步反应，制得有吡啶基的均三唑并噻二嗪化合物，并进行红外，核磁共振氢谱与碳谱测试。结果：得到原料，中间体和产物的红外光谱图，产物的核磁共振氢谱与碳谱图。结论：标题化合物红外光谱1600cm^-1处多有C＝N伸缩振动峰，1250cm^-左右有N－N＝C伸缩振动峰，700cm^-1有C－S－C弯曲振动峰；噻二嗪亚甲基氢的化学位移δ值约为4．46，吡啶基四个氢原子化学位移约为9．3、8．9、8．7、8．0，噻二嗪亚甲基碳化学位移为23。     

TSo联合IFN-γ鼻内免疫小鼠诱导的弓形虫IgA抗体特异性免疫应答

目的研究速殖子超声裂解物(TSo)和IFN-γ鼻内免疫小鼠经口感染弓形虫速殖子后,血清、小肠液和粪便IgA抗体分泌的动态变化。方法将6～7周龄BALB/c小鼠100只随机分为4组,每组25只,分别用10μl缓冲液PBS、20μgTSo、500UIFN-γ和20μgTSo 500UIFN-γ鼻内免疫小鼠。用RH株弓形虫速殖子4×104个/只灌胃攻击,分别于攻击后第7、10、13、16、19天处死小鼠,收集血清、小肠液及粪便,ELISA法测定IgA含量。结果各组血清IgA抗体水平在攻击后第10天达到峰值,TSo IFN-γ组血清IgA抗体含量高于其他各组。小肠液和粪便IgA抗体含量在攻击后第13天达到峰值,在实验期各时点TSo IFN-γ组小肠液和粪便IgA抗体含量高于其他组。小肠液与粪便IgA抗体水平呈正相关。结论TSo或IFN-γ或TSo联合IFN-γ鼻内免疫小鼠可诱导黏膜免疫,产生高水平的弓形虫特异性IgA抗体。TSo联合IFN-γ鼻内免疫优于单独免疫,免疫小鼠肠道产生大量SIgA,发挥抗虫作用。鼻黏膜免疫是一种安全有效的免疫接种途径。     

重质石油中含氮化合物的形态及分布分析Ⅱ．含氦杂环化合物的定性方法

探索了色谱保留值与质谱信息相结合的定性分析方法。用ＳＥ－５４柱代替ＳＥ－５２柱，选用六个多环芳烃化合物作为标准计算保留指数，从而改善了Ｍ．Ｌ．Ｌｅｅ保留指数的应用条件和范围；用文献值转换扩充了Ｌｅｅ的含氮杂环化合物保留指数表，并利用保留时间与沸点的关系作定性佐证。应用该法鉴定了重质石油样品子组分及萘油中的４６个含氮杂环化合物及其异构体，为质谱在异构体鉴定以及缺乏标样所产生的困难提供了可信、简便的定性鉴定方法。