Clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride on mild-to-moderate depression

BACKGROUND Depression is a common,chronic,and recurrent mood disorder that has become a worldwide health hazard.Fluoxetine hydrochloride,a common treatment method,can inhibit 5-hydroxytryptamine(5-HT)recycling in the presynaptic membrane;however,the efficacy of a single drug is inadequate.At present,mildto-moderate depression can be treated with acupuncture of ghost caves,but the clinical curative effect of combined therapy with fluoxetine hydrochloride has not been sufficiently reported.AIM To evaluate the clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride in the treatment of mild-to-moderate depression.METHODS This retrospective study included 160 patients with mild-to-moderate depression who were admitted to Shanghai Hospital of Integrated Traditional Chinese and Western Medicine,Affiliated to Shanghai University of Traditional Chinese Medicine,between January 2022 and June 2023.Patients were separated into a single-agent group(fluoxetine hydrochloride treatment,n=80)and a coalition group(fluoxetine hydrochloride treatment combined with acupuncture at ghost points,n=80).Pre-treatment symptoms were recorded,and the clinical curative effect and adverse reactions[Asberg Antidepressant Side Effects Scale(SERS)]were assessed.Depression before and after treatment[Hamilton Depression Scale(HAMD)-24],neurotransmitter levels[5-HT,norepinephrine(NE),dopamine(DA)],oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)],and sleep quality[Pittsburgh Sleep Quality Index(PSQI)]were compared.RESULTS The total efficacy rate was 97.50%in the coalition group and 86.25%in the single-agent group(P<0.05).After 2,4,6,and 8 wk of treatment,the HAMD,self-rating depression scale,and SERS scores of the coalition and single-agent groups decreased compared with pre-treatment,and the decrease was more significant in the coalition group(P<0.05).After 8 wk of treatment,the levels of NE,DA,5-HT,and SOD in the coalition and single-agent groups increased,while the levels of MDA decreased;the increases and decrease in the coalition group were more significant(P<0.05).The PSQI scores of the coalition and single-agent groups decreased,and the decrease was more significant in the coalition group(P<0.05).CONCLUSION Acupuncture at ghost points combined with paroxetine tablets can safely improve depressive symptoms and sleep disorders,regulate neurotransmitter levels,and reduce stress responses in patients with mild-to-moderate depression.

工程教育中心何以推动科教融合——荷兰4TU工程教育中心的探索性单案例研究

工程教育中心作为建立在大学或研究机构中的跨学科交叉合作平台,是连接科学研究与教育实践的纽带,在高质量工程人才培养中发挥着重要作用。荷兰4TU工程教育中心利用4所顶尖理工大学在工程学科和教育领域的独特优势,积极与研发单位、教育单位、企业部门合作,通过将前沿科学研究彻底融入工程课程设计、教学模式等多个方面,形成了独具一格的科教融合工程人才培养模式。文章从战略目标、组织架构、运行机制、质量保障4个维度详实分析了4TU工程教育中心推动科教融合的内在机制,总结归纳其在主题项目设置、教育共同体形成、课程体系迭代、创新网络构建、内外部质量保障等方面的核心特征,期望对我国科教融合的工程教育改革与建设有所启示。

Delineation of biomarkers and molecular pathways of residual effects of fluoxetine treatment in juvenile rhesus monkeys by proteomic profiling

Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective serotonin reuptake inhibitor,the possible long-term effects of fluoxetine on brain development in children are poorly understood.In the current study,we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques(Macaca mulatta)one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex(DLPFC)and cingulate cortex(CC)that correlated with impulsivity in animals,suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment.Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.

异氟烷麻醉对小鼠自发肌电及TUS/TMAS诱发肌电的影响

经颅超声刺激(TUS)和经颅磁声耦合刺激(TMAS)调控运动皮层效果明显,但受限于清醒状态动物难以束缚,已有研究大多在麻醉状态下进行,对麻醉减弱调控效果的分析集中于中枢神经系统。本研究记录了异氟烷麻醉下24只小鼠的肢体自发肌电和TUS/TMAS诱发肌电,定量分析了麻醉对自发肌电和诱发肌电发放率、潜伏期、时长和幅值的影响。结果显示,随着异氟烷输出浓度从0.40%增加至0.75%,每周期内小鼠自发肌电频次减少约50%,肌电发放时长变短,呈抑制状态;TUS/TMAS诱发肌电的成功率分别降低约50%和70%、潜伏期均延长约0.1 s、时长分别缩短约0.3和0.5 s,表明TUS/TMAS对运动皮层的调控效果随麻醉程度的加深而减弱。肢体自发和诱发肌电在发放率和时长上存在关联性特征,提示麻醉状态下小鼠自发肌电抑制状态可能是刺激效果减弱的影响因素之一。

沉默TUFM通过AMPK/mTOR信号通路调控线粒体自噬对肺源性心脏病模型大鼠肺动脉高压的影响

目的探讨线粒体翻译延伸因子Tu(TUFM)通过线粒体自噬促进肺动脉高压(PAH)血管重塑的作用机制。方法2022年1月—2023年6月于辽宁省人民医院中心实验室进行实验。将36只健康雄性Sprague-Dawley大鼠随机分为空白对照(Ctrl)组、模型(PAH)组、TUFM过表达(OE)组、OE阴性对照(OE-NC)组、短发夹RNA(Sh)敲除TUFM(Sh)组和Sh-NC阴性对照(Sh-NC)组,每组6只。除Ctrl组外,其余大鼠均一次性腹腔注射1%野百合碱(60 mg/kg)诱导心源性肺水肿PAH大鼠模型;大鼠肺动脉平滑肌细胞(PASMC)在低氧(3%O 2)条件下培养24 h模拟体内肺动脉高压微环境,分为常氧(Norm)组、低氧(Hyp)组、小干扰RNA(SiRNA)-1组、SiRNA-2组、Si-NC组、OE-NC组和OE组。右心导管插管和脉冲多普勒超声检测大鼠肺血流动力学;苏木素-伊红染色检测肺小动脉病理结构;免疫荧光共染检测TUFM组织定位;细胞计数法检测细胞增殖;透射电镜观察线粒体结构和自噬小体;蛋白免疫印迹检测TUFM、自噬、凋亡和磷酸腺苷活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)通路相关蛋白表达。结果与Ctrl组比较,PAH组大鼠TUFM蛋白表达升高,且主要与PASMC标志物α平滑肌肌动蛋白(α-SMA)在肺小动脉内膜存在共定位,而与内皮细胞标志物CD31无共定位,肺动脉收缩压(PASP)升高,肺动脉血流加速时间(PAAT)缩短,远端肺小动脉管壁呈向心性增厚,管腔狭窄几乎堵塞,TUFM、苄氯素1重组蛋白(BECN1)、人微管相关蛋白轻链3(LC3)II/I和B淋巴细胞瘤2(Bcl2)蛋白表达升高,P62、Bcl2相关X蛋白(Bax)和凋亡酶激活因子(Apaf)蛋白表达降低(P<0.05);与PAH组比较,OE组PASP升高,PAAT缩短,肺小动脉管壁厚度升高,肺动脉TUFM、BECN1、LC3II/I和Bcl2表达升高,P62、Bax和Apaf表达降低(P<0.05);与PAH组比较,Sh组PASP降低,PAAT延长,肺小动脉管壁厚度和管腔狭窄度有所改善,TUFM、BECN1、LC3II/I和Bcl2表达降低,P62、Bax和Apaf表达升高(P<0.05)。与Norm组比较,Hyp组PASMC细胞TUFM蛋白表达升高;与Si-NC组细胞相比,SiRNA-1和SiRNA-2组P62、Bax蛋白表达升高,BECN1、LC3II/I、Bcl2、TUFM表达降低,线粒体结构完整,PASMC细胞增殖活性降低,细胞p-AMPK表达降低,p-mTOR表达升高(P<0.05);与OE-NC组比较,OE组细胞P62和Bax蛋白表达降低,BECN1、LC3II/I、Bcl2和TUFM表达升高,部分线粒体损伤崩解,嵴断裂消失,PASMC细胞增殖活性明显升高,细胞p-AMPK表达升高,p-mTOR表达降低(P<0.05)。结论沉默TUFM可通过激活AMPK/mTOR信号通路促进线粒体自噬加速PAH肺动脉平滑肌细胞凋亡。

Efficacy of acupuncture at ghost points combined with fluoxetine in treating depression:A randomized study

BACKGROUND Depression affects more than 350 million people worldwide.In China,4.2%(54 million people)of the total population suffers from depression.Psychotherapy has been shown to change cognition,improve personality,and enhance the ability to cope with difficulties and setbacks.While pharmacotherapy can reduce symptoms,it is also associated with adverse reactions and relapse after drug withdrawal.Therefore,there has been an increasing emphasis placed on the use of non-pharmacological therapies for depression.The hypothesis of this study was that acupuncture at ghost points combined with fluoxetine would be more effective than fluoxetine alone for the treatment of depression.AIM To investigate the efficacy of acupuncture at ghost points combined with fluoxetine for the treatment of patients with depression.METHODS This randomized controlled trial included patients with mild to moderate depression(n=160).Patients received either acupuncture at ghost points combined with fluoxetine(n=80)or fluoxetine alone(control group,n=80).Needles were retained in place for 30 min,5 times a week;three treatment cycles were administered.The Mann–Whitney U test was used to compare functional magnet resonance imaging parameters,Hamilton depression rating scale(HAMD)scores,and self-rating depression scale(SDS)scores between the acupuncture group and control group.RESULTS There were no significant differences in HAMD or SDS scores between the acupuncture group and control group,before or after 4 wk of treatment.The acupuncture group exhibited significantly lower HAMD and SDS scores than the control group after 8 wk of treatment(P<0.05).The acupuncture group had significantly lower fractional Amplitude of Low Frequency Fluctuations values for the left anterior wedge leaf,left posterior cingulate gyrus,left middle occipital gyrus,and left inferior occipital gyrus after 8 wk.The acupuncture group also had significantly higher values for the right inferior frontal gyrus,right insula,and right hippocampus(P<0.05).After 8 wk of treatment,the effective rates of the acupuncture and control groups were 51.25%and 36.25%,respectively(P<0.05).CONCLUSION The study results suggest that acupuncture at ghost points combined with fluoxetine is more effective than fluoxetine alone for the treatment of patients with mild to moderate depression.

Fluoxetine Ameliorates the Aggravation of UC Symptoms in C57BL/6 Mice Induced by CUMS

Objective Patients with chronic ulcerative colitis(UC)often have mental symptoms such as depression and anxiety,and stress can lead to gastrointestinal diseases.However,the correlation between mental stress and UC is unclear.In this paper,chronic unpredictable mild stress(CUMS)was utilized to evaluate the involvement of mental factors in the pathogenesis of UC.Methods The CUMS model was used to evaluate the direct/indirect involvement of mental factors in the pathogenesis of UC.The behavior was evaluated by the open field,forced swimming,and tail suspension tests.Body weight,the disease activity index(DAI)score,colon length,and HE staining of colon tissue were used to evaluate the action of CUMS and fluoxetine.Results The results showed that weight loss and the DAI score increased in CUMS mice,but they had no meaningful effect on colon length and morphological structure of colon tissue.However,CUMS aggravated dextran sulfate sodium(DSS)-induced colon length shortening and colon morphological structure damage.Fluoxetine significantly improved the DAI score,shortened colon length,and damaged morphology and structure of the colons induced by CUMS combined with DSS in mice.Fluoxetine also decreased the level of IL-6 in the serum and the TNF-αand IFN-γlevels of colon tissue.Fluoxetine simultaneously improved behavioral abnormalities induced by CUMS combined with DSS in mice.Conclusion CUMS aggravated the UC symptoms induced by DSS,and fluoxetine could improve the UC symptoms due to its improvement in the inflammatory level and behavioral abnormalities.

绵羊肺炎支原体EF-Tu蛋白的原核表达及多克隆抗体制备

[目的]克隆绵羊肺炎支原体(Mycoplasma ovipneumoniae,Mo)EF-Tu基因,原核表达获得EF-Tu蛋白,制备抗EF-Tu蛋白的兔源多克隆抗体,为研究肺炎支原体EF-Tu蛋白的结构和功能奠定基础。[方法]采用重叠延伸PCR方法将pET-28a-EF-Tu质粒中EF-Tu基因中间的TGA密码子突变为TGG,并对测序结果与其他支原体参考株进行相似性比对和遗传进化分析,利用在线软件对其推测的蛋白序列进行生物信息学分析。将突变后的重组质粒转化大肠杆菌BL21(DE3)感受态细胞进行原核表达,经SDS-PAGE和Western blotting鉴定,利用镍柱亲和层析法纯化,以纯化的EF-Tu融合蛋白免疫家兔制备多克隆抗体,采用间接ELISA和Western blotting检测多克隆抗体效价及免疫反应性。[结果]试验成功突变了EF-Tu基因中TGA位点,并构建了融合表达His标签pET-28a-EF-Tu′原核表达载体。生物信息学分析表明,克隆的EF-Tu基因与绵羊肺炎支原体MoGH3-3菌株相似性最高,亲缘关系最近;编码387个氨基酸,无N-糖基化位点和跨膜区域,存在10个丝氨酸、20个苏氨酸、4个酪氨酸磷酸化位点,二级结构由无规则卷曲(35.14%)、α-螺旋(26.87%)、延伸链(26.87%)及β-转角(11.11%)构成。SDS-PAGE和Western blotting结果显示,目的蛋白大小约为43 ku,蛋白纯化浓度为0.615 g/L。ELISA和Western blotting结果显示,制备的多克隆抗体效价可达1∶128 000,能够特异性识别EF-Tu融合蛋白,具有良好的免疫反应性。[结论]本研究成功突变了EF-Tu基因的TGA密码子,原核表达并纯化获得EF-Tu融合蛋白,制备其多克隆抗体效价为1∶128 000,为后续研究肺炎支原体EF-Tu蛋白结构和生物学功能及其疫苗研发提供了试验基础。

Antidepressant fluoxetine and its potential against colon tumors

Colon cancer is one of the most common tumors worldwide,with increasing incidence in developing countries.Patients treated with fluoxetine(FLX) have a reduced incidence of colon cancer,although there still remains great controversy about the nature of its effects.Here we explore the latest achievements related to FLX treatment and colon cancer.Moreover,we discuss new ideas about the mechanisms of the effects of FLX treatment in colon cancer.This leads to the hypothesis of FLX arresting colon tumor cells at the at G1 cell-cycle phase through a control of the tumor-related energy generation machinery.We believe that the potential of FLX to act against tumor metabolism warrants further investigation.

RETRACTED: Validated UPLC-MS/MS Method for the Simultaneous Quantification of Vortioxetine and Fluoxetine in Plasma: Application to Their Pharmacokinetic Interaction Study in Wistar Rats

Short Retraction Notice The paper does not meet the standards of "American Journal of Analytical Chemistry". The article has been retracted due to the conflicts of interests between all authors to straighten the academic record. Aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused. The full retraction notice in PDF is preceding the original paper, which is marked "RETRACTED".

Fluoxetine Hydrochloride的NMR数据解析

由美国Lilly公司开发的第二代抗抑郁症药物盐酸氟西汀(Fluoxetine hydrochloride),属于选择性5-羟色胺再摄取抑制剂(SSRI),除了用于治疗各类抑郁症,包括轻性或重性抑郁症,尤宜用于老年性抑郁症之外,对于强迫症、惊恐发作、贪食症、经前期焦虑等亦有很好疗效.Fluoxetine hydrochloride是一种双环化合物,与传统的三环类、杂环类或单胺氧化酶抑制剂抗抑郁药相比,具有疗效好、不良反应轻而少,安全性高、耐受性好等特点,目前已作为一线的抗抑郁药得到广泛应用.本文对Fluoxetine hydrochloride进行了1H NMR和13C NMR检测,并通过DEPT和1H-1HCOSY、HMBC、HSQC等2D NMR技术对其1H NMR和13C NMR数据进行了较为详细的解析和比文献[1]更为全面的NMR归属,为以后的分析鉴定提供更完善的依据.

白地霉G38生物转化制备抗忧郁药(R)-fluoxetine

从200株菌中筛选出具有双酮化合物还原活力较高的菌株7株,其中以白地霉(Geotrickum, sp. )G38活力最高,而且有较好的区域选择性和立体选择性。白地霉G38能对β-羰基苯丙酸乙酯进行不对称还原,生成(R)-β-羟基苯丙酸乙酯,用于制备抗忧郁药(R)-fluoxetine。用二甲基硅橡胶包埋白地霉菌体取代游离菌体进行生物转化,可以提高反应的立体选择性,对映体过量值从49％提高到81％。

TU1无氧铜/316L不锈钢电子束焊接接头组织与性能

采用真空电子束焊分别对2mm、3mm、5mm不同厚度的TU1无氧铜板材和316L不锈钢板材进行异种材料焊接,并对焊接接头的显微组织和力学性能进行了研究。实验结果表明:焊缝区和热影响区呈现波浪形状,焊缝区存在不同程度的混合组织,接头母材区及热影响区的晶粒大小随铜钢板材厚度的增加而增加。TU1热影响区的晶粒明相比母材区,明显增大。焊缝区的硬度高于母材区。在电子束电流为10mA,加速电压为150kV,焊接速度为15mm/s的焊接参数下,2mm、3mm、5mm厚的接头抗拉强度分别是263MPa、174MPa、141MPa。2mm厚的拉伸式样断裂发生在TU1热影响区,而3mm和5mm厚拉伸式样断裂发生在焊缝处,即2mm厚的TU1无氧铜板材和316L不锈钢板材焊接接头抗拉性能最好。

Effect of <i>Citrus aurantium</i>L. Essential Oil and Its Interaction with Fluoxetine on Anxiety in Male Mice

Anxiety is a very common mental disorder among neurological diseases. Some herbs have soothing effects and play an important role in reducing anxiety. The purpose of this study is to investigate the effect of Citrus aurantium L. essential oil on anxiety and its interference with serotonergic pathway. Sixty male mice were assigned into control, sham (saline and olive oil), and experimental groups. Intraperitoneal injection of Citrus aurantium L. essential oil was applied at doses of 0.5, 2.5, and 5 percent for 5 days. In another set of experiments, after intraperitoneal injection of Citrus aurantium L. essential oil at doses of 0.5, 2.5, and 5 percent for 5 days, on the 5th day, 30 minutes before applying essential oil, fluoxetine (2 mg/kg) was injected. Then, the anxiety-related behavior was assessed using elevated plus maze test. The results revealed that injection of essential oil of Citrus aurantium L. alone or along with fluoxetine led to increasing the number of entries into the open arms and the time spent in open arms that was significantly different compared with control and sham groups (P?< 0.001). Besides, further effects revealed when fluoxetine added to essential oils, however no more effects obtained when compared to fluoxetine alone. It is concluded that Citrus aurantium L. essential oil can reduce the anxiety in male mice and due to fluoxetin potentiation and maximum response observed, the herb may express its anxiolytic effects in part, via serotonergic system.

Fluoxetine ameliorates depressive symptoms by regulating lncRNA expression in the mouse hippocampus

Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise.Recent studies have demonstrated that altered expressions of long non-coding RNAs(lncRNAs)in the brain affect neurodevelopment and manifest modulating functions during the depression.However,most lncRNAs have not yet been studied.Herein,we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors,as well as their corresponding response following antidepressant fluoxetine treatment.A chronic unpredictable mild stress(CUMS)mouse model was applied.A sixweek fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors.In addition,differential expression analysis of lncRNAs was performed following RNA-sequencing.A total of 282 lncRNAs(134 up-regulated and 148 down-regulated)were differentially expressed in CUMS-induced mice relative to non-stressed counterparts(P<0.05).Moreover,370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention.Gene Ontology(GO)analyses showed an association between significantly dysregulated lncRNAs and protein binding,oxygen binding,and transport activity,while the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways.Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus.The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.

Fluoxetine induces cytotoxic endoplasmic reticulum stress and autophagy in triple negative breast cancer

AIM: To investigate the mechanism of action of lipophilic antidepressant fluoxetine(FLX) in representative molecular subtypes of breast cancer.METHODS: The anti-proliferative effects and mechanistic action of FLX in triple-negative(SUM149PT) and luminal(T47D and Au565) cancer cells and nontransformed MCF10 A were investigated. Reverse phase protein microarray(RPPM) was performed with and without 10 μmol/L FLX for 24 and 48 h to determine which proteins are significantly changed. Viability and cell cycle analysis were also performed to determine drug effects on cell growth. Western blotting was used to confirm the change in protein expression examined by RPPM or pursue other signaling proteins. RESULTS: The FLX-induced cell growth inhibition in all cell lines was concentration- and time-dependent but less pronounced in early passage MCF10 A. In comparison to the other lines,cell growth reduction in SUM149 PT coincided with significant induction of endoplasmic reticulum(ER) stress and autophagy after 24 and 48 h of 10 μmol/L FLX,resulting in decreased translation of proteins along the receptor tyrosine kinase/Akt/mammalian target of rapamycin pathways. The increase in autophagy marker,cleaved microtubule-associated protein 1 light chain 3,in SUM149 PT after 24 h of FLX was likely due to increased metabolic demands of rapidly dividing cells and ER stress. Consequently,the unfolded protein response mediated by double-stranded RNA-dependent protein kinase-like ER kinase resulted in inhibition of protein synthesis,growth arrest at the G1 phase,autophagy,and caspase-7-mediated cell death.CONCLUSION: Our study suggests a new role for FLX as an inducer of ER stress and autophagy,resulting in death of aggressive triple negative breast cancer SUM149 PT.

Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation

BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors.Long-term fluoxetine treatment results in hepatotoxicity.Baicalin,a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant,hepatoprotective and anti-inflammatory effects.However,the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.METHODS Male albino Wistar rats were divided into seven groups.Group 1 was the normal control.Oral fluoxetine was administered at 10 mg/kg body weight to groups 2,3,4 and 5.In addition,groups 3 and 4 were also co-administered oral baicalin(50 mg/kg and 100 mg/kg,respectively)while group 5 received silymarin(100 mg/kg),a standard hepatoprotective compound for comparison.Groups 6 and 7 were used as a positive control for baicalin(100 mg/kg)and silymarin(100 mg/kg),respectively.All treatments were carried out for 28 d.After sacrifice of the rats,biomarkers of oxidative stress[superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),glutathione-S-transferase(GST),advanced oxidation protein products(AOPP),malondialdehyde(MDA)],and liver injury[alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),total protein,albumin,bilirubin]were studied in serum and tissue using standard protocols and diagnostic kits.Inflammatory markers[tumor necrosis factor(TNF-α),interleukin(IL)-6,IL-10 and interferon(IFN)-γ]in serum were evaluated using ELISA-based kits.The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers(total bilirubin,ALT,AST,and ALP)and inflammatory markers(TNF-α,IL-6,IL-10 and IFN-γ),with a decline in total protein and albumin levels.Biochemical markers of oxidative stress such as SOD,CAT,GST,GSH,MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage.Histological examination of liver tissue also showed degeneration of hepatocytes.Concurrent administration of baicalin(50 and 100 mg/kg)restored the biomarkers of oxidative stress,inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage.Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.

Serum levels of chemokines in adolescents with major depression treated with fluoxetine

BACKGROUND Major depressive disorder(MDD)is a global health issue that affects 350 million people of all ages.Although between 2%and 5.6%of affected individuals are adolescents,research on young patients is limited.The inflammatory response contributes to the onset of depression,and in adult MDD patients,symptom severity has been linked to chemokine levels.AIM To determine the differences in circulatory levels of chemokines in healthy volunteers(HVs)and adolescents with MDD,and assess the changes induced by fluoxetine consume.METHODS The 22 adolescents with MDD were monitored during the first 8 wk of clinical follow-up and clinical psychiatric evaluation was done using the Hamilton depresión rating scale(HDRS).The serum levels of monocyte chemoattractant protein-1(MCP-1),macrophage inflammatory protein(MIP)-1α,MIP-1β,interleukin(IL)-8,interferon gamma-induced protein(IP)-10,and eotaxin were measured in patients and HVs.RESULTS In all cases,significant differences were detected in circulating chemokine levels between patients before treatment and HVs(P<0.0001).All chemokines decreased at 4 wk,but only MCP-1 and IL-8 significantly differed(P<0.05)between 0 wk and 4 wk.In the patients,all chemokines rose to their initial concentrations by 8 wk vs 0 wk,but only IP-10 did so significantly(P<0.05).All patients experienced a significant decrease in HDRS scores at 4 wk(P<0.0001)and 8 wk(P<0.0001)compared with 0 wk.CONCLUSION Despite the consumption of fluoxetine,patients had significantly higher chemokine levels,even after considering the improvement in HDRS score.The high levels of eotaxin,IP-10,and IL-8 partially explain certain aspects that are affected in MDD such as cognition,memory,and learning.

Effect of fluoxetine on depression-induced changes in the expression of vasoactive intestinal polypeptide and corticotrophin releasing factor in rat duodenum

AIM: To investigate changes in vasoactive intestinal polypeptide (VIP) and corticotrophin releasing factor (CRF) in the plasma and duodenum of chronic stress- induced depressed rats and the effects of fluoxetine hydrochloride (fluoxetine) treatment on depression- induced changes in VIP and CRF. METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was produced. Thirty experimental rats were randomly divided into the following groups: control group, saline-treated depressed group, and fluoxetine-treated depressed group. Open- f ield testing was performed to assess the rats’ behavior. VIP and CRF levels in plasma were measured by ELISA. Immunofluorescence techniques combined with laser scanning confocal microscopy (LSCM) were used to investigate VIP and CRF expression in the duodenum. RESULTS: The open-field behavior, both crossing and rearing, of depression model rats, decreased signif icantly compared with those of normal control rats over 5 min. Defecation times increased significantly. Compared to the control group, FITC fluorescence of duodenal CRF expression and plasma CRF levels in the depressed rats increased significantly (fluorescence intensity of duodenal CRF: 11.82 ± 2.54 vs 25.17 ± 4.63; plasma CRF: 11.82 ± 2.54 ng/L vs 25.17 ± 4.63 ng/L, P < 0.01), whereas duodenal VIP expression and plasma VIP levels decreased signif icantly (fluorescence intensity of duodenal VIP: 67.37 ± 18.90 vs 44.51 ± 16.37; plasmaVIP: 67.37 ± 18.90 ng/L vs 44.51 ± 16.37 ng/L, P < 0.01). Fluoxetine improved depressed behavior, increased VIP expression and decreased CRF expression in plasma and the duodenal tissue of depressed rats. CONCLUSION: Chronic stress can induce injury to the duodenum, accompanied by increasing CRF and decreasing VIP in the plasma and duodenum. Treatment with fluoxetine can ameliorate pathological changes in the duodenum of depressed rats, which suggests that antidepressants are an effective therapeutic agent for some duodenal diseases caused by chronic stress. VIP is a potential therapeutic strategy.

Hypoglycemia associated with fluoxetine treatment in a patient with type 1 diabetes

We report on a patient with type 1 diabetes mellitus who presented with recurrent episodes of hypoglycemia and a marked reduction in her daily insulin requirements after introduction of fluoxetine. This 25-yearold Caucasian woman had been followed up at the outpatient clinic for type 1 diabetes mellitus and prepregnancy care. She used a continuous subcutaneous insulin infusion with lispro and her daily insulin dose was 0.5 IU/kg per day. She had no chronic diabetic complications or hypoglycemia unawareness. Fluoxetine at a daily dose of 20 mg had been started because of depressive symptoms and within one week, she presented recurrent hypoglycemic episodes that prompted a progressive reduction in the insulin dose down to 0.3 IU/kg per day. The reduced insulin requirements continued during the period of fluoxetine treatment while glycated hemoglobin remained stable. She had no concurrent additional cause to explain the reduced insulin requirements. After fluoxetine was stopped, insulin re-quirements progressively increased and returned to the patient′s usual dose.