Duloxetine: pharmacoeconomic implications of an antidepressant that alleviates painful physical symptoms

Major depressive disorder (MDD) is a prevalent, chronic, medical disorder that encompasses a broad constellation of symptoms. The salience of painful physical symptoms in depressive presentations is increasingly appreciated. Duloxetine is a novel, potent, balanced, dual monoamine reuptake-inhibitor antidepressant indicated for the symptomatic relief of MDD. Duloxetine is marketed as an antidepressant that has inherent analgesic properties for depressed patients who present with prominent painful physical symptoms. Taken together, available evidence indicates that duloxetine provides a higher probability of, and shorter time to, remission than some antidepressants (e.g., fluoxetine). Duloxetine also offers symptom relief for painful physical symptoms in depressed patients. Pharmacoeconomic and cost-impact modelling analyses should be reformulated to consider duloxetine's symptom-alleviating effect on the somatic dimension of depressive illness.     

Epidemiology and impact of rotavirus diarrhoea in Poland

Hospital and laboratory data were analysed in three hospitals to estimate rotavirus disease burden in 1994-96. Community acquired gastroenteritis was diagnosed in 757 children of whom 41% tested positive for rotavirus. A total of 196 children had rotavirus nosocomial infections (39% of all rotavirus community-acquired and nosocomial cases) Infants less than 24 months old and children less than 3 months old comprised 74% and 11.9% of admissions for rotavirus, respectively. Almost 94% of children with rotavirus infection had severe gastroenteritis (score 11). The annual rate of rotavirus associated hospitalization in Poland in 1996 was 3.1/1000 children under the age of 60 months and 5.2/1000 infants under 24 months of age. The mean hospital stay was 9.5 d (±9.8 d). We estimated that 8918 children under 60 months of age were hospitalized for rotavirus gastroenteritis in 1996; they accounted for 84899 inpatient days. We conclude that rotavirus is a leading aetiological agent of severe gastroenteritis in young children in Poland and that the Burden of this infection is significant. Rotavirus vaccine could significantly decrease the hospitalization rate and the financial impact of rotavirus Gastroenteritis in Poland. □ Acute diarrhoea, disease burden, epidemiology, gastroenteritis, rotavirus     

Marginal donor liver versus standard donor liver: A single-center observational study

Background: The effectiveness and safety of marginal donor livers remain controversial. This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation (LT). Methods: This study included 199 liver donors (including 16 split donors) and 206 liver recipients from January 1, 2018 to January 27, 2020, with case follow-up until July 31, 2021. Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers. Indices of liver and kidney functions, complications, and survival curves of the two groups were compared. Results: Compared with the standard donor group, the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation ( P < 0.05); there were no significant differences in alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels after LT (all P > 0.05); there was no significant difference in the incidence of complications after LT ( P > 0.05); there was also no significant difference in the survival curve ( P = 0.335). Conclusions: There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups. The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.     

Predictors of nonresponse to cognitive behavioural therapy or venlafaxine using glucose metabolism in major depressive disorder

Background

Longitudinal neuroimaging investigations of antidepressant treatment offer the opportunity to identify potential baseline biomarkers associated with poor outcome.

Methods

To explore the neural correlates of nonresponse to cognitive behavioural therapy (CBT) or venlafaxine (VEN), we compared pretreatment (18)F-fluoro-2-deoxy-d-glucose positron emission tomography scans of participants with major depressive disorder responding to either 16 weeks of CBT (n = 7) or VEN treatment (n = 9) with treatment nonresponders (n = 8).

Results

Nonresponders to CBT or VEN, in contrast to responders, exhibited pretreatment hypermetabolism at the interface of the pregenual and subgenual cingulate cortices.

Limitations

Limitations of our study include the small sample sizes and the absence of both arterial sampling to determine absolute glucose metabolism and high-resolution structural magnetic resonance imaging coregistration for region-of-interest analyses.

Conclusion

Our current findings are consistent with those reported in previous studies of relative hyperactivity in the ventral anterior cingulate cortex in treatment-resistant populations.     

复方黄芩制剂抗大鼠肝纤维化作用

目的：研究复方黄芩制剂抗肝纤维化的作用。方法：采用皮下注射ＣＣｌ４和营养控制两因素致大鼠肝纤维化模型，从组织病理学和组织学两方面进行观察。结果：复方黄芩制剂ｉｇ给药，５￣１０ｇ／ｋｇ能明显减轻大鼠纤维化程度（Ｐ〈０．０１）。结论：复方黄芩制剂具有显著的抗肝纤维化作用。     

三氧化二β－锗丙酸对硝基苯酯的合成和结构性质

三氧化二β－锗丙酸对硝基苯酯的合成和结构性质上官国强，张树功，倪嘉缵（山东济宁医学院化学教研室，济宁２７２１１３；中国科学院长春应用化学研究所，长春１３００２２）羧基乙基锗倍半氧化物［（ＨＯＯＣＣＨ２ＣＨ２Ｇｅ）２Ｏ３，１３２Ｇｅ］的广谱抗癌活性引起...     

大鼠单侧后牙缺失后颞颌关节内P物质、降钙素基因相关肽的表达变化

目的 :观察单侧后牙缺失造成偏侧咀嚼的大鼠颞颌关节内P物质 (substanceP ,SP)和降钙素基因相关肽 (calcitoningene relatedpeptide ,CGRP)的表达情况 ,进一步探讨颞颌关节病的发病机制。方法 :Wistar雄性大鼠 12只 ,随机分为 4组 ,包括 2个实验组及相应的对照组 ,每组 3只。拔除实验组动物右侧上、下颌磨牙 ,人为造成偏侧咀嚼。同一部位的切片分 2组 ,分别行SP ,CGRP免疫组织化学反应 (SABC法 )。光镜观察 ,并用LUZEX F型显微图像分析仪分别进行测定。结果 :每一实验组咀嚼侧和非咀嚼侧颞颌关节内单位面积内SP ,CGRP阳性纤维面积与各自对照组比较显著增加 (P <0 .0 1) ,但 3个月组较 1个月组有较低的增长趋势。在每一实验组内 ,非咀嚼侧单位面积内SP ,CGRP阳性纤维面积明显高于咀嚼侧 (P <0 .0 1)。结论 :SP ,CGRP均参与了偏侧咀嚼引起的颞颌关节病的病理变化过程 ,且在偏侧咀嚼条件下 ,两侧颞颌关节病理变化程度不同     

肝靶向抗病毒药NGA－ACV的制备及其趋肝性

以无唾液酸糖蛋白受体（ａｓｉａｌｏｇｌｙｃｏｐｒｏｔｅｉｎｒｅｃｅｐｔｏｒ，ＡＳＧＰＲ）的特异性配体半乳糖基拟糖白蛋白（ｎｅｏｇｌｙｃｏａｌｂｕｍｉｎ，ＮＧＡ）为载体，通过丁二酰基桥将抗病毒药无环鸟苷（ａｃｙｃｌｏｖｉｒ，ＡＣＶ）与ＮＧＡ偶联，得到肝靶向抗病毒药ＮＧＡＡＣＶ。差热分析和高效液相色谱分析结果表明，ＮＧＡＡＣＶ是共价键偶联物，且在血液中稳定性很好。将偶联物用１３１Ｉ标记后进行家兔放射性显像比较研究。结果，高、低药密度ＮＧＡＡＣＶ的肝脏放射性分别是全身放射性的８１．６％和８６．６％，其趋肝性无明显差别。研究小鼠体内高药密度１３１ＩＮＧＡＡＣＶ的分布，在５ｍｉｎ时肝脏放射性达到峰值，为注入量的８１．７±１０．４％。受体竞争抑制实验表明ＮＧＡＡＣＶ的肝靶向机理为受体介导的主动靶向过程。初步体外抗乙肝病毒比较研究表明，ＮＧＡＡＣＶ较ＡＣＶ的抗病毒剂量有明显降低。     

诱导分化羊骨髓间充质干细胞作为组织工程瓣膜间质种子细胞的可行性

目的:对羊骨髓间充质干细胞加以诱导分化,并与大隐静脉来源的血管间质细胞进行比较,探讨其作为组织工程瓣膜种子细胞的可行性。方法:实验于2006-02/08在西京医院心血管病研究所完成。①家猪10只,屠宰后取主动脉瓣膜,尽量剔去血管外膜,浸入Hank’s液中洗涤,制备去细胞主动脉瓣,苏木精-伊红染色比较脱细胞前后的组织特点。②成年杂种绵羊10只,麻醉后分别于股骨大转子穿刺抽取肝素化骨髓10mL,稀释,离心,弃上清及脂肪层,余细胞用LG-DMEM无血清培养基重悬,铺于等体积的Percoll淋巴细胞分离液上,离心收集单个核细胞,消化传代培养。取第二、三代骨髓间充质干细胞,加入LG-DMEM条件培养基进行体外定向诱导分化。对诱导后细胞进行形态观察、免疫组化鉴定并绘制生长曲线。③上述10只绵羊抽取骨髓后,无菌条件下取大隐静脉,剥去静脉外膜,剪成1mm3,贴壁法培养,消化传代。④取第3代骨髓间充质干细胞与血管间质细胞,分别以5×104L-1密度接种于24孔培养板,常规孵育96h。每孔各吸取培养基0.5mL,测定两种细胞上清液中的羟脯氨酸含量。完毕后用胰蛋白酶消化处于对数生长期的细胞,加入冻存液,调整细胞密度为7×109L-1,置于液氮中,1周后复苏,计算两种细胞的存活率。⑤将去细胞猪主动脉瓣修剪成0.5cm×0.5cm×0.1cm大小,骨髓间充质干细胞、血管间质细胞均按105/cm2密度接种,置入37℃、体积分数为0.05的CO2孵箱中。反复种植3次,每次间隔24h,第4天各组均取出2份样本,扫描电镜观察。第7天向其余标本中加入四唑盐,采用酶联免疫检测仪490nm处骨髓间充质干细胞组、血管间质细胞组的吸光度值,比较两种细胞在去细胞主动脉瓣上的生长能力。结果:①新鲜的猪瓣叶中含有大量的成纤维细胞及内皮细胞。去细胞后,主动脉瓣中未见任何细胞及其碎片成分,纤维网架结构保持完整。②传代培养后的骨髓间充质干细胞和血管间质细胞形态相似,呈梭形或多角型,均于24h内贴壁,3～4d铺满瓶底;两种细胞对平滑肌肌动蛋白α、波形蛋白均呈部分阳性表达;且生长曲线相似,倍增时间分别为38h和36h(P>0.05)。③诱导分化后的骨髓间充质干细胞与血管间质细胞上清液羟脯氨酸含量基本相似[(1.52±0.21),(1.43±0.20)mg/L,P>0.05]。冻存复苏后,两种细胞的存活率亦基本相似[(85±3)%,(87±4)%,P>0.05]。④诱导分化后的骨髓间充质干细胞与血管间质细胞均能够种植在去细胞猪主动脉瓣上,两种细胞的吸光度值基本相似(0.50±0.04,0.48±0.03,P>0.05)。结论:诱导分化的骨髓间充质干细胞能够黏附在去细胞猪主动脉瓣膜支架上贴壁生长,与静脉来源的血管间质细胞在存活率、复苏后生长增殖情况、合成胶原功能等方面无明显差别,是合适的组织工程瓣膜间质种子细胞。     

低强度次声对成骨样细胞骨桥素和骨粘连蛋白mRNA表达的作用

目的:观察不同频率低强度次声对成骨细胞细胞外基质骨桥素和骨粘连蛋白mRNA的影响。方法:实验于2005-09/11在解放军第四军医大学放射生物学教研室完成。采用4个6孔培养板进行小鼠成骨样细胞系MC3T3细胞的培养,设对照组,4,12,20 Hz组4组。每日上午8时分别放入次声仓内,对照组在次声仓内无次声输出,4,12,20 Hz组接受100 dB,频率为4,12,20 Hz的次声作用30 min,1次/d,连续3d。在第3天次声作用后2,4,8h分别进行成骨样细胞骨桥素及骨粘连蛋白mRNA原位杂交染色,光学显微镜下进行图像分析,测定细胞阳性物质平均灰度,进行分析。结果:①骨粘连蛋白mRNA阳性表达:次声波作用后2,4h,4,12,20 Hz组高于对照组(2h:98.3±12.4,96.3±11.2,95.9±10.4,60.3±7.9;4h:103.7±12.4,90.9±11.7,85.4±11.6,62.7±7.1;P均<0.05);至作用后8h,4组比较差异不显著,3个时间点各次声作用组间比较无差异(P>0.05)。②骨桥素mRNA阳性表达:次声波作用后2,4h,4,12,20 Hz组高于对照组(2h:95.4±11.2,98.3±12.9,92.3±12.7,56.6±7.2;4h:91.5±13.6,94.7±10.2,87.6±11.7,58.6±6.8;P均<0.05);至作用后8h,4组比较差异不显著,3个时间点各次声作用组间比较无差异(P>0.05)。结论:100 dB次声波30 min/d作用能促进成骨细胞的骨桥素及骨粘连蛋白的表达一过性增高,在4,12,20 Hz不同频率间未观察到效应差别。