右美托咪定对脂多糖诱导的脓毒症大鼠全身炎症反应和肺损伤的影响

目的观察脂多糖(LPS)对大鼠血浆和肺组织中的炎性因子和Toll样受体4(TLR4)表达的影响及右美托咪定的干预作用。方法雄性SD大鼠40只,250~300g,随机分为四组。Control组(n=10)生理盐水1ml·kg~(-1)·h~(-1)大鼠尾静脉泵注6h;DEX组(n=10)右美托咪定(负荷量6.5μg·kg~(-1)·h~(-1),10min;5μg·kg~(-1)·h~(-1)维持)大鼠尾静脉泵注6h;LPS组(n=10)经大鼠尾静脉注射7.5mg/kg的LPS后继续生理盐水泵注6h;LPS+DEX组(n=10)经大鼠尾静脉注射7.5mg/kg的LPS后泵注右美托咪定6h。以6h为实验终结点,并于此时行右心室取血和肺组织标本的制备。采用ELISA法检测血浆IL-1、IL-6、TNF-α浓度,Western blot法检测肺组织TLR4、髓样分化因子88(MyD88)、NF-κB蛋白含量;检测大鼠肺组织湿/干比(W/D);并用Murakami法评测肺损伤程度。结果与Control组比较,LPS组大鼠血浆IL-1、IL-6和TNF-α浓度明显升高,肺组织中的TLR4、MyD88、NF-κB蛋白含量明显升高(P0.01),肺W/D明显升高;LPS+DEX组上述指标差异均无统计学意义。Control组和DEX组未见明显肺损伤,LPS组肺间质水肿、炎性细胞浸润明显,LPS+DEX组肺损伤程度明显减轻(P0.01)。结论 LPS的刺激可以明显升高大鼠血浆中炎性因子以及肺组织中TLR4的表达水平,右美托咪定的干预可以减轻这一趋势,缓解大鼠的全身炎症和肺水肿的程度。     

右美托咪啶对脂多糖诱导大鼠外周血单核细胞Toll样受体4mRNA表达的影响

目的 探讨右美托咪啶对脂多糖(LPS)诱导大鼠外周血单核细胞Toll样受体4(TLR4)mRNA表达的影响.方法 健康雄性Wistar大鼠40只,取外周血分离培养单核细胞,采用随机数字表法,将其随机分为5组(n=8),A组:阴性对照;B组:单核细胞中加入LPS(终浓度为1μg/ml);C组:单核细胞中加入LPS(终浓度为1μg/ml)+右美托咪啶(终浓度为0.5 ng/ml);D组:单核细胞中加入LPS(终浓度为1μg/ml)+右美托咪啶(终浓度为5.0 ng/ml);E组:单核细胞中加入LPS(终浓度为1μg/ml)+右美托咪啶(终浓度为50.0 ng/ml).孵育24 h后,收集上清液,采用ELISA法测定TNF-α、IL-1β和IL-6的浓度,采用RT-PCR法测定TLR4 mRNA的表达.结果 与A组比较,B组TNF-α、IL-1p、IL-6的浓度升高,TLR4 mRNA表达上调(P＜0.01);与B组比较,C组、D组和E组TNF-α、IL-1β、IL-6的浓度降低,TLR4 mRNA表达下调(P＜0.05或0.01);与C组比较,D组和E组TNF-α、IL-1β、IL-6的浓度降低(P＜0.01),TLR4 mRNA表达差异无统计学意义(P＞0.05);D组和E组各指标比较差异无统计学意义(P＞0.05).结论 右美托咪啶可通过下调TLR4 mRNA表达,抑制TLR4的合成,从而抑制LPS诱导大鼠外周血单核细胞TNF-α、IL-1β和IL-6的生成与释放.

Abstract：

Objective To investigate the effects of different concentrations of dexmedetomidine on the expression of Toll-like receptor 4 (TLR4) mRNA in rat peripheral blood monocytes exposed to lipopolysaccharide ( LPS ). Methods Peripheral blood monocytes isolated from male Wistar rats were seeded in 24-well plate in RPMI 1640 liquid culture medium in CO2 incubator at 37 ℃ and 5% CO2 for 2 h, and were randomly divided into 5 groups ( n = 8 each): group A negative control; group B was exposed to LPS 1 μg/ml and C, D and E groups were exposed to LPS 1 μg/ml + dexmetomidine 0.5, 5.0 and 50.0 ng/ml respectively. The monocytes were then incubated for 24 h. The concentrations of TNF-α, IL-1β and IL-6 in the supernatant of the cultured monocytes were detected by ELISA. The expression of TLR4 mRNA in the monocytes was detected by RT-PCR.Results Exposure to LPS significantly increased the expression of TLR4 mRNA and the concentrations of TNF-α, IL-1β and IL -6 in group B as compared with group A ( P ＜ 0.01 ). Dexmedetomidine attenuated the LPS-induced increase in the expression of TLR 4 mRNA and the concentrations of TNF-α, IL-1β and IL-6 in a dose-dependent manner ( P ＜0.05or 0.01 ). Conclusion Dexmedetomidine can inhibit the synthesis of TLR4 and inhibit the secretion and dilivery of TNF-α, IL-1β and IL-6 by down-regulating the gene expression of TLR4 in rat peripheral blood monocytes exposed to LPS.     

右美托咪定在脂多糖诱导脓毒症小鼠神经炎症损伤中的作用

目的通过观察右美托咪定应用于脂多糖(LPS)诱导的脓毒症小鼠炎性因子浓度和炎性微小RNA(miRNAs)表达量的变化,探讨右美托咪定在神经炎症损伤中的作用及分子机制。方法清洁级ICR雄性小鼠160只,8～12周龄,体重20～25 g。采用随机数字表法分为四组:生理盐水组(C组)、右美托咪定组(D组)、LPS组(L组)和LPS+右美托咪定组(LD组),每组40只。C组每隔2 h腹腔注射生理盐水0.5 ml,共3次;D组每隔2 h腹腔注射右美托咪定40μg/kg加生理盐水的混合液0.5 ml,共3次;L组腹腔注射LPS 12 mg/kg建立脓毒症模型,建立模型后30 min,每隔2 h腹腔注射生理盐水0.5 ml,共3次;LD组腹腔注射LPS 12mg/kg建立脓毒症模型,建立模型后30 min,每隔2 h腹腔注射右美托咪定40μg/kg加生理盐水的混合液0.5 ml,共3次。于建立脓毒症模型后8、24 h取小鼠海马组织,采用ELISA法检测海马组织IL-18和IL-1β浓度,RT-PCR法检测海马组织和血液miR-155、miR-146、miR-21、miR-181、miR-223表达量。于建立脓毒症模型后24 h,采用TUNEL法检测海马组织神经元凋亡细胞百分比。结果与C组比较,建立模型后8、24 h L组和LD组海马组织IL-1β和IL-18浓度明显升高(P0.05),L组海马组织和血液miR-155、miR-21表达量明显升高(P0.05),miR-146、miR-181、miR-223表达量明显降低(P0.05),LD组血液miR-181、miR-223表达量明显升高(P0.05);建立模型后24 h L组海马组织神经元凋亡细胞百分比明显升高(P0.05)。与L组比较,建立模型后8、24 h LD组海马组织IL-18、IL-1β浓度明显降低(P0.05),海马组织和血液miR-155、miR-21表达量明显降低(P0.05),miR-146、miR-181、miR-223表达量明显升高(P0.05),建立模型后24 h LD组海马组织神经元凋亡细胞百分比明显降低(P0.05)。C组和D组各项指标差异均无统计学意义。结论右美托咪定通过调节炎性因子浓度和炎性miRNAs表达量,降低海马组织神经元凋亡细胞百分比,从而减轻脂多糖诱导的脓毒症小鼠神经炎症损伤。     

盐酸右美托咪定对缺血-再灌注损伤大鼠心肌Toll样受体4/核因子-κB信号通路的作用

目的研究盐酸右美托咪定对心肌缺血-再灌注损伤大鼠心肌组织中Toll样受体(toll-like receptor,TLR)-4mRNA、核因子(nuclear factor,NF)-κB mRNA的表达,探讨盐酸右美托咪定对心肌缺血-再灌注损伤大鼠心肌TLR-4/NF-κB信号通路的影响。方法健康3个月龄SD雄性大鼠21只,体重250~300g,随机均分为三组:假手术组(sham组)、缺血-再灌注组(IR组)、缺血-再灌注+盐酸右美托咪定组(DEX组)。采用结扎左冠状动脉前降支的方法制备大鼠心肌缺血-再灌注损伤模型,sham组左冠状动脉穿线不结扎。Sham组和IR组在结扎前30min经腹腔注射生理盐水100μg/kg,DEX组在结扎前30min经腹腔注射盐酸右美托咪定注射液100μg/kg(4μg/ml)。实时定量逆转录聚合酶链反应(RT-PCR)方法检测TLR-4mRNA和NF-κB mRNA的表达。结果sham、IR和DEX组的TRL-4mRNA分别为(2.21±0.11)、(7.83±0.35)和(3.91±0.21),sham、IR和DEX组的NF-κB mRNA分别为(0.013±0.166)、(0.051±0.016)和(0.015±0.004),IR、DEX组的TRL-4mRNA和NF-κB mRNA的表达明显高于sham组,且DEX组TRL-4mRNA和NF-κB mRNA的表达明显低于IR组(P0.05)。结论盐酸右美托咪定可降低缺血-再灌注损伤大鼠心肌组织TLR-4mRNA和NF-κBmRNA的表达,盐酸右美托咪定可以调控TLR/NF-κB信号通路的转导,抑制炎症反应,减轻心肌缺血-再灌注损伤,保护心肌。     

右美托咪定通过c-Fos/NLRP 3/caspase-1级联抑制LP S诱发的小胶质细胞炎症反应

目的探讨右美托咪定通过c-Fos/NLRP3/caspase-1级联抑制脂多糖(LPS)诱发的小胶质细胞炎症反应。方法选取新生的SD大鼠,取其小胶质细胞进行原代培养及分离纯化。采用LPS诱导建立小胶质细胞炎症模型。采用MTT法选取右美托咪定抑制LPS诱导小胶质细胞炎症反应的最适宜浓度。将细胞分为三组:对照组、LPS组和右美托咪定治疗组(D组)。采用实时定量PCR法测定细胞中IL-1β和TNF-α的mRNA表达量;采用ELISA法检测细胞上清液中IL-1β和TNF-α的含量;采用Western blot法检测原癌基因c-Fos、NLRP3和caspase-1的蛋白含量。结果与对照组比较,LPS组小胶质细胞中炎性因子IL-1β和TNF-α的mRNA表达量均明显升高(P0.05);D组IL-1β和TNF-α的mRNA表达量明显低于LPS组(P0.05)。与对照组比较,LPS组中小胶质细胞中炎性因子IL-1β和TNF-α的含量均明显增加(P0.05);而D组IL-1β和TNF-α的含量明显低于LPS组(P0.05)。与对照组比较,LPS组小胶质细胞中c-Fos、NLRP3和caspase-1的蛋白含量均明显增加(P0.01);而D组c-Fos、NLRP3和caspase-1的蛋白含量明显低于LPS组(P0.05)。结论右美托咪定可抑制LPS诱发的小胶质细胞中炎性因子IL-1β和TNF-α的mRNA表达量及蛋白含量,推测其作用机制可能与抑制c-Fos/NLRP3/caspase-1级联反应有关。     

腹腔巨噬细胞Sirt3表达在右美托咪定抑制脓毒症小鼠炎症反应中的作用

目的评价腹腔巨噬细胞NAD依赖性蛋白脱乙酰酶3(Sirt3)表达在右美托咪定抑制脓毒症小鼠炎症反应中的作用。方法 SPF级健康雄性C57BL6小鼠64只, 7周龄, 体重约20 g。采用随机数字表法分为4组(n=16):假手术组(S组)、脓毒症组(Sep组)、右美托咪定组(DEX组)和右美托咪定+Sirt3抑制剂3-TYP组(TYP组)。采用盲肠结扎穿孔的方法制备小鼠脓毒症模型, DEX组于制备模型前1 h时腹腔注射生理盐水0.25 ml, 30 min后腹腔注射右美托咪定50 μg/kg(生理盐水稀释至0.25 ml);TYP组于制备模型前1 h时腹腔注射3-TYP 5 mg/kg(生理盐水稀释至0.25 ml), 30 min后腹腔注射右美托咪定50 μg/kg。S组和Sep组于制备模型前1 h和30 min分别腹腔注射等量生理盐水。S组仅进行开腹、取出盲肠操作, 不结扎穿孔。于术后24 h时腹腔灌洗, 提取腹腔巨噬细胞贴壁培养, 采用qRT-PCR法检测巨噬细胞Sirt3、IL-1β和TNF-α mRNA表达, Western blot法检测Sirt3的表达, ELISA法测定腹...     

右美托咪定两种给药方法在急性腹膜炎小鼠局部组织的抗炎镇痛作用中的比较

目的通过观察比较右美托咪定静脉注射和腹腔注射两种给药方法在急性腹膜炎模型小鼠炎性内脏痛的镇痛及抗炎作用。方法 SPF级健康成年雄性小鼠60只,体重24~28 g,采用随机数字表法分为五组,每组12只:空白对照组(CK组)、急性腹膜炎模型组(VP组)、右美托咪定静脉注射组(DEX-V组)、右美托咪定腹腔注射组(DEX-P组)、右美托咪定+甲基牛扁碱组(DEX-M组)。VP组、DEX-V组、DEX-P组DEX-M组腹腔注射0.9%乙酸溶液0.1 ml/10 g建立急性腹膜炎模型,CK组腹腔注射等容量生理盐水。于造模前15 min,VP组、DEX-P组分别经腹腔注射生理盐水、右美托咪定10μg/kg,DEX-V组经尾静脉注射右美托咪定10μg/kg,DEX-M组经腹腔注射右美托咪定10μg/kg和α7nACh受体特异性拮抗剂甲基牛扁碱2.4μg/g。观察并记录小鼠急性腹膜炎模型建立后2 h内的镇静情况、扭体反应和内脏痛指数(VPI评分);建模6 h后取材并采用ELISA法检测小鼠血清和腹膜组织匀浆中IL-6、TNF-α的浓度;取小鼠腹腔注射部位壁层腹膜组织,在光镜下观察其水肿程度和中性粒细胞浸润情况。结果与CK组比较,VP组、DEX-V组、DEX-P组和DEX-M组均出现扭体反应,给药后15、30、45、60、75、90、105、120 min时VPI评分明显升高(P<0.05),血清和腹膜组织匀浆的IL-6和TNF-α浓度均明显升高(P<0.05),腹膜组织出现不同程度水肿及中性粒细胞浸润;与VP组比较,DEX-V组和DEX-P组镇静效果较好,给药后30、45、60、75 min时VPI评分明显降低(P<0.05),血清和腹膜组织匀浆的IL-6和TNF-α浓度均明显降低(P<0.05),腹膜组织水肿减轻、中性粒细胞浸润减少;与DEX-P组比较,DEX-V组腹膜组织匀浆中的IL-6和TNF-α浓度明显升高(P<0.05);DEX-M组镇静情况、给药后45、60、75、90 min时VPI评分、血清和腹膜组织匀浆的IL-6和TNF-α浓度均明显升高(P<0.05),局部腹膜组织水肿明显加重,中性粒细胞浸润增多。结论右美托咪定局部腹腔注射可以有效降低急性腹膜炎小鼠的内脏痛指数,对局部腹膜组织有抗炎作用且效果优于静脉注射,其抗炎机制可能部分与激活a7nACh受体引导的胆碱能抗炎通路有关。     

右美托咪定对大鼠内毒素性急性肺损伤时细胞焦亡的影响

目的评价右美托咪定对大鼠内毒素性急性肺损伤(ALI)时细胞焦亡的影响。方法 SPF级雄性SD大鼠60只, 6周龄, 体重200～220 g, 采用随机数字表法分为5组(n=10):对照组(C组)、ALI组和不同剂量右美托咪定组(D1～3组)。ALI组和D1～3组腹腔注射LPS 5 mg/kg制备大鼠内毒素性ALI模型。造模后即刻, D1～3组分别腹腔注射右美托咪定12.5、25.0和50.0 μg/kg, C组腹腔注射等容量生理盐水, 1次/d, 连续14 d。给药结束后, 处死大鼠, 行肺泡灌洗, 收集左支气管肺泡灌洗液, 采用ELISA法测定IL-1β、IL-6和TNF-α的浓度;取肺组织, 测定湿重/干重(W/D)比值;行HE染色, 光镜下观察肺组织病理学结果;采用Western blot法测定肺组织cleaved-caspase-1、消皮素剪切体N端(GSDMD-N)、IL-18和IL-1β的表达水平。结果与C组相比, ALI组和D1～3组肺组织W/D比值升高, 肺泡灌洗液IL-1β、IL-6和TNF-α浓度升高, 肺组织cleaved-caspase-1、GSDMD-N、IL...     

右美托咪定对大鼠内毒素性脑损伤的影响

目的 评价右美托咪定对大鼠内毒素性脑损伤的影响.方法 健康清洁级SD大鼠36只,6周龄,体重200 ～ 250 g,采用随机数字表法,将其分为3组(n=12):对照组(C组)、内毒素组(L组)和右美托咪定组(D组).D组腹腔注射右美托咪定100 μg/kg,15 min后股静脉注射LPS 7.5 mg/kg;L组腹腔注射等容量(2 ml)生理盐水,15 min后股静脉注射LPS 7.5 mg/kg;C组腹腔和股静脉注射2ml生理盐水.于LPS给药后2、4h时股动脉采血,ELISA法检测血清TNF-α浓度;LPS给药后12 h,随机取6只大鼠股静脉注射伊文思蓝(EB)3 ml/kg,1h后测定脑组织EB含量;另6只大鼠处死取脑组织,测定脑组织含水量,光镜下观察脑组织病理学结果.结果 与C组比较,L组和D组脑组织含水量、EB含量和血清TNF-α浓度升高(P＜0.05);与L组比较,D组上述指标均降低(P＜0.05).D组脑组织病理学损伤程度轻于L组.结论 右美托咪定可减轻大鼠内毒素性脑损伤,其机制可能与减轻脑组织炎性反应、改善血脑屏障通透性有关.     

右美托咪定通过抑制JAK2/STAT3通路改善脂多糖诱导的小鼠急性肺损伤

目的研究右美托咪定对脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠JAK2/STAT3通路的作用。方法雄性昆明小鼠36只,随机均分为三组:正常组(C组)、模型组(L组)和右美托咪定预处理组(D组)。取小鼠右肺下叶,称量并计算湿/干比重(W/D),对右肺上叶进行苏木素-伊红(HE)染色观察小鼠肺组织病理学改变,BCA法检测支气管肺泡灌洗液(BALF)中蛋白含量,用ELISA试剂盒检测BALF上清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)及髓过氧化物酶(MPO)水平;qRT-PCR定量分析肺组织中TNF-α、IL-6mRNA水平;Western blot方法检测肺组织中p-JAK2、JAK2、p-STAT3、STAT3蛋白的含量。结果与L组比较,C组、D组肺损伤评分明显降低、小鼠肺W/D、BALF中蛋白含量明显减少,BALF中TNF-α、IL-6及MPO浓度明显降低,肺组织TNF-α和IL-6mRNA表达明显减少,p-JAK2/JAK2和p-STAT3/STAT3相对量明显减少(P0.05)。结论右美托咪定可能通过抑制JAK2/STAT3通路减轻LPS诱导的小鼠ALI。     

2015年乳腺癌辅助化疗进展

【摘要】〓乳腺癌是危害我国女性健康的头号杀手,尽管近年来辅助化疗的研究进展突飞猛进,但临床中仍有不少问题未能明确,如辅助化疗的合适人群、化疗的开始时间、蒽环及紫杉类的地位和用法、强化维持治疗的作用、疗效及预后的生物标志物等。本文结合乳腺癌辅助化疗在临床上的常见问题和2015年各大乳腺癌会议阐述乳腺癌辅助化疗的最新进展。     

Alterations in T-Cell Subset Frequency in Peripheral Blood in Obesity

Background: Obesity affects the regulation of immune and inflammatory responses. This study characterizes differences in peripheral blood lymphocyte phenotype in obese humans. Methods: Frequencies of lymphocyte subsets among peripheral blood mononuclear cells were compared between 10 obese (BMI ≥35) and 10 lean subjects, as determined by antibodies directed against cluster differentiation (CD) markers. Results: Obese patients demonstrated an increased frequency of CD3+CD4+ T-cells (mean difference 12%, P=0.004), a decreased frequency of CD3+CD8+ T-cells (mean difference 9.4%, P=0.016) and an increased frequency of CD3+CD8+CD95+ T-cells (mean difference 13.3%, P=0.032). No other differences among T-cell or monocyte subsets were noted. Conclusions: Obesity is associated with alterations in frequencies of peripheral CD4+ and CD8+ T-cells and aberrations in the expression of CD95 among CD8+ T-cells. These data suggest both CD4+ and CD8+ T-cell compartments, as well as the regulation of CD95 expression on CD8+ T-cells, as targets for further study into obesity's effects on the immune system.     

西宁地区烧伤病人动脉血气分析观察

对高海拔地区的27例烧伤病人动脉血气变化进行了分析和观察。结果证明:无论是存活病人还是死亡病人伤后均存在有低氧血症问题。并且在死亡病人和烧伤合并吸入性损伤病人其低氧血症的发生早于单纯烧伤病人。提示:吸入性损伤病人应立即行气管切开术以保障氧气供给,单纯烧伤病人可常规吸氧以维持正常血 PaO_2,ARDS 均发生在合并吸入性损伤的病人,高频喷射通气技术对纠正低氧血症有一定效果。     

Controversies in Fistula in Ano

Managing a complex fistula in ano can be a daunting task for most surgeons; largely due to the two major dreaded complications—recurrence & fecal incontinence. It is important to understand the anatomy of the anal sphincters & the aetiopathological process of the disease to provide better patient care. There are quite a few controversies associated with fistula in ano & its management, which compound the difficulty in treating fistula in ano. This article attempts to clear some of those major controversies.     

β-半乳糖苷酶在体内外成骨细胞中的表达

目的 研究β—半乳糖苷酶(β—gal)在成骨细胞中的表达状况，为阐明MorquioB综合征的发病机制提供依据。方法 裸鼠各器官和骨组织标本行X-gal染色检测。抽取羊和人骨髓行骨髓基质细胞(BMSCs)培养，分为4组：I：Adv-hBMP-2转染组；Ⅱ：Adv—β—gal转染组；Ⅲ：未转染组；Ⅳ：地塞米松诱导组。分别行X-gal染色和RT-PCR检测β—gal的表达。结果 裸鼠骺板两侧、骨膜内面及松质骨的成骨细胞和破骨细胞可见多量β—gal的表达。未转染BMSCs组有少量β—gal的表达，其他3组细胞的β—gal表达增高。结论成骨细胞和破骨细胞可表达多量β—gal，该两种细胞的β—gal缺乏可能是MorquioB综合征骨骼异常的直接原因。     

Smoking-Attributable mortality in Spain in 2016

IntroductionSmoking-attributable mortality (SAM) is a valuable indicator that can be used to characterize the course and health burden of the smoking epidemic. The aim of this paper was to estimate SAM in Spain in 2016 in the population aged 35 and over, using the best available evidence.MethodsA smoking prevalence-dependent analysis based on the estimation of population-attributable fractions was performed. Smoking prevalence (never, former, and current smokers) was calculated from a combination of the Spanish Health Survey (2016) and the European Health Survey (2014); the relative risk of death among current and former smokers was taken from the follow-up of various cohorts; and mortality rates were obtained from National Center for Statistics data. SAM estimates are presented globally, and by sex, age groups, and major disease categories: cancer, cardiometabolic diseases and respiratory diseases.ResultsIn 2016, 56,124 deaths were attributed to tobacco consumption, 84% in men (47,000), and 50% in the population aged over 74 (27,795). Overall, 50% of SAM was due to cancer (28,281), 65% of which was lung cancer. One in 4 attributable deaths (13,849) occurred before the age of 65.ConclusionsOne in 7 deaths in Spain in 2016 were attributable to smoking. This estimation of SAM clearly highlights the great impact of smoking on mortality in Spain, mainly due to lung cancer and chronic obstructive pulmonary disease.     

MicroRNAs in hepatic pathophysiology in diabetes

MicroRNAs(miRNAs or miRs) are small approximately 22 nucleotide RNA species that are believed to regulate diverse metabolic and physiological processes.In the recent past,several reports have surfaced that demonstrate the role of miRNAs in various biological processes and numerous disease states.For a disease as complex as diabetes,the emergence of miRNAs as key regulators leading to the disease phenotype has added a novel dimension to the area of diabetes research.On the other hand,the liver,a metabolic hub,contributes in a major way towards maintaining normal glucose levels in the body as it can both stimulate and inhibit hepatic glucose output.This equilibrium is frequently disturbed in diabetes and hence,the liver assumes special significance considering the correlation between altered hepatic physiology and diabetes.While the understanding of the mechanisms behind this altered hepatic behavior is not yet completely understood,recent reports on the status and role of miRNAs in the diabetic liver have further added to the complexities of the knowledge of hepatic pathophysiology in diabetes.Here,we bring together the various miRNAs that play a role in the altered hepatic behavior during diabetes.     

Fluid-phase transcytosis in the primate epididymis in vitro and in vivo

Ligated tubules from the corpus epididymidis of men and monkeys were incubated in medium containing horseradish peroxidase (HRP) as a marker for fluid-phase endocytosis. HRP was localized by light and electron microscopy after 0, 15, 30 and 60 min of incubation. Movement between the cells was prevented by tight junctions, but bypass of this barrier was apparently achieved by an intracellular vesicular mechanism leading to a time-dependent appearance of HRP in the lumen. Uptake of HRP into basal cells and capture by the lysosomal apparatus of principal cells were also observed. HRP-filled vesicles also appeared in the basal, mid and apical cytoplasm of epithelial cells in the caput 1 h after injection of the tracer into the epididymal circulation of the monkey, suggesting that this pathway also operates in vivo.