应用PET评估地氟醚麻醉对人脑葡萄糖代谢率的影响

目的:应用正电子发射断层扫描技术(positronemissiontomography,PET),研究地氟醚麻醉对健康自愿者脑内葡萄糖代谢率(cerebralglu-cosemetabolismrate,CMRGlu)的影响。方法:选择10名自愿者,每名自愿者分别做2次PET扫描,采用PhilipsCPETPlus扫描仪及18F-FDG标记技术测定CMRGlu,第1次在清醒状态下扫描作为对照,第2次吸入地氟醚使自愿者刚好达到意识消失。分别划出额叶、颞叶、枕叶、顶叶、丘脑、基底核、舌回、扣带回、小脑、海马、桥脑、全脑等区域的感兴趣区并计数,所得数据以x珔±s表示。比较两组间计数的差异,并与BIS进行相关分析。结果:①自愿者清醒时全脑内CMRGlu计数为1940.5±165,意识消失时CMRGlu计数降低至1645.1±201(P<0.05),降低15.2%。②与清醒组比较,麻醉后脑内局部葡萄糖代谢率(rCMRGlu)计数均显著降低9.3%～16.2%(P<0.05),而以丘脑、枕叶和舌回葡萄糖代谢率计数降低更为显著(P<0.01),分别由3045.3±164,2867.7±107和3076.6±163降至1938.2±119,2002.8±169和2227.8±158,降低36.4%,30.2%和27.6%。③CMRGlu计数与BIS之间相关性良好(r=0.986,P=0.0006)。结论:吸入地氟醚麻醉使自愿者意识消失时全脑及脑内局部CMRGlu均可显著降低,并与BIS相关。丘脑、枕叶和舌回对吸入地氟醚麻醉更为敏感,     

应用PET评估地氟醚麻醉对人脑葡萄糖代谢率的影响

目的：应用正电子发射断层扫描技术(positron emission tomogmphy，PET)，研究地氟醚麻醉对健康自愿者脑内葡萄糖代谢率(cerebral glu-cose metabolism rate,CMRGlu)的影响。方法：选择10名自愿者，每名自愿者分别做2次PET扫描，采用Philipsc PET Plus扫描仪及18F-FDG标记技术测定CMRGlu，第1次在清醒状态下扫描作为对照，第2次吸人地氟醚使自愿者刚好达到意识消失。分别划出额叶、颞叶、枕叶、顶叶、丘脑、基底核、舌回、扣带回、小脑、海马、桥脑、全脑等区域的感兴趣区并计数，所得数据以x^-&;#177;s表示。比较两组间计数的差异，并与BIS进行相关分析。结果：①自愿者清醒时全脑内CMRGlu计数为1940．5&;#177;165，意识消失时CMRGlu计数降低至1645．1&;#177;201(P&;lt;0．05)，降低15．2％。②与清醒组比较，麻醉后脑内局部葡萄糖代谢率(rCMRGlu)计数均显著降低9．3％—16．2％(P&;lt;0．05)，而以丘脑、枕叶和舌回葡萄糖代谢率计数降低更为显著(P&;lt;0．01)，分别由3045．3&;#177;164，2867．7&;#177;107和3076．6&;#177;163降至1938．2&;#177;119，2002．8&;#177;169和2227．8&;#177;158，降低36．4％，30．2％和27．6％。③CMRGlu计数与BIS之间相关性良好(r=0．986．P=0．0006)。结论：吸人地氟醚麻醉使自愿者意识消失时全脑及脑内局部CMRGlu均可显著降低，并与BIS相关。丘脑、枕叶和舌回对吸人地氟醚麻醉更为敏感，可能是地氟醚麻醉在脑内作用的主要靶区。     

不同吸入麻醉剂对人脑葡萄糖代谢率的影响

目的：应用正电子发射断层扫描技术（PET）,研究吸入异氟醚和安氟醚麻醉对健康志愿者脑内葡萄糖代谢率（CMRglu）的影响。方法：选择8名志愿者,每位志愿者分别做3次PET扫描,采用PHILIPS CPET Plus扫描仪及^18FDG标记技术测定CMRglu,第1次在清醒状态下扫描作为对照,第2、3次分别吸入异氟醚和安氟醚麻醉直至意识丧失。结果：清醒时全脑CMRglu平均为（30．0±1．1）μmol／（100mg·min）,与清醒时比较,异氟醚麻醉降低全脑CMRglu22％至（23．3±1．4）μmol／（100mg·min）（P〈0．05）,安氟醚麻醉降低全脑CMRglu 19％至（24．4±0．9）μmol／（100mg·min）（P〈0．05）;吸入异氟醚或安氟醚麻醉后脑内局部葡萄糖代谢率（rCMRglu）均显著降低,其中异氟醚麻醉下以丘脑、舌回和扣带回葡萄糖代谢率降低更为显著（P〈0．01）;而安氟醚麻醉下丘脑、舌回、扣带回、额叶和桥脑等脑区葡萄糖代谢率的降低最显著（P〈0．01）。结论：全脑及脑内局部葡萄糖代谢率在吸入异氟醚和安氟醚麻醉时均可显著降低,异氟醚和安氟醚麻醉在人脑内的靶区有一定的相似性,但不完全相同。     

头部电针对抑郁症患者脑功能区葡萄糖代谢的影响

背景有研究认为抑郁症患者额叶、扣带回、尾核等脑功能区葡萄糖代谢水平低下,小脑内血流量降低.目的运用正电子发射型计算机断层显像技术观察头电针对抑郁症患者脑部功能区葡萄糖代谢的影响.设计随机对照的验证性实验.单位南方医院针灸科,广东省人民医院伟伦PET中心.对象选择2002-10/2003-10在南方医院、珠江医院门诊确诊的原发性抑郁症患者12例,男3例,女9例;年龄36～66岁,平均48岁.方法头电针取穴为顶中线、额中线和双侧额旁1线.电针前和治疗6周后分别接受正电子发射型计算机断层显像技术检测.框取双侧额叶、尾核、扣带回和小脑作为感兴趣脑区,将各脑区所得葡萄糖代谢放射性计数采用半定量方式进行治疗前后比较.主要观察指标双侧额叶、尾核、扣带回和小脑葡萄糖代谢显像的半定量分析.结果12例原发性抑郁症患者均进入结果分析.①头电针治疗后右侧额叶、左侧额叶、右侧扣带回、右侧尾核、左侧小脑葡萄糖代谢放射计数半定量结果明显高于治疗前[(2 91±0.34,2.96±0.26,2.68±0.20,2.61±0 39,2.55±0.18,2.53±0.31,2.53±0.36,2.34±0.31,2.40±0.33,2.35±0.25),(P＜0.05～0.01)],而治疗后左侧扣带回、左侧尾核、右侧小脑葡萄糖代谢放射计数半定量结果与治疗前基本相似[(2.69±0.38,2.66±0.01,2.50±0.27;2.43±0.38,2 45±0 21,2.30±0.34),(P＞0.05)].结论电针抑郁症患者顶中线、额中线和双侧额旁1线能提高部分脑区的葡萄糖代谢,头电针治疗抑郁症的机制可能与提高额叶、尾核、扣带回、小脑等部分脑区葡萄糖代谢有关.     

应用PET监测异丙酚与异氟醚对脑内葡萄糖代谢及可能作用的中枢部位的影响

目的:应用正电子发射计算机断层扫描技术(positronemissiontomogra-phy,PET),研究静脉麻醉剂异丙酚和吸入麻醉剂异氟醚对健康自愿者脑内葡萄糖代谢的影响,分析两种麻醉剂在中枢的可能作用部位。方法:选择健康自愿者10名,每一名自愿者按随机顺序分别作3次PET扫描,1次在清醒状态下扫描作为对照,1次在异丙酚(靶控效应室浓度3.0mg/L)麻醉状态下扫描,1次在异氟醚(1.0肺泡气最低有效浓度)麻醉状态下扫描。采用18F-FDG示踪技术测定脑内葡萄糖代谢。结果:①异丙酚麻醉后,与清醒状态比全脑的葡萄糖代谢率(CMGlu)降低34.1%(P<0.05),在丘脑、大脑皮质、小脑和海马等区域葡萄糖代谢率(rCMGlu)明显低于清醒状态(P<0.05),其中丘脑降幅最大达51.5%。②异氟醚麻醉后,与清醒状态比全脑的CMGlu降低37%,以丘脑和扣带回降低更为显著(P<0.05)。结论:异丙酚和异氟醚麻醉后均可使全脑和脑内各区域葡萄糖代谢显著降低,其中异丙酚对丘脑、大脑皮层和海马更为敏感,这些可能是异丙酚在中枢的作用部位;而异氟醚在脑内作用的靶区可能在丘脑、扣带回。     

应用PET监测异丙酚与异氟醚对脑内葡萄糖代谢及可能作用的中枢部位的影响

目的：应用正电子发射计算机断层扫描技术(positron emission tomography，PET)，研究静脉麻醉剂异丙酚和吸入麻醉剂异氟醚对健康自愿者脑内葡萄糖代谢的影响，分析两种麻醉剂在中枢的可能作用部位。方法：选择健康自愿者10名，每一名自愿者按随机顺序分别作3次PET扫描，1次在清醒状态下扫描作为对照，1次在异丙酚(靶控效应室浓度3．0mg／L)麻醉状态下扫描，1次在异氟醚(1．0肺泡气最低有效浓度)麻醉状态下扫描。采用18F．FDG示踪技术测定脑内葡萄糖代谢。结果：①异丙酚麻醉后，与清醒状态比全脑的葡萄糖代谢率(CMGlu)降低34．1％(P&;lt;0．05)，在丘脑、大脑皮质、小脑和海马等区域葡萄糖代谢率(rCMGlu)明显低于清醒状态(P&;lt;0．05)，其中丘脑降幅最大达51．5％。②异氟醚麻醉后，与清醒状态比全脑的CMGlu降低37％，以丘脑和扣带回降低更为显著(P&;lt;0．05)。结论：异丙酚和异氟醚麻醉后均可使全脑和脑内各区域葡萄糖代谢显著降低，其中异丙酚对丘脑、大脑皮层和海马更为敏感，这些可能是异丙酚在中枢的作用部位；而异氟醚在脑内作用的靶区可能在丘脑、扣带回。     

吗啡耐受对大鼠脊髓IL-1β和IL-6水平的影响

目的:观察吗啡耐受对大鼠脊髓促炎性细胞因子IL-1β和IL-6水平的影响。方法:SD大鼠18只,随机分为假手术组和吗啡耐受组,每组9只。参照杨建平等犤6犦的方法行蛛网膜下腔置管。吗啡耐受组鞘内注射吗啡20μg/10μL,连续5d。注射吗啡后第6天,鞘内注射吗啡5μg/10μL,进行吗啡激发试验。吗啡激发试验完成后取腰段脊髓组织,ELISA法测定IL-1β和IL-6。置管后第3天的热伤害刺激缩腿潜伏期(PWL)和对12gVonFrey丝30次刺激的缩足总数,分别表示伤害性疼痛和机械性痛敏的基础值。结果:吗啡激发试验前,吗啡撤药所致的PWL,吗啡耐受组较假手术组显著降低(P<0.01),对12gVonFrey丝30次刺激的缩足总数,吗啡耐受组显著高于假手术组(P<0.01)。吗啡激发试验后的最大镇痛百分比(%MPE),吗啡耐受组显著低于假手术组(P<0.01)。吗啡耐受组的IL-1β(25.8±4.03)pg/mgtotalprotein和IL-6(31.37±2.06)pg/mgtotalprotein均分别显著高于假手术组的(9.8±2.5)和(12.97±1.84)pg/mgtotalprotein,P<0...     

应用单光子发射式计算机断层成像评估异氟醚对健康人全脑及局部脑血流量分布的影响

目的:观察吸入不同浓度异氟醚麻醉下健康自愿者全脑血流量和局部脑血流灌注的变化特征。方法:实验于2004-05/08在解放军第四军医大学西京医院核医学科完成。选择9名签署了知情同意书的健康自愿者,分别在清醒、吸入0.5和1.0最低肺泡有效浓度异氟醚后3种状态下采用GESPECT仪进行扫描3次,勾画出额叶、颞叶、顶叶、枕叶、丘脑、基底核、舌回、扣带回、小脑、海马、全脑及全脑等区域的感兴趣区并计数,换算成血流量和局部脑血流。在麻醉过程中维持呼气末二氧化碳分压和平均动脉压相对稳定。结果:9名自愿者全部完成测试进入结果分析。①全脑血流量:清醒时,吸入0.5或1.0最低肺泡有效浓度异氟醚后比较无差异[(482±34),(496±42),(503±31)μL/(min·g),P>0.05]。②局部脑区局部脑血流量:额叶、颞叶、顶叶、枕叶、丘脑、基底核、舌回、扣带回、小脑、海马等区域在清醒时和吸入不同浓度异氟醚后比较均无差异。结论:在保持呼气末二氧化碳分压和平均动脉压不变时,吸入异氟醚麻醉不影响人脑内血流量的分布。     

急性重复性低氧暴露与小鼠脑内葡萄糖转运蛋白1,3基因表达及其耐受能力

目的:探讨急性重复性低氧暴露对小鼠脑内葡萄糖转运蛋白1,3基因表达水平及其耐受能力的影响。方法:实验于2004-07/12在北京老年医学研究所神经生物研究室完成。取健康雄性Balb/C近交系小鼠40只,随机分为缺氧0次组、缺氧1次组、重复缺氧3次组和重复缺氧5次组,每组10只。在室温18～22℃条件下,建立小鼠低氧预适应模型,依次记录5次的小鼠缺氧耐受时间;采用定量反向转录-聚合酶链式方法,观察急性重复性低氧对小鼠脑内葡萄糖转运蛋白1,3基因表达的影响。结果:40只小鼠均进入结果分析。①小鼠缺氧耐受时间:小鼠在第1,2,3,4,5缺氧密闭罐中的平均缺氧耐受时间分别是18,51,95,111和122min。②葡萄糖转运蛋白1mRNA水平比较:海马部位缺氧1次组、重复缺氧3次和5次组的吸光度分别是缺氧0次组的犤(1.46±0.15),(2.08±0.24),(1.25±0.25)犦倍;以上3组皮质部位的吸光度分别是缺氧0次组的犤(2.05±0.76),(2.24±0.65),(1.62±0.66)犦倍。③葡萄糖转运蛋白3mRNA水平比较:海马部位缺氧1次组、重复缺氧3次和5次组的吸光度分别是缺氧0次组的犤(1.67±0.26),92.40±0.21),(1.66±0.37)犦倍;以上3组皮质部位的吸光度分别是缺氧0次组的犤(2.38±1.01),(2.87±0.85),(1.92±0.52)犦倍。结论:急性重复性低氧暴露可大幅度提高小鼠     

吗啡耐受对大鼠脊髓后角星形胶质细胞的影响

目的:通过观察吗啡耐受对大鼠痛行为的影响和脊髓后角胶质细胞纤维酸性蛋白阳性产物表达的变化,探讨吗啡耐受对大鼠脊髓后角星形胶质细胞的影响。方法:实验于2003-11/2004-09在同济医院麻醉研究室完成。①造模:SD大鼠18只,随机分为对照组和吗啡耐受组,每组9只。在大鼠L3～5背部纵形切口,将细聚乙烯导管向头端插入蛛网膜下腔2cm,置管后第4天,对照组和吗啡耐受组分别经导管注射生理盐水10μL和吗啡10μL(20μg),1次/d,连续5d。吗啡耐受组注射吗啡后第6天,鞘内注射吗啡10μL(5μg)进行吗啡激发实验。②观察星形胶质细胞激活状态:应用免疫组织化学方法观察星形胶质细胞特异性标志物胶质纤维酸性蛋白染色情况,同时计算平均吸光度值和积分吸光度值,表示星形胶质细胞内胶质纤维酸性蛋白表达的强度(A值越大表示胶质纤维酸性蛋白表达越强)。③测定热伤害性缩腿反应潜伏期及非伤害性机械刺激的敏感程度:置管后第3天分别测定缩腿反应潜伏期和机械性触痛痛阈作为基础值。给药第6天吗啡激发试验前测定机械性触痛痛阈,吗啡激发实验后测定缩腿反应潜伏期,并计算最大镇痛效率。结果:18只大鼠均进入结果分析。①置管第3天及激发实验前缩足总数的变化:置管第3天的两组大鼠缩足阳性总次数基本相近犤(0.11±0.33)次犦,第6天吗啡激发试验前,对照组的缩足总数变化轻微,而吗啡耐受组缩足阳性总次数增多犤(10.66±1.41)次,(P<0.01)犦。②吗啡激发后的最大镇痛效率:对照组显著高于耐受组犤(59.20±4.00)%,(8.86±1.42)%,(P<0.01)犦。③脊髓胶质细胞胶质纤维酸性蛋白阳性表达产物相对面积、光密度和积分光密度,对照组分别少于吗啡耐受组犤3.417±0.268比6.530±0.423(P<0.01),0.357±0.024比0.520±0.025(P<0.01),1.689±0.303比2.310±0.314(P<0.01)犦。结论:脊髓吗啡耐受导致触诱发痛,激活脊髓后角星形胶质细胞,脊髓星形胶质细胞可能在吗啡耐受的形成中发挥重要作用。     

Glucose utilization in the rat brain during chronic morphine treatment and naloxone-precipitated morphine withdrawal

Rates of local cerebral glucose utilization (LCGU) were measured in morphine-dependent and morphine-abstinent rats. Morphine pellets were implanted s.c. (one pellet 7 days before glucose utilization measurement and two pellets 4 days before the measurement) to produce opioid dependence. LCGU rates in 85 brain regions of placebo- and morphine-pelleted rats were similar. In contrast, LCGU rates, 5 hr after implantation of one morphine pellet, were decreased significantly in six areas. The lack of a chronic morphine effect on LCGU suggests tolerance to morphine. Additional support for this view was that an additional dose of morphine (8 mg/kg s.c.) in morphine-dependent rats was also ineffective in altering LCGU and in an antinociception (hot plate) test. Furthermore, plasma morphine levels in chronically treated animals were greater than those in acutely treated animals. Naloxone-precipitated morphine withdrawal enhanced LCGU, most notably in thalamic and limbic areas, but also in some hypothalamic and hindbrain regions. The findings identify brain areas that may be important in the opioid abstinence syndrome. Furthermore they suggest that adaptations in the brain produce tolerance to morphine, reflected in LCGU rates and latencies in the hot-plate test.     

Effect of cyclo(Leu-Gly) on cyclic GMP-phosphodiesterase activity changes associated with development of tolerance to morphine-induced antinociception, catalepsy, respiratory depression and mydriasis.

A biochemical basis for the development of tolerance to morphine has yet to be defined. Although a number of models have been proposed, none can account for complete tolerance to this drug. Previous studies in our laboratory indicated that the development of complete tolerance to certain morphine-induced behaviors (antinociception, catalepsy and respiratory depression) is associated with changes in the activity of some form(s) of phosphodiesterase with cyclic GMP as substrate (cGMP-PDE) activity in the brain areas that mediate these behaviors (periaqueductal gray, striatum and medulla). In the present study, experiments were performed in which Cyclo(Leu-Gly), a dipeptide that inhibits the development of tolerance to morphine, was administered daily (2 mg/kg) to morphine-naive rats, coadministered with morphine or coadministered with morphine to morphine-tolerant rats and the cGMP-PDE activity was measured. The development of tolerance to the effects was inhibited or reversed by administration of cyclo(Leu-Gly) and there were corresponding changes in cGMP-PDE activity in various brain regions. Differences in cGMP hydrolysis between brain regions from morphine-tolerant animals, tolerance-inhibited animals and tolerance-reversed animals strengthens the evidence for direct involvement of cGMP-PDE(s) in tolerance phenomena.     

Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors

Dopamine's role in inhibitory control is well recognized and its disruption may contribute to behavioral disorders of discontrol such as obesity. However, the mechanism by which impaired dopamine neurotransmission interferes with inhibitory control is poorly understood. We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects. To assess if the reductions in dopamine D2 receptors were associated with activity in prefrontal brain regions implicated in inhibitory control we assessed the relationship between dopamine D2 receptor availability in striatum with brain glucose metabolism (marker of brain function) in ten morbidly obese subjects (BMI > 40 kg/m²) and compared it to that in twelve non-obese controls. PET was used with [¹¹C]raclopride to assess D2 receptors and with [¹⁸F]FDG to assess regional brain glucose metabolism. In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices. In controls correlations with prefrontal metabolism were not significant but comparisons with those in obese subjects were not significant, which does not permit to ascribe the associations as unique to obesity. The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. The association between striatal D2 receptors and metabolism in somatosensory cortices (regions that process palatability) could underlie one of the mechanisms through which dopamine regulates the reinforcing properties of food.     

Physical activity and television viewing in relation to risk of undiagnosed abnormal glucose metabolism in adults

OBJECTIVE: The goal of this study was to assess the associations of physical activity time and television (TV) time with risk of "undiagnosed" abnormal glucose metabolism in Australian adults. RESEARCH DESIGN AND METHODS: This population-based cross-sectional study using a stratified cluster design involving 42 randomly selected Census Collector Districts across Australia included 8,299 adults aged 25 years or older who were free from new type 2 diabetes and self-reported ischemic disease and did not take lipid-lowering or antihypertensive drugs. Abnormal glucose metabolism (impaired fasting glycemia [IFG], impaired glucose tolerance [IGT], or new type 2 diabetes) was based on an oral glucose tolerance test. Self-reported physical activity time and TV time (previous week) were assessed using interviewer-administered questionnaires. RESULTS: After adjustment for known confounders and TV time, the odds ratio (OR) of having abnormal glucose metabolism was 0.62 (95% CI 0.41-0.96) in men and 0.71 (0.50-1.00) in women for those engaged in physical activity >or=2.5 h/week compared with those who were sedentary (0 h/week). The ORs of having abnormal glucose metabolism were 1.16 (0.79-1.70) in men and 1.49 (1.12-1.99) in women who watched TV >14 h/week compared with those who watched 14 h/week) was also associated with an increased risk of new type 2 diabetes in men and women and IGT in women compared with those watching <14 h/week. Total physical activity of >or=2.5 h/week was associated with a reduced risk of IFG, IGT, and new type 2 diabetes in both sexes; however, only the association with IGT in women was statistically significant. CONCLUSIONS: These findings suggest a protective effect of physical activity and a deleterious effect of TV time on the risk of abnormal glucose metabolism in adults. Population strategies to reduce risk of abnormal glucose metabolism should focus on reducing sedentary behaviors such as TV time, as well as increasing physical activity.     

Evidence for involvement of cyclic GMP phosphodiesterase in morphine tolerance

Preliminary evidence had suggested that changes in cyclic GMP (cGMP) hydrolysis via cyclic nucleotide phosphodiesterase(s) occurred during development of tolerance to morphine. To examine this finding further and its possible role in development of tolerance to morphine, rats (150-175 g) were injected with 1 ml of a sustained-release morphine preparation (40 mg/ml). Control rats received 1 ml of the oily vehicle. Antinociception, decreased locomotor activity, respiratory depression and mydriasis were measured at various times from 0.5 through 96 hr of exposure to the drug. Particulate and soluble cGMP hydrolysis were measured for the same time periods from periaqueductal gray (PAG), striatum, medulla and oculomotor nucleus, the brain areas believed to mediate the respective behaviors. Each of the behaviors except mydriasis showed development of complete tolerance (no difference from control behaviors) during the 96 hr of continuous exposure. During development of tolerance, particulate cGMP hydrolysis decreased in PAG and increased in striatum and medulla. Particulate cGMP hydrolysis was not altered in oculomotor nucleus, the brain area mediating mydriasis to which tolerance development was partial or incomplete. Significant changes in soluble cGMP hydrolysis occurred only in PAG before decline in the behavioral effect and did not appear to be involved in tolerance phenomena. Modulation of cyclic nucleotide levels by changes in particulate cGMP hydrolysis may produce or allow for development of complete tolerance to various morphine-induced behaviors.     

年龄对健康人大脑葡萄糖代谢率影响作用的初步研究

目的：采用基于体素水平的图像分析法，初步探讨年龄对健康人大脑葡萄糖代谢率的影响作用。方法：对40例健康人进行静息状态下的^18F-FDG PET脑显像。根据年龄将受试者分为29例年轻组和11例老年组，对两组之间的^18F_FDG PET数据进行基于体素水平的图像分析。结果：老年组双侧额叶、颞叶、顶叶及前扣带回等部位葡萄糖代谢较年轻组减低；年轻组双侧额叶内侧部、扭带回、楔前叶及小脑半球等部位葡萄糖代谢较老年组减低。结论：不同年龄组健康人的大脑葡萄糖代谢率不同，随着年龄增加健康人大脑葡萄糖代谢率减低的脑区主要包括双侧额叶、扣带回及颞叶等部位。     

Influence of L-tryptophan on morphine analgesia, tolerance and physical dependence.

Four hours after the acute administration of L-tryptophan (75 mg/kg) to either, nontolerant or morphine-tolerant mice, the antinociceptive effect of morphine was partially and significantly antagonized. Daily tryptophan administration to rats and mice during a 3-day morphine pellet implantation period increased the rates of both morphine tolerance development and development of physical dependence. The accelerating effect of tryptophan on tolerance and dependence development in mice was antagonized by pretreatment with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine. Acute tryptophan administration (75 mg/kg) significantly increased mouse brain 5-hydroxytryptamine levels for at least 4 hours. Although chronic tryptophan treatment increased 5-hydroxytryptamine turnover in morphine-treated mice, no effect of chronic morphine or tryptophan treatment on the particulate tryptophan hydroxylase activity of whole mouse brain was observed. Slight increases in tryptophan hydroxylase activity were observed in the caudate-putamen and septal areas of rat brain 3 and 6 days, respectively, after s.c. morphine pellet implantation. These and previous studies from our laboratory indicate that the development of morphine tolerance and dependence can be modified by agents affecting serotonergic mechanisms.     

FGF19 action in the brain induces insulin-independent glucose lowering

Insulin-independent glucose disposal (referred to as glucose effectiveness [GE]) is crucial for glucose homeostasis and, until recently, was thought to be invariable. However, GE is reduced in type 2 diabetes and markedly decreased in leptin-deficient ob/ob mice. Strategies aimed at increasing GE should therefore be capable of improving glucose tolerance in these animals. The gut-derived hormone FGF19 has previously been shown to exert potent antidiabetic effects in ob/ob mice. In ob/ob mice, we found that systemic FGF19 administration improved glucose tolerance through its action in the brain and that a single, low-dose i.c.v. injection of FGF19 dramatically improved glucose intolerance within 2 hours. Minimal model analysis of glucose and insulin data obtained during a frequently sampled i.v. glucose tolerance test showed that the antidiabetic effect of i.c.v. FGF19 was solely due to increased GE and not to changes of either insulin secretion or insulin sensitivity. The mechanism underlying this effect appears to involve increased metabolism of glucose to lactate. Together, these findings implicate the brain in the antidiabetic action of systemic FGF19 and establish the brain’s capacity to rapidly, potently, and selectively increase insulin-independent glucose disposal.     

'Healthy living' and sulphonylurea theraphy have different effects on glucose tolerance and risk factors for vascular disease in subject with impaired glucose tolerance

This study was undertaken to determine whether impaired glucosetolerance and associated risk factors for cardiovascular diseasecan be improved with ‘healthy living’ by diet andexercise or with sulphonylurea therapy. Patients were recruitedby screening subjects with either a family history of type IIdiabetes, previous gestational diabetes, or a previously raisedplasma glucose (5.6–6.6 mmol/l). Impaired glucose tolerancewas defined as hyperglycaemia on two separate tests, an achievedglucose level after a glucose infusion test above the 90th percentileof an age-matched normal population (> 9.3 mmol/l) or a fastingplasma glucose above the 95th percentile (> 5.6 mmol/l).Thirty-seven subjects with impaired glucose tolerance were enteredinto a randomized, prospective study for 6 months with allocationsto healthy living or double blind to sulphonylurea (gliclazide40 mg twice daily) or placebo tablets. The study took placein an outpatient setting, with three times weekly exercise sessionsat a Sports Centre. After 6 months the placebo group showedno change in plasma glucose, cholesterol and blood pressure.The subjects receiving gliclazide showed improved glucose levels(mean fasting plasma glucose levels fell from 5.8 to 5.1 mmol/l,p<0.05) but no significant change in plasma cholesterol orblood pressure. The healthy living group, after exclusion offour non-compliant subjects, showed no change in glucose levels,but a decreased systolic blood pressure (fall in mean from 124to 116 mmHg, p<0.05) and plasma cholesterol levels (fallin mean from 5.2 to 4.5 mmol/l, p0.01) with an increase in HDL:LDLratio (rise in mean from 0.39 to 0.46, p<0.05). Subjectswith impaired glucose tolerance may benefit in different waysfrom gliclazide and healthy living. The metabolic responsesto each therapy may help to decrease the risk of developingdiabetes and cardiovascular disease.     

Detection of Visual Activation in the Rat Brain Using 2-deoxy-2-[18F]fluoro-d-glucose and Statistical Parametric Mapping (SPM)

Purpose  This study was designed to assess changes in brain glucose metabolism in rats after visual stimulation. Materials and methods  We sought to determine whether visual activation in the rat brain could be detected using a small-animal positron emission tomography (PET) scanner and 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG). Eleven rats were divided into two groups: (a) five animals exposed to ambient light and (b) six animals stimulated by stroboscopic light (10 Hz) with one eye covered. Rats were injected with FDG and, after 45 min of visual stimulation, were sacrificed and scanned for 90 min in a dedicated PET tomograph. Images were reconstructed by a three-dimensional ordered subset expectation maximization algorithm (1.8 mm full width at half maximum). A region-of-interest (ROI) analysis was performed on 14 brain structures drawn on coronal sections. Statistical parametric mapping (SPM) adapted for small animals was also carried out. Additionally, the brains of three rats were sliced into 20-μm sections for autoradiography. Results  Analysis of ROI data revealed significant differences between groups in the right superior colliculus, right thalamus, and brainstem (p ≤ 0.05). SPM detected the same areas as the ROI approach. Autoradiographs confirmed the existence of hyperactivation in the left superior colliculus and auditory cortex. Conclusions  To our knowledge, this is the first report that uses FDG-PET and SPM analysis to show changes in rat brain glucose metabolism after a visual stimulus.