碘难治性分化型甲状腺癌诱导再分化治疗研究进展

分化型甲状腺癌（DTC）大多进展缓慢,经手术、促甲状腺素抑制治疗和（或）放射性碘（RAI）等规范化治疗后总体预后好,但仍有部分患者治疗后出现复发或远处转移,并可能在自然病程或治疗过程中丧失摄碘能力,不能从后续RAI治疗中获益,成为碘难治性分化型甲状腺癌（RAIRDTC）。RAIR-DTC患者可选择的治疗方法有限,且效果欠佳。近年来,随着对RAIR-DTC分子机制研究的不断深入,诱导再分化联合RAI治疗在RAIR-DTC中展现出一定的应用前景。本文综述了信号通路抑制剂、组蛋白去乙酰化酶抑制剂（HDACi）、DNA甲基化酶抑制剂、维甲酸类药物及过氧化物酶体增殖物激活受体（PPAR）激动剂在RAIR-DTC诱导再分化治疗中的进展。     

紫外分光光度法测定转移因子透析液中多肽含量

 以凯氏定氮法测定结果为基础,采用紫外分光光度法测定转移因子透析液中的多肽含量?该法的回收率及相对标准偏差分别为99.56%?1.48%(n=6);经与Folin-酚法相比较,确定两种方法测得含量的比值为7.17,RSD为3.77%(n=20)?相关系数为0.93;并推算出当吸收值为15.10时,多肽含量为1.0mg/ml?从而为转移因子透析液中多肽的定量提供了一个快速?简便?准确的方法?     

Variability and reproducibility of hepatic FDG uptake measured as SUV as well as tissue‐to‐blood background ratio using positron emission tomography in healthy humans

Introduction: To investigate variability and reproducibility of hepatic [¹⁸F]‐2‐fluoro‐2‐deoxy‐d ‐glucose (FDG) uptake in healthy individuals. Methods:  Static images were obtained 70 min after the injection of 160 MBq FDG in six healthy subjects at two occasions with 13 days’ interval. FDG uptake was adjusted for tissue‐to‐blood background ratio (T/B), or measured as standardized uptake value (SUV). Small regions of interest (ROIs) of 10 cm³ in two different hepatic regions were analysed as well as the total liver. Results: Mean SUV was 1·16 ± 0·15 and mean T/B corrected values was 1·87 ± 0·17. The maximal values were 2·70 (SUV) and 4·67 (T/B). Reproducibility was 6·7% for the mean SUV and 0·2% for the max SUV values. The corresponding figures for the T/B corrected mean values were 6·4% and for the max T/B values 13·0%. In general, the small ROIs had a comparable or even lower CV% for SUV values, but a higher CV% for T/B corrected values. Conclusions: In normal subjects hepatic FDG‐uptake is high and homogeneous with a low CV% between days. T/B corrected values are largely comparable to SUV values but not superior, probably due to the standardization of procedures and homogeneity of the subjects. The T/B corrected method is theoretically superior in a more inhomogeneous population or when using different scanners and is shown here to be easy to apply. Small ROIs of 10 cm³ are representative with respect to mean FDG uptake in the total liver and reproducibility, but do not identify the max FDG uptake.     

芦荟多糖的抗疲劳作用研究

目的探讨芦荟多糖的抗疲劳作用。方法160只昆明种雄性小鼠随机均分成4组,用芦荟多糖低、中、高3个剂量给小鼠灌胃,对照组给等剂量蒸馏水,15d后小鼠游泳造成疲劳,测定小鼠力竭时游泳时间、血乳酸（LAC）、血清尿素氮（BUN）及肝糖原。结果芦荟多糖能明显延长小鼠负重游泳时间,明显提高小鼠运动后肝糖原的含量,降低BUN和LAC的含量。结论芦荟多糖对小鼠具有显著抗疲劳作用。     

Assessing cytotoxicity of (iron oxide‐based) nanoparticles: an overview of different methods exemplified with cationic magnetoliposomes

Iron oxide nanoparticles are the most widely used T₂/T₂* contrast agents and for biomedical research purposes, one of the main applications is the in vitro labeling of stem or therapeutic cells, allowing them to be subsequently tracked in vivo upon transplantation. To allow this, the nanoparticles used should not show any sign of cytotoxicity and not affect cellular physiology as this could impede normal cell functionality in vivo or lead to undesired side‐effects. Assessing the biocompatibility of the nanoparticles has proven to be quite a difficult task. In the present work, a small overview of commonly used assays is presented in order to assess several aspects, such as cell viability, induction of reactive oxygen species, nanoparticle uptake, cellular morphology, cellular proliferation, actin cytoskeleton architecture and differentiation of stem cells. The main focus is on comparing the advantages and disadvantages of the different assays, highlighting several common problems and presenting possible solutions to these problems as well as pointing out the high importance of the relationship between intracellular nanoparticle concentration and cytotoxicity. Copyright © 2009 John Wiley & Sons, Ltd.     

Onset of antidepressant effect of olanzapine and olanzapine/fluoxetine combination in bipolar depression

OBJECTIVES: The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination. METHODS: Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed. The Montgomery-Asberg Depression Rating Scale measured depressive symptoms. Multiple analytic methods were applied, including traditional (mean differences) analysis, pattern analysis, survival analysis of sustained response, mixed-effects regression, and area-under-the-curve analysis. RESULTS: Traditional analysis showed significantly greater improvement in depression scores at week 1 for olanzapine/fluoxetine combination versus placebo (-9.55 versus -5.08, p < 0.001) and for olanzapine versus placebo (-8.31 versus -5.08, p < 0.001). Pattern analysis revealed olanzapine/fluoxetine combination had a significantly greater percentage of early persistent responders than placebo or olanzapine (32.4% versus 12.7%, p < 0.001; and 18.3%, p < 0.05, respectively). Survival analysis showed a significantly shorter time to sustained response for the combination versus placebo (p < 0.001), for olanzapine versus placebo (p = 0.04), and for the combination versus olanzapine (p = 0.03). Mixed-effects regression analysis revealed a significant therapy-by-time interaction (p < 0.001). Early area-under-the-curve analysis revealed a significantly greater percentage of improvement for the combination versus placebo (26.7% versus 13.9%, p < 0.001) and for olanzapine versus placebo (22.0% versus 13.9%, p < 0.001). CONCLUSIONS: Based on consistent results from related methods of measuring onset, olanzapine/fluoxetine combination demonstrated rapid onset of antidepressant effect (within 7 days) compared to placebo that was sustained over 8 weeks of treatment in a sample of BD patients. Using multiple statistical techniques may help profile a drug's onset of effect.     

Effects of the triple reuptake inhibitor amitifadine on extracellular levels of monoamines in rat brain regions and on locomotor activity

Major depressive disorder is a prevalent disease, and current pharmacotherapy is considered to be inadequate. It has been hypothesized that a triple reuptake inhibitor (TRI) that activates dopamine (DA) neurotransmission in addition to serotonin and norepinephrine (NE) circuitries may result in enhanced antidepressant effects. Here, we investigated the pharmacological effects of a serotonin-preferring TRI-amitifadine (EB-1010, formerly DOV 21947). The effects of amitifadine (10 mg/kg ip.) on extracellular concentrations of monoamines and their metabolites in rat brain regions were investigated using the in vivo microdialysis technique. The effects of amitifadine on locomotor activity and stereotyped behavior were also evaluated. A major metabolite of amitifadine, the 2-lactam compound, was investigated for inhibition of monoamine uptake processes. Amitifadine markedly and persistently increased extracellular concentrations of serotonin, NE, and DA in prefrontal cortex. The extracellular concentrations of DA were also increased in the DA-rich areas striatum and nucleus accumbens. The extracellular concentrations of the metabolites of serotonin, 5-hydroxyindoleacetic acid, and DA, 3,4-dihydroxyphenylacetic and homovanillic acid, were also markedly decreased in brain regions. Amitifadine did not increase locomotor activity or stereotypical behaviors over a broad dose range. The lactam metabolite of amitifadine weakly inhibited monoamine uptake. Thus, amitifadine increased extracellular concentrations of serotonin, NE, and DA, consistent with TRI. Although amitifadine significantly increased DA in the nucleus accumbens, it did not induce locomotor hyperactivity or stereotypical behaviors. The enhancement of serotonin, NE, and DA in rat brain regions associated with depression suggest that amitifadine may have novel antidepressant activity.     

Astrocytes restrict discharge duration and neuronal sodium loads during recurrent network activity

Influx of sodium ions into active neurons is a highly energy‐expensive process which must be strictly limited. Astrocytes could play an important role herein because they take up glutamate and potassium from the extracellular space, thereby dampening neuronal excitation. Here, we performed sodium imaging in mouse hippocampal slices combined with field potential and whole‐cell patch‐clamp recordings and measurement of extracellular potassium ([K⁺]_o). Network activity was induced by Mg²⁺‐free, bicuculline‐containing saline, during which neurons showed recurring epileptiform bursting, accompanied by transient increases in [K⁺]_o and astrocyte depolarizations. During bursts, neurons displayed sodium increases by up to 22 mM. Astrocyte sodium concentration increased by up to 8.5 mM, which could be followed by an undershoot below baseline. Network sodium oscillations were dependent on action potentials and activation of ionotropic glutamate receptors. Inhibition of glutamate uptake caused acceleration, followed by cessation of electrical activity, irreversible sodium increases, and swelling of neurons. The gliotoxin NaFAc (sodium‐fluoroacetate) resulted in elevation of astrocyte sodium concentration and reduced glial uptake of glutamate and potassium uptake through Na⁺/K⁺‐ATPase. Moreover, NaFAc extended epileptiform bursts, caused elevation of neuronal sodium, and dramatically prolonged accompanying sodium signals, most likely because of the decreased clearance of glutamate and potassium by astrocytes. Our experiments establish that recurrent neuronal bursting evokes sodium transients in neurons and astrocytes and confirm the essential role of glutamate transporters for network activity. They suggest that astrocytes restrict discharge duration and show that an intact astrocyte metabolism is critical for the neurons' capacity to recover from sodium loads during synchronized activity. GLIA 2015;63:936–957     

Valeriana officinalis does not alter the orofacial dyskinesia induced by haloperidol in rats: role of dopamine transporter

Chronic treatment with classical neuroleptics in humans can produce a serious side effect, known as tardive dyskinesia (TD). Here, we examined the effects of V. officinalis, a medicinal herb widely used as calming and sleep-promoting, in an animal model of orofacial dyskinesia (OD) induced by long-term treatment with haloperidol. Adult male rats were treated during 12 weeks with haloperidol decanoate (38 mg/kg, i.m., each 28 days) and with V. officinalis (in the drinking water). Vacuous chewing movements (VCMs), locomotor activity and plus maze performance were evaluated. Haloperidol treatment produced VCM in 40% of the treated rats and the concomitant treatment with V. officinalis did not alter either prevalence or intensity of VCMs. The treatment with V. officinalis increased the percentage of the time spent on open arm and the number of entries into open arm in the plus maze test. Furthermore, the treatment with haloperidol and/or V. officinalis decreased the locomotor activity in the open field test. We did not find any difference among the groups when oxidative stress parameters were evaluated. Haloperidol treatment significantly decreased [(3)H]-dopamine uptake in striatal slices and V. officinalis was not able to prevent this effect. Taken together, our data suggest a mechanism involving the reduction of dopamine transport in the maintenance of chronic VCMs in rats. Furthermore, chronic treatment with V. officinalis seems not produce any oxidative damage to central nervous system (CNS), but it also seems to be devoid of action to prevent VCM, at least in the dose used in this study.     

Characterization of guanine and guanosine transport in primary cultured rat cortical astrocytes and neurons

In this study, we examined the transport mechanisms for guanine and guanosine in rat neurons and astrocytes, and compared their characteristics. In the both types of cell, the uptake of [(3)H]guanine and [(3)H]guanosine was time-, temperature-, and concentration-dependent, and Na(+)-independent. Their uptake decreased on the addition of purine and pyrimidine nucleobases or nucleosides, and the inhibitory effect of the purine analogues was greater than that of the pyrimidine ones. In both cell types, equilibrative nucleoside transporter (ENT) 1 and ENT2 expression was confirmed at the mRNA level, and nitrobenzylmercaptopurine riboside, a representative inhibitor for ENT, decreased their uptake at concentrations of over 10 microM. Comparing uptake characteristics between the substrates, [(3)H]guanine uptake exhibited higher affinity and clearance than [(3)H]guanosine uptake in each type of cell. Although between neurons and astrocytes, there was no difference in the apparent uptake clearance for [(3)H]guanine and [(3)H]guanosine, which was calculated based upon the cellular protein content, the cellular uptake clearance was significantly greater in astrocytes than in neurons. These findings indicate that guanine and guanosine, of which the former is a preferable substrate, are taken up into both neurons and astrocytes via ENT2, and that the extracellular concentrations of guanine and guanosine are mainly regulated by astrocytes to maintain brain physiology.