• 【B细胞慢性淋巴细胞白血病患者T细胞中的信号分子和细胞因子产生: 氟达拉滨和阿仑单抗治疗的长期影响。】 复制标题 收藏 收藏
    DOI:10.1080/10428190600565503 复制DOI
    作者列表:Kiaii S,Choudhury A,Mozaffari F,Rezvany R,Lundin J,Mellstedt H,Osterborg A
    BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.
    背景与目标: : 氟达拉滨和阿仑单抗通常用于治疗b细胞慢性淋巴细胞白血病 (b-cll)。本研究旨在比较在氟达拉滨或阿仑单抗治疗后长期未维持缓解/平台期的b-cll患者的T细胞与惰性/未治疗的b-cll患者和健康的T细胞的信号分子表达和细胞因子产生供体。通过流式细胞术检查CD4和CD8 T细胞中TCR-CD3zeta链,p56lck,p59fyn,ZAP-70,PI3-kinase和干扰素 (IFN)-γ/白细胞介素 (IL)-4产生的频率和强度。通过纯化蛋白衍生物 (PPD) 和植物血凝素 (PHA) 刺激来评估T细胞功能。尽管数量减少,但患者T细胞中IFN-γ/IL-4的表达显着高于健康供体。与健康供体相比,接受治疗的患者中大多数信号分子的强度相对不受影响,但低于未经治疗的惰性患者。然而,在患者中表达每种信号分子的T细胞总数减少,而氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中,T细胞对PHA的反应降低,但对PPD的反应降低。结果表明,尽管信号分子发生了一些变化,T细胞数量减少,但在用氟达拉滨和阿仑单抗治疗后,总体T细胞功能可能长期保持良好。
  • 【ERCP透皮三硝酸甘油的前瞻性,随机,安慰剂对照试验: 对技术成功和ERCP后胰腺炎的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.gie.2005.11.060 复制DOI
    作者列表:Kaffes AJ,Bourke MJ,Ding S,Alrubaie A,Kwan V,Williams SJ
    BACKGROUND & AIMS: BACKGROUND:Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE:To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN:Prospective, double-blind, placebo-controlled trial. SETTING:Tertiary referral university hospital. PATIENTS:A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS:Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS:Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS:There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS:Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.
    背景与目标:
  • 【阿片肽对 μ 受体选择性的直接作用: 豚鼠室旁和视上核的细胞内记录。】 复制标题 收藏 收藏
    DOI:10.1016/0306-4522(90)90426-5 复制DOI
    作者列表:Wuarin JP,Dudek FE
    BACKGROUND & AIMS: :Responses to [D-Ala2, MePhe4, Gly-ol5]enkephalin, a selective agonist for mu-receptors, were recorded intracellularly from 26 neurons in slices of guinea-pig hypothalamus. Of eight cells tested in the supraoptic nucleus, all of which had electrical properties characteristic of magnocellular neuroendocrine cells, four were sensitive to the agonist applied in the perfusion bath or with microdrops. The main effect was a decrease or suppression of spontaneous firing. In the paraventricular nucleus, seven of 18 cells tested also had electrophysiological characteristics similar to magnocellular neurons: two of them were sensitive to the mu-agonist and the effect was similar to that observed in the supraoptic nucleus. The remaining paraventricular neurons displayed low-threshold Ca2+ spikes, and thus had electrophysiological characteristics different from putative magnocellular neurons. Ten of 11 cells with low-threshold Ca2+ spikes were hyperpolarized by more than 10 mV by the mu-agonist, and showed a 33 +/- 1.9% (S.E.M.) decrease in input resistance. In both types of cells, when synaptic transmission was blocked with tetrodotoxin, the mu-agonist could still induce a hyperpolarization, suggesting that the effect was in part direct. Hyperpolarization was also obtained when the Cl- reversal potential was shifted to more positive values by using KCl electrodes, thus excluding a Cl- conductance mechanism. These results provide evidence that opioid peptides can directly inhibit hypothalamic neurons, that the mechanism is an increase in K+ conductance, and that two types of hypothalamic neurons appear to have different sensitivities to a mu-agonist.
    背景与目标: : 从豚鼠下丘脑切片中的26个神经元在细胞内记录了对 [D-Ala2,MePhe4,Gly-ol5] 脑啡肽 (mu受体的选择性激动剂) 的反应。在视上核中测试的八个细胞中,所有这些细胞均具有大细胞神经内分泌细胞的电特性,其中四个对灌注浴或微滴中使用的激动剂敏感。主要效果是减少或抑制自发发射。在室旁核中,测试的18个细胞中有7个具有类似于大细胞神经元的电生理特征: 其中两个对mu激动剂敏感,其作用类似于在视上核中观察到的作用。其余的室旁神经元显示出低阈值的Ca2尖峰,因此具有与假定的大细胞神经元不同的电生理特征。具有低阈值Ca2尖峰的11个细胞中的10个被mu激动剂超极化超过10 mV,并显示输入阻力降低了33/- 1.9% (s.e.M.)。在两种类型的细胞中,当河豚毒素阻断突触传递时,mu激动剂仍可诱导超极化,这表明该作用部分是直接的。当使用KCl电极将Cl反转电位移至更多正值时,也获得了超极化,从而排除了Cl电导机制。这些结果提供了证据,表明阿片肽可以直接抑制下丘脑神经元,其机制是K电导的增加,并且两种类型的下丘脑神经元似乎对mu激动剂具有不同的敏感性。
  • 【压力限制通气期间持续气管气吹入对急性肺损伤家兔肺表面活性物质的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Zhu GF,Zhang W,Zong H,Liang Y
    BACKGROUND & AIMS: BACKGROUND:Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (V(T)) while maintaining constant partial arterial CO2 pressure (PaCO(2)). We hypothesised that TGI limited peak inspiratory pressure (PIP) and V(T) and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI). METHODS:ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n = 8 for each group), and subsequently ventilated with limited PIP and V(T) to maintain PaCO(2) within 35 to 45 mmHg for 4 hours. Physiological dead space to V(T) ratio (V(D)/V(T)), dynamic respiratory compliance (Cdyn) and partial arterial O(2) pressure (PaO(2)) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (V(V)), myeloperoxidase and interleukin (IL)-8. RESULTS:TGI resulted in significant (P < 0.05 or P < 0.01) decrease in PIP [(22.4 +/- 1.8) cmH2O vs (29.5 +/- 1.1) cmH2O], V(T) [(6.9 +/- 1.3) ml/kg vs (9.8 +/- 1.11) ml/kg], V(D)/V(T) [(32 +/- 5)% vs (46 +/- 2)%], TP [(109 +/- 22) mg/kg vs (187 +/- 25) mg/kg], SA/LA (2.5 +/- 0.4 vs 5.4 +/- 0.7), myeloperoxidase [(6.2 +/- 0.5) U/g tissue vs (12.3 +/- 0.8) U/g tissue] and IL-8 [(987 +/- 106) ng/g tissue vs (24 +/- 3) mN/m] of BALF, and significant (P < 0.05) increase in Cdyn [(0.47 +/- 0.02) ml.cmH2O(-1).kg(-1) vs (0.31 +/- 0.02) ml.cmH2O(-1).kg(-1)], PaO(2) [(175 +/- 24) mmHg vs (135 +/- 26) mmHg], TPL/TP (52 +/- 8 vs 33 +/- 11) and Vv (0.65 +/- 0.05 vs 0.44 +/- 0.07) as compared with CMV. CONCLUSIONS:In this animal model of ALI, TGI decreased ventilatory requirements (PIP, V(T) and V(D)/V(T)), resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI.
    背景与目标:
  • 【辐射诱导的旁观者和其他非靶向效应: 癌症治疗的新干预要点?】 复制标题 收藏 收藏
    DOI:10.2174/156800906777723976 复制DOI
    作者列表:Mothersill C,Seymour C
    BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.
    背景与目标: : 寻找新的癌症药物靶标的一个主要问题是,这些药物通常对正常组织有毒,需要高剂量才能杀死肿瘤细胞。因此,似乎涉及对癌症治疗的低剂量反应的细胞靶标是特别令人感兴趣的,因为它们可以选择性地靶向不被治疗靶向的正常组织,并且因此可能导致令人不快的副作用或可能易于利用以提高治疗比率。作为本综述主题的一个这样的目标是辐射诱导的旁观者效应 [RIBE],该效应导致在未辐照的细胞中观察到类似辐射的反应。RIBE是一种新现象,表明在低剂量下,细胞信号传导比直接DNA损伤更重要。从历史上看,DNA一直被认为是放射治疗的目标。越来越多的意识到信号很重要,这开辟了一些重要的治疗策略,这些策略将在本文中进行讨论。RIBE似乎是组织或细胞中普遍应激反应的结果,该应激反应在组织,器官或生物体的水平而不是单个细胞的水平上表达。信号可能由所有暴露的细胞产生,但是响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET (x射线或伽马射线) 辐射暴露的主要反应是死亡反应。这具有许多凋亡特征,但可以在没有p53表达的细胞系中检测到,尽管在许多肿瘤细胞系中死亡反应受到抑制。虽然肿瘤周围未照射的正常细胞的死亡反应似乎是不利的,但实际上它可以起到保护作用并从人群中清除受损的细胞。如果正确使用,它可能会导致新药的开发,其目的不是组织破坏,而是使稳态机制能够控制肿瘤的扩张。在这种情况下,有害或有益反应的水平将与细胞群体携带的背景损害以及确定对损害反应的遗传程序有关。在尝试预测涉及辐射和其他细胞毒性药物的混合疗法的后果时,此重点可能很重要。在这篇综述中,我们对电离辐射诱导旁观者效应的潜在机制的当前知识进行了综述,并讨论了如何利用旁观者效应来生产旨在稳定组织稳态而不是组织破坏的新一代抗癌药物的问题。
  • 【一种新的胆囊收缩素类似物 (JMV 236) 对大鼠食物摄入和脑单胺的影响。】 复制标题 收藏 收藏
    DOI:10.1016/0143-4179(90)90158-u 复制DOI
    作者列表:Gourch A,Orosco M,Rodriguez M,Martinez J,Cohen Y,Jacquot C
    BACKGROUND & AIMS: :JMV 236, a new cholecystokinin-octapeptide-sulfate (CCK 8 S) derivative (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) has been synthesized in the Centre de Pharmacologie-Endocrinologie (Montpellier). This peptide has been shown to present the same activity as CCK 8 S on pancreatic amylase secretion and has the advantage of a better chemical stability. With a view to further characterization, the effect of JMV 236 on food intake and brain monoamine and metabolite variations was assayed in the rat after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administrations. JMV 236 decreased food intake 2 and 3 hours after i.p. administration of 12.5 and 50 micrograms/kg but was inactive after i.c.v. injection. Its global action was similar to that of CCK 8 S, but was less marked with delayed onset of response. As in our previous work with CCK 8 S, JMV 236 was more potent in inducing monoaminergic variations after i.p. than after i.c.v. administration. The main effects were decreases in striatal dopamine metabolite levels and increases in hypothalamic and striatal serotonin metabolite (5-HIAA) levels. These effects are classically observed with CCK 8 S and are described in our previous reports. The interesting peptide will require further characterization and may serve as a possible reference compound for studies on CCK derivatives.
    背景与目标: : JMV 236,一种新的胆囊收缩素-八肽-硫酸盐 (CCK 8 S) 衍生物 (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) 已在药物内分泌中心 (蒙彼利埃) 合成。已显示该肽在胰腺淀粉酶分泌上具有与CCK 8 s相同的活性,并且具有更好的化学稳定性的优势。为了进一步表征,在腹膜内 (i.p.) 和脑室内 (i.c.v.) 给药后,在大鼠中测定了JMV 236对食物摄入以及脑单胺和代谢物变化的影响。静脉注射后2小时和3小时,JMV 236降低了食物摄入量。施用12.5和50微克/千克,但在静脉注射后无效。它的全局作用与CCK 8 s相似,但反应延迟发作的特征较小。与我们先前使用CCK 8 s的工作一样,JMV 236在i.p.之后更有效地诱导单胺能变化。比i.c.v.管理后还要多。主要影响是纹状体多巴胺代谢物水平降低,下丘脑和纹状体5-羟色胺代谢物 (5-HIAA) 水平升高。这些影响在CCK 8 s中经典观察到,并在我们之前的报告中进行了描述。该有趣的肽将需要进一步的表征,并且可以作为CCK衍生物研究的可能参考化合物。
  • 【ATP诱导的腿部血管舒张对人体最大运动过程中VO2峰值和腿部O2提取的影响。】 复制标题 收藏 收藏
    DOI:10.1152/ajpregu.00746.2005 复制DOI
    作者列表:Calbet JA,Lundby C,Sander M,Robach P,Saltin B,Boushel R
    BACKGROUND & AIMS: :During maximal whole body exercise VO2 peak is limited by O2 delivery. In turn, it is though that blood flow at near-maximal exercise must be restrained by the sympathetic nervous system to maintain mean arterial pressure. To determine whether enhancing vasodilation across the leg results in higher O2 delivery and leg VO2 during near-maximal and maximal exercise in humans, seven men performed two maximal incremental exercise tests on the cycle ergometer. In random order, one test was performed with and one without (control exercise) infusion of ATP (8 mg in 1 ml of isotonic saline solution) into the right femoral artery at a rate of 80 microg.kg body mass-1.min-1. During near-maximal exercise (92% of VO2 peak), the infusion of ATP increased leg vascular conductance (+43%, P<0.05), leg blood flow (+20%, 1.7 l/min, P<0.05), and leg O2 delivery (+20%, 0.3 l/min, P<0.05). No effects were observed on leg or systemic VO2. Leg O2 fractional extraction was decreased from 85+/-3 (control) to 78+/-4% (ATP) in the infused leg (P<0.05), while it remained unchanged in the left leg (84+/-2 and 83+/-2%; control and ATP; n=3). ATP infusion at maximal exercise increased leg vascular conductance by 17% (P<0.05), while leg blood flow tended to be elevated by 0.8 l/min (P=0.08). However, neither systemic nor leg peak VO2 values where enhanced due to a reduction of O2 extraction from 84+/-4 to 76+/-4%, in the control and ATP conditions, respectively (P<0.05). In summary, the VO2 of the skeletal muscles of the lower extremities is not enhanced by limb vasodilation at near-maximal or maximal exercise in humans. The fact that ATP infusion resulted in a reduction of O2 extraction across the exercising leg suggests a vasodilating effect of ATP on less-active muscle fibers and other noncontracting tissues and that under normal conditions these regions are under high vasoconstrictor influence to ensure the most efficient flow distribution of the available cardiac output to the most active muscle fibers of the exercising limb.
    背景与目标: : 在最大的全身运动期间,VO2峰值受到O2输送的限制。反过来,尽管在接近最大运动时的血流必须受到交感神经系统的限制,以维持平均动脉压。为了确定在人类接近最大和最大运动期间,增强腿部的血管舒张是否会导致较高的O2递送和腿部VO2,七名男子在自行车测功机上进行了两次最大增量运动测试。以随机顺序,进行一次测试,其中一次 (对照运动) 以80微克kg身体mass-1.min-1的速率将ATP (8 mg在1毫升的等渗盐溶液中) 输注到右股动脉中。在接近最大运动 (VO2峰的92%) 期间,ATP的输注增加了腿部血管电导 (43%,P<0.05),腿部血流量 (20%,1.7 l/min,P<0.05) 和腿部O2的输送 (20%,0.3 l/min,P<0.05)。未观察到对腿部或全身vo2的影响。腿部O2分数提取在输注的腿部从85 +/-3 (对照) 降低到78 +/-4% (ATP) (P & lt; 0.05),而在左腿保持不变 (84 +/-2和83 +/-2%; 对照和ATP; n = 3)。最大运动时ATP输注可增加17% (P<0.05),而腿部血流量可增加0.8 l/min (P = 0.08)。然而,在对照和ATP条件下,由于O2提取从84 +/-4降低到76 +/-4% 而增强的体循环或腿部峰值VO2值都没有增强 (P<0.05)。总而言之,在人类几乎最大或最大的运动中,肢体血管舒张不会增强下肢骨骼肌的VO2。ATP输注导致运动腿部O2提取减少的事实表明,ATP对活动较少的肌纤维和其他非收缩组织具有血管舒张作用,并且在正常条件下,这些区域处于较高的血管收缩作用下,以确保最有效的血流分布。锻炼肢体的肌肉纤维。
  • 【冷暴露对大鼠肾上腺酪氨酸羟化酶的影响: RNA,蛋白质,酶活性和辅因子水平的分析。】 复制标题 收藏 收藏
    DOI:10.1111/j.1471-4159.1990.tb01232.x 复制DOI
    作者列表:Baruchin A,Weisberg EP,Miner LL,Ennis D,Nisenbaum LK,Naylor E,Stricker EM,Zigmond MJ,Kaplan BB
    BACKGROUND & AIMS: :Long-term cold exposure (5-7 days) is known to induce concomitant increases in the levels of adrenomedullary tyrosine hydroxylase (TH) RNA, protein, and enzyme activity. In this report, we compare the time courses of these changes and investigate the effects of cold exposure on the levels of biopterin, the cofactor required for tyrosine hydroxylation. After only 1 h of cold exposure, TH mRNA abundance increased 71% compared with nonstressed controls. Increases in total cellular TH RNA levels were maximal (threefold over control values) within 3-6 h of cold exposure and remained elevated throughout the duration of the experiment (72 h). TH protein levels increased rapidly after 24 h of cold exposure and reached a maximal value threefold above that of controls at 48-72 h. Despite the relatively rapid and large elevations in TH RNA and protein content, only modest increases in TH activity were detected during the initial 48 h of cold exposure. Adrenomedullary biopterin increased rapidly after the onset of cold exposure, rising to a level approximately twofold that of the nonstressed controls at 24 h, and remained at this level throughout the duration of the stress period. Taken together, the results of this time course study indicate that cold-induced alterations in adrenal TH activity are mediated by multiple cellular control mechanisms, which may include pre- and posttranslational regulation. Our findings also suggest that cold stress-induced increases in the levels of the TH cofactor may represent another key event in the sympathoadrenal system's response to cold stress.
    背景与目标: : 已知长期冷暴露 (5-7天) 会引起肾上腺髓质酪氨酸羟化酶 (TH) RNA,蛋白质和酶活性的同时增加。在本报告中,我们比较了这些变化的时间过程,并研究了冷暴露对酪氨酸羟基化所需的辅因子生物蝶呤水平的影响。冷暴露仅1小时后,与无应激对照相比,TH mRNA丰度71% 增加。在冷暴露的3-6小时内,总细胞TH RNA水平的增加最大 (是对照值的三倍),并且在整个实验期间 (72小时) 保持升高。冷暴露24小时后,TH蛋白水平迅速增加,并在48-72小时达到对照组的三倍的最大值。尽管TH RNA和蛋白质含量的升高相对较快且较大,但在冷暴露的最初48小时内仅检测到TH活性的适度增加。冷暴露开始后,肾上腺髓质生物蝶呤迅速增加,在24小时时升至非应激对照的大约两倍,并在整个应激期内保持在该水平。总之,该时间过程研究的结果表明,冷诱导的肾上腺TH活性的改变是由多种细胞控制机制介导的,其中可能包括翻译前和翻译后的调节。我们的发现还表明,冷应激引起的TH辅因子水平的增加可能是交感肾上腺系统对冷应激反应的另一个关键事件。
  • 【早期大剂量左甲状腺素治疗对先天性甲状腺功能减退儿童入学听觉脑事件相关电位的影响。】 复制标题 收藏 收藏
    DOI:10.1159/000095069 复制DOI
    作者列表:Marti S,Alvarez M,Simoneau-Roy J,Leroux S,Van Vliet G,Robaey P
    BACKGROUND & AIMS: AIMS:We tested whether brain event-related potentials (ERPs) are normal in children with congenital hypothyroidism (CH) after early high-dose levothyroxine treatment. METHODS:Auditory ERPs were recorded in 33 normal controls and in 15 children with CH at 5 years 9/12. Based on bone maturation at diagnosis, the CH group was divided into severe (n = 8) and moderate (n = 7) subgroups. CH patients were treated at a median age of 14 days with a mean initial dose of levothyroxine of 11.6 microg/kgxday. Two ERP components (N100 and N200) were measured and clinical follow-up variables collected. RESULTS:The functional anatomical and cognitive organisation of the auditory system, as revealed by the analyses of ERP measures, did not differ between CH and controls, or between severe and moderate CH subjects. However, N200 latency was globally longer in the CH than in the control group (p = 0.01) and was positively correlated with the over-treatment index (r = 0.61; p < 0.05) and verbal IQ. N200 amplitude was negatively correlated with initial dose (r = -0.74; p < 0.005). CONCLUSION:These data suggest that sensitive tools such as ERPs can reveal differences between CH and controls and relate these differences to the adequacy of treatment of CH.
    背景与目标:
  • 【冰按摩对艾滋病患者神经性疼痛的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.jana.2006.07.002 复制DOI
    作者列表:Ownby KK
    BACKGROUND & AIMS: :Peripheral neuropathic pain is a unique form of chronic pain that afflicts up to 50% of persons with AIDS. The purpose of this pilot study was to examine the effects of ice massage to reduce neuropathic pain and improve sleep quality and to determine the feasibility of a larger study. A repeated measures design was used. The three treatments consisted of ice massage, dry-towel massage, and presence. Consecutive sampling was used to select 33 persons with AIDS who had neuropathic pain. Although the results of the study were negative, there was a decrease in pain intensity over time with both the ice massage and towel massage, suggesting that the intervention has some clinical benefit.
    背景与目标: : 周围神经性疼痛是一种独特的慢性疼痛形式,困扰多达50% 的艾滋病患者。这项初步研究的目的是检查冰按摩减轻神经性疼痛和改善睡眠质量的效果,并确定进行更大规模研究的可行性。使用了重复测量设计。这三种治疗方法包括冰按摩,干毛巾按摩和在场。连续抽样选择33例患有神经性疼痛的艾滋病患者。尽管研究结果为阴性,但随着时间的推移,冰按摩和毛巾按摩的疼痛强度有所降低,这表明该干预措施具有一定的临床益处。
  • 【过氧化物酶体增殖物激活受体配体的直接抗氧化和抗炎作用与链脲佐菌素诱导的糖尿病大鼠主动脉中血管紧张素转化酶表达的抑制有关。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejphar.2006.08.036 复制DOI
    作者列表:Toba H,Miki S,Shimizu T,Yoshimura A,Inoue R,Sawai N,Tsukamoto R,Murakami M,Morita Y,Nakayama Y,Kobara M,Nakata T
    BACKGROUND & AIMS: :Peroxisome proliferator-activated receptors (PPARs) are expressed on vascular tissue. To investigate the direct vasoprotective effects of PPARgamma and PPARalpha ligands, pioglitazone (3 mg/kg/day) and bezafibrate (10 mg/kg/day) were given by gavage to streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.p.) significantly increased NADPH oxidase, vascular call adhesion molecule-1 (VCAM-1), and osteopontin mRNA levels in the aorta, as determined by reverse transcription (RT)-polymerase chain reaction (PCR). Immunohistochemical analysis revealed that the expression of osteopontin protein was also enhanced in the streptozotocin-injected rat aorta. Pioglitazone or bezafibrate attenuated the streptozotocin-induced increase in the expression of NADPH oxidase and VCAM-1 mRNA. The enhanced expression of osteopontin gene and protein induced by streptozotocin was suppressed by pioglitazone, whereas treatment with bezafibrate had no effect on the expression of osteopontin. We also demonstrated that pioglitazone or bezafibrate prevented the streptozotocin-induced increase in angiotensin converting enzyme (ACE) gene and protein content, by the means of RT-PCR and Western blotting. On the other hand, the treatment of pioglitazone or bezafibrate in the present study did not affect glucose tolerance, serum insulin or lipid level in streptozotocin-induced diabetic rats. These results suggest that the direct anti-oxidant and anti-inflammatory effects of PPARs ligands in the aorta of streptozotocin-induced diabetic rats were not likely to have been mediated by the normalization of glucose or lipid metabolism, but instead these salutary effects appear to have been associated with the inhibition of the expression of ACE. In addition, pioglitazone appeared to be more effective on the suppression of osteopontin expression compared with bezafibrate.
    背景与目标: : 过氧化物酶体增殖物激活受体 (ppar) 在血管组织上表达。为研究PPARgamma和PPARalpha配体的直接血管保护作用,将吡格列酮 (3 mg/kg/天) 和苯扎贝特 (10 mg/kg/天) 灌胃给链脲佐菌素诱导的糖尿病大鼠4周。通过逆转录 (RT)-聚合酶链反应 (PCR) 测定,链脲佐菌素 (65 mg/kg,i.p.) 显着增加主动脉中的NADPH氧化酶,血管呼叫粘附分子-1 (VCAM-1) 和骨桥蛋白mRNA水平。免疫组织化学分析显示,在注射链脲佐菌素的大鼠主动脉中,骨桥蛋白的表达也得到了增强。吡格列酮或苯扎贝特减弱了链脲佐菌素诱导的NADPH氧化酶和VCAM-1 mRNA表达的增加。吡格列酮抑制了链脲佐菌素诱导的骨桥蛋白基因和蛋白的增强表达,而苯扎贝特治疗对骨桥蛋白的表达没有影响。我们还证明,吡格列酮或苯扎贝特通过rt-pcr和Western印迹阻止了链脲佐菌素诱导的血管紧张素转化酶 (ACE) 基因和蛋白质含量的增加。另一方面,本研究中吡格列酮或苯扎贝特的治疗不会影响链脲佐菌素诱导的糖尿病大鼠的葡萄糖耐量,血清胰岛素或脂质水平。这些结果表明,链脲佐菌素诱导的糖尿病大鼠主动脉中ppar配体的直接抗氧化和抗炎作用不太可能由葡萄糖或脂质代谢的正常化介导。但是,这些有益的作用似乎与抑制ACE的表达有关。此外,与苯扎贝特相比,吡格列酮似乎对抑制骨桥蛋白表达更有效。
  • 【不同类型刺激对兔颈动脉体循环AMP含量的影响: 功能意义。】 复制标题 收藏 收藏
    DOI:10.1111/j.1471-4159.1990.tb03137.x 复制DOI
    作者列表:Pérez-García MT,Almaraz L,González C
    BACKGROUND & AIMS: :Cyclic AMP levels in rabbit carotid bodies incubated under control conditions, 100% O2- or 95% O2/5% CO2- equilibrated medium, are close to 1 pmol/mg wet tissue (range 0.4-2.43 pmol/mg). Isobutylmethylxanthine (0.5 mM) increases cyclic AMP levels by a factor of 14 and 8 in HEPES- and CO2/CH3O(-)-buffered medium, respectively. Forskolin (0.5-10 microM) applied during 30 min increases cyclic AMP levels in a dose-dependent manner. Incubation of carotid bodies at low O2 tensions resulted in an elevation of cyclic AMP levels both in the absence and in the presence of isobutymethylxanthine. In the latter conditions cyclic AMP increase was maximum at an O2 tension of 46 mm Hg and tended to decrease at extremely low PO2. In isobutylmethylxanthine-containing Ca2(+)-free medium, cyclic AMP increased linearly with decreasing PO2 from 66 to 13 mm Hg; the absolute cyclic AMP levels attained in Ca2(+)-free medium were smaller than those observed in Ca2(+)-containing medium at any PO2. The differences between Ca2(+)-free and Ca2(+)-containing media appear to be due to the action of released neurotransmitters in the latter conditions, because dopamine and norepinephrine, which are known to be released by hypoxia in a Ca2(+)-dependent manner, increase cyclic AMP in the carotid body. Low pH/high PCO2 and high [K+]e increase cyclic AMP levels only in Ca2(+)-containing medium. Forskolin potentiates the release of catecholamines induced by low PO2. These results suggest that cyclic AMP plays an important role in the modulation of the chemoreception process.
    背景与目标: : 在100% O2-或95% O2/5% CO2平衡的培养基的对照条件下孵育的兔颈动脉体中的循环AMP水平接近1 pmol/mg湿组织 (范围0.4-2.43 pmol/mg)。在HEPES-和CO2/CH3O(-) 缓冲介质中,异丁基甲基黄嘌呤 (0.5 mM) 使环状AMP水平分别增加14和8倍。在30分钟期间施加的福司可林 (0.5-10微米) 以剂量依赖性方式增加循环AMP水平。在低O2张力下孵育颈动脉体会在不存在和存在异丁甲基黄嘌呤的情况下导致环状AMP水平升高。在后一种条件下,循环AMP的增加在46毫米Hg的O2张力下最大,并在极低的po2下趋于降低。在含异丁基甲基黄嘌呤的无Ca2 () 的培养基中,环状AMP随着PO2从66 Hg降低到13毫米Hg而线性增加; 在无Ca2 () 的培养基中获得的绝对环状AMP水平小于在任何PO2下在含Ca2 () 的培养基中观察到的绝对环状AMP水平。不含Ca2(+) 和含Ca2(+) 的培养基之间的差异似乎是由于在后一种情况下释放的神经递质的作用,因为多巴胺和去甲肾上腺素,已知它们是由缺氧以Ca2(+) 依赖性方式释放的,增加颈动脉体中的循环AMP。低pH/高PCO2和高 [K] e仅在含Ca2 () 的培养基中增加循环AMP水平。Forskolin可增强低po2诱导的儿茶酚胺的释放。这些结果表明,循环AMP在化学感受过程的调制中起着重要作用。
  • 【天花叶提取物对四氧嘧啶糖尿病大鼠代谢紊乱和氧化应激的保护作用。】 复制标题 收藏 收藏
    DOI:10.1186/s12906-017-1835-8 复制DOI
    作者列表:Ben Salem M,Ben Abdallah Kolsi R,Dhouibi R,Ksouda K,Charfi S,Yaich M,Hammami S,Sahnoun Z,Zeghal KM,Jamoussi K,Affes H
    BACKGROUND & AIMS: BACKGROUND:Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. METHODS:We determinate the antioxidant activity by ABTS .+ and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. RESULTS:The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS .+ (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p < 0.001) the α-amylase levels in serum of diabetic rats, respectively associated with significant reduction (p < 0.001) in blood glucose rate of 42,84% and 37,91% compared to diabetic groups after 28 days of treatment, a significant lowered of plasma total cholesterol (T-Ch) by 18,11% and triglyceride (TG) by 60,47%, significantly and low-density lipoproteins (LDL-C) by 37,77%, compared to diabetic rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was confirmed by histological study. CONCLUSION:These observed strongly suggest that ethanol extract from the leaves of C. scolymus has anti-hyperglycemic properties, at least partly mediated by antioxidant and hypolipidemic effects.
    背景与目标:
  • 【辣木通过抗氧化剂,抗炎和抗血管生成机制对链脲佐菌素诱导的糖尿病大鼠的视网膜保护作用。】 复制标题 收藏 收藏
    DOI:10.1089/jop.2012.0089 复制DOI
    作者列表:Kumar Gupta S,Kumar B,Srinivasan BP,Nag TC,Srivastava S,Saxena R,Aggarwal A
    BACKGROUND & AIMS: PURPOSE:The present study was aimed to evaluate the retinoprotective effects of Moringa oleifera (MO) in Streptozotocin-induced diabetic rats. METHODS:The study was continued for 24 weeks and evaluated for inflammatory (tumor necrosis factor [TNF]-α and interleukin [IL]-1β, angiogenic (vascular endothelial growth factor [VEGF] and protein kinase C [PKC]-β) and antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Retinal leakage was checked by Fluorescein angiography (FA) and fundus photographs were evaluated for retinal vessel caliber (arteriolar and venular). Transmission electron microscopy was done to determine basement membrane (BM) thickness. RESULTS:The results of the present study showed potential hypoglycemic and retinal antioxidant effects of MO. In the present study, a significant rise in the expression of retinal inflammatory (TNF-α and IL-1β) and angiogenic (VEGF and PKC-β) parameters was observed in diabetic retinae as compared to normal retinae. However, MO-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic parameters. Further, in the present study, diabetic retinae showed dilated retinal vessels as compared to normal. However, MO-treated retinae showed marked prevention in the dilatation of retinal vessels. Fluorescein angiograms obtained from diabetic retinae showed leaky and diffused retinal vasculature. On the other hand, MO-treated retinae showed intact retinal vasculature. Further, results of the transmission electron microscopy study showed thickened capillary BM in the diabetic retina as compared to normal retinae. However, treatment with MO prevented thickening of capillary BM. CONCLUSION:Our result suggests that MO may be useful in preventing diabetes induced retinal dysfunction.
    背景与目标:
  • 【咖啡因对正常血压健康年轻人运动过程中血压反应的影响。】 复制标题 收藏 收藏
    DOI:10.1016/0002-9149(90)91435-9 复制DOI
    作者列表:Sung BH,Lovallo WR,Pincomb GA,Wilson MF
    BACKGROUND & AIMS: :The possible combined effects of caffeine and exercise on blood pressure (BP) regulation were examined in 34 healthy, normotensive (BP less than 135/85 mm Hg) young men (mean age 27 +/- 3 years) in a placebo-controlled, double-blind crossover design. Each subject performed submaximal and symptom-limited maximal supine bicycle exercise 1 hour apart after ingestion of placebo or caffeine (3.3 mg/kg). Heart rate, BP, cardiac output and peripheral vascular resistance were compared for placebo and caffeine days. Postdrug baseline showed that caffeine increased systolic and diastolic BP and peripheral vascular resistance (p less than 0.001 for each) and decreased heart rate (p less than 0.01) but did not change stroke volume or cardiac output. BP and vascular resistance effects of caffeine remained during submaximal exercise resulting in an additive increase in BP while negative chronotropic effects of caffeine disappeared. At maximal exercise substantially more subjects (15 on caffeine vs 7 on placebo, p less than 0.02) had systolic BP greater than or equal to 230 mm Hg and/or greater than or equal to 100 mm Hg for diastolic BP. Plasma norepinephrine levels were not significantly different across days, but epinephrine was higher at maximal exercise and cortisol was increased post-drug and throughout maximal exercise on caffeine days. Data indicate that caffeine increases BP additively during submaximal exercise and may cause excessive BP responses at maximal exercise for some individuals. The pressor effects of caffeine appear to be due to increasing vascular resistance rather than cardiac output.
    背景与目标: : 在安慰剂对照中,在34名健康,血压正常 (血压低于135/85mm Hg) 的年轻男性 (平均年龄27/- 3岁) 中检查了咖啡因和运动对血压 (BP) 调节的可能综合作用,双盲交叉设计。每个受试者在摄入安慰剂或咖啡因 (3.3 mg/kg) 后1小时间隔进行次最大和症状受限的最大仰卧自行车运动。比较安慰剂和咖啡因天数的心率,血压,心输出量和外周血管阻力。药物后基线显示,咖啡因增加收缩压和舒张压以及周围血管阻力 (每个p小于0.001) 和降低心率 (p小于0.01),但不改变中风量或心输出量。在次最大运动期间,咖啡因的BP和血管阻力效应仍然存在,导致BP的累加性增加,而咖啡因的负变时性效应消失了。在最大运动时,明显更多的受试者 (咖啡因组15例,安慰剂组7例,p小于0.02) 的收缩压大于或等于230毫米Hg和/或舒张压大于或等于100毫米Hg。血浆去甲肾上腺素水平在不同的日子没有显着差异,但肾上腺素在最大运动时较高,皮质醇在服药后和咖啡因的整个最大运动中增加。数据表明,咖啡因在次最大运动期间会增加BP,并可能导致某些人在最大运动时产生过多的BP反应。咖啡因的升压作用似乎是由于血管阻力增加而不是心输出量增加所致。

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