BACKGROUND & AIMS: Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface, classically provided by activated platelets. We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells (VSMCs) undergoing apoptosis after serum withdrawal. In this study, using a chromogenic assay, we have shown thrombin generation by apoptotic VSMCs expressing c-myc (VSMC-myc) with an area under the thrombin-generation curve (AUC) of 305 +/- 17 nmol x min/L and a peak thrombin (PT) of 154 +/- 9 nmol/L. The thrombin-generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets (P = .003 for AUC; P = .0002 for PT) and similar to calcium-ionophore activated platelets (AUC of 332 +/- 15 nmol x min/L, P = .3; PT of 172 +/- 8 nmol/L, P = .2). Thrombin activation was also seen with apoptotic human VSMCs (AUC of 211 +/- 8 nmol x min/L; PT of 103 +/- 4 nmol/L) and was inhibited by annexin V (P < .0001 for AUC and PT). VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal (P = .0002 for AUC and PT). VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin (AUC of 260 +/- 2 nmol x min/L; PT of 128 +/- 4 nmol/L). We conclude that apoptotic VSMCs possess a significant thrombin-generating capacity secondary to phosphatidylserine exposure. Apoptotic cells within atherosclerotic plaques may allow local thrombin activation, thereby contributing to disease progression.

背景与目标： 凝血酶激活需要在阴离子磷脂表面上组装活化的凝血因子的凝血酶原复合物，通常由活化的血小板提供。我们以前已经表明，阴离子磷脂酰丝氨酸被大鼠血管平滑肌细胞 (VSMCs) 暴露，在血清戒断后发生凋亡。在这项研究中，使用显色测定法，我们已经显示表达c-myc (VSMC-myc) 的凋亡VSMC产生凝血酶，凝血酶产生曲线 (AUC) 下面积为305 +/- 17 nmol × min/L，凝血酶峰 (PT) 为154 +/- 9 nmol/L。凋亡的VSMC-myc细胞的凝血酶生成潜力大于未激活的血小板 (AUC P = .003; PT P = .0002)，与钙离子载体激活的血小板相似 (AUC为332 +/- 15 nmol x min/L，P = .3; PT为172 +/- 8 nmol/L，P = .2)。在凋亡的人VSMCs中也可以看到凝血酶活化 (AUC为211 +/- 8 nmol × min/L; PT为103 +/- 4 nmol/L)，并被膜联蛋白V抑制 (P < .0001 AUC和PT)。维持在血清中的VSMC-myc细胞产生的凝血酶少于血清戒断后 (对于AUC和PT，P = .0002)。来源于人冠状动脉粥样硬化斑块的VSMCs，即使在血清中凋亡也产生凝血酶 (AUC为260 +/- 2 nmol × min/L; PT为128 +/- 4 nmol/L)。我们得出的结论是，凋亡的VSMCs在磷脂酰丝氨酸暴露后具有显着的凝血酶生成能力。动脉粥样硬化斑块内的凋亡细胞可能会激活局部凝血酶，从而促进疾病进展。

BACKGROUND & AIMS: These experiments were designed to determine whether glycogenolysis was influenced by the glycogen concentration of vascular smooth muscle. Segments of hog carotid artery smooth muscle were allowed to synthesize variable amounts of 1-[13C]glucosyl units of glycogen. Artery segments were then isometrically contracted in the presence of 2-[13C]glucose. Prior to and after isometric contraction, measurements were made of tissue glycogen content and superfusate glucose and lactate concentrations. 2-[13C]Lactate and 3-[13C]lactate peak intensities in the superfusate were measured using 13C-NMR spectroscopy. The tissue glycogen content decreased exponentially during the 4.5 h of isometric contraction (R2 = 0.990), despite more than a 3-fold range of glycogen concentration prior to contraction. The extent of glycogen utilization during a 3 h isometric contraction varied linearly with the precontraction glycogen concentration (R2 = 0.727). Lactate production specifically from glycogen breakdown increased with an increase in precontraction glycogen concentration (R2 = 0.620). During a 3 h isometric contraction neither the glucose utilization (R2 = 0.007) nor lactate production specifically produced from glucose (R2 = 0.00002) varied with the precontraction glycogen concentration. It is concluded that the rate of glycogenolysis is determined by the content of glycogen during prolonged contractions. In addition, precontraction glycogen levels influence the pathway for glycogen utilization but not the pathway for glucose utilization. Therefore, glycolysis and glycogenolysis behave independently in vascular smooth muscle.

背景与目标： 这些实验旨在确定糖原分解是否受血管平滑肌糖原浓度的影响。允许猪颈动脉平滑肌段合成可变量的1-[13C] 糖原葡萄糖单元。然后在2-[13C] 葡萄糖存在下等距收缩动脉段。在等距收缩之前和之后，测量组织糖原含量和超融合物葡萄糖和乳酸浓度。使用13C-NMR光谱测量超融合物中的2-[13C] 乳酸和3-[13C] 乳酸峰强度。组织糖原含量在等距收缩的4.5小时内呈指数下降 (R2 = 0.990)，尽管收缩前糖原浓度超过3倍。在3 h等距收缩期间糖原利用的程度随收缩前糖原浓度线性变化 (R2 = 0.727)。糖原分解产生的乳酸产量随着收缩前糖原浓度的增加而增加 (R2 = 0.620)。3小时的等距收缩葡萄糖利用率 (R2 = 0.007) 和特别由葡萄糖产生的乳酸产量 (R2 = 0.00002) 都不随收缩前糖原浓度而变化。结论是糖原分解速率由长期收缩期间糖原含量决定。此外，收缩前糖原水平会影响糖原利用的途径，但不会影响葡萄糖利用的途径。因此，糖酵解和糖原分解在血管平滑肌中独立运作。

BACKGROUND & AIMS: :Continuous changes in the length of smooth muscles require a highly organized sarcolemmal structure. Yet, smooth muscle cells also adapt rapidly to altered environmental cues. Their sarcolemmal plasticity must lead to profound changes which affect transmembrane signal transduction as well as contractility. We have established porcine vascular and human visceral smooth muscle cultures of epithelioid and spindle-shaped morphology and determined their plasma membrane properties. Epithelioid cells from both sources contain a higher ratio of cholesterol to glycerophospholipids, and express a less diverse range of lipid-associated annexins. These findings point to a reduction in efficiency of membrane segregation in epithelioid cells. Moreover, compared to spindle-shaped cells, cholesterol is more readily extracted from epithelioid cells with methyl-beta-cyclodextrin and its synthesis is more susceptible to inhibition with lovastatin. The inability of epithelioid cells to process vasoactive metabolites, such as angiotensin or nucleotides further indicates that contractile properties are impaired. Phenotypic plasticity extends beyond the loss of smooth muscle cell marker genes. The plasma membrane has undergone profound functional changes which are incompatible with cyclic foreshortening, but might be important in the development of vascular disease.

背景与目标： : 平滑肌长度的持续变化需要高度组织化的肌膜结构。然而，平滑肌细胞也迅速适应改变的环境线索。它们的肌膜可塑性必须导致深刻的变化，从而影响跨膜信号转导以及收缩力。我们已经建立了上皮样和纺锤形形态的猪血管和人内脏平滑肌培养物，并确定了它们的质膜特性。来自两种来源的上皮样细胞均含有较高的胆固醇与甘油磷脂比例，并且表达与脂质相关的膜联蛋白的范围较少。这些发现表明上皮样细胞的膜分离效率降低。此外，与纺锤形细胞相比，胆固醇更容易从上皮样细胞中提取甲基-β-环糊精，其合成更容易受到洛伐他汀的抑制。上皮样细胞无法处理血管活性代谢产物，例如血管紧张素或核苷酸，进一步表明收缩特性受损。表型可塑性超出了平滑肌细胞标记基因的丧失。质膜发生了深刻的功能变化，与循环缩短不相容，但在血管疾病的发展中可能很重要。

BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌痛患者持续静脉输注 (CIVI) 吗啡与持续皮下输注 (CSCI) 吗啡的剂量，疗效和副作用。符合条件的患者被转诊到姑息治疗计划，并正在接受稳定剂量的CIVI吗啡。该设计是患者内部的单向交叉; 其中每个患者在吗啡从CIVI切换到CSCI之前和之后提供数据。“抢救” 剂量是根据需要每2小时给予的每小时剂量的50%。通过McGaw/AccuPro容积输液泵静脉内 (i.v.) 和皮下 (s.c.) 注入吗啡。获得包括副作用和疼痛评估在内的基线数据后，每天两次评估患者的毒性和镇痛效果。那些连续48小时稳定的CIVI剂量的人以与静脉 (i.v.) 阶段相同的剂量交叉到CSCI。稳定剂量定义为无剂量变化，在之前的24小时内有四个或更少的抢救剂量，并且疼痛等级为无或轻度。如果连续96个小时保持这些标准，CIVI被认为等于CSCI。进入了57名患者，其中40名可评估 (15名女性和25名男性)。中位年龄为67岁 (范围30-83岁)。所有40名参与者在整个静脉内保持稳定剂量后。阶段，越过s.C.阶段并保留在s.c.至少48小时。32名患者在整个静脉内保持稳定剂量。和南卡罗来纳州阶段。平均稳定的静脉注射。剂量 (第2天) 为5.05 mg/hr，平均稳定s.c.剂量 (第4天) 为5.7 mg/hr (P = 0.01)。第2天的平均抢救剂量为每24小时0.83次，而第4天的平均抢救剂量为每24小时0.80次 (P = 0.6)。第2天和第4天的平均分类疼痛评分为0.83，0.85 (P = 0.7)。第2天的平均视觉模拟量表 (VAS) 为22.9毫米，第4天为17.6毫米 (P = 0.1)。第2天和第4天的平均副作用发生率为1.7，2.0 (P = 0.2)。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点局部毒性 (轻度红斑) 的报告，需要改变部位。我们的40名患者均使用CIVI和CSCI吗啡进行了足够的疼痛控制。在没有保持相同i.v.的八名参与者中。和南卡罗来纳州剂量，都有足够的疼痛控制，并且在较高的s.C.上有相似的副作用。吗啡剂量。这些数据表明，静脉注射和南卡罗来纳州当作为连续输注给药时，大多数患者的途径是等镇痛。疼痛控制和副作用特征非常相似且可以接受。吗啡是静脉注射的绝佳替代品需要胃肠外吗啡治疗疼痛的住院患者和门诊患者的吗啡。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.

背景与目标： : 交感神经的维持性疼痛可以通过交感神经传出和传入伤害性纤维之间的触感相互作用来介导，也可以通过儿茶酚胺诱导的伤害性神经末梢的激活来介导。我们在此报告了一名患有交感持续疼痛的患者的C伤害感受器的单纤维记录，其中交感神经阻滞反复消除了双腿的持续疼痛。我们根据八种C纤维的机械响应性和与活动有关的传导速度减慢 (在0.125Hz下20个脉冲的0.5/-1.1与7.1/-2.0 ms的潜伏期增加)，将它们分类为机械敏感的伤害感受器。强烈的内源性交感神经爆发后，两根C纤维被激活，延迟数秒; 在将去甲肾上腺素 (10 microl，0.05%) 注射到其神经支配区域后，它们也被兴奋约3分钟。在这两种纤维中，记录了通过注射低pH溶液 (磷酸盐缓冲液，pH 6.0，10μl) 而延长的活化以及前列腺素E2注射后它们的热响应的敏化，证明了它们的传入性质。此外，对于机械不敏感的伤害感受器，它们的活性依赖性减慢是典型的。我们得出的结论是，内源性释放的儿茶酚胺可以激活敏感的机械不敏感伤害感受器，从而可能导致交感疼痛。没有发现交感传出和伤害性传入纤维之间的触觉相互作用的证据。

BACKGROUND & AIMS: AIM:To research possible associations between previous exposure to specific torture techniques and prevalent pain in the head and face, back, and feet. METHODS:221 refugees, 193 males and 28 females, previously exposed to torture in their home country, were subject to a clinical interview at a rehabilitation clinic for torture victims. The interview focused on exposure to torture and somatic symptoms prevalent at examination. RESULTS:The mean number of times imprisoned was 2.3; the mean number of months imprisoned was 19.7; the mean duration from initial imprisonment to final release was 3.7 years; and the mean duration from final release to preliminary interview was 8.4 years. The most frequent physical torture method reported was beating (92.3%) and the main mental torture method was deprivation (84.6%). Pain in the head and face was found to be strongly associated with torture against head and face (OR 3.89, 95% CI 1.49-10.20) and with the cumulative number of physical torture methods exposed to. Pain in the back was associated with sexual torture (OR 2.75, 95% CI 1.07-7.12). Besides beating of the lower extremities (OR 5.98, 95% CI 2.47-14.48), the strongest predictor for pain in the feet was general abuse of the whole body (OR 5.64, 95% CI 1.93-16.45). CONCLUSION:In spite of many factors being potentially co-responsible for prevalent pain, years after the torture took place it presents itself as strongly associated with specific loci of pain, with generalized effects, and with somatizing.

背景与目标：

BACKGROUND & AIMS: :Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management.

背景与目标： : 脊髓NMDA受体激活后过度兴奋可能导致慢性疼痛。天然衍生的哺乳动物肽组织蛋白可能具有NMDA拮抗剂活性。这项研究探讨了稳定的类似物 [Ser1] 组织蛋白 (SHG) 可以减轻慢性疼痛的可能性。使用慢性收缩损伤模型 (CCI) 诱发神经病理性疼痛。鞘内注射SHG可显着减轻由CCI引起的痛觉过敏和异常性疼痛，几乎使反应正常化。这些结果表明，天然肽组织粒蛋白可能是神经性疼痛管理的新型辅助手段。

BACKGROUND & AIMS: :It is well-recognised that steady-state isometric muscle force is decreased following active shortening (force depression, FD) and increased following active stretch (force enhancement, FE). It has also been demonstrated that passive muscle force is increased following active stretch (passive FE). Several studies have reported that FD increases with shortening amplitude and that FE and passive FE increase with stretch amplitude. Here, we investigate whether these trends continue with further increases in shortening or stretch amplitude. Experiments were performed using in situ cat soleus muscles (n=8 for FD; n=7 for FE and passive FE). FD, FE and passive FE were measured after shortening or stretch contractions that covered as wide a range of amplitudes as practically possible without damaging the muscles. FD increased approximately linearly with shortening amplitude, over the full range of amplitudes investigated. This is consistent with the hypothesis that FD arises from a stress-induced inhibition of crossbridges. FE increased with stretch amplitude only up to a point, and then levelled off. Passive FE, and the transient increase in force at the end of stretch, showed relationships to stretch amplitude that were qualitatively very similar to the relationship for FE, increasing only until the same critical stretch amplitude had been reached. We conclude that FE and passive FE do not increase with stretch amplitude under all circumstances. This finding has important consequences for determining the mechanisms underlying FE and passive FE because any mechanism that is proposed to explain them must be able to predict it.

背景与目标： : 众所周知，主动缩短 (力降低，FD) 后，稳态等距肌肉力降低，主动拉伸 (力增强，FE) 后，稳态等距肌肉力增加。还已证明，主动拉伸 (被动FE) 后，被动肌肉力量会增加。一些研究报告说，FD随缩短幅度而增加，FE和被动FE随拉伸幅度而增加。在这里，我们研究这些趋势是否随着缩短或拉伸幅度的进一步增加而继续。使用原位猫比目鱼肌进行实验 (FD为n = 8; FE和被动FE为n = 7)。在缩短或拉伸收缩后测量FD，FE和被动FE，这些收缩实际上覆盖了尽可能宽的振幅范围，而不会损坏肌肉。在所研究的整个振幅范围内，FD随振幅的缩短而近似线性增加。这与FD由应力诱导的交叉桥抑制引起的假设是一致的。FE仅随拉伸幅度增加到一个点，然后趋于平稳。被动FE和拉伸结束时的瞬时力增加显示出与拉伸幅度的关系，在质量上与FE的关系非常相似，仅在达到相同的临界拉伸幅度之前才增加。我们得出的结论是，在所有情况下，FE和被动FE都不会随拉伸幅度而增加。这一发现对于确定FE和被动FE的潜在机制具有重要的影响，因为提出的任何解释它们的机制都必须能够预测它。

BACKGROUND & AIMS: :Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+ -activated K+ (IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+ -activated K+ (BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 microM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 microM myristoylated protein kinase C inhibitor peptide 20-28 or 10 microM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 microM Rp-cyclic 3', 5'-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 microM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 microM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.

背景与目标： : Angiostensin II (Ang II) 调节血管平滑肌细胞的迁移和增殖。最近的研究表明，中间电导Ca2激活的K (IKca) 通道在细胞迁移和增殖中起重要作用。但是，尚不清楚Ang II的作用是否与IKca通道调节有关。在这里，我们研究了Ang II对动脉平滑肌细胞中IKca通道的调节。使用膜片钳技术研究了培养的胚胎大鼠主动脉平滑肌 (A10) 细胞中功能性IKca通道的表达。这些细胞主要表达IKca通道。相反，在切除的贴片中很少观察到大电导Ca2激活的K (BKca) 电流。Ang II以依赖于收缩的方式增加了IKca电流。氯沙坦 (1.0 microM)，一种AT1选择性拮抗剂，通过Ang II消除了IKca通道的激活。用100 microM肉豆蔻酰化蛋白激酶C抑制剂肽20-28或10 microM GF109203X进行预处理完全消除了AngII诱导的IKca电流的激活，而在存在100 microM Rp-环状3 '，5'-磷酸氢腺苷三乙基铵的情况下，Ang II的作用没有被阻止，蛋白激酶a抑制剂，或1.0 microM KT-5823，蛋白激酶G抑制剂。二酰基甘油1,2-二酰基-sn-甘油 (10 microM) 的膜渗透类似物诱导了IKca电流的激活。这些数据表明Ang II通过激活蛋白激酶C激活IKca通道，AT1受体参与了这些通道的调节。

BACKGROUND & AIMS: :The purpose of this study was to test the hypothesis that runners having different running economies show differences in the mechanical and morphological properties of their muscle-tendon units (MTU) in the lower extremities. Twenty eight long-distance runners (body mass: 76.8+/-6.7 kg, height: 182+/-6 cm, age: 28.1+/-4.5 years) participated in the study. The subjects ran on a treadmill at three velocities (3.0, 3.5 and 4.0 m s(-1)) for 15 min each. The V(O(2)) consumption was measured by spirometry. At all three examined velocities the kinematics of the left leg were captured whilst running on the treadmill using a high-speed digital video camera operating at 250 Hz. Furthermore the runners performed isometric maximal voluntary plantarflexion and knee extension contractions at eleven different MTU lengths with their left leg on a dynamometer. The distal aponeuroses of the gastrocnemius medialis (GM) and vastus lateralis (VL) were visualised by ultrasound during plantarflexion and knee extension, respectively. The morphological properties of the GM and VL (fascicle length, angle of pennation, and thickness) were determined at three different lengths for each MTU. A cluster analysis was used to classify the subjects into three groups according to their V(O(2)) consumption at all three velocities (high running economy, N=10; moderate running economy, N=12; low running economy, N=6). Neither the kinematic parameters nor the morphological properties of the GM and VL showed significant differences between groups. The most economical runners showed a higher contractile strength and a higher normalised tendon stiffness (relationship between tendon force and tendon strain) in the triceps surae MTU and a higher compliance of the quadriceps tendon and aponeurosis at low level tendon forces. It is suggested that at low level forces the more compliant quadriceps tendon and aponeurosis will increase the force potential of the muscle while running and therefore the volume of active muscle at a given force generation will decrease.

背景与目标： : 这项研究的目的是检验以下假设: 具有不同跑步经济性的跑步者在下肢的肌肉肌腱单位 (MTU) 的机械和形态特性上存在差异。28名长跑运动员 (体重: 76.8 +/-6.7千克，身高: 182 +/-6厘米，年龄: 28.1 +/-4.5岁) 参加了这项研究。受试者在跑步机上以三种速度 (3.0、3.5和4.0 m s(-1)) 分别运行15分钟。通过肺活量测定法测量V(O(2)) 的消耗量。在所有三个检查的速度下，使用以250Hz运行的高速数字摄像机在跑步机上跑步时捕获左腿的运动学。此外，跑步者在测力计上的左腿以11种不同的MTU长度进行了等距最大的自愿plant屈和膝盖伸展收缩。在plant屈和膝关节伸展过程中，分别通过超声观察腓肠肌内侧 (GM) 和股外侧 (VL) 的远端腱膜。对于每个MTU，以三种不同的长度确定GM和VL的形态特性 (分束长度，顶角和厚度)。使用聚类分析根据受试者在所有三个速度下的V(O(2)) 消耗将受试者分为三组 (高运行经济，N = 10; 中等运行经济，N = 12; 低运行经济，N = 6)。GM和VL的运动学参数和形态特性均未在组之间显示出显着差异。最经济的跑步者在肱三头肌MTU中显示出更高的收缩强度和更高的归一化肌腱刚度 (肌腱力和肌腱应变之间的关系)，而在低水平的肌腱力下，股四头肌腱和腱膜的顺应性更高。建议在低水平的力下，更顺应性的股四头肌腱和腱膜会增加跑步时肌肉的力势，因此在给定的力产生下活动肌肉的体积会减少。

BACKGROUND & AIMS: Epoxyeicosatrienoic acids (EETs) are endothelium-derived arachidonic acid metabolites of cytochrome P450. They dilate coronary arteries, open K+ channels, and hyperpolarize vascular smooth muscles. However, the mechanisms of these smooth muscle actions remain unknown. This study examined the effects of EETs on the large-conductance Ca(2+)-activated K+ channel (KCa) in smooth muscle cells of small bovine coronary arteries. In cell-attached patch-clamp experiments, 11,12-EET produced a 0.5- to 10-fold increase in the activity of the KCa channels when added in concentrations of 1, 10, and 100 nmol/L. In the inside-out excised membrane patch mode, 11,12-EET was without effect on the activity of the KCa channel unless GTP (0.5 mmol/L) or GTP and ATP (1 mmol/L) were added to the bath solution. In the presence of GTP and ATP, the increase in the KCa channel activity with 11,12-EET in inside-out patches was comparable to that in cell-attached patches. This effect of 11,12-EET in inside-out patches was blocked by the addition of GDP-beta-S (100 mumol/L). In outside-out patches, 11,12-EET also increased the KCa channel activity when GTP and ATP were added to the pipette solution. The addition of a specific anti-Gs alpha antibody (100 nmol/L) in the pipette solution completely blocked the activation of the KCa channels induced by 11,12-EET. An anti-G beta gamma or anti-Gi alpha antibody was without effect. We conclude that 11,12-EET activates the KCa channels by a Gs alpha-mediated mechanism. This mechanism contributes to the effects of EETs as endothelium-derived hyperpolarizing factors to hyperpolarize and relax arterial smooth muscle.

背景与目标： 环氧二十碳三烯酸 (EETs) 是细胞色素p450的内皮衍生的花生四烯酸代谢产物。它们扩张冠状动脉，打开K通道，并使血管平滑肌超极化。然而，这些平滑肌作用的机制仍然未知。这项研究检查了EETs对小冠状动脉平滑肌细胞中大电导Ca(2) 激活的K通道 (KCa) 的影响。在细胞附着的膜片钳实验中，当以1、10和100 nmol/L的浓度添加时，11,12-eet使KCa通道的活性增加了0.5至10倍。在由内向外切除的膜贴片模式中，11,12-eet对KCa通道的活性没有影响，除非将GTP (0.5 mmol/L) 或GTP和ATP (1 mmol/L) 添加到浴液中。在存在GTP和ATP的情况下，由内而外的贴片中11,12-eet的KCa通道活性增加与细胞附着的贴片相当。由内而外的贴片中11,12-eet的这种作用被添加GDP-β-S (100 mumol/L) 所阻断。在向外贴剂中，当将GTP和ATP添加到移液器溶液中时，11,12-eet也会增加KCa通道活性。在移液器溶液中添加特异性抗Gs α 抗体 (100 nmol/L) 完全阻断了由11,12-eet诱导的KCa通道的激活。抗G β γ 或抗Gi α 抗体无效。我们得出的结论是，11,12-eet通过Gs α 介导的机制激活了KCa通道。该机制有助于EETs作为内皮衍生的超极化因子，使动脉平滑肌超极化和松弛。

BACKGROUND & AIMS: :The distinction between ectopic hamartomatous thymoma and sarcoma is difficult, and preoperative biopsy and intraoperative histopathological examination fail to give a definitive diagnosis. It is important to recognise ectopic hamartomatous thymoma as one of the differential diagnoses of a cervical tumour.

背景与目标： : 异位错构瘤性胸腺瘤和肉瘤之间的区别很困难，术前活检和术中组织病理学检查未能给出明确的诊断。重要的是要认识到异位错构瘤性胸腺瘤是宫颈肿瘤的鉴别诊断之一。

BACKGROUND & AIMS: :The vascular endothelial growth factor (VEGF) family of cytokines is involved in the maintenance of existing adult blood vessels as well as in angiogenesis, the sprouting of new vessels. To study the proangiogenic activation of VEGF receptors (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational model of VEGF isoforms (VEGF(121), VEGF(165)), their cell surface receptors, and the extracellular matrix in in vivo tissue. We build upon our validated model of the biochemical interactions between VEGF isoforms and receptor tyrosine kinases (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro. The model is general and could be applied to any tissue; here we apply the model to simulate the transport of VEGF isoforms in human vastus lateralis muscle, which is extensively studied in physiological experiments. The simulations predict the distribution of VEGF isoforms in resting (nonexercising) muscle and the activation of VEGFR signaling. Little of the VEGF protein in muscle is present as free, unbound extracellular cytokine; the majority is bound to the cell surface receptors or to the extracellular matrix. However, interstitial sequestration of VEGF(165) does not affect steady-state receptor binding. In the absence of neuropilin, VEGF(121) and VEGF(165) behave similarly, but neuropilin enhances the binding of VEGF(165) to VEGFR-2. This model is the first to study VEGF tissue distribution and receptor activation in human muscle, and it provides a platform for the design and evaluation of therapeutic approaches.

背景与目标： : 细胞因子的血管内皮生长因子 (VEGF) 家族参与现有成人血管的维持以及血管生成，新血管的萌发。为了研究骨骼肌中VEGF家族成员对VEGF受体 (VEGFRs) 的促血管生成激活，我们建立了VEGF同工型 (VEGF(121)，VEGF(165))，它们的细胞表面受体和细胞外基质的计算模型。体内组织。我们建立在我们验证的VEGF同工型与受体酪氨酸激酶 (VEGFR-1和VEGFR-2) 之间的生化相互作用的模型，以及体外非信号neuropilin-1共受体。该模型是通用的，可以应用于任何组织; 在这里，我们应用该模型来模拟人外侧肌中VEGF同工型的运输，这在生理实验中得到了广泛的研究。模拟预测了静息 (非运动) 肌肉中VEGF亚型的分布以及VEGFR信号传导的激活。肌肉中几乎没有VEGF蛋白以游离的，未结合的细胞外细胞因子的形式存在; 大多数与细胞表面受体或细胞外基质结合。然而，VEGF(165) 的间质隔离不影响稳态受体结合。在不存在神经菌毛蛋白的情况下，VEGF(121) 和VEGF(165) 表现相似，但是神经菌毛蛋白增强VEGF(165) 与VEGFR-2的结合。该模型是第一个研究人肌肉中VEGF组织分布和受体激活的模型，它为治疗方法的设计和评估提供了平台。

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。