腕管综合征及其生物力学研究进展

腕管综合征(carpal tunnelsyndrome, CTS)是腕部正中神经受到卡压而引起的一种神经病症. 它所带来的高昂的社会和经济花费使得腕管综合征的研究应运而生, 并且在过去的10年里得到突飞猛进的发展. 常规的手术方式是将腕横韧带(transversecarpal ligament)切开, 以释放正中神经(mediannerve)所受到的压力. 本文不仅对腕管的解剖结构、腕管综合征的症状和发病机理、以及诊断和治疗等方面作了简要概述,还主要从以下几个方面探讨了近年来与腕管综合征相关的生物力学研究工作及其进展: (1)影响腕管内压力的因素,包括腕部姿势, 手指、肌腱或手掌所受外荷载的大小, 以及手工劳作的不同频率等; (2)腕管结构的稳定性研究, 如切开腕横韧带或腕骨间掌横韧带对腕刚度的影响, 以及从动力学角度分析腕管减压手术会导致的腕骨失稳现象; (3)腕管内容物(如肌腱、正中神经)的运动及内容物之间以及腕管内容物与腕横韧带之间的相互作用;(4)腕横韧带的延展实验, 如利用外荷载或移位搭接的方法拉长腕横韧带, 以达到降低腕管内压力的目的. 本文旨在加强人们对腕管综合征尤其是对与腕管综合征相关的生物力学研究进展的了解, 并从生物力学的观点提出利用有限元方法对腕管结构进行三维建模与分析将有可能成为腕管综合征进一步研究的一个重要发展方向.      

检测有机磷神经毒剂及模拟物的荧光探针

有机磷神经毒剂是一类具有极大杀伤力的化学毒剂,这类有机磷酸盐通过破坏人体内的神经递质乙酰胆碱酯酶麻痹人的中枢神经,很小的剂量就可致人死亡,因此对有机磷神经毒剂进行快速简便地检测具有重要意义。荧光化学传感具有灵敏度高、选择性好和响应时间短等优点,近些年来应用荧光传感方法对有机磷神经毒剂及其模拟物的检测越来越受到研究人员的关注。本篇综述对荧光传感的原理做了简要介绍,综述了近年来国内外研究者开发的各种用于有机磷神经毒剂及其模拟物检测的荧光新材料与新方法,并对荧光传感方法应用于有机磷神经毒剂检测的未来进行了展望。     

小腿皮神经伴行血管蒂逆行岛状皮瓣的解剖与设计

研究小腿皮神经伴行血管皮瓣的血供方式,并设计其逆行岛状皮瓣供临床参考应用.对30侧成人下肢标本经股动脉加压灌注红色乳胶后进行解剖观测.腓浅神经、腓肠神经及隐神经均有主要伴行动脉营养,并与其他动脉皮穿支吻合营养相应区域的皮肤.根据小腿皮神经伴行血管设计的逆行岛状皮瓣血供可靠,并为沿皮神经轴设计长皮瓣提供了可能.     

The Role of Microglial Purinergic Receptors in Pain Signaling

Pain is an essential modality of sensation in the body. Purinergic signaling plays an important role in nociceptive pain transmission, under both physiological and pathophysiological conditions, and is important for communication between both neuronal and non-neuronal cells. Microglia and astrocytes express a variety of purinergic effectors, and a variety of receptors play critical roles in the pathogenesis of neuropathic pain. In this review, we discuss our current knowledge of purinergic signaling and of the compounds that modulate purinergic transmission, with the aim of highlighting the importance of purinergic pathways as targets for the treatment of persistent pain.     

亚砷酸钠对大鼠离体坐骨神经干复合动作电位的影响

应用电生理方法观察了不同浓度的亚砷酸钠对大鼠离体坐骨神经干复合动作电位的幅度、阈强度、传导速度及持续时间的影响。结果表明:亚砷酸钠溶液浸泡大鼠坐骨神经干30分钟,当浓度高于3×10-4mol/L时,复合动作电位的幅值较对照组明显降低(P<0.01)。复合动作电位的阈强度随亚砷酸钠浓度的升高而增加,差异有显著性(P<0.01)。复合动作电位的传导速度随亚砷酸钠浓度的升高而变慢,但只有亚砷酸钠浓度高于10-3mol/L时,复合动作电位传导速度与对照组相比差异才有显著性(P<0.01)。复合动作电位的持续时间随亚砷酸钠浓度增加而延长,但与对照组相比无差异(P>0.05)。这说明亚砷酸钠可影响大鼠坐骨神经干复合动作电位。     

Cebranopadol as a Novel Promising Agent for the Treatment of Pain

Opioids are used to treat pain, but despite their effectiveness, they possess several side effects such as respiratory depression, tolerance and physical dependence. Cebranopadol has been evaluated as a solution to this problem. The compound acts on the mu opioid receptor and the nociceptin/orphanin receptor and these receptors co-activation can reduce opioid side-effects without compromising analgesia. In the present review, we have compiled information on the effects of cebranopadol, its pharmacokinetics, and clinical trials involving cebranopadol, to further explore its promise in pain management.     

氯诺昔康在神经外科术后静脉自控镇痛中的应用

目的:观察经额部、颞部入路的神经外科病人术后的疼痛情况以及氯诺昔康用于此类神经外科病人术后静脉自控镇痛的临床效果.方法:36例择期经额部、颞部入路的神经外科手术病人,随机分为二组:氯诺昔康组(L组)镇痛药物为氯诺昔康每mL0.8 mg;对照组(N组)术后当病人主诉疼痛明显,难以忍受时予口服颅痛定30mg.记录各组病人术前及术后4、16、24、48 h的心率、平均动脉压、呼吸频率、脉搏氧饱和度及瞳孔变化.记录各组病人术后4、16、24及48 h的疼痛模拟评分(VAS)、Ramsay镇静评分及术后的凝血指标和术后发生恶心呕吐的情况.结果:L组病人的心率、平均动脉压术前与术后各时段点比较无显著差异(P＞0.05);N组病人术后4 h的心率、平均动脉压较术前显著增加,差异有统计学意义(P＜0.05).两组病人均未出现明显的呼吸抑制,Ramsay镇静评分均不超过3分,在术后各时段点差异均无统计学意义(P＞0.05).术后4、16 h L组VAS评分均显著低于N组(P＜0.05),术后24、48 h二组VAS评分差异无显著性(P＞0.05).未镇痛组的病人在术后24 h内有10例需要使用颅痛定.两组病人术前术后血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)均在正常值范围内.L组和N组病人均有不同程度的恶心呕吐情况出现,各组的呕吐发生率均为33.33%.结论:经额、颞部入路的神经外科病人手术后存在术后疼痛,且大多发生在术后第1 d.氯诺昔康能为其提供良好的术后镇痛疗效,术后镇痛中无明显的呼吸抑制、镇静及凝血指标异常等不良反应.     

Kaempferol 3-Rhamnoside on Glutamate Release from Rat Cerebrocortical Nerve Terminals Involves P/Q-Type Ca2+ Channel and Ca2+/Calmodulin-Dependent Protein Kinase II-Dependent Pathway Suppression

Excess synaptic glutamate release has pathological consequences, and the inhibition of glutamate release is crucial for neuroprotection. Kaempferol 3-rhamnoside (KR) is a flavonoid isolated from Schima superba with neuroprotective properties, and its effecton the release of glutamate from rat cerebrocortical nerve terminals was investigated. KR produced a concentration-dependent inhibition of 4-aminopyridine (4-AP)-evoked glutamate release with half-maximal inhibitory concentration value of 17 µM. The inhibition of glutamate release by KR was completely abolished by the omission of external Ca²⁺ or the depletion of glutamate in synaptic vesicles, and it was unaffected by blocking carrier-mediated release. In addition, KR reduced the 4-AP-evoked increase in Ca²⁺ concentration, while it did not affect 4-AP-evoked membrane potential depolarization. The application of selective antagonists of voltage-dependent Ca²⁺ channels revealed that the KR-mediated inhibition of glutamate release involved the suppression of P/Q-type Ca²⁺ channel activity. Furthermore, the inhibition of release was abolished by the calmodulin antagonist, W7, and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibitor, KN62, but not by the protein kinase A (PKA) inhibitor, H89, or the protein kinase C (PKC) inhibitor, GF109203X. We also found that KR reduced the 4-AP-induced increase in phosphorylation of CaMKII and its substrate synapsin I. Thus, the effect of KR on evoked glutamate release is likely linked to a decrease in P/Q-type Ca²⁺ channel activity, as well as to the consequent reduction in the CaMKII/synapsin I pathway.     

Analgesic Characteristics of NanoBEO Released by an Airless Dispenser for the Control of Agitation in Severe Dementia

Chronic pain is one of the most common causes of the need for clinical evaluation, acquiring more importance in the elderly with cognitive impairment. Reduced self-reporting capabilities cause unrelieved pain contributing to the development of agitation. Safe and effective pain treatment can afford the management of agitation without the serious increase in death risk associated with neuroleptics. To this aim, the essential oil of bergamot (BEO), proven by rigorous evidence to have strong preclinical anti-nociceptive and anti-allodynic properties, has been engineered (NanoBEO, patent EP 4003294) to allow randomized, double-blind, placebo-controlled trials (BRAINAID, {"type":"clinical-trial","attrs":{"text":"NCT04321889","term_id":"NCT04321889"}}NCT04321889). The present study: (1) assesses the analgesic effects of a single therapeutic dose of NanoBEO, as supplied by an airless dispenser for clinical translation, in models of inflammatory, neuropathic, and sensitization types of pain relevant to clinic; (2) provides a dose–response analysis of the efficacy of NanoBEO on scratching behavior, a typical behavioral disturbance occurring in dementia. A single therapeutic dose of NanoBEO confirms efficacy following thirty minutes pre-treatment with capsaicin and on the central sensitization phase induced by formalin. Moreover, it has an ID50 of 0.6312 mg and it is efficacious on static and dynamic mechanical allodynia. Altogether, the gathered results strengthen the potential of NanoBEO for clinical management of pain and agitation.     

Anticancer Effect of Cathelicidin LL-37, Protegrin PG-1, Nerve Growth Factor NGF,and Temozolomide: Impact on the Mitochondrial Metabolism,Clonogenic Potential,and Migration of Human U251 Glioma Cells

Glioblastoma (GBM) is one of the most aggressive and lethal malignancy of the central nervous system. Temozolomide is the standard of care for gliomas, frequently results in resistance to drug and tumor recurrence. Therefore, further research is required for the development of effective drugs in order to guarantee specific treatments to succeed. The aim of current study was to investigate the effects of nerve growth factor (NGF), human cathelicidin (LL-37), protegrin-1 (PG-1), and temozolomide on bioenergetic function of mitochondria, clonogenicity, and migration of human U251 glioma cells. Colony formation assay was used to test the ability of the glioma cells to form colonies in vitro. The U251 glioma cells migration was evaluated using wound-healing assay. To study the mitochondrial metabolism in glioma cells we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) using a Seahorse XF cell Mito stress test kit and Seahorse XF cell Glycolysis stress kit, respectively. We revealed that LL-37, NGF, and TMZ show strong anti-tumorigenic activity on GMB. LL-37 (4 μM), TMZ (155 μM), and NGF (7.55 × 10⁻³ μM) inhibited 43.9%–60.3%, 73.5%–81.3%, 66.2% the clonogenicity of glioma U251 cells for 1–2 days, respectively. LL-37 (4 μM), and NGF (7.55 × 10⁻³ μM) inhibited the migration of U251 glioma cells on the third and fourth days. TMZ also inhibited the migration of human glioma U251 cells over 1–3 days. In contrast, PG-1 (16 μM) stimulated the migration of U251 glioma cells on the second, fourth, and sixth days. Anti-mitogenic and anti-migration activities of NGF, LL-37, and TMZ maybe are relation to their capacity to reduce the basal OCR, ATP-synthetase, and maximal respiration of mitochondria in human glioma U251 cells. Glycolysis, glycolytic capacity and glycolytic spare in glioma U251 cells haven`t been changed under the effect of NGF, LL-37, PG-1, and TMZ in regard to control level. Thus, LL-37 and NGF inhibit migration and clonogenicity of U251 glioma cells, which may indicate that these compounds have anti-mitogenic and anti-migration effects on human glioma cells. The study of the mechanisms of these effects may contribute in the future to the use of NGF and LL-37 as therapeutic agents for gliomas.