Ibuprofen sodium (IBP) is a commonly used NSAID for multiple pain conditions. However, despite its extensive use, it is associated with multiple GIT adverse effects after oral administration. In the present study, we have fabricated thermoresponsive gel depot using Poly (N-vinylcaprolactam) and sodium alginate as polymers. The designed formulations are intended to be used as IBP depot after being administered subcutaneously. The sol-gel phase transition temperature and gelation time of gel samples were optimized by tube inversion, rheological exploration and optical transmittances. Temperature sweep experiments confirmed that optimized gel samples have sol-gel transition between 32°C and 37°C. Swelling and in vitro drug release displayed that optimized gels have maximum swelling and IBP release at pH 7.4 and at 35°C confirming their pH/thermo sensitivity. The degradation profile of hydrogels displayed controlled degradation for 6 days that with increasing contents. MTT assay showed L929 cells displayed more than 90% cell viability against blank and IBP-loaded PNVCL/NaAlg hydrogels at optimized concentrations. Fourier transform infrared spectroscopy confirmed the polymer blend hydrogels structure formation. Thermogravimetric analysis confirmed the presence of thermoresponsive moieties and thermal stability of polymer blend hydrogel sample. While scanning electron microscopy showed that hydrogel has channels in structure that might facilitate the diffusion of solvent. Results concluded that PNVCL/NaAlg hydrogels can be utilized as IBP sustained depot following subcutaneous application invivo and GIT adverse effects could be avoided associated with its oral administration.

2025-12-01·Child's Nervous System

Osteoid osteoma and osteoblastoma of the cervical spine in the pediatric population: analysis of the literature and experience with four operated cases

Review

作者: Di Rocco, Federico ; Almeida, Laryssa Crystinne Azevedo ; de Laurentis, Camilla ; Vinchon, Matthieu ; Beuriat, Pierre-Aurélien ; Szathmari, Alexandru

BACKGROUND AND AIMOsteoid osteoma (Oo) and osteoblastoma (Ob) are rare primary bone tumors with a higher prevalence in the second decade of life. Treatment can be conservative, but in cases of spinal location, resective surgery is of great importance but may be challenging.MATERIAL AND METHODSWe report four pediatric cases of Oo and Ob managed in our unit, with different locations at the level of the cervical spine. All four patients had a common complaint of persistent and progressive neck pain, two reported worsening pain at night, and three underwent NSAID treatment attempts without significant response. The radiological examination revealed a lesion of bone origin in the cervical spine in all cases: two at the pediculolaminar complex, one at the laminar, and one at the level of the C2 body and odontoid. A comprehensive literature review was carried out by comparing the data and a discussion of the cases.RESULTSA complete surgical resection was performed by a posterior approach in three patients and a transoral in one. A hard neck collar under molding ensured postoperative stability in all cases. Control imaging studies demonstrated satisfactory lesion resection. Histologically, three cases were an osteoblastoma and one an osteoid osteoma. Control imaging studies demonstrated satisfactory lesion resection with good late bone reconstruction. Ultimately, none showed late instability requiring fixation. The mean follow-up time is 36 (16-63) months. None had a recurrence nor late instability requiring fixation.CONCLUSIONTreatment of pediatric cervical spine of osteoid osteoma and osteoblastoma should seek a complete resection. In regions with a risk for secondary instability, the preservation of capsule-ligamental structures and temporary orthopedic immobilization can allow bone regeneration with no need for fixation. Extended follow-up is recommended especially in very young children to avoid late instability.

2025-02-01·Neurochemistry International

Celecoxib paradoxically induces COX-2 expression and astrocyte activation through the ERK/JNK/AP-1 signaling pathway in the cerebral cortex of rats

Article

作者: Lin, Jun-Ting ; Lin, Chia-Ho ; Wei, Kai-Che

Previous studies have shown that celecoxib or NSAID may paradoxically induce cyclooxygenase-2 (COX-2) expression and trigger inflammation-like responses in airway smooth muscle cells and renal mesangial cells. Despite the extensive research on celecoxib, its atypical biological effect on the induction of COX-2 in astroglial cells within the central nervous system (CNS) remains unexplored. In the present study, we investigated the impact of celecoxib on COX-2 and Glial Fibrillary Acidic Protein (GFAP) expression and explored the mechanisms underlying celecoxib-regulated COX-2 expression in cortical astrocytes of rats. Cortical astrocytes were treated with celecoxib (20 μM) for 24 h, resulting in a significant increase in COX-2 expression and up-regulation of GFAP, a marker of astrocyte activation, and the COX-2 induced by celecoxib is functionally active in prostaglandin E2 (PGE2) synthesis. Celecoxib also enhanced LPS-induced COX-2 expression, but its ability to inhibit PGE2 synthesis decreased at higher concentrations. Celecoxib induced phosphorylation of Extracellular signal-regulated Kinase (ERK) and c-Jun N-terminal Kinase (JNK) but not p38 Mitogen-Activated Protein Kinase (p38 MAPK), and inhibition of activity of ERK and JNK by U0126 and SP600125 effectively blocked COX-2 and GFAP induction by celecoxib. Celecoxib increased the accumulation of transcription factor AP-1 (composed of phosphorylated c-Jun and c-fos) in the nucleus. Inhibition of AP-1 activity with SR11302 significantly prevented celecoxib-induced COX-2 and GFAP expression. Additionally, the inhibiting activity of ERK and JNK can effectively suppress AP-1 expression and activity induced by celecoxib. These findings demonstrated that celecoxib induces COX-2 expression and astrocyte activation through the ERK/JNK/AP-1 signaling pathway, highlighting its potential effect in modulating inflammatory responses in the central nervous system.

项与 NSAID (SpyGlass Pharma) 相关的新闻（医药）

2025-01-06

·赞Med

直面“帕”痛|帕金森病疼痛相关文献解读

点击上方“蓝字”关注我们吧！疼痛是帕金森病（PD）患者最常见的非运动症状，同时也是PD最早的症状之一，其患病率约为40-85%，尽管它严重影响着患者的生活质量，但仍经常被低估甚至漏诊，并且患者通常只能得到非系统性的治疗，据报道，大约有50%的PD疼痛患者从未接受过任何镇痛治疗。疼痛的病因和病理生理学特征复杂多样，关于治疗的建议也十分有限。目前的研究表明，除了多巴胺能系统外，5-羟色胺能、去甲肾上腺素能、谷氨酸能和GABA能途径可能也参与其中。此外，除PD本身及其他相关继发疾病（如骨关节炎）导致的疼痛外，PD的运动或非运动症状（如运动迟缓或抑郁）本身就会放大疼痛。因此，我们试图总结概述PD患者中疼痛的分类和治疗，为临床更好的疼痛管理提供建议1-2。 1.疼痛的分类 Wasner和Deuschl提出的分类方法在临床实践中使用较为广泛，他们将PD中的疼痛分为四个层次，结合了之前分类的特点和慢性疼痛分类的原则（图1）。图1：PD疼痛的分类另一种常用的分类方法是Ford的方法，它将疼痛分为五类：肌肉骨骼疼痛、肌张力障碍性疼痛、神经病理性/根性疼痛、中枢性/原发性疼痛以及静坐不能性疼痛。 2.疼痛的治疗肌肉骨骼疼痛是PD患者最常提及的类型，通常源于肌肉或关节的痉挛和疼痛，沙非胺已被证明可改善PD患者的肌肉骨骼疼痛3。此外，深部脑刺激（DBS）、非甾体抗炎药（NSAID）或其他镇痛药、关节内注射皮质类固醇或手术也可根据临床情况进行选择。肌张力障碍是一种不受控制且剧烈的肌肉收缩，导致畸形和姿势异常。肌张力障碍是多巴胺能治疗的并发症。因此推荐优化治疗以稳定多巴胺血浆水平，比如使用单胺氧化酶B（MAO-B）或儿茶酚胺-O-甲基转移酶（COMT）抑制剂，可减少白天和夜间的疼痛性运动波动以及早晨运动迟缓。在基于两项大型随机对照试验（RCT）汇总数据的事后分析中4-5，沙非胺作为左旋多巴治疗的附加疗法，与安慰剂相比，减少了疼痛药物的使用（约24%），并在PDQ-39量表的三个子项中有两项（肌肉骨骼和神经病理性疼痛）得分显著降低。神经病理性/根性疼痛可能伴有感觉异常（刺痛）和麻木，沿着外周神经或神经根的支配区域分布，一线药物包括三环类抗抑郁药（TCAs）、抗癫痫药（如普瑞巴林和加巴喷丁）以及血清素和去甲肾上腺素再摄取抑制剂（如度洛西汀）。沙非胺也可能对根性疼痛有效3。弱阿片类药物（曲马多）被视为二线药物，而利多卡因或辣椒素贴片仅推荐用于外周神经病变。中枢性疼痛是最难描述的感觉之一，热感、灼烧感、针刺感，甚至刺痛都较为常见，多巴胺能药物在缓解这种疼痛方面并不特别有效。因此，通常使用传统的镇痛药，如阿片类药物、三环类抗抑郁药（TCAs）和氯氮平。大麻素和双侧亚核团深部脑刺激（subthalamic DBS）也可能有效。静坐不能是一种以内心不安和持续的冲动去移动或改变位置为特征的疾病，在病理上与中皮质通路的多巴胺缺乏有关，氯氮平可能在治疗上有所帮助。 3.临床研究现状 2024年1月发表在《Lancet》中的《Medical, surgical, and physical treatments for Parkinson’s disease》对目前帕金森病的治疗进行了系统综述6，其中疼痛部分见表1。表1：PD非运动症状中疼痛的治疗 2021年在日本PD患者中的 2/3 期临床研究的事后分析提示4，沙非胺50mg和100mg降低了PD患者的UPDRS第17项评分，尤其是在关期。中度至重度运动迟缓和早期肌张力障碍患者可能受益于沙非胺的治疗（图2、3）。图2：在关期和开期UPDRS第17项评分从基线到第24周的平均变化*P值与安慰剂相比图3：关期（A）和开期（B）UPDRS第17项评分相对于基线的平均变化 2018年一项研究沙非胺对PD患者慢性疼痛长期（2年）疗效的研究表明5，与安慰剂相比，沙非胺显著改善了PDQ-39中第37项（“痛苦的痉挛或痉挛”，p = 0.0074）和第39项（“令人不快的热或冷”，p = 0.0209）（图4），并显著减少了26.2%伴随疼痛治疗的数量（p = 0.005），且沙非胺组中治疗 2 年后未使用止痛药的患者比例更高（p = 0.0478）（图5）。图4：PDQ-39中第37-39项从基线到第 102 周（2年）的变化图5：第102周（2年）同时使用疼痛治疗的情况 4.总结疼痛对PD患者的生活质量有重大影响，并且常常被临床医生忽视。但导致PD疼痛表现出如此广泛谱系的原因至今未明。其中，运动症状（如肌肉僵硬、姿势障碍、运动波动等）与肌肉骨骼疼痛、肌张力障碍性疼痛和神经性疼痛相关，非运动症状，如自主神经功能障碍、睡眠障碍和情绪障碍，也发挥着重要作用。因此，对疼痛进行分类有助于选择适当的管理策略。疼痛的治疗方案较为复杂，建议进行多学科综合管理，目前在中国上市的甲磺酸沙非胺片无疑为PD患者的疼痛治疗提供新选择，多篇临床研究及系统综述均阐述了其对PD患者疼痛的积极影响，且经过2年研究观察长期有效。希望在日后诊疗中，“帕”痛不再被忽视，早期识别和处理可大大减轻患者残疾，从而改善远期生活质量。参考文献 [1] Cattaneo C, Jost WH. Pain in Parkinson's Disease: Pathophysiology, Classification and Treatment. J Integr Neurosci. 2023 Sep 8;22(5):132. [2] Buhmann C, Kassubek J, Jost WH. Management of Pain in Parkinson's Disease. J Parkinsons Dis. 2020;10(s1):S37-S48. [3]Cattaneo C, Barone P, Bonizzoni E, Sardina M. Effects of Safinamide on Pain in Fluctuating Parkinson’s Disease Patients: A Post-Hoc Analysis. Journal of Parkinson’s Disease. 2017; 7: 95–101. [4] Tsuboi Y, Koebis M, Kogo Y, et al. Effects of safinamide adjunct therapy on pain in patients with Parkinson’s disease: post hoc analysis of a Japanese phase 2/3 study. J Neurol Sci 2021; 429: 118070. [5]Cattaneo C, Kulisevsky J, Tubazio V, Castellani P. Long-term efficacy of safinamide on Parkinson’s disease chronic pain. Adv Ther 2018; 35: 515–22. [6] Foltynie T, Bruno V, Fox S, Kühn AA, Lindop F, Lees AJ. Medical, surgical, and physical treatments for Parkinson's disease. Lancet. 2024 Jan 20;403(10423):305-324. [7]Bruno V, Freitas ME, Mancini D, Lui JP, Miyasaki J, Fox SH. Botulinum toxin type A for pain in advanced Parkinson’s disease. Can J Neurol Sci 2018; 45: 23–29. [8]Rieu I, Degos B, Castelnovo G, et al. Incobotulinum toxin A in Parkinson’s disease with foot dystonia: a double blind randomized trial. Parkinsonism Relat Disord 2018; 46: 9–15. [9]Iwaki H, Ando R, Tada S, et al. A double-blind, randomized controlled trial of duloxetine for pain in Parkinson’s disease. J Neurol Sci 2020; 414: 116833 提示：本材料仅供医疗卫生专业人士进行医学科学交流，不用于推广目的。

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