Cortistatin modulates the expression and release of corticotrophin releasing hormone in rat brain. Comparison with somatostatin and octreotide

Cortistatin (CST) is an endogenous neuropeptide characterized by remarkable structural and functional resemblance to somatostatin (SST), both peptides sharing the ability to bind and activate all five SST receptor subtypes. Evidence is also available showing that CST exerts biological activities independently from SST, perhaps via the activation of specific receptors that remain to be fully characterized at present. Here we have investigated the effects of CST on the gene expression and release of corticotrophin releasing hormone (CRH) from rat hypothalamic and hippocampal explants; moreover, we compared the effects of CST with those of SST and octreotide (OCT) in these models. We found that: (i) CST inhibits the expression and release of CRH from rat hypothalamic and hippocampal explants under basal conditions as well as after CRH stimulation by well known secretagogues; (ii) SST does not modify basal CRH secretion from the hypothalamus or the hippocampus, while it is able to reduce KCl-stimulated CRH release from both brain areas; (iii) OCT inhibits both basal and KCl-induced CRH secretion from rat hypothalamic explants, while it has no effect on CRH release from the hippocampus, either under basal conditions or after stimulation by high K(+) concentrations; (iv) at variance with CST; SST and OCT have not effect whatsoever on veratridine-induced CRH release from the hypothalamus. In conclusion the present findings provide in vitro evidence in support of the hypothesis that CST plays a role in the regulation of endocrine adaptive responses to stress.     

维生素C辅助奥曲肽治疗对急性胰腺炎患者肠黏膜屏障功能和外周血T淋巴细胞亚群的影响

摘要 目的：探讨维生素C辅助奥曲肽治疗急性胰腺炎（AP）患者对肠黏膜屏障功能和外周血T淋巴细胞亚群的影响。方法：选取2020年1月~2022年1月安徽省合肥市第二人民医院收治的65例AP患者作为研究对象,使用信封法将其随机分为试验组（33例）和对照组（32例）。对照组予以奥曲肽+常规治疗,试验组在对照组治疗基础上,另予维生素C治疗。比较两组患者治疗后胃肠功能恢复指标、治疗前后肠黏膜屏障功能和外周血T淋巴细胞亚群指标及不良反应。结果：治疗后,试验组患者腹痛消失时间、呕吐缓解时间、肠鸣音复常时间和肛门首次排气时间均明显少于对照组（P＜0.05）,且内毒素、二胺氧化酶（DAO）及D-乳酸水平均低于明显低于对照组（P＜0.05）;试验组CD8⁺明显水平低于对照组（P＜0.05）,而CD4⁺水平及CD4⁺/CD8⁺均显著高于对照组（P＜0.05）;试验组不良反应发生率（18.18%）与对照组（12.50%）无显著性差异（P＞0.05）。结论：使用维生素C辅助奥曲肽治疗AP患者,可有效改善肠黏膜屏障功能和外周血T淋巴细胞亚群指标,安全性高。     

肠道益生菌联合奥曲肽对肝硬化合并胃食管静脉曲张初次出血患者血流动力学及预后的影响

目的:研究肠道益生菌联合奥曲肽对肝硬化合并胃食管静脉曲张初次出血患者血流动力学及预后的影响。方法:选取2016年5月-2017年4月我院收治的肝硬化合并胃食管静脉曲张初次出血患者96例,以随机数字表法分成研究组(n=48)和对照组(n=48)。对照组予以奥曲肽治疗,研究组则采用肠道益生菌联合奥曲肽治疗,疗程均为28天。分别比较两组临床治疗总有效率、再出血率、病死率、临床症状改善时间、止血时间以及住院时间,观察并比较治疗前后血流动力学、血清内皮素(ET)、一氧化氮(NO)、内毒素脂多糖(LPS)水平。结果:研究组临床治疗总有效率为93.75%(45/48),高于对照组的79.17%(38/48)(P0.05)。治疗后两组患者心输出量(CO)、心脏指数(CI)、门静脉血流量(PVF)、食管曲张静脉变化(EVD)均较治疗前降低,且研究组低于对照组(P0.05)。治疗后两组患者血清ET、NO、LPS水平均较治疗前降低,且研究组低于对照组(P0.05)。与对照组比较,研究组再出血率、临床症状改善时间、止血时间以及住院时间均降低(P0.05),而两组病死率比较差异无统计学意义(P0.05)。结论:肠道益生菌联合奥曲肽治疗肝硬化合并胃食管静脉曲张初次出血患者的临床疗效明显,能够改善患者血流动力学和促进肠道菌群的平衡,预后较佳。     

Synthesis and radiolabeling of 111In-core-cross linked polymeric micelle-octreotide for near-infrared fluoroscopy and single photon emission computed tomography imaging

The objective of this study was the development of a dual-modality imaging device, namely ¹¹¹In-core-cross-linked polymeric micelle (CCPM)-octreotide, for neuroendocrine tumor detection, using near-infrared fluoroscopy (NIRF) and single photon emission computed tomography (SPECT). The tumor targeting ability of the ¹¹¹In-labeled CCPM-octreotide was evaluated in a tumor mouse model. SPECT/CT, NIRF and gamma imaging results showed high tumor uptake of ¹¹¹In-labeled CCPM-octreotide. In contrast, there was a much lower signal in the same mouse model injected with ¹¹¹In-labeled CCPM. The high accumulation of ¹¹¹In-labeled CCPM-octreotide in U87 tumor was reduced after co-injection with an excess amount of CCPM-octreotide. These results suggested CCPM-octreotide’s potential applications in tumor diagnosis, drug delivery and molecular imaging.     

Octreotide in the treatment of malignant thymoma – Case report

Thymomas are the most common mediastinal tumors. Systemic therapy for patients with unresectable or recurrent thymomas is a challenging field in the current oncology research. There is some evidence that somatostatin analogs combined with corticosteroids may have a role in the treatment of advanced malignant thymoma; however, the role of these agents have not been fully evaluated.Case reportA 39-year-old man with metastatic thymoma was administered long-acting depot injection form of octreotide. Octreotide scan before the treatment initiation revealed low uptake. CT control after three months of the treatment revealed marked regression of pleural metastases, while the primary tumor mass remained stable. The treatment response was lasting for 9 months.ConclusionWe describe an interesting case of marked clinical and radiological response of advanced malignant thymoma to the treatment with octreotide in a heavily pre-treated patient, even though octreotide scan revealed low uptake.     

奥曲肽联合黄芩素抑制胰腺神经内分泌肿瘤细胞增殖和迁移

摘要 目的：探讨奥曲肽（Octreotide，Oct）联合黄芩素（Baicalein，BE）对胰腺神经内分泌肿瘤（Pancreatic neuroendocrine neoplasms, pNENs）的影响。方法：用不同浓度的奥曲肽和黄芩素处理pNENs来源的QGP-1细胞，CCK8法检测细胞的存活率，以其半抑制浓度（IC₅₀）的比值作为浓度梯度进行联合用药，并用Compusyn软件进行联合指数（CI）分析，取细胞毒性效应适中且CI值较低的浓度（奥曲肽150 μmol/L，黄芩素20 μmol/L）进行表型实验。将QGP-1细胞分为四组：对照组、奥曲肽组、黄芩素组、奥曲肽和黄芩素联用组。通过克隆形成实验、EdU增殖检测、划痕实验、细胞凋亡和周期检测评价四组细胞的增殖、迁移能力以及凋亡和细胞周期的情况。结果：药物处理24 h后，奥曲肽和黄芩素均能够呈浓度依赖性抑制QGP-1细胞增殖（P<0.05），奥曲肽的IC₅₀为329.90 μmol/L，黄芩素的IC₅₀为42.86 μmol/L，两者IC₅₀的比值约为7.5:1，联用组细胞活性明显低于单药组（P<0.05），且CI值随着药物浓度的增加而降低。克隆形成实验和EdU增殖检测结果表明，奥曲肽和黄芩素均可抑制QGP-1细胞增殖（P<0.05），且联用组的克隆形成率和EdU阳性细胞百分比均低于单药组（P<0.05）。划痕实验结果表明，奥曲肽和黄芩素均可降低QGP-1细胞的迁移率（P<0.05），且联用组的迁移率低于单药组（P<0.05）。细胞凋亡和周期检测结果表明，黄芩素可促进QGP-1细胞的凋亡（P<0.05），并使QGP-1细胞阻滞于G0/G1期（P<0.05），而奥曲肽对QGP-1细胞的凋亡和细胞周期无明显影响（P>0.05），两药联用对其凋亡和周期无协同作用。结论：奥曲肽和黄芩素联合用药可协同抑制QGP-1细胞增殖和迁移，对细胞凋亡和周期无明显协同作用。