甲基强的松龙联合中剂量环磷酰胺治疗重症肌无力危象的临床效果

目的:探究甲基强的松龙联合中剂量环磷酰胺(CTX)治疗重症肌无力危象(MGC)的临床效果及安全性。方法:选取2012年1月~2015年6月在我院神经内科就诊的MGC患者90例,随机分为对照组(45例)和观察组(45例),对照组患者接受甲基强的松龙治疗,观察组采用甲基强的松龙联合中剂量CTX治疗。比较两组患者的临床疗效及不良反应的发生情况。结果:观察组患者呼吸困难消失时间、吞咽功能恢复时间和肢体无力症状改善时间均明显短于对照组(P0.05);观察组用药7 d内治疗有效率86.7%明显高于对照组(P0.05),肺部感染发生率20%,较对照组显著降低,差异均具有统计学意义(P0.05)。结论:甲基强的松龙联合中剂量CTX可有效提高MGC的治疗效果,促进患者早日康复,且肺部感染的发生率降低。     

Effects of glucocorticoids on the respiratory burst of Chlamydia-primed THP-1 cells

We previously observed that the respiratory burst of human monocytes (THP-1 cell line) triggered by phorbol myristate acetate was strongly enhanced by a priming of the cells by Chlamydia pneumoniae [Biochem. Biophys. Res. Commun. 287 (2001) 781]. We describe here the modifications of the responses of Chlamydia-primed THP-1 cells to hydrocortisone (HCT) and methylprednisolone (MPL). HCT and MPL inhibited the production of the cytokines TNFα and IL-8. But HCT, which inhibited the respiratory burst in LPS-primed monocytes, paradoxically stimulated the phenomenon in Chlamydia-primed cells; MPL exerted no significant effect. Both glucocorticoids did not significantly modify the triggering effect of Chlamydia on NF-κB binding activity. On the expression of p22^phox, a protein subunit of the NADPH oxidase, HCT had an increasing and MPL a decreasing effect. Glucocorticoids thus had unexpected effects on the inflammatory response of Chlamydia-primed monocytes.     

Quantitative determination of several synthetic corticosteriods by gas chromatography-mass spectrometry after purification by immunoaffinity chromatography

A study was conducted to test a multiresidue analytical procedure for detecting and quantifying several corticosteroids on which the European Union imposes maximum residue limits (MRLs). Primary extracts from different matrices (liver, milk, urine, faeces) were first purified on C₁₈ cartridges. A new immunoaffinity clean-up step was included. The immunoaffinity gel was used to purify several corticosteroids simultaneously with enrichment of the corresponding fractions. The extracts were treated with an aqueous solution of pyridinium chlorochromate to fully oxidise all corticosteroids and to facilitate their extraction with dichloromethane. After evaporation, the final extract was reconstituted with toluene before injection into the GC-MS apparatus. The analysis was performed in the CI-negative ionisation mode using ammonia as the reactant gas. The estimated detection and quantification limits were, respectively, 0.25 and 0.5 ppb or lower. Overall, the method is reproducible to within 20%. Recovery is between 50 and 80% according to the corticosteroid.     

不同剂量甲泼尼龙治疗老年AECOPD的疗效及其对炎症因子水平的影响比较

目的:观察和比较不同剂量甲泼尼龙治疗老年慢性阻塞性肺疾病急性加重(AECOPD)的疗效及其对炎症因子的影响。方法:选取2014年1月到2017年1月收治的114例老年AECOPD患者,随机将患者分为A组、B组和C组各38例。A组采用甲泼尼龙40 mg/d静脉推注,B组采用甲泼尼龙80 mg/d静脉推注,C组不使用甲泼尼龙。对比三组患者的临床疗效以及治疗前后的改良版英国医学研究委员会呼吸问卷(mMRC)评分、动脉血氧分压(PaO_2)、动脉二氧化碳分压(PaCO_2)、下去白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)以及C反应蛋白(CRP)水平的变化。结果:治疗后,A组的总有效率为89.47%,B组的总有效率为92.11%,均显著高于C组(均P0.05)。A组和B组治疗后的mMRC评分、PaCO_2水平均显著低于C组,而PaO_2水平显著高于C组(均P0.05);B组治疗后的m MRC评分、PaCO_2均显著低于A组,而PaO_2显著高于A组(均P0.05);A组和B组治疗后的血清IL-6、IL-8、TNF-α以及CRP水平均显著低于C组(均P0.05);B组治疗后的血清IL-6、IL-8、TNF-α、CRP水平均显著低于A组(均P0.05)。三组患者不良反应发生率的对比差异均无统计学意义(均P0.05)。结论:与40 mg/d甲泼尼龙相比,短期80 mg/d甲泼尼龙静脉推注可更显著减轻AECOPD患者的炎症反应,提高临床疗效,同时具有良好的安全性。     

甲泼尼龙琥珀酸钠对外伤性脑水肿患者血清NO、ET、LPO和SOD水平的影响

目的:观察甲泼尼龙琥珀酸钠用于治疗外伤性脑水肿的疗效及对患者血清一氧化氮(NO)、内皮素(ET)、过氧化脂质(LPO)、超氧化物歧化酶(SOD)水平的影响。方法:选择我院2014年11月~2016年11月收治的104例外伤性脑水肿患者,按治疗方式分为对照组与研究组,每组52例。对照组采用常规治疗,研究组在对照组基础上联合甲泼尼龙琥珀酸钠治疗,两组均持续治疗7天。观察并比较两组临床疗效,治疗前后血清NO、ET、LPO、SOD水平、脑水肿体积、神经功能缺损程度评分(NIHSS)、格拉斯哥昏迷评分(GCS)的变化及并发症的发生情况。结果:治疗后,研究组的治疗总有效率高于对照组(P0.05);两组血清NO、SOD、GCS水平均较治疗前显著上升,且研究组明显高于对照组;两组血清ET、LPO、NIHSS、脑水肿体积均较治疗前明显降低,且研究组显著低于对照组,差异均有统计学意义(P0.05)。两组并发症的发生情况比较差异无统计学意义(P0.05)。结论:甲泼尼龙琥珀酸钠可显著提高外伤性脑水肿的临床疗效,可能与其能够有效调节血清NO、ET、LPO、SOD水平有关。     

儿童难治性肺炎支原体肺炎的危险因素及甲泼尼龙治疗的最佳剂量探讨

摘要 目的：分析儿童难治性肺炎支原体肺炎（RMPP）发生的危险因素,并探讨甲泼尼龙治疗的最佳剂量。方法：选择2018年7月~2021年8月期间我院收治的肺炎支原体肺炎（MPP）患儿183例。根据病情程度的不同将患儿分为普通肺炎支原体肺炎（GMPP）组（n=90）和RMPP组（n=93）,构建多因素Logistic回归方程分析儿童RMPP发生的危险因素。RMPP患儿均在常规治疗基础上应用甲泼尼龙治疗,并按照给药剂量的不同分为低剂量组[2 mg/（kg?d）]、中剂量组[3 mg/（kg?d）]和高剂量组[4 mg/（kg?d）],每组各31例,对比三组的疗效、临床症状消失时间和不良反应发生情况。结果：单因素分析结果显示：RMPP组发热天数长于GMPP组,特异性体质、肺外并发症患儿比例以及中性粒细胞百分比、降钙素原（PCT）、C反应蛋白（CRP）、乳酸脱氢酶（LDH）、白细胞介素-6（IL-6）水平高于GMPP组,淋巴细胞百分比低于GMPP组（P<0.05）。多因素Logistic回归分析结果显示：发热天数≥10 d、特异性体质、有肺外并发症、CRP≥24 mg/L、LDH≥250 IU/L、IL-6≥17 pg/mL是RMPP发生的危险因素（P<0.05）。高剂量组的临床总有效率高于中剂量组、低剂量组（P<0.05）,但中剂量组与低剂量组间临床总有效率无统计学差异（P>0.05）。高剂量组和中剂量组的咳嗽消失时间、体温恢复正常时间、肺部啰音消失时间和住院时间均短于低剂量组,且高剂量组上述时间均短于中剂量组（P<0.05）。低中高剂量三组间不良反应发生率比较无统计学差异（P>0.05）。结论：儿童RMPP的发生受到发热天数、特异性体质、肺外并发症以及CRP、LDH、IL-6水平等因素影响。应用4 mg/（kg?d）剂量甲泼尼龙治疗儿童RMPP疗效较好,可明显缩短患儿临床症状消失时间。     

丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症手足口病患儿的临床研究

目的:探讨丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症手足口病(HFMD)患儿的临床效果。方法:选择我院2013年1月至2014年1月收治的重症HFMD患儿80例,按随机数字表法平均分为两组,研究组及对照组各40例。对照组患者在常规治疗基础上给予甲泼尼龙琥珀酸钠治疗,研究组患者给予丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗,比较两组患儿治疗疗效,发热、疱疹、神经系统受累症状消退时间及住院时间。结果:研究组患儿治疗总有效率为97.5%,明显高于对照组87.5%,比较差异具有统计学意义(x2=3.85,P0.05)。研究组患儿发热消退时间、疱疹消退时间、神经系统受累症状消退时间及住院时间均明显短于对照组,比较差异具有统计学意义(均P0.05)。结论:丙种球蛋白联合注射用甲泼尼龙琥珀酸钠治疗重症HFMD患儿疗效显著,可有效改善患儿临床症状,值得临床推广应用。     

Evaluation of the Neuroprotective Effects of Citicoline after Experimental Spinal Cord Injury: Improved Behavioral and Neuroanatomical Recovery

Spinal cord injury (SCI) caused by trauma mainly occurs in two mechanisms as primary and secondary injury. Secondary injury following the primary impact includes various pathophysiological and biochemical events. Methylprednisolone is the only pharmacological agent having clinically proven beneficial effects on SCI. Citicoline has been shown to have clinical and experimental beneficial effects on brain ischemia. This study aims to investigate the neuroprotective effect of citicoline in an experimental SCI model in rats. Sixty adult Wistar albino rats were randomized into five groups. SCI was performed by the weight-drop model. Group 1 underwent laminectomy alone. The Group 2 underwent laminectomy followed by SCI and received no medication. Group3, Group 4 and Group 5 underwent laminectomy followed by SCI and received medication. Group 3 and Group 5 received citicoline and Group 4 and Group 5 received methylprednisolone. The rats were divided into two subgroups for biochemical analysis (sacrificed at 24 h after surgery) and neurobehavioral and histopathological evaluation (sacrificed at 6 weeks after surgery). Malonildialdehyde levels, nitric oxide levels and trauma size ratios were lower and reduced glutathione levels were higher in Group 3, Group 4 and Group 5 as compared to Group 2. Posttraumatic neurological recovery after surgery was significantly better in Group 3, Group 4 and Group 5 compared to Group 2. In conclusion, this study demonstrates that citicoline is as effective as methylprednisolone. The efficacy of citicoline combined with methylprednisolone is not superior to either citicoline or methylprednisolone alone.     

High-performance size-exclusion chromatographic analysis of dextran–methylprednisolone hemisuccinate in rat plasma

A size exclusion chromatographic method is presented for the measurement of the concentrations of a macromolecular prodrug of methylprednisolone (MP), dextran–methylprednisolone succinate (DEX–MPS), in rat plasma. After precipitation of the plasma (100 μl) proteins with perchloric acid, the samples are injected into a size exclusion column with a mobile phase of water:acetonitrile:glacial acetic acid (75:25:0.2) and a flow-rate of 1 ml/min. The DEX–MPS conjugate, detected at 250 nm, elutes at a retention time of 6.5 min, free of endogenous peaks. Excellent linear relationships (r²=0.997) were found between the detector response and the concentrations of DEX–MPS in the range of 2–100 μg/ml (MP equivalent), with intra- and inter-run C.V.s of <6% and error values of <5%. The application of the assay was also demonstrated by measurement of the plasma concentrations of DEX–MPS after single 5 or 10 mg/kg doses of the conjugate administered intravenously to rats.     

Effects of Methylprednisolone on Extracellular Lactic Acidosis and Amino Acids After Severe Compression Injury of Rat Spinal Cord

Abstract: We evaluated in rats with severe spinal cord compression at T8–9 the influence of methylprednisolone (MP) on lactic acidosis and extracellular amino acids, which may cause secondary, perifocal injuries of the cord. MP (30 mg/kg) was given intravenously 30 min before compression and hourly thereafter (15 mg/kg). Other rats with compression, given saline, served as controls. Samples from the extracellular fluid of one dorsal horn were collected by microdialysis and analyzed by HPLC. Microdialysis was performed for 1.5 h to establish basal levels. Samples were collected for 3 h after compression. MP-treated rats showed a reduction of dialysate lactic acid and arginine levels during the first 1–2 h after trauma. The mean dialysate levels of glutamate in MP-treated rats were lower than those of the controls, but the difference was not statistically significant. MP treatment did not influence dialysate levels of aspartate, glutamine, histidine, glycine, threonine, taurine, alanine, GABA, and tyrosine. Our study shows that MP has several effects, including reduced lactic acid formation, reduced levels of arginine (the substrate for nitric oxide production), and a trend toward decreased extracellular accumulation of the excitotoxic amino acid glutamate. We conclude that MP has the capacity to change the composition of the extracellular edema fluid after trauma to the spinal cord. These changes may counteract free radical formation and may be important mechanisms by which MP exerts its beneficial actions.