阿莫西林联合甲强龙治疗老年支气管肺炎患者的临床效果及机制分析

目的：探讨阿莫西林联合甲强龙治疗老年支气管肺炎患者的临床效果及其可能的作用机制。方法：选取我院呼吸科收治的 老年支气管肺炎患者84例,根据治疗方案不同分为常规组及试验组。比较两组患者治疗前后临床体征、IgA、IgM、IgG、CD4+及 CD8+T 淋巴细胞、NK 细胞及血清LDH3、LDH4、HBDH水平的变化情况。结果：治疗后,试验组咳喘、高热、肺内干湿罗音的恢复 时间明显短于常规组,IgA、IgM、IgG、LDH、HBDH、NK 细胞及CD8+T 淋巴细胞水平明显低于常规组,CD4+T 淋巴细胞水平明显 高于常规组,差异均具有统计学意义(P<0.05)。结论：阿莫西林联合甲强龙可有效快速改善老年支气管肺炎患者的临床症状,这可 能与其降低IgA、IgM、IgG、LDH、HBDHNK 细胞及CD8+T 淋巴细胞水平及提高CD4+T 淋巴细胞水平有关。     

Effects of Methylprednisolone and the Combination of α-Tocopherol and Selenium on Arachidonic Acid Metabolism and Lipid Peroxidation in Traumatized Spinal Cord Tissue

Traumatic injury of the spinal cord leads to a series of pathological events that result in tissue necrosis and paralysis. Among the earliest biochemical reactions are hydrolysis of fatty acids from membrane phospholipids, production of biologically active eicosanoids, and peroxidation of lipids. This study examines the effect of agents purported to improve recovery following spinal cord trauma, methylprednisolone sodium succinate (MPSS) and the combination of alpha-tocopherol and selenium (Se), on the posttraumatic alterations of membrane lipid metabolism. Pretreatment with either MPSS or alpha-tocopherol and Se reduced the trauma-induced release of total FFA including arachidonate in the injured spinal cord tissue. In addition, these agents decreased the postinjury levels of prostanoids. Pretreatment with either MPSS or alpha-tocopherol and Se also completely prevented the trauma-induced loss of cholesterol while inhibiting the increase of a cholesterol peroxidation product, 25-hydroxycholesterol. These data suggest that: perturbation of membrane lipid metabolism may contribute to the tissue necrosis and functional deficit of spinal cord injury and MPSS or the combination of alpha-tocopherol and Se may protect injured spinal cord tissue, at least in part, by limiting these posttraumatic membrane lipid changes.     

甲基强的松龙对急性脊髓损伤患者神经生长因子水平变化的影响及其临床疗效

目的:探讨甲基强的松龙对急性脊髓损伤患者神经生长因子水平变化及临床疗效的影响。方法:回顾性研究我院收治的68例急性脊髓损伤患者的临床资料,随机分为实验组和对照组,每组34例。对照组患者给予常规治疗,实验组患者在对照组基础上给予甲基强的松龙治疗。观察并比较治疗前后两组患者神经生长因子(NGF)、脑源性神经营养因子(BDNF)水平变化及神经功能评分和并发症的发生情况。结果:与治疗前相比,两组患者治疗后血清NGF及BDNF水平均升高,且感觉功能评分及运动功能评分均升高,差异具有统计学意义(P0.05);与对照组相比,实验组患者治疗后血清NGF及BDNF水平较高,感觉功能评分及运动功能评分较高,差异具有统计学意义(P0.05);与对照组相比,实验组患者并发症的发生率较低,差异具有统计学意义(P0.05)。结论:甲基强的松龙治疗急性脊髓损伤的临床疗效较好,能够提高患者血清NGF及BDNF水平,改善感觉功能评分及运动功能评分,同时降低并发症的发病率。     

康复新液与甲泼尼龙治疗重症手足口病的临床疗效及对患儿免疫功能的影响*

目的:探讨康复新液与甲泼尼龙联合治疗重症手足口病疗效及对生化指标的影响。方法:选自2014年1月~2015年12月我院收治的重症手足口病患儿94例,随机分为观察组与对照组,每组47例。对照组采用甲泼尼龙治疗,观察组在对照组基础上结合康复新液治疗。观察并比较两组的治疗疗效、症状体征消退时间,心肌酶和免疫功能水平的变化情况,以及不良反应。结果:观察组总有效率(93.62%)高于对照组(72.34%)(P0.05);观察组体温恢复正常、口腔溃疡愈合时间、手足皮疹消退时间优于对照组(P0.05);两组肌磷酸激酶、乳酸脱氢酶水平治疗后明显降低(P0.05);观察组肌磷酸激酶、乳酸脱氢酶水平治疗后低于对照组(P0.05);两组免疫球蛋白A(Immunoglobulin A,IgA)、免疫球蛋白G(Immunoglobulin G,IgG)水平治疗后明显增加(P0.05),而免疫球蛋白M(Immunoglobulin M,IgM)水平治疗前后比较无统计学差异(P0.05);观察组IgA、IgG水平治疗后高于对照组(P0.05);两组均未见严重不良反应。结论:康复新液与甲泼尼龙联合治疗重症手足口病疗效显著,可降低患儿心肌酶指标,提高患儿免疫功能,且安全性良好。     

甲强龙对重型颅脑损伤患者血清IL-1beta和TNF-alpha表达的影响

目的：探讨甲强龙对重型颅脑损伤患者血清中白细胞介素-1beta(IL-1beta)及肿瘤坏死因子-alpha(TNF-alpha)的表达影响。方法：收集我 院神经外科以重型颅脑损伤为诊断收治入院的患者68 例，并将其随机分为实验组和对照组。实验组予以甲强龙治疗，对照组则 给予地塞米松治疗，同时两组均予以利尿、降颅压、抗感染、抑酸、营养支持等常规对症支持治疗。分别于治疗前、治疗后第1、3、7 天进行血清IL-1beta和TNF-alpha水平测定，并于治疗3 个月后按GOS预后评分标准进行预后评估。结果：①与治疗前比较，治疗后1 天IL-1beta水平及TNF-alpha水平较高(P＜0.05)，第3、7 天IL-1beta水平及TNF-alpha水平较低(P＜0.05)。与对照组同期比较，实验组第1 天 IL-1beta水平及TNF-alpha水平较高(P＜0.05)，第3、7 天IL-1beta水平及TNF-alpha水平较低(P＜0.05)，②治疗后实验组死亡率明显低于对照 组，差异有统计学意义(P＜0.05)。结论：甲强龙可显著改善重型颅脑损伤患者的预后，这可能与其抑制血清IL-1茁和TNF-琢的表 达有关。     

Effects of combining methylprednisolone with rolipram on functional recovery in adult rats following spinal cord injury

Methylprednisolone (MP) has been widely used as a standard therapeutic agent for the treatment of spinal cord injury (SCI). Because of its controversial beneficial effects, the combination of MP and other pharmacological agents aimed at enhancing functional recovery is desirable. The phosphodiesterase 4 (PDE4) inhibitor rolipram has been implicated in promotion of regeneration due to elevating cAMP. In the present study, we sought to determine the effects of MP and rolipram, administered in combination, after spinal cord injury (SCI) in adult rats. Here we show that in vitro administration of rolipram and MP significantly increased neuron survival and promoted neurite outgrowth of neurons on the inhibitory substrate CSPGs by upregulation of MMP-2 expression; in vivo administration of rolipram and MP inhibited CSPG expression and increase CSPG digestion after rat SCI. Rolipram and MP combining treatment promoted significant neuroprotection through reduced motoneuron death, minimized lesion cavity, and increased regeneration of lesioned corticospinal tract (CST) axons beyond the lesion site after SCI. Enhanced functional recovery was also observed. Overall, our study strongly suggested that the combination treatment of MP and rolipram may represent a promising strategy for clinically applicable pharmacological therapy for rapid initiation of neuroprotection after SCI.     

甲基强的松龙对体外循环下心脏瓣膜置换患者肾功能的影响

背景与目的：有研究表明甲基强的松龙可减轻体外循环所致的肺损伤,但其对体外循环患者术后肾功能损害的作用尚不十分清楚。本文探讨甲基强的松龙是否有效抑制体外循环心内直视术中的炎症反应,并对肾脏有保护作用。方法：随机选取40例体外循环下择期行心脏瓣膜置换手术的患者,年龄30-55岁,心功能II～III级,随机分为甲基强的松龙组和对照组,每组20例。甲基强的松龙（MPS）组于体外循环前以甲基强的松龙10mg／kg预冲,对照组（Ns）以等量的生理盐水代替。于CPB前（T1）,CPB结束后2h（T2）、CPB结束后12h（T3）,CPB结束后24h（T4）,等时点留取中心静脉血和尿液,以酶联免疫吸附实验（ELISA）法检测炎性介质（IL-6、TNF—α、IL-10）;取尿上清液检测反映肾功能的早期敏感指标：尿-N-乙酰氨基-葡萄糖苷酶（NAG）、尿α1-微球蛋白（α1-MG）、尿视黄醇结合蛋白（RBP）的水平。结果：CPB前两组炎性介质和肾功检测指标,差异均无统计学意义（P〉0．05）,而CPB结束后,两组炎性介质的水平和肾功各项指标均较术前增高。与NS相比,MP组T2～T4时点IL-6水平明显降低（P〈0．05）。在T2～T3时点TNF-α的水平明显低于对照组（P〈0．05）。两组IL-10的水平在CPB后均增加,但在T2～T3时点MP组升高幅度明显高于NS组（P〈0．05）。与NS}匕较,MP组在CPB后各时点尿NAG、α1-MG、RBP的水平均明显降低（P〈0．05）。结论：CPB可导致全身炎性反应及肾功能损伤;甲基强的松龙可减轻炎性反应,同时对肾功能有一定的保护作用。     

Kinetics of drug release from a hyaluronan-steroid conjugate investigated by NMR spectroscopy

The methylprednisolone steroid ester of hyaluronan was hydrolyzed under physiological conditions in vitro, and the kinetics of drug release was investigated by NMR spectroscopy. Transverse relaxation times are correlated with the molecular rotational freedom, which undergoes large changes for methylprednisolone when released. Multi-exponential decays were observed, which together with the corresponding population gave valuable insights into the conformational changes that occur in the biopolymer during hydrolysis. The biomaterial exists in aqueous solution in two conformations, ‘collapsed’ and ‘water-exposed’, in equilibrium. Under physiological conditions, the methylprednisolone is completely released within 48 h. Transverse relaxation times proved to be an appropriate tool for monitoring the drug release in vitro.     

早期激素性股骨头坏死模型的建立

目的:建立早期股骨头坏死模型,为研究其发病机制及合理治疗方法的提供可靠的模型基础。方法:用单一剂量脂多糖LPS(10μg/kg)联合三次甲强龙MPS(10 mg/kg)注射,每次间隔24h,诱导建立兔早期股骨头坏死模型,通过影像学及组织病理性学方法评估模型建立情况。结果:4周后,模型组死亡1例,模型组16例X线检查未见异常表现,2例X线提示股骨头密度不均,未出现股骨头塌陷,18例HE染色示骨细胞空骨陷窝增多,脂肪细胞体积变大,数量增多。结论:用脂多糖(LPS)联合甲强龙可成功诱导建立兔早期股骨头坏死模型,模型成功率高、死亡率低。     

High-performance liquid chromatography analysis, preliminary pharmacokinetics, metabolism and renal excretion of methylprednisolone with its C6 and C20 hydroxy metabolites in multiple sclerosis patients receiving high-dose pulse therapy

A gradient eluent HPLC analysis in human plasma and urine was developed and validated for methylprednisolone (MP), its prodrug methylprednisolone-21-hemisuccinate (MPS) with the metabolites 6β-hydroxy-6α-methylprednisolone (MPA), 20-hydroxymethylprednisolone (MPC), 6β-hydroxy-20α-hydroxymethylprednisolone (MPB), 6β-hydroxy-20β-hydroxymethylprednisolone (MPE), 20-carboxymethylprednisolone (MPD), methylprednisolone-glucuronide (MPF) and 21-carboxymethylprednisolone (MPX). The column was Cp Spherisorb C8 5 μm, 250 mm×4.6 mm I.D. (Chrompack, Bergen op Zoom, The Netherlands) with a guard column 75 mm×2.1 mm, packed with pellicular reversed-phase. The eluent was a mixture of acetonitrile and 0.067 M KH₂PO₄ buffer, pH 4.5. At t=0, the eluent consisted of 2% acetonitrile and 98% buffer (v/v). Over the following 35 min the eluent changed linearly until it attained a composition of 50% acetonitrile and 50% buffer (v/v). At 37 min (t=37) the eluent was changed over 5 min to the initial composition, followed by equilibration over 3 min. The flow-rate was 1.5 ml/min and UV detection was achieved at 248 nm. Preliminary pharmacokinetic data were obtained from one patient who showed illustrative plasma concentration–time curves and renal excretion-time profiles after a short-lasting infusion (0.5 h) of 1 g of methylprednisolone hemisuccinate. The half-life of prodrug methylprednisolone-21-hemisuccinate (MPS) was 0.3 h, that of metabolite MPX (21-carboxy MP) was 0.4 h and that of the parent drug methylprednisolone (MP) was 1.4 h. The half-lives of the metabolites are almost similar (4 h). The main compounds in the urine are methylprednisolone hemisuccinate (prodrug, 15.0%), methylprednisolone (parent drug, 14.6%), metabolite MPD (20-carboxy, 11.7%), and metabolite MPB (13.2%). The renal clearance values of metabolites MPB, MPC and MPD are approximately 500 ml/min, that of MP is 100 ml/min.