p38 MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) IS ACTIVATED BY NORADRENALINE AND SERVES A CARDIOPROTECTIVE ROLE, WHEREAS ADRENALINE INDUCES p38 MAPK DEPHOSPHORYLATION

• 1 The aim of the present study was to investigate the role of p38 mitogen‐activated protein kinases (MAPK) in mediating the effect of noradrenaline (NA) on cardiomyocyte cell viability.
• 2 Cardiomyocytes from embryonic chick heart were treated with various concentrations of NA, phenylephrine or isoproterenol and p38 MAPK activation was determined by western blotting. Total cell death was assessed by the 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay. Apoptosis was determined by specific DNA fragmentation.
• 3 At 100 µmol/L, NA produced a significant increase in cell death that was associated with microscopic changes and DNA fragmentation indicative of apoptosis. The p38 MAPK inhibitor SB202190 (at 1 µmol/L beginning 1 h before NA), reduced NA‐induced p38 MAPK activation and significantly accentuated NA‐induced cell death. In contrast, the mitogen‐activated protein kinase kinase ERK1/2 inhibitor PD98059 (at 1 µmol/L beginning 1 h before NA) did not significantly alter NA‐induced cell death. These effects of NA were mediated, in part, through α‐adrenoceptor because phenylephrine (100 µmol/L), like NA, also induced p38 MAPK activation. However, 100 µmol/L isoproterenol produced a sustained dephosphorylation of p38 MAPK.
• 4 These data show that NA‐induced p38 MAPK activation, through α‐adrenoceptor, has a protective role in cardiomyocytes to antagonize NA‐induced cell death. In contrast, β‐adrenoceptor stimulation produces dephosphorylation of p38 MAPK.

     

Beneficial effects of danshensu, an active component of Salvia miltiorrhiza, on homocysteine metabolism via the trans-sulphuration pathway in rats

Background and purpose:

Elevated plasma total homocysteine (tHcy) level has been established as an independent risk factor for cardiovascular diseases. Danshensu, an active ingredient of Salvia miltiorrhiza, shows wide cardiovascular benefit. However, in terms of its own methylation, danshensu could elevate tHcy level, which would act against its cardiovascular benefit, thus posing a ‘therapeutic paradox’. As this paradox has not been fully assessed, we have evaluated the effects of danshensu on tHcy levels to uncover the underlying mechanisms.

Experiment approach:

We evaluated the influence of danshensu on homocysteine (Hcy) metabolism in rats with normal tHcy levels and in rat models of elevated tHcy (single intravenous methionine loading model and a hyperhomocysteinemic model after 3 weeks methionine dosing, with and without 3 weeks of danshensu treatment). We also quantified some metabolic intermediates (S-adenosyl methionine, S-adenosyl-l-homocysteine, cysteine and glutathione) relevant to Hcy metabolism in rat liver and kidney.

Key results:

Acute treatment with a single dose of danshensu in rats with normal tHcy did not change plasma tHcy. In contrast, danshensu significantly lowered tHcy in rats with elevated tHcy. The relatively higher cysteine and glutathione levels after treatment with danshensu indicated that its tHcy-lowering effect was via increased activity of the trans-sulphuration pathway.

Conclusions and implications:

Our results suggested that danshensu may act both acutely to increase trans-sulphuration and after chronic exposure to up-regulate the activity of the trans-sulphuration enzymes. The tHcy-lowering effect of danshensu is another cardiovascular benefit provided by S. miltiorrhiza and suggests a potential tHcy-lowering therapy.     

Immunohistochemical expression of matrix metalloproteinases in the granulomatous rosacea compared with the non‐granulomatous rosacea

Background There is a granulomatous variant which is recognized in the rosacea spectrum. However, the pathogenesis of granuloma formation in rosacea has not been clearly demonstrated. Matrix metalloproteinases (MMPs) are required for recruitment of inflammatory cells and for tissue remodelling, making way for the development of well‐organized granuloma. Objective The aim of this study was to investigate the expression of transforming growth factor (TGF)‐β, TGF‐β type II receptor (TβRII), Tumour necrosis factor (TNF)‐α, MMP‐1, 2 and 9 in the granulomatous rosacea (GR) compared with the non‐granulomatous rosacea (NGR) and test the hypothesis that the changes of these profiles in GR would be related with chronic ultraviolet radiation (UVR)‐exposure. Methods Facial skin samples were obtained from 20 patients with GR and NGR (control group). The sections were stained using haematoxylin and eosin, Verhoeff’s elastic stain, and antibodies to TGF‐β, TβRII, TNF‐α, MMP‐1, ‐2 and ‐9. Results The amount of elastotic material was significantly increased in the dermis of GR lesions. Expression of TGF‐β was significantly decreased in the epidermis of GR lesions compared with NGR lesions. In addition, the expression of MMP‐9 was significantly increased in the dermis of GR lesions compared with NGR lesions, especially at the centre of the granuloma on a semi‐quantitative analysis. MMP‐2 expression was also increased in GR lesions, although the difference between the two groups was not statistically significant. Conclusions The results of this study suggest that the increased expression of MMPs in the dermis may participate in granuloma formation of GR in association with UVR.     

从髌股关节的生物力学评价髌骨骨折的治疗

从髌股关节的生物力学分析176例髌骨骨折。髌骨骨折后疗效的好坏与髌股关节的生物力学特点及髌骨功能恢复的程度密切相关。治疗髌骨骨折的原则应是保留髌骨，并充分恢复其解剖关系。     

阿霉素羧甲基葡聚糖微球犬肝动脉栓塞后阿霉素的体内过程

研究了阿霉素羧甲基葡聚糖微球经肝动脉栓塞后的体内动力学过程、靶向特征和微球在体内的肝动脉栓塞效果。对犬进行肝动脉栓塞实验,并与肝动脉阿霉素(ADM)溶液灌注组进行对照。用HPLC荧光检测外周静脉和组织中药物浓度。结果表明:微球组峰浓度为0.558μg/ml,溶液组为1.013μg/ml;微球组的T_1/2(α),T_1/2(β)和MRT分别为溶液组的2.82,3.19和1.28倍。栓塞不同部位组织中ADM浓度,微球组分别是溶液组的8.0和9.1倍。动态血管造影表明:肝内外未见侧枝循环形成,栓塞作用持久,16周后微球仍未见完全降解。     

VDR基因敲除鼠一氧化氮合酶和内皮素-1基因的表达

目的探讨维生素D受体(VDR)基因敲除鼠血压变化以及与血压水平密切相关的内皮型一氧化氮合酶、内皮素-1基因在主动脉的表达情况,了解维生素D、维生素D受体与血压的联系及可能机制。方法小鼠血压采用动脉血管插管法直接测定,主动脉内皮型一氧化氮合酶、内皮素-1基因表达采用实时定量聚合酶链式反应检测。结果内皮型一氧化氮合酶、内皮素-1基因均能在野生型正常鼠及维生素D受体基因敲除鼠主动脉表达。与野生型正常鼠比较,纯合子维生素D受体基因敲除鼠收缩压、舒张压明显升高,主动脉内皮型一氧化氮合酶基因表达明显下调,内皮素-1基因表达明显上调(P均<0.05),杂合子维生素D受体基因敲除鼠收缩压、舒张压及主动脉内皮型一氧化氮合酶、内皮素-1基因表达则无明显改变(P均>0.05)。相关性研究发现主动脉内皮型一氧化氮合酶基因表达水平与收缩压、舒张压水平呈负相关,与收缩压、舒张压水平呈正相关(P均<0.05)。结论纯合子维生素D受体基因敲除鼠存在与血压密切相关的主动脉内皮型一氧化氮合酶、内皮素-1基因表达水平明显异常。     

Abnormalities in surfactant in sudden infant death syndrome as a postmortem marker and possible test of risk

To determine whether physical abnormalities in lung surfactant, particularly inversion of the hysteresis between surface tension and surface area, are an effective postmortem marker for sudden infant death syndrome (SIDS).

Methodology:

Bronchoalveolar lavage (BAL) was employed to obtain lung rinsings from 55 infants under 24 months of age at autopsy, comprising 34 index cases and 21 controls. Folch reagent was used to extract the lipoid content which was then applied at two surface concentrations, fixed and BAL-determined (BALD), to the pool of a Langmuir trough in which surface tension (γ) was measured continuously by the Wilhelmy method as surface area ( A ) was cycled.

Results:

The γ: A loops from SIDS samples were inverted relative to controls (i.e. they were hysteresis reversed, this inversion being quantified by an empirical surface tension:area reversal (STAR) score). There was a wide scatter of STAR scores, but a critical value was found which offered a significant ( P = 0.017) separation of SIDS cases from controls for a fixed surface concentration and a highly significant separation ( P = 1.0 × 10^-4) for BALD surface concentrations. Differences in the yields of phospholipid and proteolipid, or their correlation to STAR scores, did not reach statistical significance.

Conclusions:

Inversion of the γ: A loops (i.e. hysteresis inversion) would appear to offer a better postmortem marker of SIDS than any reported previously, the procedure having potential for development as a prospective test indicating the risk of this disease.     

Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration. J Neurosci Res 53:426-432.

Kim YC, Kim SR, Markelonis GJ, Oh TH (1998): Ginsenosides Rb₁ and Rg₃ protect cultured rat cortical cells from glutamate-induced neurodegeneration. J Neurosci Res 53:426–432. On page 427 of the article referenced above, under the heading Assessment of Neurotoxicity in the Materials and Methods section, the formula given for the assessment of percentage cell viability was printed incorrectly. The formula is correctly stated in a footnote to Table 1 on page 429. The correct formula appears below: 100 × (OD of glutamate + ginsenoside-treated – OD of glutamate-treated)/(OD of control – OD of glutamate-treated). The publisher regrets this error.     

自体骨髓干细胞移植治疗神经系统损伤和变性疾病42例报告

目的:观察42例神经系统损伤和变性疾病患者经自体骨髓干细胞移植后,其神经系统症状与体征的改善。方法:①选取2005-06/2006-09解放军第四六三医院神经外科收治的神经系统损伤和变性疾病患者42例,对本试验均签署知情同意书。其中各种原因所致脊髓损伤30例,脑血管意外引起的偏瘫4例,老年痴呆2例,小脑疾患引起的共济失调2例,运动神经元变性疾病4例。患者入院后常规检查身体各项指标以评估是否适合行干细胞移植术。②术前患者均于皮下注射粒细胞集落刺激因子进行骨髓干细胞动员,5～12μg/(kg.d),连续4～5d。动员结束后患者在局麻状态下,于髂后上棘采集自体骨髓血约200mL,去除红细胞,密度梯度离心,分离出单个核细胞,再将收获的单个核细胞制成1.5mL细胞悬液(约1×108个细胞)备用。③通过手术或立体定向的方法将干细胞直接移植在神经损伤或变性部位,然后再根据病情经腰穿或静脉途径进行细胞移植,每次给予干细胞量按(2～3)×102个/kg计算,1次/周,共4周。④自体骨髓干细胞移植治疗过程中,为促进干细胞的生长和分化,根据患者病情及个人身体状况给予物理疗法、作业疗法等相应的康复功能锻炼,同时配以针灸、高压氧及药物营养神经和改善微循环治疗。结果:42例神经系统损伤和变性疾病患者均进入结果分析。自体骨髓干细胞移植治疗后1～3个月,17例脊髓损伤患者肢体症状明显改善,尤其是脑损伤后遗症引起的脊髓损伤其肢体症状改善更为显著;2例脑出血和1例脑血栓引起偏瘫的患者其肢体症状改善效果均较好;遗传性共济失调的2例患者疗效均不明显;1例老年痴呆患者其老年痴呆症状得到明显改善,并能在搀扶下行走,与旁人进行正常的交流;运动神经元变性病中1例患者肌萎缩性侧索硬化症改善效果较好,肌张力正常,颤抖减轻及至消失,多发性硬化中2例患者症状减轻。结论:干细胞移植配合功能锻炼等辅助手段对神经系统损伤和变性疾病的治疗效果肯定,有一定的临床应用价值。     

内固定基础上应用骨形态发生蛋白人工骨与自体髂骨植骨治疗骨质疏松性髋骨折的效果比较

目的:比较采用骨形态发生蛋白人工骨植骨加骨折内固定与自体髂骨植入加骨折内固定治疗骨质疏松性转子间骨折的效果。方法:选择2003-10/2005-10桂林医学院附属医院骨科收治的Ⅲ、Ⅳ、V型骨质疏松性转子间骨折患者51例,均知情同意。实验分组:随机将病例分为2组,骨形态发生蛋白人工骨植入组26例,自体髂骨植入组25例。实验干预:采用股骨上段外侧切口,DHS或加防旋钉内固定,骨形态发生蛋白人工骨由处理后的牛松质骨与成品重组人骨形态发生蛋白2按一定比例复合而成,骨折固定后在骨折缺损处、内侧及骨折周围植骨,骨形态发生蛋白人工骨组采用骨形态发生蛋白人工骨植入,自体髂骨组取自体髂骨植入。实验评估:术后定期随访,比较二组患者的基本情况、临床效果和影像学结果(骨折愈合情况和颈干角的变化)。随访时关节功能评定参照采用黄公怡等提出的标准,分为优、良、可、差4级。髋内翻分类标准为颈干角<100°。结果:术后随访1年,51例患者全部进入结果分析。①术后X射线片观察:骨形态发生蛋白人工骨组临床愈合时间短于自体髂骨组[(94.50±22.45),(116.96±15.90)d,P<0.01];骨形态发生蛋白人工骨组术后1年颈干角大于自体髂骨组[(127.19±3.23)°,(120.4±5.22)°,P<0.01]。②髋关节功能及不良事件和副反应:骨形态发生蛋白人工骨组术后以1年髋关节功能优良率优于自体髂骨组(P<0.05);骨形态发生蛋白人工骨组髋内翻、下肢短缩(>2cm)的发生率均低于自体髂骨组[髋内翻(n):4,7;下肢短缩(n):3,5,P均<0.01];钉退出二组差异均无显著性意义(P>0.05)。结论:伴有骨质疏松的转子间骨折患者,采用骨形态发生蛋白人工骨植骨优于自体髂骨植骨,可缩短骨折愈合期,减少髋内翻等并发症的发生率,提高术后髋关节功能优良率,提示骨形态发生蛋白人工骨能替代自体髂骨植骨治疗骨质疏松性转子间骨折。