拉莫三嗪对电刺激大鼠运动皮层惊厥模型干预的病理生理学研究

目的探讨拉莫三嗪对电刺激大鼠运动皮层惊厥模型干预的脑保护作用。方法建立电刺激大鼠运动皮层惊厥模型,将25只模型动物随机分为5组,拉莫三嗪高剂量组(37.5mg·kg-1·d-1)、拉莫三嗪中剂量组(25mg·kg-1·d-1)、拉莫三嗪低剂量组(12.5mg·kg-1·d-1)、阳性对照组(生理盐水5mg·kg-1·d-1)和阴性对照组(不给刺激仅给生理盐水5mg·kg-1·d-1)。除阴性对照组外,其他各组大鼠每天刺激2次并纪录惊厥阈值;实验各组每周记录一次大鼠在刺激前和刺激后的脑电图;6周末(42~43d)处死大鼠取脑组织行组织形态学检查。结果给电刺激后的各个实验组其惊厥阈值都呈现下降趋势,但拉莫三嗪药物组的惊厥阈值下降延迟,并且在实验末期相对稳定在一个较高水平,其脑电图的棘(尖)波指数也明显减少,组织学检查可见大鼠海马CA3区的神经元细胞损伤较轻。结论在持续6周的实验中,拉莫三嗪对电刺激大鼠运动皮层惊厥模型有脑保护作用,并呈剂量依赖。     

Neuromuscular blockade with vecuronium in paediatric patients with burn injury.

1. The effect of body surface area (BSA) burn injury on neuromuscular pharmacodynamics of vecuronium was evaluated. 2. The neuromuscular responses of 15 burned children were compared with those in five controls. 3. The effective dose for 50% suppression of twitch tension (ED50) was 34 micrograms kg-1 for patients with less than 40% BSA burn, 55 micrograms kg-1 for 40-60% BSA burn, and 65 micrograms kg-1 for patients with greater than 60% BSA burn. These values were significantly higher than the value for control patients, which was 18 micrograms kg-1. 4. Burn injury induces a resistance to the neuromuscular effects of vecuronium, the magnitude of which is related to burn size.     

丙种球蛋白序贯治疗儿童心内膜弹力纤维增生症4 例临床分析

目的:为临床应用大剂量丙种球蛋白序贯治疗儿童心内膜弹力纤维增生症提供参考。方法:收集兰州大学第二医院儿童医院小儿心血管科2015 年收治的4 例心内膜弹力纤维增生症患儿的临床资料,分析应用大剂量丙种球蛋白序贯治疗的效果。结果:4 例患儿中,2 例婴儿(<1 岁)因就医及时,治疗6 个月后临床缓解(其中1 例全程治疗1 年后治愈),1 例幼儿因就医不及时最终死亡,1 例儿童因经济原因终止治疗。结论:及时、全程、大剂量的丙种球蛋白序贯治疗可以促进婴儿特发性心内膜弹力纤维增生症的治愈。     

Interaction of streptonigrin with metals and with DNA.

The antitumor antibiotic, streptonigrin, interacted with zinc, copper, and manganese but not with calcium or magnesium, as indicated by spectral shifts and difference spectra. The titration data showed the formation of 1:1 complexes, and further titration continued to show spectral shifts until a molar ratio for zinc to streptonigrin of 5-10 to 1 was reached. Streptonigrin interacted with DNA only in the presence of a metal ion such as zinc. Streptonigrin titration with DNA at varying zinc molar equivalents revealed that one antibiotic molecule required 5-7 moles of zinc and 20-25 moles of DNA-phosphorus for complexation. Similar values were obtained from gel permeation chromatography.     

Antihypertensive effect of atenolol alone or combined with chlorthalidone in patients with essential hypertension

1 The effect of atenolol, a cardioselective β-adrenoceptor acting drug, was studied alone or combined with chlorthalidone on blood pressure, heart rate, systolic time intervals, limb blood flow and limb vascular resistance. Plasma renin activity and plasma atenolol levels were also measured in the study.

2 Supine blood pressure was reduced in group A (11 patients) from 169.4 ± 5.06/111.2 ± 2.63 mmHg to 136.9 ± 2.55/90.9 ± 1.19 mmHg (P < 0.001) during the administration of atenolol alone. Concomitantly supine heart rate was decreased from 83.9 ± 4.10 beats/min to 59.7 ± 1.67 beats/min (P < 0.01) — 4th week. After the administration of atenolol over 8 weeks, supine blood pressure was 138.6 ± 1.21/94.4 ± 2.12 mmHg and supine heart rate was 59.5 ± 2.05 beats/min.

3 Supine blood pressure was reduced in group B (27 patients) from 183.6 ± 4.58/118.7 ± 2.01 mmHg (mean ± s.e. mean of systolic and diastolic blood pressure) to 171.3 ± 4.08/108.9 ± 2.26 mmHg (P < 0.01) during the administration of atenolol alone. Concomitantly supine heart rate was decreased from 84.0 ± 1.89 to 68.7 ± 1.94 (P < 0.001) beats/min. When atenolol was combined with chlorthalidone, supine blood pressure was reduced from 171.3 ± 4.08/108.9 ± 2.26 mmHg to 143.5 ± 3.68/94.8 ± 2.63 mmHg (P < 0.001). Heart rate did not alter significantly with the addition of chlorthalidone.

4 After the administration of atenolol alone in 12 patients of group B, there was a decrease of mean blood pressure from 131.8 ± 2.88 (mean ± s.e. mean) mmHg to 119.0 ± 4.05 mmHg (P < 0.001); of heart rate from 76.4 ± 3.58 beats/min to 57.0 ± 2.55 beats/min (P < 0.001); of calf blood flow from 9.23 ± 1.39 ml 100 g^-1 min^-1 to 5.05 ± 0.89 ml 100 g^-1 min^-1 (P < 0.001); and an increase of calf vascular resistance from 16.54 ± 1.90 (mmHg min^-1 100 g^-1)/ml to 28.53 ± 3.40 (mmHg min^-1 100 g^-1)/ml (P < 0.005). Atenolol did not alter significantly pre-ejection period index (P < 0.1). In atenolol-treated patients upon addition of chlorthalidone, there was a further decrease of mean blood pressure from 119.0 ± 4.05 mmHg to 105.9 ± 4.12 mmHg (P < 0.001). There were no further significant alterations of heart rate, pre-ejection period index, calf blood flow, and calf vascular resistance (P> 0.01).

5 Atenolol decreased plasma renin activity from 4.69 ± 0.87 to 2.85 ± 0.68 ng ml^-1 h^-1 (P < 0.05), and chlorthalidone increased it from 2.85 ± 0.68 to 3.81 ± 0.98 ng ml^-1 h^-1 (P < 0.05). Plasma renin activity on atenolol plus chlorthalidone was not significantly different from that on placebo (P> 0.1).

6 There was a 7.8 fold-interindividual variability in the relationship between plasma atenolol concentrations and the atenolol dose upon administration of a single oral dose of 100 mg.

     

Reactions with 2-Mercaptopyridoimidazole

2-Mercaptopyridoimidazole (1) reacts with monochloroacetic acid to give 2 , which in turn reacts with aromatic aldehydes or aryldiazonium chloride to give 3 and 4 . On reaction with maleic anhydride 1 affords 6 . Cyanoethylation of 1 leads to the compounds 7 and 8 .     

尼莫地平联合阿卡波糖治疗糖尿病周围神经病变的临床研究

目的观察尼莫地平联合阿卡波糖治疗糖尿病周围神经病变的临床疗效及对神经传导速度与神经相关生长因子的影响。方法将我院收治的76例糖尿病周围神经病变患者,随机分为试验组和对照组,每组38例。对照组给予尼莫地平40 mg,每天3次;试验组在对照组的基础上给予阿卡波糖50 mg,每天3次。所有患者均连续治疗1个月。比较2组患者的临床疗效、神经传导速度、神经相关生长因子和药物不良反应发生情况。结果治疗后,试验组的临床总有效率为89.47%(34例/38例),对照组为60.53%(23例/38例),差异有统计学意义(P<0.05)。治疗后,试验组腓总神经、正中神经运动神经传导速度(MCV)和感觉神经传导速度(SCV)分别为(45.88±4.06),(51.69±4.56),(44.12±4.09),(46.29±5.71)m·s^-1;对照组分别为(41.16±3.83),(44.98±4.46),(39.52±3.19),(43.13±4.46)m·s^-1,差异均有统计学意义(均P<0.05)。试验组的游离脂肪酸(FFA)、肿瘤坏死因子-α(TNF-α)、人磷髓脂碱性蛋白(MBP)水平分别为(471.45±44.28)μmol·L^-1,(11.15±1.18)pg·mL^-1,(1.90±0.14)μg·L^-1;对照组分别为(542.79±46.68)μmol·L^-1,(18.21±1.92)pg·mL^-1,(3.41±0.38)μg·L^-1(均P<0.05)。试验组血管内皮生长因子(VEGF)、人脑源性神经营养因子(BDNF)水平分别为(943.39±97.85),(4.87±0.58)ng·L^-1;对照组分别为(755.94±70.11),(3.09±0.26)ng·L^-1,差异均有统计学意义(均P<0.05)。试验组出现腹泻1例,腹胀3例,药物不良反应发生率为10.53%(4例/38例);对照组出现轻度头晕1例,消化道反应2例,腹胀和轻度腹部不适2例,药物不良反应发生率为13.16%(5例/38例),差异无统计学意义(P>0.05)。结论尼莫地平联合阿卡波糖治疗糖尿病周围神经病变,能有效改善患者神经传导速度与神经相关生长因子,临床疗效良好,安全性高。     

Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab

The study aimed to investigate whether polymorphisms in genes of the EGFR signaling pathway are associated with clinical outcome in advanced colorectal cancer (CRC) patients treated with single-agent Cetuximab. Polymorphisms of interest in the EGFR pathway include: cyclin D1 (CCND1) A870G, cyclooxygenase 2 (Cox-2) G-765C, epidermal growth factor (EGF) A61G, epidermal growth factor receptor (EGFR) codon R497 K, EGFR CA dinucleotide repeat in intron 1, interleukin (IL)-8 T-251A and vascular endothelial growth factor (VEGF) C936 T gene polymorphisms. Thirty-nine metastatic CRC patients were enrolled in the IMCL-0144 trial and treated with single-agent Cetuximab. Using the polymerase chain reaction-restriction fragment length polymorphism method, gene polymorphisms of CCND1, COX-2, EGF, EGFR, IL-8 and VEGF were assessed from genomic DNA extracted from blood samples. A significant association was found between the CCND1 A870G polymorphism and overall survival in our 39 CRC subjects. Patients with the AA homozygous genotype survived for a median of 2.3 months [95% confidence interval (CI)=2.1-5.7], whereas those with any G allele (AG, GG genotype) survived for a median of 8.7 months (95% CI=4.4-13.5) (P=0.019, log-rank test). When we analysed the cyclin D1 and EGF polymorphisms together, patients with favourable genotypes (EGF any A allele and CCND1 any G allele) showed a median survival time of 12 months (95% CI=4.8-15.2), whereas patients with any two unfavourable genotypes (EGF GG or CCND1 AA) showed a median survived time of 4.4 months (95% CI=2.1-5.7) (P=0.004, log-rank test). The findings of this pilot study suggest that the cyclin D1 A870G and the EGF A61G polymorphisms may be useful molecular markers for predicting clinical outcome in CRC patients treated with single-agent Cetuximab.     

Vav1在胃癌中的表达及其与预后的相关性

目的 研究胃癌中 Vav1 的表达情况, 分析 Vav1 表达与胃癌临床病理因素及预后的关系。 方法 实时定量 PCR 检测并比较胃癌细胞株（HGC-27、SGC7901、MGC803）及正常胃黏膜细胞株（GES-1）中 Vav1 mRNA 的表达,免疫组化检测 105 例胃癌病理组织石蜡标本中 Vav1 蛋白的表达情况, 分析胃癌患者临床病理学特征与 Vav1 蛋白阳性表达间的关系, Kaplan-Meier 法及 Cox 回归分析影响胃癌预后的相关因素。 结果 Vav1 mRNA 的表达在胃癌细胞株（HGC-27、SGC7901、MGC803）明显高于正常胃黏膜细胞株（GES-1）, 差异有统计学意义。 在胃癌组织标本中, Vav1 蛋白阳性表达与肿瘤直径和淋巴结转移有关（P < 0.05）。 预后生存分析中, 单因素分析显示肿瘤直径、分化程度、浸润深度、淋巴结转移和 Vav1 表达与胃癌预后有关（P < 0.05）。 Cox 回归显示肿瘤浸润深度深（HR=2.764, 95%CI 1.316～ 5.817, P=0.007）, 淋巴结转移分级高（HR=1.298, 95%CI 1.098～ 1.534, P=0.002）和 Vav1 阳性表达（HR= 2.577, 95%CI 1.066～ 3.946, P=0.006）是影响本组胃癌患者预后的危险因素。 结论 Vav1 在胃癌的侵袭和迁移中发挥着重要的作用, 且与胃癌预后密切相关。     

Fused azepinones with antitumor activity

Based on the observation that some simple [1]benzazepin-2-ones exhibit in vivo antitumor activity, studies directed to several new structure classes with this partial motif have been reported recently, comprising 7,12-dihydro-indolo[3, 2-d][1]benzazepin-6(5H)-ones (paullones), 5H-qui nolino[3, 2-d][1]benzazepin-6(7H)-ones, 2,4-diaryl-5H-pyrido[3, 2-d][1]benzazepin-6(7H)-ones, spiro[1-benzazepine-4,1 -cyclohexane] deriva-tives, and naphthannelated benzazepinones. For the syntheses of these heterocyclic compounds, 1H-[1]benzazepine-2,5(3H,4H)-diones were employed as readily available starting materials. In each of the mentioned series, entities with in vitro antitumor activity have been detected. Considering potency and in vitro cell line selectivity, both the 2,4-diaryl-5H-pyrido[3, 2-d][1]benzazepin-6(7H)-ones and the paullones are apparently suitable for a further development. A biological mechanism probably related to the anti proliferative activity has been established only for the paullones. These compounds represent a novel class of selective inhibitors of cyclin-dependent kinases, a family of enzymes whose function seems to be deregulated in many human tumors.     

阿托伐他汀联合氯吡格雷治疗短暂性脑缺血发作的临床研究

目的 对盐酸维拉佐酮的合成工艺进行改进。方法 以4-（4-乙酰基哌嗪-1-基）苯酚为起始原料,经Duff反应、取代、环化、脱保护、酰胺化得到关键中间体5-（1-哌嗪基）-苯并呋喃-2-甲酰胺,再与3-（4-氯丁酰基）-1H-吲哚-5-甲氰缩合、成盐得到盐酸维拉佐酮。结果 合成了目标化合物盐酸维拉佐酮,并利用¹H-NMR、MS确证了结构,质量分数为99.8%,该路线的总收率为22.5%。结论 该合成工艺原料廉价易得、操作简单,适于工业化生产。     

多西他赛联合奥沙利铂及氟尿嘧啶治疗晚期胃癌的临床研究

目的：观察多西他赛联合奥沙利铂及氟尿嘧啶治疗晚期胃癌的近期疗效和毒副反应。方法：18例晚期胃癌患者采用多西他赛联合奥沙利铂及氟尿嘧啶方案化疗,多西他赛75mg／m^2（第1、8天）;奥沙利铂130mg／m^2（第1天）;氟尿嘧啶500mg／m^2（第1至5天）,21天为I周期,治疗2周期后评价疗效。结果：18例患者中完全缓解1例,部分缓解9例,总有效率55．6％;毒副反应主要为骨髓抑制、腹泻和脱发。结论：多西他赛联合奥沙利铂及氟尿嘧啶方案治疗晚期胃癌缓解率高,毒副反应可以耐受。     

原发性肝癌患者血清可溶性细胞间黏附分子-1的水平及其与肝纤维化的关系

目的 研究原发性肝癌(primary hepatic carcinoma,PHC)患者血清可溶性细胞间黏附分子-1(soluble intercellular adhesion molecule-1,sICAM-1)水平及其与肝纤维化的关系.方法 选取2014年1月-2016年2月就诊并接受手术治疗的40例PHC患者作为PHC组,另选取40例肝脏良性病变患者与40例正常体检者作为良性病变组与正常组.采用酶联免疫吸附法检测3组血清sICAM-1及肝纤维化指标Ⅲ型前胶原肽(PCⅢ)、Ⅳ型胶原(Ⅳ-C)、层黏蛋白(LN)和透明质酸(HA)的水平.并比较血清sICAM-1与肝纤维化指标的相关性.结果 PHC组的血清sICAM-1、LN、PCⅢ、HA、Ⅳ-C水平明显高于良性病变组与正常组(P＜0.05),良性病变组血清sICAM-1水平高于正常组(P＜0.05).血清sICAM-1与LN、PCⅢ、HA、Ⅳ-C呈正相关性(r=0.575、0.679、0.541和0.577,P均＜0.05).结论 血清sICAM-1检测可反应PHC的发生、发展及肝细胞的损伤程度,并且与肝纤维化指标呈正相关,对PHC的早期诊断与治疗具有重要意义.     

异丙酚与麻黄碱用于15例老年患者全麻诱导

观察异丙酚与麻黄碱伍用作为老年全麻患者诱导用药的疗效。方法30例＞65岁的老年患者随机分为两组，各15例。Ⅰ组用异丙酚1.5mg·kg     

Diastereoisomeric N-tetrahydrofurfurylnoroxymorphones with opioid agonist--antagonist properties.

The two diastereoisomeric N-tetrahydrofurfurylnoroxymorphones and their hydrochlorides 1a and 1b have been prepared and studied pharmacologically; The N-(R)-tetrahydrofurfuryl derivative 1a proved to be an opioid agonist--antagonist and the N-(S)-tetrahydrofurfuryl derivative 1b a pure antagonist. As an analgesic, 1a is 25 times more potent than morphine, but it does not show morphine-like side effects in mice. In withdrawn morphine-dependent rhesus monkeys, 1a only partially suppresses abstinence. Its therapeutic ratio is exceptionally favorable compared with those of morphine and pentazocine. As antagonists, 1a and 1b have comparable potencies of 0.25 and 0.20 of that of nalorphine, respectively, in vivo. In vitro, however, 1a is 28 times (guinea pig ileum) or 6.5 times (mouse vas deferens) more potent than 1b. The antagonist properties of 1a and 1b were not anticipated according to known structure--activity relationships.     

N-phenylpiperazine derivatives with hypocholesterolemic activity

A series of new 4-(4-phenyl-1-piperazinyl)-1-(4-fluorophenyl)-2-(acyloxy)-1-butanones and 4-aryl-5-[omega-(4-aryl-1-piperazinyl)alkyl]-1,3-dioxol-2-ones were synthesized and tested preliminarily for hypolipemic activity. Plasma cholesterol-lowering activity in normal rats was found especially in several dioxolones, two of the most active compounds (6 and 8) being more potent than clofibrate. 4-(4-Chlorophenyl)-5-[2-(4-phenyl-1-piperazinyl)ethyl]-1,3-dioxol- 2-one (8, LR-19,731) has been selected for clinical trials.     

食管癌伴糖尿病25例围术期的护理

目的探讨食管癌合并糖尿病患者的围术期护理注意事项。方法对72例食管癌合并糖尿病患者给予严格正确的围手术期护理,降低并发症的发生。结果 72例患者中,2例发生吻合口瘘,其中1例死亡;3例发生脂肪液化、切口感染,其中1例切口裂开,重新缝合;1例出现重症肺部感染;1例出现胃壁坏死。其余患者均未发生并发症。结论精心的围术期护理是手术成功及患者康复的有力保障。     

卡马西平联用尼美舒利相关粒细胞缺乏症

1例78岁男性患者因带状疱疹神经痛、慢性阻塞性肺疾病合并感染,给予头孢唑肟钠（2.25 g静脉滴注,1次/d）、卡马西平（0.2 g口服,2次/d）、尼美舒利（100 mg口服,2次/d）、二羟丙茶碱（0.5 g静脉滴注,1次/d）、甲钴胺（0.5 mg口服,3次/d）、地塞米松（5 mg,静脉滴注1次）、盐酸哌替啶（25 mg,肌内注射1次）和盐酸布桂嗪（100 mg,肌内注射3次）等药物治疗。第7天,停用头孢唑肟钠,改为磷霉素钠（8 g静脉滴注,1次/d）。第11天,血常规检查示白细胞计数1.6×10^9/L,中性粒细胞0.03,中性粒细胞绝对值0.1×10^9/L,淋巴细胞绝对值0.9×10^9/L。立即停用所有药物,给予对症支持治疗。第15天,外周血白细胞计数0.9×10^9/L,中性粒细胞0.02,中性粒细胞绝对值0.1×10^9/L,淋巴细胞绝对值0.7×10^9/L。行骨髓穿刺检查,诊断为粒细胞缺乏症。第17天患者出现右肺气胸、肺不张。第20天出现急性呼吸衰竭、多脏器衰竭合并重症感染,经抢救无效死亡。     

Improvement in endothelial dysfunction in patients with systemic lupus erythematosus with N-acetylcysteine and atorvastatin

Objective:

To study the effects of N-acetylcysteine (NAC) and atorvastatin on endothelial dysfunction in patients with systemic lupus erythematosus (SLE).

Materials and Methods:

Thirty-two SLE patients and age, sex-matched 10 healthy control subjects were studied. The patients were between 17 and 65 years of age and positive for diagnostic tests, such as antinuclear antibodies (ANA). Photoplethysmogram (PPG) detects the changes in the amount of light absorbed by hemoglobin, which reflects changes in the blood volume. Pulse wave analysis was performed at rest, 30 s, 90 s after shear stress, and 10 min after 300 μm of salbutamol inhalation.

Results:

Stiffness index (SI) of patients before the treatment was 8.46±2.78 cm/s and of controls was 6.07±1.4 cm/s (P = 0.002) and that of reflection index (RI) was 73±13 for patients and 65±7 for controls (P = 0.001). The percentage change in RI after salbutamol inhalation for controls and patients were -16±6 and -7±4 (P = 0.001), respectively, indicating the presence of endothelial dysfunction. The percentage decrease in RI after salbutamol inhalation was from -2.36±0.76 to ?7.92±1.46 in patients treated with N-acetylcysteine (NAC, P = 0.007). The percentage decrease in RI after salbutamol inhalation was from ?6.36΁1.21 to -9.92±1.21 in patients treated with atorvastatin (P = 0.05). This indicated the improvement in endothelial function. There was decrease in C-reactive protein (CRP) from 1.03±0.72 mg/dL to 0.52±0.22 mg/dL and that of malondialdehyde (MDA) from 11.20±4.07 nmol/mL to 8.81±2.79 nmol/mL with N-acetylcysteine treatment (P < 0.05). The CRP was decreased from 1.11±0.92 mg/dL to 0.440.16 mg/dL (P = 0.05) and that of MDA was decreased from 9.37±3.29 nmol/mL to 8.51±3.27 nmol/mL after treatment with atorvastatin. It showed improvement in oxidative stress with these treatments.

Conclusion:

The presence of arterial stiffness indicated endothelial dysfunction. There was reduction in RI and SI with treatment of N-acetylcysteine and atorvastatin suggesting improvement in endothelial dysfunction. There was decrease in CRP (a marker of inflammation) and MDA after treatment with N-acetylcysteine suggesting improvement in endothelial dysfunction. There was reduction in CRP after treatment with atorvastatin, suggesting improvement in endothelial function. Improvement in endothelial dysfunction is associated with decreased incidence of cardiovascular and cerebrovascular accidents.