EFFECTS OF ACIDIC AZOPROTEINS ON PLASMA TRIGLYCERIDE LEVELS AND ON THE HEPARIN-ACTIVATED CLEARING SYSTEM

When injected into the rabbit 3 acidic azoproteins produced marked changes in the blood triglyceride levels. 4-Arsonophenylazoproteins, which were found to act similarly in 2 other mammalian species, produced a gross and prolonged hyperlipemia. 4-sulfono- and 4-carboxyphenylazoproteins in the rabbit produced an initial elevation and later lowering in blood triglyceride levels. The correlation between these changes and the action of the azoproteins on clearing factor lipase provides further evidence for the importance of this enzyme in fat transport mechanisms. 4-Arsonophenylazoprotein is powerfully inhibitory to the lipase. 4-Carboxy- and 4-sulfonophenylazoprotein in vivo initially inhibit the enzyme and later produce a heparin-like activation.     

舒芬太尼对福尔马林痛小鼠的镇痛作用及其对血液中IL-6和IL-10的影响

目的:研究舒芬太尼对福尔马林致痛小鼠细胞因子IL-6,IL-10的变化,以进一步探讨舒芬太尼对镇痛及细胞因子平衡的影响。方法:选择97只昆明清洁级小鼠随机分四组,完全空白对照组(7只)、假给药组(C组,n=30)、舒芬太尼组(S组,n=30)、芬太尼组(F组,n=30)。C、S、F组右后脚趾部皮下注射3%福尔马林0.05ml致痛,在此基础上腹腔分别注射生理盐水0.3ml,舒芬太尼0.05mg/kg,芬太尼0.2mg/kg,25min后记录注射福尔马林后0～5min(Ⅰ相)和15～60min(Ⅱ相)的疼痛反应评分及在注射药物后1h、3h、6h、9h、12h和24h检测血液中IL-6,IL-10水平变化。结果:舒芬太尼抑制福尔马林Ⅰ相和Ⅱ相痛反应(P<0.05)。在Ⅰ相痛反应中,S组和F组比较有显著差异(P<0.05);C、S、F组IL-6含量明显高于完全空白对照组,C组在3小时达峰值,而S组和F组6小时达峰值;S组和F组的IL-10含量明显高于C组和空白对照组(P<0.05),S组和F组之间无统计学意义(P>0.05)。结论:在福尔马林致痛模型中,舒芬太尼起效快,镇痛作用强,延迟IL-6的分泌,促进IL-10分泌,通过有效的镇痛维持细胞因子的平衡。     

Purinogenic Immunodeficiency Diseases: DIFFERENTIAL EFFECTS OF DEOXYADENOSINE AND DEOXYGUANOSINE ON DNA SYNTHESIS IN HUMAN T LYMPHOBLASTS

Deoxyadenosine and deoxyguanosine are toxic to human lymphoid cells in culture and have been implicated in the pathogenesis of the immunodeficiency states associated with adenosine deaminase and purine nucleoside phosphorylase deficiency, respectively. We have studied the relative incorporation of several labeled nucleosides into DNA and into nucleotide pools to further elucidate the mechanism of deoxyribonucleoside toxicity. In the presence of an inhibitor of adenosine deaminase [erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA], 5 muM], deoxyadenosine (1-50 muM) progressively decreased the incorporation of thymidine, uridine, and deoxyuridine into DNA, but did not affect uridine incorporation into RNA. This decrease in DNA synthesis was associated with increasing dATP and decreasing dCTP pools. Likewise, incubation of cells with deoxyguanosine caused an elevation of dGTP, depletion of dCTP, and inhibition of DNA synthesis.To test the hypothesis that dATP and dGTP accumulation inhibit DNA synthesis by inhibiting the enzyme ribonucleotide reductase, simultaneous rates of incorporation of [(3)H]uridine and [(14)C]thymidine into DNA were measured in the presence of deoxyadenosine plus EHNA or deoxyguanosine, and in the presence of hydroxyurea, a known inhibitor of ribonucleotide reductase. Hydroxyurea (100 muM) and deoxyguanosine (10 muM) decreased the incorporation of [(3)H]uridine but not of [(14)C]thymidine into DNA; both compounds also substantially increased [(3)H]cytidine incorporation into the ribonucleotide pool while reducing incorporation into the deoxyribonucleotide pool. In contrast, deoxyadenosine plus EHNA did not show this differential inhibition of [(3)H]uridine incorporation into DNA, and the alteration in [(3)H]cytidine incorporation into nucleotide pools was less impressive.These data show an association between accumulation of dATP or dGTP and a primary inhibition of DNA synthesis, and they provide support for ribonucleotide reductase inhibition as the mechanism responsible for deoxyguanosine toxicity. Deoxyadenosine toxicity, however, appears to result from another, or perhaps a combination of, molecular event(s).     

小剂量氯胺酮辅助芬太尼镇痛对患者术后C-反应蛋白和白细胞介素-6的影响

目的：观察小剂量氯胺酮辅助芬太尼术后镇痛效果以及对患者术后血清C-反应蛋白（CRP）和白细胞介素-6（IL-6）水平的影响。方法：择期全身麻醉下行上腹部手术患者60例，随机分为三组，Ⅰ组患者不接受静脉自控镇痛（PCIA）；Ⅱ组患者以芬太尼行PCIA；Ⅲ组患者以芬太尼＋氯胺酮行PCIA。监测患者术后48h内生命体征、疼痛视觉模拟评分（VAS）、焦虑视觉模拟评分（AVAT）以及患者对镇痛治疗的总体印象评分（PJA）。分别于术前和术后抽取静脉血测定血清CRP和IL-6浓度。随访镇痛相关并发症。结果：Ⅱ、Ⅲ组患者术后生命体征、VAS、AVAT、PJA明显优于Ⅰ组（P＜0．05）；Ⅲ组患者VAS、AVAT、PJA优于Ⅱ组（P＜0．05）。患者术后血清CRP和IL-6浓度Ⅱ、Ⅲ组低于Ⅰ组（P＜0．05）；Ⅲ组患者低于Ⅱ组（P＜0．05）。结论：术后镇痛中小剂量辅助使用氯胺酮可以在一定程度上降低炎症反应，缓解手术后应激反应，提高术后镇痛效果。     

氯诺昔康对福尔马林炎症痛大鼠血液一氧化氮和β-内啡肽含量的影响

目的：应用福尔马林炎症痛模型，观察氯诺昔康对大鼠血液中一氧化氮（NO）和β-内啡肽（β-EP）含量的影响，以探讨其镇痛机制。方法：选择Wistar大鼠30只，随机等分为5组：Ⅰ组：右后脚趾部皮下注射5％福尔马林0．1ml；Ⅱ组-Ⅴ组：腹腔分别注射生理盐水2ml以及2mg／kg、4mg／kg、8mg／kg氯诺昔康2ml；25min后记录注射福尔马林后0～5min（Ⅰ相）和15～60min（Ⅱ相）的累计痛评分及血液中NO和B．EP含量。结果：氯诺昔康抑制福尔马林Ⅱ相痛反应（P〈0．01），对Ⅰ相无影响（P〉0．05）；Ⅰ组和Ⅱ组间NO和B．EP含量无差异（P〉0．05），而Ⅲ-Ⅴ组分别与Ⅰ和Ⅱ组比较，差异非常显著（P〈0．01）。结论：在福尔马林炎症痛模型中，氯诺昔康通过降低血液内NO和增加β-EP含量，发挥镇痛作用。     

A MULTICENTRE, HOSPITAL STUDY OF THE EFFICACY AND SAFETY OF TERAZOSIN AND ITS EFFECTS ON THE PLASMA CHOLESTEROL LEVELS OF PATIENTS WITH ESSENTIAL HYPERTENSION

The safety, efficacy and the effect on the plasma total cholesterol of once-daily terazosin hydrochloride administered either as monotherapy or in combination with other antihypertensive therapy were evaluated in patients with mild-moderate uncontrolled essential hypertension in this U.K., open, multicentre hospital, 3-month study. Patients initially received 1 mg of terazosin as monotherapy or in addition to their current antihypertensive therapy followed by dose titration, if necessary, to a maximum of 10 mg over the first 6 weeks depending upon blood pressure control. Patients then continued treatment for a further 6 weeks on their optimum dosage. There were highly significant mean reductions in systolic and diastolic blood pressures at the end of 12 weeks for 439 patients of 18.5 and 14.0 mmHg (P less than 0.001), respectively, and were similar to the reductions shown when subgrouping the patients into either those 197 patients who were treated with terazosin as monotherapy (17.6/13.7 mmHg, P less than 0.001) or those 242 patients treated with terazosin in combination with other antihypertensive agents (19.3/14.2 mmHg, P less than 0.001). In addition, in a sub-group of 132 patients who had their mean total cholesterol measured at the end of 12 weeks' treatment, there was a significant reduction of -0.4 mmol/l (P less than 0.01). A similar significant mean reduction for total cholesterol was also shown when this subgroup was divided into those 50 patients who were treated with terazosin as monotherapy (-0.56 mmol/l, P less than 0.01), but not for those 82 patients treated with terazosin in combination with other antihypertensive agents (-0.3 mmol/l, P greater than 0.05 less than 0.1). No serious toxicity or safety problems were observed. Once daily administration of terazosin, either as monotherapy or in combination with other antihypertensive agents, proved to be safe and effective in reducing the blood pressure of patients with uncontrolled mild-moderate essential hypertension and favourably reduced the total plasma cholesterol level.     

THE EFFECTS OF CAPTOPRIL AND ENALAPRIL ON TISSUE LEVELS OF VARIOUS ELEMENTS IN SPONTANEOUSLY HYPERTENSIVE RATS

The effects of two inhibitors of angiotensin I converting enzyme, captopril and enalapril, on the concentrations of Na, K, Ca, Mg, Fe, S, P, Sr, Mn, Cu and Zn ions in blood, plasma, heart, skeletal muscle, liver and kidney of spontaneously hypertensive rats (SHR) were studied. Captopril and enalapril were given by the intraperitoneal route for 15 days, at 160 mumols/kg/d and 40 mumols/kg/d, respectively. Elements in tissues were determined by inductively coupled plasma emission spectrometry with a JY 48 instrument. The common changes produced with the two drugs were: a decrease of Na in muscle (-10%), a decrease of Ca in plasma and kidney (less than -10%) and a decrease of Mn in liver (-15%). The main effects observed with only one of the two drugs were: an increase of Cu in plasma (+26%) with captopril, and increases of Sr in heart (+56%), muscle (+79%) and liver (+74%) with enalapril. Zinc concentration in tissues was not modified, except for an increase in liver with captopril (+13%) and a decrease in heart with enalapril (-11%).     

罗哌卡因硬膜外持续输注联合氯诺昔康PCA效应及病人血浆IL-6、IL-10的变化

目的：观察妇科术后硬膜外罗哌卡因持续输注联合氯诺昔康PCA的镇痛效应及病人血浆IL-6、IL-10水平的变化。方法：60名妇科经腹子宫全切手术的病人，随机分为三组：氯诺昔康（L）组、吗啡（M）组与对照（C）组。L组与M组采用双泵行PCA治疗，c组采用病房传统的方式镇痛。评估术后五个时间点的视觉模拟评分（VAS）、BCS舒适评分、病人对PCA总体满意度评分，观察并记录镇痛期间有关不良反应。每组（n=10）分别采集切皮前30min、切皮后2h以及术后4h、24h、48h静脉血，采用酶联免疫吸附法检测血浆IL-6、IL-10水平。结果：L组、M组病人在术后8h、12h、24h的VAS、BCS评分以及镇痛后总体满意度评分明显优于C组。三组病人在切皮后2小时IL-6水平都迅速增高，并在术后24h达峰值，M和C组峰值显著高于L组。C组病人血浆IL-10水平在切皮后2h达峰值，L组与M组则于术后4h达峰值，L和M组的血浆IL-10水平显著高于C组。结论：罗哌卡因硬膜外持续输注与静脉氯诺昔康或吗啡PCA的联合镇痛效果好。静脉氯诺昔康PCA辅助罗哌卡因持续硬膜外镇痛可使术后血浆IL-6水平下调，有利于机体促炎／抗炎细胞因子的平衡。     

ANTIBODY PRODUCTION IN VITRO : II. EFFECTS OF ACTINOMYCIN D AND PUROMYCIN ON THE SECONDARY RESPONSE TO SHEEP ERYTHROCYTES

The effects of actinomycin D and puromycin on spleen cell suspensions from rabbits immunized to SRC's were studied. These inhibitors, in high concentration, suppressed PFC's when added initially to recently isolated cells. When such cells were incubated for several days in the presence of both antigen and inhibitor, both actinomycin D and puromycin produced an increase in PFC's after the initial suppression. This recovery effect was best seen with cells from rabbits killed 3 days after boosting with SRC's, and was usually absent when cells were taken from rabbits killed 2 days after boosting. When actinomycin D or puromycin was added after several days in culture in the presence of SRC's, surviving PFC's were found to be not only resistant to these inhibitors, but there was also an increased number of PFC's compared to similar cultures incubated without these agents. Radioautographic studies showed that PFC's stimulated by the presence of actinomycin D or puromycin were not incorporating precursors for RNA or protein synthesis. In view of the known mode of action of these inhibitors, it was postulated that they were stimulating antibody production by PFC's in vitro either by interfering with represser mechanisms or stimulating the completion of antibody molecules, perhaps by causing the release of preformed antibody chains from ribosomes. Since the presence of specific antigens in vitro were necessary for these observed stimulatory effects on PFC's, and since antigens were producing an effect on antibody production on cells which were being suppressed by these inhibitors, added initially, it was further suggested that one role of antigen in the immune response was concerned with the completion of antibody synthesis on the ribosomes, perhaps by acting as an inducer as has been suggested previously (1).     

雌激素对大鼠内脏痛觉感受及结肠5-羟色胺合成的影响

目的:研究雌激素对大鼠内脏痛觉感受及结肠5-羟色胺(5-hydroxytryptamine,5-HT)合成的影响。方法:Wistar雌性大鼠采用随机数字表分组,分为假手术组,卵巢切除组及卵巢切除+雌激素组。卵巢切除+雌激素组动物皮下注射苯甲酸雌二醇(30μg·kg~(-1)),连续给药2周。给药结束后次日测定大鼠内脏痛阈值、血清雌激素和孕激素水平;收集结肠组织测定5-HT含量、嗜铬细胞数量及色氨酸羟化酶的表达。结果:雌激素替代给药后显著提高卵巢切除大鼠血清雌激素水平、降低内脏痛阈值、明显提高结肠嗜铬细胞数量、5-HT含量及色氨酸羟化酶的表达。结论:雌激素对结肠5-HT合成具有正性调控作用,该机制可能参与雌激素介导的内脏痛觉感受增强。     

DEFICIENCY OF C1r IN HUMAN SERUM : EFFECTS ON THE STRUCTURE AND FUNCTION OF MACROMOLECULAR C1

The experiments presented here utilize a human serum markedly deficient in hemolytic complement activity to show that: (a) The hemolytic deficiency is the result of a selective deficiency in hemolytic C1. (b) The relative absence of hemolytic C1 is due to a profound deficit in C1r function associated with less than normal C1s protein and hemolytic function and normal C1q protein concentration and function. This deficit in C1r in the face of normal C1q suggests that different cell types are responsible for the synthesis of each of these components. (c) Whatever the basis for the deficiency of C1r function, this defect results in an inadequate association of the remaining C1 subcomponents, C1q and C1s, even in the presence of calcium ions, thus suggesting that C1r has an important role in the assembly and/or maintenance of macromolecular C1.     

慢性疼痛患者治疗前后血浆miR-206表达差异的临床研究

目的:观察慢性疼痛患者治疗前后血浆mi RNA-206的表达水平改变,探索mi RNA-206在慢性疼痛发病及治疗中的作用。方法:选择西南医科大学附属中医医院疼痛科2013年6月至2014年6月期间符合慢性疼痛患者(n=30)与年龄、性别比例相一致的健康成人(n=30)进行比较。慢性疼痛患者组于治疗前后分两次进行视觉模拟评分(visual analogue scale,VAS)、自评抑郁量表评分(SelfRating Depression Scale,SDS)和简化麦吉尔疼痛量表评分(Short-form of Mc Gill Pain Questionnaire,SFMPQ),并用实时荧光定量PCR法检测血浆mi RNA-206表达水平。对照组仅检测血浆中mi RNA-206的表达水平。结果:(1)慢性疼痛患者组较对照组血浆mi RNA-206的相对表达量显著升高(P<0.05);(2)慢性疼痛患者组治疗后较治疗前血浆mi RNA-206的相对表达量、VAS、SDS及SF-MPQ均显著降低(P<0.05)。结论:mi RNA-206在慢性疼痛的发病机制中发挥重要作用,并有可能作为慢性疼痛的治疗靶点。