不稳定型心绞痛患者红细胞分布宽度与冠状动脉病变严重程度的相关性分析

目的 探讨老年不稳定型心绞痛患者红细胞分布宽度(RDW)与冠状动脉病变严重程度的相关性.方法 经冠状动脉造影检查确诊为不稳定型心绞痛的老年患者356例(A组),根据RDW四分位数分为A1组(RDW≤12.4％,108例)、A2组(12.4％＜RDW≤12.7％,74例)、A3组(12.7％＜RDW≤13.1％,89例)和A4组(RDW＞13.1％,85例).选取同期排除冠心病的老年患者60例作为对照(C组).检测血清RDW、WBC、RBC、Hb和红细胞比容(Hct)水平,分析其与Gensini评分的相关性.结果 A组血清RDW水平较C组升高(P＜0.01),两组血清WBC、RBC、Hb、Hct比较无统计学差异(P＞0.05).A1组Gensini评分低于A2、A3、A4组(P＜0.05或P＜0.01),A2组Gensini评分低于A3、A4组(P＜0.01),A3组Gensini评分低于A4组(P＜0.05).A组患者血清RDW、WBC与Gensini评分呈正相关(r=0.479、0.197,P＜0.01).结论 老年不稳定型心绞痛患者血清RDW水平升高,与冠状动脉病变严重程度密切相关.     

大剂量促红细胞生成素治疗血液透析患者肾性贫血的效果及对血清铁蛋白、叶酸水平的影响研究

目的探究大剂量促红细胞生成素(EPO)治疗血液透析患者肾性贫血的效果与对血清铁蛋白、叶酸水平的影响。方法选择我院2015年3月～2018年3月收治的114例血液透析患者随机分为对照组(n=57,常规治疗)与观察组(n=57,大剂量EPO治疗),观察两组贫血指标、铁代谢指标与叶酸水平、不良反应情况。结果治疗后,两组贫血指标[血红蛋白(Hb)、红细胞压积(Hct)]与叶酸水平显著升高(P <0.05),且观察组升高幅度更大(P <0.05);两组铁代谢指标[血清铁(SI)、转铁蛋白饱和度(TSAT)、血清铁蛋白(SF)]水平显著升高(P <0.05),且观察组升高幅度更大(P <0.05);治疗期间两组不良反应发生率差异无统计学意义(P> 0.05)。结论大剂量EPO可有效纠正血液透析患者肾性贫血状态,有利于血液透析治疗。     

癌性贫血与血清促红细胞生成素关系研究

目的分析癌性贫血患者血清促红细胞生成素(Epo)的水平及其与血红蛋白(Hb)水平的关系.方法对53例癌性贫血、71例癌症无贫血和20例正常对照的血清用ELISA法检测Epo值.结果(1)癌性贫血组、癌症无贫血组、对照组的血清Epo分别为(63.08±104.1)mu/ml、(12.48±9.96)mu/ml和(8.10±4.97)mu/ml.癌性贫血组与癌症无贫血组及与对照组相比较有统计学意义(分别为P＜0.001和P＜0.05).癌症无贫血组与对照组无统计学意义(P＞0.05).(2)癌性贫血患者的Epo水平与Hb水平存在负相关(r=-0.693,P＜0.001).结论癌性贫血患者的Epo值高于癌症无贫血患者和正常人,并与Hb值呈负相关.     

促红细胞生成素对慢性肾衰竭贫血患者骨髓超微结构的影响

目的 探讨促红细胞生成素(EPO)对慢性肾衰竭(CRF)贫血患者骨髓超微结构的影响.方法 对23例CRF贫血患者给予重组人红细胞生成素(rhEPO)100 U/kg,每周3次,并进行常规血液透析,于治疗前及治疗12周后检测血常规,观察骨髓超微结构改变情况.结果 治疗后血红蛋白、血细胞比容、网织红细胞和血小板较治疗前均升高(P＜0.05,P＜0.01);骨髓造血微环境恢复,三系各阶段血细胞超微结构恢复正常.结论 EPO是治疗CRF贫血的决定性生长因子.     

环胞菌素A联合促红细胞生成素治疗纯红细胞再生障碍性贫血

目的 观察环胞菌素(CSA)联合促红细胞生成素(EPO)治疗纯红细胞再生障碍性贫血疗效及不良反应.方法 选住院纯红细胞再生障碍性贫血20例,随机分为治疗组和对照组,分别应用CSA联合EPO和单用CSA,观察两组起效时间、疗效、缓解时间,复发率及不良反应.结果 治疗组起效时间(18±2)天与对照组(30±4)天比较差异有显著性,缓解时间治疗组(90±10)天与对照组(180±20)天相比差异有显著性(P＜0.01),两组有效率(显著加有效)分别为90%、80%,比较差异无显著性(P＞0.05).结论 CSA联合EPO治疗纯红细胞性再生障碍性贫血起效快,缓解快,复发率低,安全有效.     

血清促红细胞生成素在噬血细胞综合征患者中的表达水平及临床意义

目的 研究血清促红细胞生成素(EPO)在噬血细胞综合征(HPS)患者中的表达水平,并观察其临床意义,为临床诊疗提供依据。方法 选取HPS患者60例为观察组,另选取健康体检者60例为对照组,应用酶联免疫吸附法检测入选者血清EPO水平,并观察其与实验室指标的关系。结果 观察组EPO水平显著高于对照组,差异有统计学意义(P＜0.05),感染相关性HPS与肿瘤相关性HPS性血清中EPO比较,差异无统计学意义(P＞0.05);相关性分析显示:EPO与铁蛋白水平呈正相关(P＜0.05),与其他指标(红细胞、血红蛋白、血肌酐、尿素氮、甘油三酯、纤维蛋白原)无相关关系(P＞0.05)。结论 HPS患者会出现EPO升高,EPO升高与铁蛋白水平有关。     

促红细胞生成素对慢性肾功能衰竭大鼠肾功能的影响

目的:研究促红细胞生成素(EPO)对慢性肾功能衰竭(CRF)大鼠肾功能的影响及其作用机制.方法:将5/6肾切除大鼠随机分为3组:Ⅰ组为假手术组;Ⅱ组为CRF组;Ⅲ组为给予促红细胞生成素的CRF组.第2次术后8周检测各组血压、尿蛋白、血清尿素氮、血肌酐、血红蛋白;观察肾组织病理改变,检测血清及肾组织中血红蛋白氧合酶 1(HO 1)活性;用免疫组化方法检测HO 1在肾脏中的表达.结果:Ⅲ组与Ⅱ组比较,血压、尿蛋白、血肌酐及尿素氮水平明显降低(P＜0.05),肾小球系膜增生及间质纤维化程度明显减轻(P＜0.05);HO 1活性检测显示,Ⅲ组大鼠血清中HO 1活性明显高于Ⅱ组(P＜0.05),免疫组化显示Ⅲ组大鼠肾组织中HO 1表达明显高于Ⅱ组(面密度、平均光度)(P＜0.05).结论:EPO使CRF大鼠肾功能得到改善,并使CRF大鼠血清及肾组织中HO 1表达及活性明显升高.     

系统性红斑狼疮贫血与促红细胞生成素

目的　探讨促红细胞生成素 (EPO)与系统性红斑狼疮 (SLE)贫血的关系。方法　测定 36例SLE贫血患者血清EPO(s EPO)水平 ,分析其与血红蛋白 (Hb)的相关性。结果　SLE贫血患者s EPO水平4 4 2 ( 7 8～ 192 2 )U/L ,明显高于正常对照组 4 2 ( 0 74～ 18 4 )U/L及SLE非贫血患者 6 8( 1 2～ 2 9 7)U/L ,但低于慢性失血所致缺铁性贫血 (IDA)患者 93( 15 5～ 389 2 )U/L(P <0 0 5 )。SLE贫血组和IDA组Hb与s EPO水平呈负相关 (P <0 0 5 )。结论　SLE贫血患者s EPO水平相对降低可能是SLE贫血的原因之一。     

慢性肾衰血透患者对红细胞生成素疗效与C-反应蛋白关系的研究

目的为了解慢性肾衰竭(CRF)血透患者对红细胞生成素(EPO)治疗贫血的疗效与C-反应蛋白(CRP)之间的关系.。方法对血液透析稳定、充分,伴有贫血的60例患者,排除缺铁、感染、继发性甲旁亢后,测定CRP、血清白蛋白、血常规,同时使用EPO,3 000 U皮下注射,2次/周,观察疗程12周。比较CRP升高组与CRP正常组患者上述参数治疗前后的变化。结果CRF患者中19例(31.6%)CRP升高,经EPO治疗后血红蛋白、红细胞压积、血清白蛋白与治疗前相比差异不显著(P>0.05),CRP正常组治疗后各项参数与治疗前相比差异显著(P〉0.05)。结论慢性肾衰竭患者较普遍存在慢性炎症状态,并伴随着低白蛋白血症,CRP升高也是EPO抵抗的原因之一。     

促红细胞生成素对慢性肾衰竭贫血患者骨髓祖细胞的影响

目的 观察促红细胞生成素(EPO)对慢性肾衰竭(CRF)贫血骨髓祖细胞的影响,探讨CRF血液系统改变及EPO治疗机制.方法 对20例CRF贫血采用国产济脉欣(EPO)3000～6000 U,皮下注射,每周3次,于治疗前及连续治疗12周后在髂后上棘同一部位行骨髓穿刺抽取等量骨髓液,观察EPO治疗前后血常规和骨髓祖细胞变化情况.结果 治疗后血红蛋白、血细胞比容、白细胞及血小板升高,而血清肌酐下降,与治疗前比较差异有统计学意义(P<0.01).骨髓红系造血祖细胞(CFU-E)、粒-单系祖细胞(CFU-GM)、成纤维祖细胞(CFU-F)集落数较治疗前均明显增多,差异均有统计学意义(P<0.01).骨髓CFU-F集落产率与CFU-E和CFU-GM集落产率呈正相关(r=0.32,r=0.49,P＜0.05).结论 EPO治疗CRF贫血可使骨髓造血微环境恢复,保护造血干细胞,并恢复其自我复制、增殖与分化.     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.     

Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination

The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers.The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml^–1·h, and from 63.4 to 74.6 ng·ml^–1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide.The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril.Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.