肿瘤性贫血病人血清促红细胞生成素和睾酮水平的研究

目的　研究血清促红细胞生成素 (EPO)和睾酮 (T)与肿瘤性贫血的关系。方法　用ELISA法及放射免疫法测定肿瘤性贫血病人血清EPO和T的水平 ,并与正常对照及化疗前后比较。结果　肿瘤性贫血病人血清EPO含量 (2 78± 0 73μg/ml)显著高于正常对照 (1 6 0± 0 5 6 μg/ml) ,P <0 0 1,于化疗后升高更显著 ;而血清睾酮的水平 (16 6± 7 86nmol/L)显著低于正常对照 (19 18± 9 6 9nmol/L) ,且化疗后降低更明显。结论　肿瘤性贫血病人内源性EPO水平升高 ,睾酮水平下降 ,化疗和雄性激素治疗可能有助于改善EPO对肿瘤性贫血的疗效     

红细胞生成素大剂量冲击维持疗法治疗血液肿瘤贫血的临床研究

目的研究红细胞生成素(EPO)大剂量冲击维持疗法治疗血液肿瘤贫血患者的临床疗效和安全性.方法采用开放性非随机的临床研究方法,恶性血液肿瘤患者在化疗同时,于第1周采用EPO 120,000 U冲击用药(40,000 U皮下d1、d3、d5),随后EPO每周40,000 U皮下(d8、d15、d22)维持用药,共4周.比较治疗前后每周的血红蛋白(Hb)和红细胞压积(Hct)水平,并评价EPO治疗的不良反应.结果 2003年10月～2005年12月共入组42例同期化疗的血液肿瘤贫血患者.所有患者给予EPO治疗后Hb水平呈持续上升趋势,在治疗后第2、4周Hb比治疗前上升≥2.0g/d1的患者分别占26.8%和52.6%.在治疗后第2、4周Hb的平均值分别为85.6g/d1和92.8 g/d1,与治疗前相比均具有显著性差异(P＜0.05).治疗前后平均Hct值亦有显著性差异(P＜0.05).所有使用EPO大剂量冲击维持疗法治疗的患者均耐受良好.结论血液肿瘤贫血患者使用EPO大剂量冲击维持疗法,可有效改善患者的贫血状况,且使用安全,耐受良好.     

促红细胞生成素治疗晚期非小细胞肺癌化疗相关贫血的临床观察

目的了解促红细胞生成素(EPO)对晚期非小细胞肺癌(NSCLC)化疗相关贫血的疗效。方法48例晚期NSCLC化疗后贫血患者,治疗组 25例予皮下注射EPO,剂量为150u/kg,每周三次,持续使用4周或当血红蛋白(Hb)值>120g/L时停用。结果4周后治疗组患者血红蛋白(Hb)值明显上升,与对照组相比,差异有显著性。结论EPO对晚期NSCLC化疗相关贫血的疗效显著。     

大剂量重组人促红细胞生成素治疗腹透患者贫血的临床疗效

目的 :观察重组人促红细胞生成素 (r HuEPO) 1万U ,qw ,在改善腹透患者贫血的有效性及其药物不良反应。方法 :从上海 3家医院的腹透患者中选择透析稳定的贫血患者 4 8例 ,给予r HuEPO 1万U ,sc ,qw ,疗程 6mo ,期间如Hb快速上升至 10 0g·L-1,减量至每 2wk 1次或更少。分别于给药前和给药后wk 2、4、8、12、16、2 0、2 4 ,测定Hb、RBC和血细胞比容 (HCT)观察疗效。结果 :①治疗贫血的总有效率达 89 6 % ,其中显效率 75 % ,Hb从治疗后wk 4起显著上升 (P =0 0 0 2 1) ;② 7例患者因Hb在wk 8达较高水平〔Hb(94 9± 16 9)g·L-1,HCT(2 8 2± 5 1) %〕 ,用药剂量维持在每 10～ 14d 1万U ,16wk后复查发现HCT仍维持在 (2 8 6± 3 8) % (P >0 0 5 ) ;③平均动脉压总体稳定 (从用药前 99 8mmHg至治疗 2 4wk时 10 1 9mmHg,P >0 0 5 )。 1例患者因头痛、BP上升而退出研究。结论 :r HuEPO 1万U ,qw ,能明显改善腹膜透析患者的贫血 ,使用安全。对于Hb已达较高水平的腹透患者可以选用更长间隔的给药方式     

慢性肾衰患者促红细胞生成素与血红蛋白的相关性研究

目的探讨慢性肾衰（CRF）贫血患者血清促红细胞生成素（sEPO）与血红蛋白（Hb）的关系。方法20例慢性肾衰贫血患者，采用放射免疫法测定其血清促红细胞生成素（Serum erythropoietin，sEPO）的水平，分析sEPO与Hb的相关性；同时以缺铁性贫血（IDA）患者的sEPO对贫血的反应作为贫血状态下sEPO对Hb正常相关关系的对照，测定20例IDA患者的sEPO，并进行相关回归分析。结果20例慢性肾衰贫血组的sEPO水平明显低于IDA患者（P〈0．001）。慢性肾衰贫血组及IDA组的Hb与sEPO均呈明显的直线负相关关系（rIDA=-0.458，PIDA〈0.005；rCRF=-0．226，PCRF〈0．05）。慢性肾衰贫血组Hb—sEPO回归直线的斜率（bCRF=-0．0123）与在Y轴上的截距（aCRF=1．98）均小于IDA组（bIDA=-0．0183，aIDA=2．797）。结论慢性肾衰贫血患者普遍存在sEPO相对缺乏，表现为sEPO对贫血反应迟钝。     

重组人促红细胞生成素治疗食管癌癌性贫血的临床观察

目的观察重组人促红细胞生成素（rhEPO）治疗食管癌癌性贫血的最佳时间。方法67例轻度贫血食管癌患者,化疗前基础血红蛋白（Hb）为100～120g／L。将其随机分为两组,早使用组31例患者在入组与化疗时同时使用rhEPO,晚使用组36例患者在Hb降低至〈90g／L时使用rhEPO。rhEPO剂量为150U／kg,3次／周,皮下注射。治疗期间发生铁缺乏、疗效不明显的患者加用琥珀酸亚铁0．1g口服,3次／d。结果早使用组和晚使用组患者Hb基础水平分别为（110．0±0．7）g/L和（112．0±0．9）g/L。早使用组患者的Hb及血细胞比容（HCT）显著增加（P〈0．05）。晚使用组患者的Hb和HCT值有所下降（P〈0．05）,用药5～8周时与化疗前相比差异有统计学意义（P〈0．05）。结论早使用重组人促红细胞生成索能显著提高患者的Hb水平,改善食管痛痛忡贫向患者的牛活质量．     

促红细胞生成素不同给药方式治疗恶性肿瘤化疗所致贫血的临床效果

目的 评价促红细胞生成素(EPO)两种不同给药方式治疗晚期恶性肿瘤化疗所致贫血的临床疗效.方法 60例同期接受全身化疗且伴随肿瘤相关性贫血的晚期恶性肿瘤患者均分为两组:试验组按EPO 60×103U静脉滴注每周1次;对照组化疗同时采用EPO 10×103U皮下注射每周3次;均治疗4周.观察治疗2周及4周后的疗效.结果 EPO治疗2周及4周后,两组的Hb、红细胞压积(Hct)和RBC值均较治疗前明显增高(P＜0.05),同期试验组各项观察指标均比对照组明显增加(P＜0.05).结论 两种给药方式对改善晚期恶性肿瘤化疗所致贫血均有效,静脉给药方式临床疗效更佳.     

促红细胞生成素对慢性心衰患者血栓风险的影响

目的:研究促红细胞生成素对慢性心衰患者血栓风险的影响。方法:43例慢性心力衰竭合并轻度贫血的患者,随机分为2组:促红细胞生成素(EPO)组(22例)及对照组(21例)。EPO组患者给予多糖铁复合物胶囊150mg,2次/d加EPO每周10000～15000U。对照组患者给予多糖铁复合物胶囊150mg,2次/d。血红蛋白目标值为135g/L,疗程为3个月。治疗3个月后,用ELISA法测定4种血栓分子标志物浓度,包括凝血酶-抗凝血酶Ⅲ复合物(TAT)、凝血酶原片段1 2(F1 2)、D-二聚体(D-D)、纤溶酶-抗纤溶酶复合物(PAP)。结果:EPO组治疗前后以及EPO组和对照组治疗后,4种血栓分子标志物的比较差异均无统计学意义(P均>0.05)。结论:慢性心力衰竭患者接受EPO每周10000～15000U治疗未明显增加潜在血栓风险。     

重组人类促红细胞生成素防治早产儿贫血的临床研究

目的　应用不同剂量国产重组人类促红细胞生成素 (rhu EPO)防治早产儿贫血 ,探讨其最适剂量和疗效。方法　 83例孕周 <36周 ,出生体重 <2 5 0 0克早产儿 ,以入院顺序按rhu EPO剂量随机分为第 1组 2 5例 (rhu EPO 75 0IU·kg-1·w-1) ,第 2组 18例 (45 0IU·kg-1·w-1) ,第 3组 2 0例(30 0IU·kg-1·w-1) ,分为每周 3次 ,静脉注射 ,疗程 4周。另设第 4组 2 0例为对照组。结果　 4组早产儿生后血红蛋白 (Hb)、红细胞压积 (Hct)渐行下降。第 1组下降最轻 ,第 2组次之 ,对照组最明显 ,经方差分析有显著性差异 (P <0 0 1) ;网织红细胞 (Ret)明显增高 ,且Ret升高程度和rhu EPO剂量有关 ;治疗后血清EPO浓度以第 1组最高 ,对照组最低 ,有显著性差异 (P <0 0 1) ,但第 3组与对照组比较无显著性差异 (P >0 0 5 ) ;血清铁 (Fe)生后均逐渐下降 ,治疗各组略低于对照组 ,无显著性差异。结论　早期rhu EPO治疗可提高Hb、Hct、Ret,并且疗效和剂量有关 ,体内充足的铁储备是确保rhu EPO疗效的重要因素。     

左卡尼丁联合促红细胞生成素治疗维持性血液透析患者肾性贫血

目的观察左卡尼丁联用促红细胞生成素(EPO)对维持性血液透析患者肾性贫血的疗效及EPO用量的影响。方法采用同期随机对照研究,选择2009年3-9月于我院血液净化中心行维持性血液透析的患者共36例,随机分为3组,常规剂量EPO治疗组(A组)12例、小剂量EPO加左卡尼丁治疗组(B组)13例及常规剂量EPO加左卡尼丁治疗组(C组)11例,观察各组方法治疗8周后贫血指标的变化。结果治疗后第4周,各组血红蛋白(Hb)和红细胞压积(Hct)水平均较治疗前升高,但各组之间比较差异无统计学意义(P>0.05);治疗第8周时,各组患者Hb、Hct水平明显上升(P<0.01),但C组患者Hb、Hct高于A、B组(P<0.05);B组患者EPO用量较A组少,但B组患者Hb、Hct水平高于A组,两组比较差异有统计学意义(P<0.05)。结论左卡尼丁与EPO联用可提高治疗维持性血液透析患者肾性贫血的疗效,纠正贫血,减少EPO的用量。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.