循环利钠肽胶原水平与慢性心力衰竭的关系

目的：探讨慢性心力衰竭（CHF）患者循环利钠肽、胶原水平与心功能的关系。方法：采用放射性免疫法和酶联免疫吸附法检测63例CHF（CHF组：其中NYHAⅡ级17例,Ⅲ级27例,Ⅳ级19例）及17例健康者（对照组）血浆心纳素（ANP）、脑纳素（BNP）、C型利钠肽（CNP）、Ⅰ型前胶原羧基端肽（PICP）、Ⅲ型前胶原端肽（PCⅢ）的浓度,同时用多谱勒超声心动要测定左室射血分数（LVEF）。结果：（1）与对照组比较,心力衰竭患者血浆ANP、BNP、CNP、PICP、PCⅢ浓度显著升高（．P〈0．01）。（2）CHF患者血浆ANP、BNP、PICP、PCⅢ浓度随心功能的恶化逐渐升高（均P〈0．01）,血浆CNP浓度在NYHAⅡ级患者显著升高（P〈0．01）,而NYHAⅢ-Ⅳ级患者血浆CNP浓度无明显改变（P〉0．05）。（3）ANP、BNP、PICP、PCⅢ浓度与LVEF之间呈明显的负相关,BNP的相关性更为显著（P〈0．05。P〈0．01。P〈0．05。P〈0．05）,CNP浓度与LVEF之间无明显相关性（P〉0．05）。结论：血浆利钠肽可反映CHF的发生发展,BNP可评价CHF的严重程度．PICP、PCⅢ可作为CHF时心脏胶原重塑严重程度的检测指标．     

Graves'病患者血清Ⅰ型胶原相关肽水平研究及临床意义

目的:探讨Graves'病毒患者血清中Ⅰ型胶原蛋白相关肽的代谢规律及临床意义.方法:采用放射免疫分析法(RIA)检测51例Graves'病毒患者及35例健康体检者血清Ⅰ型胶原羧端肽(ICTP)及Ⅰ型原胶原羧端延长肽(PICP)水平,同时测定Ca2+、p3+、AKP.结果:Graves'病患者组ICTP及PICP均较健康组非常显著升高(p＜0.01),ICTP及PICP水平与FT3水平均呈正相关(r=0.563和0.515),血清Ca2+、P3+值两组间无明显差异(P＞0.05),Graves'病组血清AKP较对照组显著升高(P＜0.05).结论:Graves'病患者骨吸收及骨形成呈高度活跃状态,检测ICTP和PICP对预测甲亢性骨质疏松有重要意义.     

Graves′病患者血清Ⅰ型胶原相关肽水平研究及临床意义

目的 :探讨 Graves′病毒患者血清中 型胶原蛋白相关肽的代谢规律及临床意义。方法 :采用放射免疫分析法 (RIA)检测 5 1例 Graves′病毒患者及 35例健康体检者血清 型胶原羧端肽 (ICTP)及 型原胶原羧端延长肽(PICP)水平 ,同时测定 Ca2 +、P3 +、AKP。结果 :Graves′病患者组 ICTP及 PICP均较健康组非常显著升高 (P<0 .0 1) ,ICTP及 PICP水平与 FT3水平均呈正相关 (r=0 .5 6 3和 0 .5 15 ) ,血清 Ca2 +、P3 +值两组间无明显差异 (P>0 .0 5 ) ,Graves′病组血清 AKP较对照组显著升高 (P<0 .0 5 )。结论 :Graves′病患者骨吸收及骨形成呈高度活跃状态 ,检测ICTP和 PICP对预测甲亢性骨质疏松有重要意义     

黄芪注射液对病毒性心肌炎患者血清胶原前肽的影响

目的 研究黄芪注射液对心肌炎患心脏胶原代谢的影响。方法 83例临床心肌炎患与20例健康志愿作为研究对象，心肌炎患予黄芪注射液治疗2周，在治疗前、后以ELISA法分别检查其血清中I型胶原羧基末端肘(ICTP)和Ⅲ型前胶原氨基末端肽(PⅢNP)浓度。健康志愿不予用药作为空白对照。结果 心肌炎患血清胶原前肽水平较健康志愿明显增高。经连续2周黄芪注射液治疗后，心肌炎患ICTP和PⅢNP血清浓度均下降，其中ICTP接近正常水平。结论 黄芪注射液治疗心肌炎疗效可靠，黄芪注射液可能通过干预胶原代谢，抑制胶原过度增生而改善患预后，减少并发症的发生。     

老年性肾性骨病骨代谢的特点及治疗的探讨

目的：探讨老年性肾性骨病骨代谢的特点及治疗方法,方法：44例慢性肾功能衰竭甲状旁腺激素升高,按年龄分为非老年组及老年组。分别测定血清完整甲状旁腺激素（iPTH）、骨钙素（BGP）、Ⅰ型胶原交联氨基末端肽（NTX）、钙(Ca)、磷（P）,并测定骨密度（BMD）、骨矿含量（BMC）,对部分有腰痛症状进行X线检查,各组分别给添生维生素D及活性维生素D加钙剂,治疗3个月后重复进行X线检查,结果：老年性肾性骨病患明显低钙,骨转化不平衡,骨折发生率高（22％）,非老年组无骨折发生,老年组患BMD及BMC明显减低。其iPTH、NTX及BGP均明显下降（P＜0．01及＜0．05）。而老年患有活性维生素D治疗抵抗,加用钙剂后,iPTH、NTX明显下降,血钙升高（P＜0．01）,效果明显增加,结论：老年性肾性骨病的骨代谢有其特征性,在治疗上,除应用活性维生素D外,必须加用钙剂。     

扩张型心肌病动物模型的建立及实验室研究

目的：观察阿霉素建立扩张型心肌病（dilated cardiomyopathy,DCM）动物模型后,大鼠心肌细胞及血浆纤维蛋白的变化。方法：7周龄雄性SD大鼠阿霉素腹腔注射建立大鼠扩张型心肌病模型。观察DCM组SD大鼠与正常对照组超声心动图的改变,并对DCM大鼠心肌组织的病理改变及血浆中I型前胶原羧基端肽（PICP）、Ⅲ型前胶原氨基端肽（PIIINP）的浓度进行评估。结果：与正常对照组相比,DCM组心腔明显扩张,左室舒张期末内径（LVED）、左室收缩期末内径（LVES）明显增加;左室内径缩短率（FS）及左室射血分数（LVEF）明显降低。与正常对照组相比,DCM组血浆中的PICP、PⅢNP的浓度明显升高,差异具有统计学意义（P〈0．01]。结论：用腹腔注射阿霉素可成功复制DCM大鼠模型,且在DCM发生发展过程中心肌发生了纤维化。     

绝经后女性外周骨超声速率与PINP的相关性研究

目的 观察绝经后女性指骨、桡骨、胫骨超声速率(SOS)随年龄变化的规律及其与骨代谢指标血清Ⅰ型前胶原氨基端前肽(PINP)、骨钙素(BGP)和甲状旁腺激素(PTH)的关系.方法 入选绝经后女性84例(42～85岁),其骨代谢生化指标血清PINP和PTH采用酶联免疫法测定,BGP采用放射免疫法测定;应用sunlight omnisense 7000TM型超声骨量测定系统测量研究对象的SOS.结果 绝经后女性桡骨、指骨和胫骨SOS指标值随年龄段递增而下降,但只有桡骨SOS在各年龄段之间差异存在统计学意义(P＜0.05);PINP、BGP和PTH随年龄段递增有变化但(P＞0.05),且与各部位超声骨量SOS的直线相关分析及多元线性回归均无统计学意义.结论 绝经后女性桡骨SOS能够反映绝经后女性骨密度随年龄的衰减,可能是超声骨量测定反映绝经后女性骨量变化的最佳部位.     

依普黄酮对绝经后妇女骨质疏松性骨折愈合的临床研究

目的探讨依普黄酮对骨质疏松性骨折愈合影响。方法对60例绝经后骨质疏松性骨折的患者随机分成试验组(口服依普黄酮)、对照组,比较两组在治疗后3个月时的X线下的骨痂的变化,血清骨性碱性磷酸酶(BALP)、Ⅰ型前胶原羧基端肽(PICP)、骨钙素(BGP)骨形成生化指标及骨强度检测结果的变化情况。结果试验组BALP、PICP、OC水平显著下降(P<0郾01),而两组骨强度差异无统计学意义(P>0郾05)。结论依普黄酮对绝经后妇女可调节骨代谢,促进骨形成,对骨质疏松性骨折临床愈合有明显作用。     

心肌梗死后心脏胶原重塑与血清基质金属蛋白酶及其抑制因子的变化

目的探讨心肌梗死（M1）后患者心脏胶原重塑与血清基质金属蛋白酶-1（MMP-1）及其抑制因子（TIMP-1）水平的变化。方法测定首次发病的MI住院患者（MI组）发病后1周、3个月、6个月的血清I型前胶原羧基端肽（PICP）和Ⅲ型前胶原（PCⅢ）、MMP-1、TIMP-1的水平，并计算PICP／PCⅢ比值。以48例健康体检者作为正常对照组。结果与对照组比较，MI组PICP水平在MI后3个月、6个月组明显高于对照组（P〈0．05），血清PCⅢ水平在MI后各时间点均明显升高（P〈0．05），MI后各时间点的PICP／PCⅢ比值和血清MMP-1、TIMP-1水平均明显降低（P〈0．05）。结论MI后心脏胶原合成代谢旺盛，MMP-1／TIMP-1参与MI后心脏胶原重塑的病理生理进程。     

甲状腺功能亢进患者骨密度与骨代谢指标的临床观察

目的观察甲状腺功能亢进患者骨密度（BMD）与骨代谢指标的改变。方法应用双能X线测定仪（DXA）检测86例甲状腺功能亢进患者BMD和髋关节强度指数（FSI）,同时测定血清骨钙素（BGP）、总Ⅰ型前胶原氨基端延长肽（PINP）和B-胶原降解产物（B-Crosslaps）。结果甲状腺功能亢进患者并发骨质疏松发生率20．9％,并发骨量减少占40．7％,与对照组比较,甲状腺功能亢进忠者BMD和FSI明显低于对照组（P〈0．05）,骨代谢指标BGP、PINP和B-Crosslaps明显升高（P〈0．05,P〈0．01）。结论甲状腺功能亢进时反映成骨细胞活性的BGP和PINP和反映破骨细胞活性的8-CrossLaps均明显升高,且以破骨指标升高明显,呈高转换型骨质疏松。     

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.