血清同型半胱氨酸水平与冠心病的相关性探讨

目的：探讨血清同型半胱氨酸（Hcy）、叶酸及维生素（Vit)B12水平与冠心病（CHD）的相关性。方法：应用荧光微粒子发光法（测定Hcy及VitB12）及离子捕捉法（测定叶酸）检测CHD组（A组）、其它心血管疾病组（B组）和健康对照组（C组）各30例受检查血清Hcy、叶酸、VitB12水平。结果：A组血清Hcy含量明显高于B组（P＜0．01）及C组（P＜0．01）；A组血清叶酸含量明显低于B组（P＜0．01）及C组（P＜0．01）；A组血清VitB12含量明显低于B组（P＜0．05）及C组（P＜0．05）。结论：血清Hcy水平的升高与CHD可能有明显的关系。叶酸和VitB12水平的下降与Hcy水平的升高在CHD的发生中可能起着相似的作用。     

2型糖尿病患者脂蛋白(a)水平与冠状动脉病变的关系

目的：研究2型糖尿病患者血清脂蛋白(a)[LP(a)]水平与冠状动脉病变的关系。方法：将368例按冠状动脉造影结果分为糖尿病合并冠心病(A)组，单纯冠心病(B)组，单纯糖尿病(C)组和对照组(D)4组，测定血脂水平。结果：冠状动脉病变组(A组和B组)LP(a)水平高于无冠状动脉病变组(C组和D组)，差别有统计学意义(P＜0．01)，且A组LP(a)水平明显高于B组(P＜0．01)；LP(a)水平随着冠状动脉病变支数和积分的增加而递增；A组和B组LP(a)水平与冠状动脉病变积分之间呈明显的正相关，而LP(a)水平与A组正相关关系更为明显(A组：r=0．62，t=5．42；B组：r=0．45，t=3．25)。结论：高水平LP(a)与糖尿病合并严重而弥漫的冠状动脉病变密切相关。     

血清同型半胱氨酸及高敏C反应蛋白与冠心病相关性分析

目的：探讨血清同型半胱氨酸（ Hcy ）、高敏 C 反应蛋白（ hs-CRP ）与冠心病的相关性。方法测定111例冠心病患者组（冠心病组）及77例健康志愿者（健康对照组） Hcy、hs-CRP水平,分析其与冠心病的关系。应用循环酶法检测Hcy,应用免疫比浊法检测hs-CRP。冠心病组患者根据病情不同分为稳定型心绞痛（ SAP）组、不稳定型心绞痛（ UAP）组、急性心肌梗死（ AMI）组,分析各亚组Hcy、hs-CRP水平差异性。结果冠心病组患者血清Hcy、hs-CRP水平明显高于健康对照组[（21±9）μmol/L比（9±6）μmol/L,（15．1±1．4）mg/L比（1．0±0．9）mg/L]（P＜0．05）。冠心病各亚组比较：AMI组患者血清Hcy、hs-CRP水平明显高于SAP组及UAP组[（24±8）μmol/L比（16±5）、（19±6）μmol/L,（23．7±5．9）mg/L比（4．0±3．0）、（15．4±3．2）mg/L]（P＜0．05）。 UAP组患者血清Hcy水平、血清hs-CRP水平明显高于SAP组[（19±6）μmol/L 比（16±5）μmol/L,（15．4±3．2） mg/L 比（4．0±3．0） mg/L]（P ＜0．05）。结论血清Hcy及hs-CRP水平与冠心病病情相一致,检测血清Hcy及hs-CRP水平可以判断冠心病病情,对于指导治疗有积极的意义。     

糖尿病心脏病患者血清同型半胱氨酸水平及其干预研究

目的:探讨糖尿病心脏病(DC)患者血清同型半胱氨酸(Hcy)水平,观察叶酸、维生素B12和甲钴铵治疗高同型半胱氨酸血症的疗效.方法:确诊的DC患者(干预组)36 例及正常对照组36 例,用高效液相色谱法测定血浆Hcy水平,用放免法测定血浆叶酸和维生素B12浓度.其中高Hcy血症患者每天服用叶酸5 mg,每日3次,甲钴胺针0.5 mg肌肉注射,每日1次,2周后改为口服甲钴胺片500 μg,每日3次.观察4周血浆Hcy、叶酸和维生素B12水平变化.结果:DC患者血浆Hcy水平明显高于正常对照组(P＜0.05),叶酸和维生素B12水平则明显低于正常对照组(P＜0.05);干预治疗4周后,干预组血浆Hcy水平明显下降(P＜0.05);叶酸和维生素B12水平则明显升高(P＜0.05).结论:DC患者血浆Hcy水平明显高于正常人,高Hcy血症是DC的危险因素之一,叶酸和甲钴铵干预治疗可使DC患者血浆Hcy浓度明显降低.     

2型糖尿病患者高同型半胱氨酸血症的临床干预方法

目的：探讨2型糖尿病伴高同型半胱氨酸（ Hcy）血症的长期临床治疗方法,防止2型糖尿病病程发展。方法选择门诊2型糖尿病伴高同型半胱氨酸血症患者120例,随机分为3组,每组40例。 A组每日口服叶酸0构．2 mg、维生素B62．5 mg、维生素B12100μg;B组每日口服叶酸5 mg、维生素B630 mg、维生素B121．5 mg;C组每日口服叶酸15 mg。3组均连续给药24个月,统计检测治疗前和治疗后4周、8周、12周、半年、1年、2年的血清同型半胱氨酸水平,观察临床治疗效果及不良反应。结果用药后3组血清同型半胱氨酸水平均显著下降,3组之间差异无统计学意义（ P ＞0．05）;治疗过程中A组无不良反应,B、C组有明显不良反应,部分参与者被迫停药,其临床治疗安全性存在差异有统计学意义（ P ＜0．05）。结论每日口服叶酸0．2 mg、维生素B62．5 mg、维生素B12100μg方案能够在较长时间内安全有效地干预2型糖尿病患者髙同型半胱氨酸血症,可以防止或延缓糖尿病及其慢性并发症的临床进程,有推广使用价值。     

冠心病及合并糖尿病患者冠脉病变程度和同型半胱氨酸及心率变异性的相关性研究

目的 探讨冠心病及冠心病合并糖尿病患者冠脉病变程度和同型半胱氨酸(Hcy)和心率变异性(HRV)的相关性。方法 连续纳入住院并行冠脉造影的患者共116例,并根据冠脉造影结果及既往史及血糖情况分为冠心病组(CHD组)48例、冠心病合并糖尿病组(CHD+T2DM组) 33例及正常组35例。对入选对象的冠脉造影结果进行Gensini评分,测定血清Hcy水平,进行HRV分析,比较各组间的差异。结果 (1)三组间比较冠心病组和冠心病合并糖尿病组血清Hcy水平明显升高,冠脉病变程度增加,HRV(包括SDNN、SDANN)水平下降(P＜0.05);(2)CHD+T2DM组Hcy水平及Genisi评分在三组中最高;(3)通过对单支、双支、多支分组比较发现随着冠脉病变严重程度的增加Hcy水平升高,HRV下降;(4)Gensini评分和血清Hcy呈正相关,差异有统计学意义(P＜0.05)。结论 冠心病患者血清Hcy水平和 HRV变化对冠脉病变程度有评估意义。     

血清同型半胱氨酸、维生素B12、叶酸水平与老年性骨折的相关性分析

目的：探究血清同型半胱氨酸（ Hcy）、维生素B12、叶酸水平与老年性骨折的相关性。方法将160例老年性骨折患者作为观察组,在常规治疗基础上,进行维生素B12和叶酸的治疗,同期收集在该院体检中心进行体检的健康老年人130例作为对照组。检测2组Hcy、维生素B12、叶酸水平,并进行比较。比较观察组治疗前后Hcy水平,探讨血清Hcy水平与维生素B12水平、叶酸的相关性。结果观察组血清Hcy水平明显高于对照组,维生素B12、叶酸水平低于对照组,差异均有统计学意义（P＜0．05）;观察组入院时血清Hcy水平为（18．73±5．61）μmol／L高于治疗后的（11．21±4．20）μmol／L,差异有统计学意义（P＜0．05）。观察组老年性骨折患者的血清Hcy水平分别与维生素B12水平、叶酸水平呈负相关（r＝－0．3,－0．2,P均＜0．05）。结论老年性骨折患者Hcy水平明显升高,补充维生素B12、叶酸可降低血清Hcy水平,降低老年性骨折的发生率。     

MTHFR基因多态性与冠心病的关系

目的研究天津地区人群N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因C 677 T多态性与冠心病的关系.方法应用聚合酶链反应(PCR)技术和限制性酶切片段长度多态性(RFLP)分析技术检测50例冠心病患者(冠心病组)和50例正常人(对照组)MTHFR基因C 677 T多态性,应用高效液相色谱法测定血浆同型半胱氨酸(Hcy)水平,采用125Ⅰ标记放免法测定血清叶酸浓度.结果(1)冠心病组与对照组MTHFR基因频率分布不同(P＜0 05),对照组CC型、TC型、TT型基因频率分别为52.0%,28.0%,20.0%;冠心病组分别为26.0%,44.0%,30.0%.冠心病组T等位基因频率为52.0%,C等位基因频率为48.0%,与对照组比较有显著性差异(P＜0.05).(2)两组的TT基因型者血浆Hcy浓度均明显高于CC和TC基因型者(P＜0.05),而后两者间无显著性差异(P＞0.05).(3)冠心病组Hcy浓度高于对照组(P＜0.05).两组叶酸水平无显著性差异(P＞0.05),血浆Hcy浓度与叶酸水平均呈显著负相关(r分别为-0.617和-0.588,P＜0.05).结论MTHFR基因C 677 T点突变与冠心病发病密切相关,MTHFR基因纯合突变是引起高Hcy血症的一个重要的遗传因素.     

2型糖尿病并发脑梗塞与血同型半胱氨酸水平的关系研究

目的 探讨2型糖尿病(T2DM)并发脑梗塞与血同型半胱氨酸(Hcy)水平的关系.方法 选择50例T2DM合并脑梗塞患者纳入观察组,随机选取未合并脑梗塞的T2DM患者50例纳入对照组,比较两组患者血清Hcy、超敏C反应蛋白(hs-CRP)及颈动脉内膜中层厚度(IMT)水平,并分析血清Hcy、hs-CRP与颈动脉IMT的相关性.结果 观察组患者血清Hcy及hs-CRP均明显高于对照组,观察组患者颈动脉IMT明显高于对照组,差异均有统计学意义(均P＜ 0.05).2型糖尿病并发脑梗塞患者血清Hcy、hs-CRP水平与颈动脉IMT水平均呈正相关性(r=0.623、0.414,P＜ 0.05).结论 2型糖尿病患者脑梗塞的发生与Hcy有关,其机制可能是Hcy参与T2DM患者动脉粥样硬化进程的关系.     

冠心病合并2型糖尿病患者N末端脑钠肽前体和D-二聚体的相关性

目的：探讨冠心病合并2型糖尿病患者血清中D-二聚体水平与N末端脑钠肽前体（ NT-porB-NP）的相关性。方法选取50例冠心病合并2型糖尿病患者作为研究组,并选取同期体检健康者30例为健康对照组。检测两组血清中 D-二聚体水平和 NT-porBNP 的含量水平,并经统计学分析两者的相关性。结果研究组血清中D-二聚体、NT-porBNP水平分别为（2．43±0．58）mg/L、（1487．8±201．5）pg/L,均高于健康对照组的（0．26±0．13）mg/L、（83．3±21．4）pg/L（t＝21．34、32．12,均P＜0．05）。 D-二聚体水平和NT-porBNP的含量水平呈明显正相关（r＝0.564,P＜0．05）。结论冠心病合并2型糖尿病患者血清中D-二聚体和NT-proBNP的含量水平密切相关,且高水平表达。     

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.

---

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.