甲状腺过氧化物酶抗体与亚临床甲减病程演变的相关性研究

目的研究甲状腺过氧化物酶抗体（TPOAb）的不同血清学水平与亚临床甲减患者病情程度的关系;并通过随访患者1年时间,研究TPOAb在亚临床甲减病程演变中的作用。方法通过测定血清促甲状腺激素（TSH）、游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）来确诊亚临床甲减患者;根据血清TPOAb水平,将135例亚临床甲减患者分为阳性组（54例）和阴性组（81例）,在没有任何干预亚临床甲减的情况下,定期监测患者的甲状腺功能指标（FT3、FT4和TSH）,随访1年后,观察其病程演变情况。结果 TPOAb阳性组患者TSH值为（14.4±7.1）μIU/ml,阴性组为（7.1±4.0）μIU/ml,且两者之间差异有统计学意义（P〈0.01）。不同患者随访1年后,TPOAb阳性组临床甲减发生率为5.5%,阴性组为0.5%,且两者之间差异有统计学意义（P〈0.05）。结论①血清TPOAb及TSH的水平均与亚临床甲减病情程度相关;②血清TPOAb的水平可以预测亚临床甲减向临床甲减的转化,应早期、定期监测,适时给予干预及治疗。     

维生素D缺乏与桥本氏甲状腺炎的相关性研究

目的：观察桥本氏甲状腺炎（HT）患者血清中1,25（OH）2 D3的水平与甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TGAb）的关系,并探讨补充骨化三醇对甲减患者血清 FT3、FT4、TSH 、TPOAb 、TGAb 水平的影响。方法选取未经治疗的 HT 患者46例及同期健康体检者40例作为观察组和对照组,检测其血清 FT3、FT4、TSH 、TPOAb 、TGAb 水平。另外选择 HT 组血清1,25（OH）2 D3低于正常值的患者,分为两组,HTl 组仅口服左旋甲状腺素;HT2组除口服左旋甲状腺素外,加用骨化三醇口服,连续2个月,检测患者血清 TGAb 、TPOAb 、FT3、FT4、TSH 、1,25（OH）2 D3水平。结果⑴ HT 甲减组血清1,25（OH）2 D3明显低于正常组（P＜0．05）。⑵两组血清1,25（OH）2 D3治疗后均较治疗前升高（P＜0．05）;治疗后血清1,25（OH）2 D3水平 HT2组较 HT1组明显升高（P＜0．05）;两组 TGAb 及 TPOAb 治疗后均较治疗前降低,且 HT2组下降幅度优于 HT1组（P＜0．05）;治疗后 HT2组较 HT1组甲状腺功能明显改善（P＜0．05）。结论 HT 甲减患者存在1,25（OH）2 D3缺乏,提示1,25（OH）2 D3在甲状腺自身免疫过程中发挥一定作用;补充维生素 D 具有降低甲状腺自身抗体,抑制甲状腺自身免疫反应的作用。     

甲状腺相关性眼病患者甲状腺自身抗体检测的临床意义

目的 探讨甲状腺自身抗体与甲状腺相关性眼病（TAO）的关系.方法 选取我院诊治的35例TAO患者为TAO组,单纯甲状腺功能亢进无突眼患者37例为对照组.分别检测2组患者的甲状腺球蛋白抗体（TGAb）、抗甲状腺过氧化物酶抗体（TPOAb）和促甲状腺激素受体抗体（TRAb）.结果 TAO组与对照组的TGAb分别为（0.26±0.02）IU/L和（0.27±0.01）IU/L,TPOAb分别为（0.10±0.01）IU/L和（0.10±0.01）IU/L,TRAb分别为（27.54±4.62）U/L和（11.48±3.55）U/L.TAO组与对照组TGAb、TPOAb水平比较,差异无统计学意义（P＞0.05）;而2组TRAb水平差异有统计学意义（P＜0.05）.结论 TGAb、TPOAb对TAO的诊断意义较小;而TRAb对TAO的早期诊断、治疗和随访有较大的价值.     

甲状腺过氧化物酶抗体和甲状腺球蛋白抗体阳性临界值的确定及其临床意义

目的 探讨甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(Tg Ab)阳性临界值的确定及其临床意义。方法 500例健康体检的正常人,测定其TPOAb、Tg Ab及促甲状腺激素(TSH)水平。结果 TPOAb高值95%可信区间上限为37.8 IU/ml,Tg Ab高值95%可信区间上限为38.6 IU/ml。当TPOAb浓度为37.8 IU/ml或Tg Ab浓度为38.6 IU/ml时,TSH升高(>4.8 IU/ml)或TSH降低(<0.3 IU/ml)的比例差异有统计学意义(P<0.05)。结论 本次研究认为当TPOAb为37.8 IU/ml及Tg Ab为38.6 IU/ml时可定义为阳性临界值。     

血清 TPOAb 水平对 Graves 病患者抗甲状腺药物治疗的影响

摘要： 目的 分析血清甲状腺过氧化物酶抗体 （TPOAb） 水平对初发 Graves 病 （GD） 患者抗甲状腺药物 （ATD） 治疗的影响。方法 选择应用 ATD 治疗满 12 个月的初发 GD 患者 121 例, 将其分为 TPOAb 阴性组 49 例（TPOAb≤ 35 IU/mL）和阳性组 72 例（TPOAb＞35 IU/mL）, 根据 TPOAb 滴度水平将阳性组分为阳性低组（35 IU/mL＜TPOAb≤ 200 IU/mL, 19 例）、 中组（200 IU/mL＜TPOAb≤500 IU/mL, 20 例）、 高组（500 IU/mL＜TPOAb≤1 000 IU/mL, 13 例）、 极高组（TPOAb＞1 000 IU/mL, 20 例）, 比较治疗 12 个月各组 ATD 总用量以及治疗 3、 6、 12 个月时阴性组和阳性组促甲状腺激素（TSH）恢复正常的比例。结果 TPOAb 阳性组 ATD 的总用药量为（1 743.82±265.38） mg, 低于阴性组（1 889.18±125.51） mg; TPOAb 阳性低、 中、 高、 极高组总用药量分别为（1 759.71±230.29） mg、（1 793.75±299.02） mg、（1 731.54±236.44） mg 和（1 710.00±290.73） mg。TPOAb 阳性组在治疗 3 个月时 TSH 恢复正常的比例明显高于阴性组 （P＜0.05）。结论 GD 患者血清 TPOAb 阳性会导致 ATD 治疗的疗程缩短、 总用药量减少。     

左旋甲状腺素联合曲安西龙治疗自身免疫性甲状腺疾病并发甲状腺功能减退30例

目的观察口服左旋甲状腺素（LT4） 联合小剂量曲安西龙治疗自身免疫性甲状腺疾病（AITD）并发甲状腺功能减退（甲减）的疗效。方法将60例临床诊断为AITD并发甲减的患者随机分为LT4治疗组（A组）和LT4、曲安西龙联合治疗组（B组）各30例。两组于治疗前及治疗后4个月分别测定血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺素（TSH）、甲状腺球蛋白抗体（TGAb）及甲状腺过氧化物酶抗体（TPOAb）;B组测定皮质醇、促肾上腺皮质激素（ACTH）、血浆葡萄糖水平。结果两组治疗后FT3、FT4、TSH较治疗前均有所改善,但B组FT4、TSH改善更明显,TGAb和 TPOAb下降明显,且治疗4个月时所需LT4的平均剂量明显低于A组。结论口服LT4联合小剂量曲安西龙能明显降低血清TGAb和 TPOAb水平,更快恢复甲状腺功能。     

甲状腺抗体检测在 Graves 病与桥本甲状腺炎诊断中的意义

目的：探讨甲状腺抗体检测在Graves病和桥本甲状腺炎诊断中的应用价值。方法选取248例Graves病患者和92例桥本甲状腺炎患者为研究对象,同时选取体检的健康人群30例为对照组。三组受试者均接受促甲状腺激素受体抗体（ TRAb）、甲状腺过氧化物酶抗体（ TPOAb）、甲状腺球蛋白抗体（ TGAb）水平的检测,对比三组患者的甲状腺抗体水平。结果 Graves 病组患者 TGAb 的检测结果为（127．17±208.79）IU/L,TRAb的检测结果为（23．11±19．86）IU/L,TPOAb的检测结果为（194．26±283．35）IU/L;桥本甲状腺炎组患者TGAb 的检测结果为（725．39±898．96） IU/L,TRAb的检测结果为（10．42±6．17） IU/L, TPOAb的检测结果为（551．27±385．74） IU/L;Graves病组和桥本甲状腺炎组患者的TGAb、TRAb、TPOAb水平均显著高于对照组（均P＜0．05）;桥本甲状腺炎组患者TGAb和TPOAb水平均显著高于Graves病组（均P＜0．05）,而TRAb水平则显著低于Graves病组（P＜0．05）。结论 TGAb的检测是Graves病诊断的重要指标,TPOAb、TRAb的检测是桥本甲状腺炎诊断的重要指标,上述指标的检测可为Graves病和桥本甲状腺炎的鉴别诊断提供重要的依据。     

中西药联合治疗2型糖尿病伴甲状腺功能亢进的疗效观察

目的 观察中西药结合对2型糖尿病合并甲状腺功能亢进患者的疗效.方法 收集选择2型糖尿病合并甲状腺功能亢进患者83例,随机分为治疗组44例和对照组39例,其中对照组给予二甲双胍片0.25g/次、3次/日,甲巯咪唑40 mg/天口服;治疗组在对照组给药基础上给予中药逍遥丸6g/次、2次/日;两组患者分别治疗28天后观察患者治疗前后空腹血糖（GLU）、促甲状腺素（TSH）、游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）含量.结果 两组患者治疗后血糖均降低,治疗组治疗前后为（8.85±1.91） mmol/L和（5.21±1.33）mmol/L;对照组治疗前后为（7.22±1.37） mmol/L和（5.81±1.01） mmol/L,空腹血糖值治疗前后比较差异有统计学意义（P＜0.05）,治疗后组间比较差异无统计学意义（P＞0.05）;治疗组治疗前TSH、FT3和FT4含量分别为（13.21±0.85）pmol/L、（38.11±8.73）pmol/L和（0.29±0.05）μIU/ml,治疗后分别为（7.55±0.63）pmol/L、（20.57±1.25） pmol/L和（0.45±0.04）μIU/ml;对照组治疗前分别为（12.88±0.77） pmol/L、（37.27±9.12） pmol/L和（0.31±0.02）μIU/ml,治疗后分别为（9.18±1.37） pmol/L、（23.31±2.27）pmol/L和（0.36±0.03）μIU/ml;两组患者治疗前后TSH、FT3和FT4含量比较差异有统计学意义（P＜0.05）,治疗后组间比较差异有统计学意义（P＜0.05）.结论 中西药结合对2型糖尿病合并甲状腺功能亢进者的疗效确定.     

血清甲状腺过氧化物酶抗体对 Graves 病合并桥本 甲状腺炎的诊断意义

目的 探讨血清甲状腺过氧化物酶抗体（TPOAb）对 Graves 病（GD）、 Graves 病合并桥本甲状腺炎（GH）诊 断的临床意义。方法 选取 2008 年 1 月—2014 年 12 月天津医科大学总医院外科临床确诊为 GD、 并经手术治疗的 患者 58 例, 术后依据甲状腺病理结果分为 GD 组 39 例和 GH 组 19 例。比较 2 组血清 TPOAb 水平及甲状腺内淋巴 细胞浸润程度。结果 GD 组术前血清 TPOAb 水平明显低于 GH 组［60.0（15.0, 317.0）IU/mL vs. 800.0（231.6, 1 000.0） IU/mL, P＜0.01］; 甲状腺淋巴细胞浸润程度明显低于 GH 组（Z=4.334, P＜0.01）。结论 GH 患者相比于单 纯 GD 患者血清 TPOAb 水平更高、 甲状腺内淋巴细胞浸润程度更重。     

阿法骨化醇联合厄贝沙坦治疗早期糖尿病肾病疗效观察

目的观察阿法骨化醇联合厄贝沙坦治疗早期糖尿病肾病的临床疗效。方法将42例符合入选条件的门诊及住院早期糖尿病肾病患者随机分为单用厄贝沙坦组（口服厄贝沙坦150 mg/d）和联合治疗组（口服阿法骨化醇0.25μg/d、厄贝沙坦150 mg/d）,各12例,疗程均为12周,治疗前后观察患者糖化血红蛋白（HbA1c）、血压、尿素氮（BUN）、肌酐（Cr）、血钙、血钾、24 h尿微量白蛋白等。结果两组患者治疗后24 h尿微量白蛋白水平均下降,差异均有统计学意义（P〈0.05）,联合治疗组下降更明显,与厄贝沙坦组比较,差异有统计学意义（P〈0.05）。结论阿法骨化醇联合厄贝沙坦治疗早期糖尿病肾病能显著降低患者尿微量白蛋白水平,较单独运用厄贝沙坦效果更好。     

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.