支气管哮喘患者嗜酸性粒细胞水平变化及意义

目的探讨支气管哮喘患者外周血和痰中嗜酸性粒细胞（EOS）水平变化及在支气管哮喘发病中的作用。方法分别对65例支气管哮喘急性发作患者（哮喘组,其中轻度组24例、中度组22例、重度组19例）及20例健康体检者（对照组）进行痰及外周血中EOS检测,比较各组间的差异。结果重度组痰中EOS（38．6±13．9）％高于中度组（26．8±14．8）％（P〈0．05）和轻度组（15．4±9．5）％（P〈0．05）;而中度组和轻度组比较差异无统计学意义（P〉0．05）;轻、中、重三组痰中EOS水平显著高于血（3．8±1．9、4．4±1．8、5．1±2．0）％（均P〈0．01）,但三组血中EOS水平比较差异无统计学意义（P〉0．05）。哮喘急性发作期患者治疗2周后,哮喘组痰和血中EOS占白细胞百分比分别为（20．8±11．5）％、（2．7±1．4）％均较治疗前（29．6±12．7）％、（4．2±1．9）％明显降低（均P〈0．01）,与对照组的（1．9±1．2）％、（0．9±0．5）％比较,差异有统计学意义（t=2．14、2．87,均P〈0.01）。结论外周血和痰中EOS检测对评价支气管哮喘的炎症程度和病情有一定的价值,且检测痰优于血液。     

肺炎支原体感染与小儿咳嗽变异性哮喘相关性与探讨

目的探讨肺炎支原体感染在小儿咳嗽变异性哮喘发病中的相关性。方法选择212例咳嗽变异性哮喘患儿为观察组,180例反复上呼吸道感染患儿为对照组,检测血清肺炎支原体IgM抗体、外周血嗜酸性粒细胞计数和血清总IsE水平,比较两组患儿肺炎支原体IgM抗体阳性率及肺炎支原体IgM抗体阳性患儿外周血嗜酸性粒细胞计数和血清总IgE水平。结果观察组肺炎支原体IgM抗体阳性率为35．8％（76／212）,对照组是14．4％（26／180）,两组比较差异有统计学意义（P〈0．05）。两组患儿5～12岁组血清肺炎支原体IgM抗体阳性率较1—5岁组高（P〈0．05）。观察组肺炎支原体IgM抗体阳性患儿的血清总IgE水平和外周血嗜酸性粒细胞计数均明显高于对照组患儿,差异有统计学意义（P〈0．05）。结论肺炎支原体是小儿咳嗽变异性哮喘发生的危险因素,肺炎支原体容易诱发咳嗽变异性哮喘,两者关系密切。     

CpG-ODN对哮喘小鼠Th1/Th2相关细胞因子表达的影响

目的：探讨CpG-ODN对哮喘小鼠Th1/Th2相关细胞因子的调节作用及气道炎症的抑制作用。方法：采用酶联免疫中附法（ELISA）分别检测CpG-ODN对哮喘小鼠抗原首次激发后24小时和抗末次激发后24小时血清及支气管肺泡灌洗液（BALF）中Th2细胞因子IL－4和Th1细胞因子IFNγ水平的影响，并与激素治疗组和哮喘组对照。结果：（1）抗原末次激发后24小时，CpG-ODN 血清及BALF中IFNγ水平高于哮喘组及地塞米松组（P＜0．001）。（2）抗原首次激发后24小时及抗原末次激发后24小时血清和BALF中IL－4水平低于哮喘组（P＜0．05），与地塞米松组比较无显著性差异（P＞0．05）。（3）抗原末次激发后24小时，CpG-ODN组外周血和BALF中嗜酸性粒细胞计数均低于哮喘组（P＜0．001）。结论：CpG-ODN不仅有具有与地塞米松相同的下调Th2细胞因子表达和抑制嗜酸性粒细胞的作用，而且还具有地塞米松所没有的诱导Th1细胞因子表达的作用。说明其可能通过调节Th1/Th2平衡而达到在早期抑制哮喘发病的目的。     

支气管哮喘急性发作期患者治疗前后对外周血嗜酸性粒细胞计数的影响及其意义

目的探讨孟鲁司特钠对支气管哮喘急性发作期的患者治疗前后外周血嗜酸性粒细胞（Eosinophil,EOS）水平的影响。方法应用过氧化酶法测定30例支气管哮喘急性发作期患者（治疗组）和20例健康者（对照组）的外周血EOS数量,同时用EHSA测定两组患者血清中嗜酸性粒细胞趋化因子（Eotaxin）水平,分析两组间EOS数量和Eotaxin水平的相关陛。结果治疗组治疗前患者的外周血EOS数量（0．98±0．20）×10^9／L和治疗前血清Eotaxin水平（322．520±91．376）pg／ml明显高于治疗后及对照组（JP〈0．05）,治疗3月后外周血EOS数量（0．25±0．11）×10^9／L和血清Eotaxin水平（126．367±48．536）pg／ml与对照组比较差异无显著性（P〉0．05）,治疗组治疗前外周血EOS数量与治疗前血清Eotaxin水平呈正相关（r=0．594,P〈0．05）。结论孟鲁司特钠能降低支气管哮喘患者外周mEOS数量．从而控制EOS的炎疖反廊。     

咳嗽变异性哮喘患者外周血细胞计数及基质金属蛋白酶-9的变化分析

目的探讨咳嗽变异性哮喘（CVA）患者血清中基质金属蛋白酶-9（MMP-9）的表达情况。方法选择典型哮喘30例,咳嗽变异性哮喘40例,正常对照组20例,用ELISA法分别测定各组病例血清中MMP-9水平并测定各病例外周血嗜酸性粒细胞计数（Eos）、淋巴细胞计数（Lym）。结果CVA组与典型哮喘组血清中MMP-9水平显著高于健康对照组（P〈0.01）,CVA组与典型哮喘组之间无显著性差异（P〉0.05）。嗜酸性粒细胞计数CVA组与典型支气管哮喘组显著高于健康对照组（P〈0.05）,CVA组与典型支气管哮喘组无明显差异（P〉0.05）;淋巴细胞计数CVA组显著高于典型哮喘组与健康对照组（P〈0.05）,典型哮喘组与健康对照组无明显差异（P〉0.05）;CVA组MMP-9水平与外周血嗜酸细胞计数、淋巴细胞计数皆呈显著正相关关系（r=0.581,P〈0.05;r=0.627,P〈0.05）。结论CVA是以嗜酸性粒细胞、淋巴细胞浸润为主的慢性气道炎症,MMP-9参与了CVA的气道炎症及气道重塑。     

母牛分枝杆菌菌苗对哮喘豚鼠肺组织嗜酸性粒细胞凋亡的影响

目的 研究母牛分枝杆菌菌苗对哮喘豚鼠肺组织嗜酸性粒细胞凋亡的影响。方法30只豚鼠随机分为对照组、哮喘组及母牛分枝杆菌菌苗组各10只，应用卵清蛋白建立哮喘模型。最后一次激发豚鼠后，计数支气管肺泡灌洗液中炎症细胞，观察肺组织病理改变，应用末端标记法研究肺组织嗜酸性粒细胞的凋亡。结果母牛分枝杆菌菌苗组豚鼠支气管肺泡灌洗液中嗜酸性粒细胞数量为(0.22±0.12)×108·L^-1，显著低于哮喘组的(1.18±036)×108·L^-1 (P＜0.01)；肺组织哮喘炎症反应明显轻于哮喘组；肺组织嗜酸性粒细胞凋亡指数为(23.8±5.4)%，显著高于哮喘组的(4.6±0.7)%( P＜0.01)。结论母牛分枝杆菌菌苗能减少哮喘豚鼠支气管肺泡灌洗液中嗜酸性粒细胞数量，减轻气道哮喘炎症反应，与其诱导哮喘豚鼠肺组织嗜酸性粒细胞凋亡有关。     

咳喘宁对支气管哮喘患者外周血白细胞计数的影响

目的观察咳喘宁对支气管哮喘患者外周血白细胞计数的影响。方法采用随机临床对照观察方法，咳喘宁治疗152例为治疗组，以桂龙咳喘宁胶囊治疗146例为对照组，观察两组患者治疗前后症状评分，嗜酸粒细胞、淋巴细胞、中性粒细胞计数的变化，并比较两组的临床疗效。结果与治疗前比较，治疗后两组白天及夜间哮喘症状评分、嗜酸粒细胞计数明显下降（P〈0．01），淋巴细胞、中性粒细胞计数差异均无统计学意义（P〉0．05）；治疗组治疗后白天及夜间哮喘症状评分低于对照组（P〈0．01），临床总有效率为98．6％，明显优于对照组89．0％（P〈0．01）。结论咳喘宁可减少嗜酸粒细胞计数，改善慢性炎症反应，疗效优于桂龙咳喘宁胶囊。     

咪喹莫特抑制哮喘大鼠气道炎症转录水平的研究

目的：探讨咪喹莫特拮抗支气管哮喘气道炎症的分子机制。方法：卵清蛋白腹腔注射与雾化吸入建立大鼠哮喘模型，采用逆转录－聚合酶链反应（RT－PCR）测定了不同剂量咪喹莫特对哮喘大鼠肺组织白介素（IL）－4mRNA、IL－5mRNA、IL－12mRNA和干扰素（IFN）－γ mRNA表达的影响。结果：咪喹莫特各治疗组及地塞米松组能显抑制哮喘大鼠肺组织中IL－4、IL－5mRNA的表达（与哮喘相比，均为P＜0．001；与空白对照组比，均为P＞0．05），各咪喹莫特组同时能显增加IL－12、IFN－γ mRNA表达（与哮喘组比，均为P＜0．001；与空白对照组比，均为P＞0．05），而地塞米松组不能增加IL－12、IFN－γ mRNA的表达（与哮喘组比，均为P＞0．05；与空白对照组比，均为P＜0．001）。咪喹莫特各治疗组间无显性差异。结论：咪喹莫特能降低哮喘大鼠肺组织中IL－4和IL－5基因转录，增加IL－12和IFN－γ基因转录，进而 抑制嗜酸性粒细胞的聚集、活化，发挥其抗气道炎症的作用。     

支气管哮喘患者血清嗜酸性粒细胞阳离子蛋白（ECP）在特异性免疫治疗中的变化

目的通过观察支气管哮喘患者接受特异性免疫治疗前后血清嗜酸性粒细胞阳离子蛋白（eosinophilcationicprotein,ECP）的变化,评价免疫治疗的效果,探讨其治疗机制。方法60例支气管哮喘患者随机分为治疗组40例,对照组20例,治疗组用阿罗格变应原浸液特异性免疫治疗（specificimmu．notherapy,SIT）,对照组吸人布地奈德,在治疗前后抽静脉血查ECP。结果两组治疗后患者血清ECP均有降低,有显著性差异（治疗组P〈0．01,对照组P〈0．05）,但治疗组明显优于对照组（P〈0．01）。结论特异性免疫治疗能有效降低患者血清ECP,其可能的免疫机制是有效地抑制了嗜酸性粒细胞在气管的聚集与活化,降低其释放ECP的能力,起到治疗作用。     

支气管哮喘患者外周血单核细胞因子Th1/Th2失衡的检测

目的观察支气管哮喘患者在发病期是否存在Th1／Th2失衡。方法用酶联免疫吸附试验（ELISA）分别检测三组（哮喘发作组、哮喘缓解组及健康对照组，每组17例）外周血单核细胞（PBMC）产生的肿瘤坏死因子γ（IFN-γ）、白细胞介素4（IL-4）。结果与健康对照组比较哮喘急性发作组患者PBMC产生的IFN-γ[（139．6±13．0）pg／L]明显降低（P〈0．01），而IL-4[（114．7±20．8）pg／L]水平增高（P〈0．01），哮喘缓解组两种细胞因子水平与健康对照组差异无统计学意义。结论支气管哮喘急性发作期存在着Th1／Th2失衡。     

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.