MIC-1、PCNA在人脑星形细胞瘤中的表达及意义

目的研究巨噬细胞抑制因子-1(MIC-1)与增殖细胞核抗原(PCNA)在人脑星形细胞瘤中的表达,分析其表达水平与肿瘤恶性程度及病理级别的关系。方法采用免疫组化法,检测60例不同病理级别人脑星形细胞瘤标本及5例正常人脑组织中的MIC-1和PCNA的表达。结果 MIC-1和PCNA在正常脑组织中不表达,而在人脑星形细胞瘤中的表达程度随着肿瘤的病理级别的增高明显增高,二者表达的阳性率在正常脑组织、低级别和高级别星形细胞瘤各组间比较差异均有统计学意义(P<0.05),且二者在星形细胞瘤中的表达呈正相关(P<0.05)。结论 MIC-1与PCNA在人脑星形瘤细胞中的表达呈正相关,提示MIC-1的过度表达对肿瘤细胞增殖具有促进作用,MIC-1有可能成为新的候选肿瘤标志物,为判断肿瘤恶性程度及病理级别提供有价值的理论和依据。     

星形细胞瘤MRI弥散成像、瘤周水肿与HIF-1α表达水平的相关性分析

目的通过磁共振成像（MRI）和MRI定量指标来研究星形细胞瘤弥散成像、瘤周水肿与肿瘤缺氧诱导因子-1α（HIF-1α）表达水平的相关性,以及星形细胞瘤在缺氧环境下的浸润、生长、增殖能力及恶性度,更好地指导临床治疗及预后评估。方法选取经手术病理证实的33例星形细胞瘤患者,术前均进行磁共振弥散加权成像（DWI）检查,并计算肿瘤实质部分的ADC值;计算MRI水肿指数（EI）,采用免疫组化法检测HIF-1α的表达情况。结果低级别星形细胞瘤（WHOⅠ－Ⅱ级）的平均ADC值高于高级别星形细胞瘤（WHOⅢ－Ⅳ级）,低级别星形细胞瘤平均EI值低于高级别星形细胞瘤,高、低级别星形细胞瘤中HIF-1α均有表达,且星形细胞瘤的HIF-1α表达水平随着星形细胞瘤临床病理程度增高而加强,低级别星形细胞瘤内部平均HIF-1α指数低于高级别星形细胞瘤;肿瘤区ADC值与HIF-1α呈显著负相关,肿瘤区ADC值和EI值呈负相关,HIF-1α和EI值无明显相关性。结论核磁共振定量参数ADC值、EI值与常规MRI联合应用及HIF-1α的表达可显著提高星形细胞瘤术前分级的准确性,进而指导治疗方案的选择;MRI虽然能很好地间接反应星形细胞瘤的分子生物学行径,但瘤周水肿不能用单一理论解释。     

Livin,PTEN蛋白在脑星型细胞瘤中的表达及其与肿瘤恶性度相关性的研究

目的:研究星形细胞瘤组织中Livin蛋白和PTEN蛋白的表达及其相关性,研究其在星形细胞瘤发生、发展中的意义.方法:用免疫组化方法检测Livin蛋白和PTEN蛋白在50例不同级别星形细胞瘤中的表达.结果:Livin和PTEN蛋白在低级别脑胶质瘤(Ⅰ级+Ⅱ级)与高级别脑胶质瘤(Ⅲ级+Ⅳ级)差异具有显著性(P＜0.05),...     

ULK1、p53在大肠癌及癌前病变中的表达及临床意义

目的:探讨在大肠癌及癌前病变中ULK1和p53的表达及其临床意义。方法:收集4组不同的组织标本,分别为20例正常黏膜组织、30例大肠腺瘤伴低级别上皮内瘤变组织、30例大肠腺瘤伴高级别上皮内瘤变组织和40例大肠癌组织。采用免疫组化法(Maxvision3)检测上述组织中ULK1和p53表达,分析ULK1和p53的表达与临床病理特征的关系。结果:在正常大肠黏膜组织、低级别上皮内瘤变、高级别上皮内瘤变、大肠癌组织中,ULK1阳性率表达呈升高趋势,各组阳性率表达差异有显著性意义(P0.05);p53阳性率表达也呈升高趋势,各组阳性率表达差异也均有显著性意义(P0.05)。大肠癌ULK1、p53表达在分化程度、浸润深度、淋巴结转移、TNM分期中差异均有显著性意义(P0.05),在肿瘤大小中差异没有显著性意义。结论:临床检测ULK1、p53在大肠癌早期诊断、治疗等方面具有重要的临床应用价值。     

星形细胞瘤中p15与p27基因的表达及相关性研究

目的 探讨p15与p27基因与星形细胞瘤发生、发展,恶性程度的关系.方法 采用S-P免疫组化法染色观察50例人星形细胞瘤组织中p15和p27基因蛋白的表达情况.结果 p27基因在低级别及高级别星形细胞瘤平均阳性细胞百分率分别为(38.16±10.79)%、(11.00±3.24)%.p15基因在低级别与高级别星形细胞瘤平均阳性细胞百分率分别为(32.53±12.46)%、(10.50±2.01)%.结论 p15与p27基因蛋白的平均阳性细胞百分率与星形细胞瘤的病理分级和恶性程度有密切关系,可能在星形细胞瘤发生,发展中起重要作用.     

E-cadherin、TGF-β1和Twist1在结直肠癌变过程中的表达及意义

目的:检测E-cadherin、TGF-β1和Twist1在结直肠癌组织中的表达,并探讨其临床意义。方法:采用免疫组织化学EnVision二步法检测E-cadherin、TGF-β1和Twist1在70例结直肠癌组织、60例高级别上皮内瘤变组织、60例低级别上皮内瘤变组织及30例癌旁组织中的表达,并分析结直肠癌E-cadherin、TGF-β1和Twist1表达与临床病理特征的关系,以及结直肠癌E-cadherin、TGF-β1和Twist1表达之间的相关性。结果:各组E-cadherin、TGF-β1和Twist1阳性率比较均有显著性差异(P0.05),且随着结直肠癌组织、高级别上皮内瘤变组织、低级别上皮内瘤变组织、癌旁组织,E-cadherin阳性率明显升高(P0.05),而TGF-β1和Twist1阳性率明显降低(P0.05);结直肠癌E-cadherin、TGF-β1和Twist1表达在分化程度、Duke分期、浸润深度、淋巴结转移等方面均存在显著性差异(P0.05),而在性别、年龄等方面无明显差异(P0.05);结直肠癌E-cadherin与TGF-β1、Twist1均呈负相关性关系(r=-0.632,-0.584,P0.05),TGF-β1与Twist1呈正相关性关系(r=0.617,P0.05)。结论:检测结直肠癌组织E-cadherin、TGF-β1和Twist1表达有助于早期诊断结直肠癌和指导临床治疗。     

脑星形细胞瘤中PTEN表达和微血管密度相关性研究

目的探讨人脑星形胶质细胞瘤中PIEN表达与微血管密度（microvessel density,MVD）之间的关系及意义。方法60例人脑星形胶质瘤标本和8例正常脑组织采用免疫组织化学ABC方法检测PIEN表达和MVD。结果在正常脑组织及各级别的星形细胞瘤中均有CD34表达,表达强度不等。高级别胶质的MVD与低级别胶质瘤MVD之间、低级别胶质瘤与正常脑组织之间差异均有统计学意义（P〈0．01）。结论PIEN蛋白存在于人脑胶质瘤细胞中,PTEN的表达与MVD的测定可作为判断脑星形细胞瘤恶性潜能的重要生物学指标,对判断人脑胶质瘤的临床病理分级具有重要价值。     

磁共振弥散加权成像在星形细胞瘤分级及瘤周水肿区的应用研究

目的 运用DWI（ 磁共振弥散加权成像） 评价星形细胞瘤的分级及瘤周水肿区肿瘤细胞的浸润情况.方法 对38 星形细胞瘤行常规MRI、DWI检查,并测量、计算rADC 值.结果 低级别星形细胞瘤中心区的rADC 值高于高级别星形细胞瘤;高级别星形细胞瘤近侧水肿区rADC 值明显低于远侧水肿区rADC 值.结论 DWI 可以反映星形细胞瘤的恶性程度,反映脑肿瘤瘤周水肿区内有无肿瘤细胞浸润.     

脑星形细胞瘤中PTEN和VEGF蛋白的表达及其相关性

目的探讨PTEN基因及血管内皮生长因子(VEGF)在脑星形细胞瘤中表达及其相关性。方法采用SP免疫组化法检测PTEN和VEGF在65例脑星形细胞瘤组织(A组)和10例正常脑组织(B组)中的表达。结果 A组PTEN表达阳性率为49.2%,明显低于B组的100%(P<0.01);A组VEGF表达阳性率为64.6%,B组无阳性表达。与低恶性度组比较,高恶性度组的PTEN低,而VEGF表达明显增高(P<0.05)。在脑星形细胞瘤组织中,PTEN与VEGF蛋白的表达呈负相关(r=-0.980,P<0.05)。结论 PTEN及VEGF均与脑星形细胞瘤发生及恶性程度密切相关;检测两者表达情况可为脑星形细胞瘤的临床诊治及预后判断提供依据。     

绒毛蛋白及核苷酸还原亚单位M1在不同胃黏膜病变组织中表达研究

目的:观察绒毛蛋白及核苷酸还原亚单位M1(RRM1)在不同胃黏膜病变组织中的表达情况,并对其临床意义进行探讨。方法:选择某院收集的210例胃黏膜活检标本,其中慢性胃炎35例,肠上皮化生36例,低级别上皮内瘤变31例,高级别上皮内瘤变20例,胃癌88例。全部标本予以免疫组织化学方法进行绒毛蛋白及RRM1检测,并对检测结果进行分析。结果:肠上皮化生组、低级别上皮内瘤变组、高级别上皮内瘤变组、胃癌组标本的绒毛蛋白阳性率显著高于慢性胃炎组(P<0.05);低级别上皮内瘤变组、高级别上皮内瘤变组、胃癌组标本的绒毛蛋白阳性率显著低于肠上皮化生组(P<0.05);低级别上皮内瘤变组、高级别上皮内瘤变组、胃癌组标本的RRM1阳性率显著高于慢性胃炎组及肠上皮化生组(P<0.05);慢性胃炎组标本中的RRM1阳性率显著高于肠上皮化生组(P<0.05);绒毛蛋白、RRM1在高中分化胃癌阳性表达显著高于低分化胃癌,差异具有统计学意义(P<0.05)。结论:绒毛蛋白及RRM1的表达与胃癌的发病发展及预后存在一定关系,早期检测能够有效对胃癌进行诊断、病情评估及采取合理的治疗方案,从而改善患者的预后。     

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.