16型人乳头瘤病毒疫苗研究进展

16型人乳头瘤病毒(HPV16)与宫颈癌的发生关系密切,由于该病毒尚不能在体外有效培养,而限制了疫苗的研究进展.目前通过分子生物学方法在体外表达的HPV16病毒样颗粒(VLP)成为疫苗研究的热点.研究表明VLP可诱导机体产生抗病毒攻击的细胞免疫和体液免疫应答,从而为基因工程亚单位疫苗的研制提供了科学依据.     

治疗性乙型肝炎疫苗临床研究进展

 乙型肝炎病毒感染所致的慢性肝炎是严重的全球性公共卫生问题,目前使用的药物仅能抑制病毒复制,不能彻底清除病毒。如何有效、全面地激发患者的免疫系统,重建对乙型肝炎病毒的免疫力,可能是消除慢性感染的关键。治疗性乙型肝炎疫苗有望成为新的治疗策略。目前,国内外研究的治疗性乙型肝炎疫苗主要包括蛋白疫苗、多肽疫苗、DNA疫苗和树突状细胞疫苗,此文对疫苗的临床试验进展及其与抗病毒药物联合应用研究进行综述。     

E肝移植患者病毒性肝炎的药物治疗

病毒性肝炎肝功能衰竭患者行肝脏移植术后,病毒性肝炎的复发是影响其生存率的主要因素.但是,近年来随着对病毒性肝炎发病机制认识的加深和新型抗病毒药物的不断问世,其复发率得到良好控制?由于供者短缺,有些移植中心甚至采用肝炎病毒阳性的供者,同时使用抗病毒药物,实行抗病毒治疗和免疫治疗,短期随访效果良好.乙型肝炎所致的终末期肝硬化患者行肝移植后,应用乙型肝炎免疫球蛋白和抗病毒药物拉米夫定进行治疗;对于丙型肝炎则主要应用干扰素与利巴洛韦.近来研究多采用联合用药.今后,核苷酸类似物、反义核苷酸和免疫疫苗的应用为病毒性肝炎的防治带来新的希望.     

丙型肝炎疫苗的研究进展与挑战

丙型肝炎病毒(hepatitis C vires,HCV)是具有高度基因变异性的RNA病毒,恢复期患者或黑猩猩再次暴露于不同型(株)病毒时可发生再感染.因此,研发HCV疫苗存在着巨大的挑战.HCV预防性疫苗黑猩猩体内研究证实,诱导并保持针对多个病毒表位的辅助T细胞和细胞毒性T细胞(cytotoxic T-lymphocyte,CTL)的免疫应答,是清除病毒和防止慢性感染的必要环节.多特异性B细胞应答可快速诱导产生交叉中和抗体,这些抗体有助于细胞免疫应答.此文总结候选HCV疫苗在分子病毒学和抗病毒免疫应答中的研究进展,并就疫苗在黑猩猩和HCV感染者的体内试验研究进行综述.     

16型人乳头瘤病毒疫苗研究进展

16型人乳头瘤病毒（HPV16）与宫颈癌的发生关系密切,由于该病毒尚不能在体外有效培养,而限制了疫苗的研究进展。目前通过分子生物学方法在体外表达的HPV16病毒样颗粒（VLP）成为疫苗研究的热点。研究表明VLP可诱导机体产生抗病毒攻击的细胞免疫和体液免疫应答,从而为基础工程亚单位疫苗的研制提供了科学依据。     

病毒化疗法

尽管实验室中存在着无数抗病毒药物,然而真正能够直接或间接地在临床上治疗人类病毒感染的药物却寥寥无几。抗病毒药物的研究工作已经进行了多年,但病毒化疗法这一概念在美国仍未很好地被接受。一方面是因为缺乏安全有效的抗病毒药物,另一主要原因是由于疫苗已能成功地抵御很多病毒性疾病。仅仅在近几年中,病毒化疗法的概念开始为人们所接受。在美国,有从事这方面工作的研究部门,但“疾病控制中心”基本上还是倾向于疫苗。苏联的情况则不同,政府组织大规模的病毒化疗研究计划,与疫苗、干扰素的研究同时并进。     

广谱抗呼吸道病毒中药研发的价值与途径

包括新型冠状病毒(SARS-CoV-2)在内的呼吸道病毒为世界公共卫生及人类的生命安全带来巨大威胁.呼吸道病毒易感染、易变异、易流行和跨物种传播的特点为传统抗病毒药物及疫苗的研发提出挑战,安全有效的广谱抗病毒药物研发势在必行.中药多成分、多靶点、多途径的作用特点使其在抗呼吸道病毒新药开发方面具有极大的优势和潜力.本文在...     

新型冠状病毒疫苗研发进展及其潜在不良反应

新型冠状病毒感染是目前危害全球的传染性疾病,造成约1亿人感染和200万人死亡.在缺乏有效抗病毒药物的情况下,疫苗成为全球防控新冠病毒的重要方法,在我国已经有超过1 000万人注射了灭活疫苗.从疫苗的研发机制、研发进展和潜在的不良反应3个方面,系统综述新型冠状病毒的灭活疫苗、减毒疫苗、亚单位疫苗、RNA疫苗、DNA疫苗和...     

基于碳水化合物的抗肿瘤疫苗研发进展

糖生物学研究新技术的发展为碳水化合物疫苗的研究提供了新思路。从理论上讲,各种类型细胞的表面抗原决定簇都可用于疫苗的开发。近年来已经研制成多种碳水化合物疫苗,此文主要介绍抗肿瘤碳水化合物疫苗的研究新进展。     

肠道病毒71型病毒样颗粒疫苗研究进展

肠道病毒71型(enterovirus 71,EV71)是引起儿童手足口病的主要病原体之一.由于尚无有效的抗病毒药物,故研发安全有效的疫苗是控制手足口病的有效措施.目前研发的EV71疫苗以灭活疫苗和病毒样颗粒(virus-like particle,VLP)疫苗为主,研究表明,VLP具有良好的免疫原性和稳定性.此文对目前EV71 VLP疫苗的研究进展做一综述,以期为预防EV71相关手足口病及其他手足口病的新型疫苗的研制提供思路.     

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.