Salvianolic acid A prevented cerebrovascular endothelial injury caused by acute ischemic stroke through inhibiting the Src signaling pathway

Stroke is an acute cerebrovascular disease caused by ruptured or blocked blood vessels.For the prevention of ischemic stroke,the coagulation state of blood and cerebrovascular protection should be considered.Our previous study has shown that salvianolic acid A(SAA),which is a water-soluble component from the root of Salvia Miltiorrhiza Bge,prevents thrombosis with a mild inhibitory effect on platelet aggregation.In this study we investigated the preventive effects of SAA on cerebrovascular endothelial injury caused by ischemia in vivo and oxygen-glucose deprivation(OGD)in vitro,and explored the underlying mechanisms.An autologous thrombus stroke model was established in SD rats by electrocoagulation.SAA(10 mg/kg)was orally administered twice a day for 5 days before the operation.The rats were sacrificed at 24 h after the operation.We showed that pretreatment with SAA significantly improved the neurological deficits,intracerebral hemorrhage,BBB disruption,and vascular endothelial dysfunction as compared with model group.In human brain microvascular endothelial cells(HBMECs),pretreatment with SAA(10μM)significantly inhibited OGD-induced cell viability reduction and degradation of tight junction proteins(ZO-1,occludin,claudin-5).Furthermore,we found that SAA inhibited the upregulation of Src signaling pathway in vivo and vitro and reversed the increased expression of matrix metalloproteinases(MMPs)after ischemic stroke.In conclusion,our results suggest that SAA protects cerebrovascular endothelial cells against ischemia and OGD injury via suppressing Src signaling pathway.These findings show that pretreatment with SAA is a potential therapeutic strategy for the prevention of ischemic stroke.     

狂犬病诊治进展

人类的狂犬病是一种中枢神经系统病毒感染性疾病,常由患狂犬病动物的唾液污染伤口而传染;一旦出现症状,病人基本上100%死亡,从狂犬病后康复的病例极为罕见,仅有3例报道。临床表现为特有的恐水怕风、咽肌痉挛、进行性瘫痪等。狂犬病在87个国家有流行,主要流行于东南亚、非洲及拉     

苯扎溴铵溶液的稳定性观察

目的:评价在常温和0℃下存放的苯扎溴铵(新沽尔灭)的杀茵效果.方法:采用厂家3个批号的苯扎溴铵,分别于常温和0℃下存放24 h.稀释成1:50浓度后,将3种标准菌株置于其中,分别在作用5,10,15,30,60,120 min后取出药液,倾入培养基,置35℃培养箱培养48 h,观察菌株的存活情况.结果:经两种温度、不同时间的菌株培养结果观察,苯扎溴铵的杀菌效果一致,均能快速杀灭3种标准菌株.结论:苯扎溴铵消毒液保存在0℃下,不影响其杀菌效力,只要在保质期内,结冰的消毒液仍可使用,其性能稳定.     

布洛芬对乙酰氨基酚退热疗效对比

长期以来,发热是儿科关注的问题,发热程度有助于判断病情,儿童多因与病情不成比例,轻微疾病即可出现发烧,父母常常不了解这一现象而引起不必要的恐慌,随意应用退热药即成为儿科普遍的现象[1].采用安全有效的退热药物值得临床探讨.     

Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence

Midbrain dopaminergic(DA)neurons are governed by an endogenous cholinergic system,originated in the mesopontine nuclei.Nicotine hijacks nicotinic acetylcholine receptors(nAChRs)and interferes with physiological function of the cholinergic system.In this review,we describe the anatomical organization of the cholinergic system and the key nAChR subtypes mediating cholinergic regulation of DA transmission and nicotine reward and dependence,in an effort to identify potential targets for smoking intervention.Cholinergic modulation of midbrain DA systems relies on topographic organization of mesopontine cholinergic projections,and activation of nAChRs in midbrain DA neurons.Previous studies have revealed thatα4,α6,andβ2 subunit-containing nAChRs expressed in midbrain DA neurons and their terminals in the striatum regulatefirings of midbrain DA neurons and activity-dependent dopamine release in the striatum.These nAChRs undergo modification upon chronic nicotine exposure.Clinical investigation has demonstrated that partial agonists of these receptors elevate the success rate of smoking cessation relative to placebo.However,further investigations are required to refine the drug targets to mitigate unpleasant side-effects.     

Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I

Cancer cachexia is a multifactorial metabolic syndrome that affects～50%–80%of cancer patients,and no effective therapy for cancer cachexia is presently available.In traditional Chinese medicine,a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits.In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I,an active component of tonifying TCM BaiZhu,in the mouse model.Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells,whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors,including limited feeding,fatigue,and purging.The mouse model was characterized by both cachexia and spleen deficiency characteristics,including significant body weight loss,cancer growth,muscle atrophy,fat lipolysis,spleen,and thymus atrophy as compared with healthy control mice,cancer cachexia mice,and spleen deficiency mice.Oral administration of atractylenolide I(20 mg·kg?1per day,for 30 days)significantly ameliorated the reduction in body weight and atrophy of muscle,fat,spleen,and thymus in mice with spleen deficiency and cachexia.The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms.     

春季食养贵在肝脾

主持人的话 过了立春和春节,大地开始逐渐由寒变暖.这就预示着春暖花开的季节即将来到了. 从立春到立夏前,包括立春、雨水、惊蛰、春分、清明、谷雨6个节气,是生发的季节.这段时间,春归大地,阳气生发,冰雪消融,蛰虫苏醒,自然界生机勃发,一派欣欣向荣的景象.此时养生,需适应季节变化,使机体与外界统一起来.中医称之为"春气之应,养生之道也".     

抢救儿童有机磷中毒21例临床体会

<正>有机磷农药可因食入、吸入或皮肤吸收而中毒。小儿中毒原因多为:误食被有机磷农药污染的食物;误用污染农药的玩具或农药容器;母亲在使用农药后未认真洗手及换衣服而给婴儿哺乳,不恰     

对于自杀,一个就太多了

"活着"是每个人至高无上的权利,可有些人偏偏选择了放弃。9月是开学的日子,文文告别了父母兄妹,揣着东挪西凑的学费上了北京。她是乡里第一个考上北京名牌大学的学生,全乡人都以她为自豪。同宿舍的女生都来自城里,一个个时尚、新潮。看着她     

由中、英、法药品监管现状的比较看我国的中药监管

为进一步了解英、法等发达国家的药品监管体系,借鉴其在药品监管信息化建设方面的成功经验,北京市药品监督管理局东城分局与北京市科学技术委员于不久前赴英国、法国实地考察,并与英国药理学会(British Pharmacological Society)、法国退休专家志愿者协会(France Volunteer Association of the Retired Experts)进行了深入的交流.     

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.