胞二磷胆碱致头痛5例报告

胞二磷胆碱为一中枢兴奋剂，笔者在临床使用中发现用药后发生头痛，现报道如下。１　一般资料本组记录用药后发生头痛共５例，其中脑梗塞３例，脑萎缩１例，脑出血１例。５例均系有语言表达能力，神志清楚的老年患者。２　头痛发生与临床的关系２．１　与剂量的关系，常用量为０．５～１．０ｇ＋５％葡萄糖２５０～５００ｍｌ·ｄ－１静滴，ｑｄ，其中用量为０．５ｇ·ｄ－１发生１例，０．７５·ｄ－１３例，１．０ｇ·ｄ－１１例。２．２　与用药时间的关系　全部头痛病例出现在用药后２～３ｈ，持续３～５ｈ后自然缓解。２．３　排除其它…     

影响边疆儿童白血病治疗的主要社会因素

我们将近７年来我院收治的白血病患儿及相关社会因素加以分析，报道如下：１ 资料及方法１．１ 一般资料：七年间我院收治的白血病患儿共９２例，均经骨髓检查确诊，其中急性淋巴细胞白血病７５例，急性非淋巴细胞白血病１７例。１．２ 回顾性分析９２例患儿坚持治疗及其与家庭经济状况，家长文化素质、社会保险（指儿童住院保险）情况的关系。１．２．１ 家庭经济状况分为好及差。城镇居民年平均每人纯收入大于４０６４．９３元为好，反之则为差。农民家庭年平均每人纯收入大于１０１０．９７元为好，反之为差［１］。１．２．２ 父母双方…     

左半结肠破裂一期修补外置10例体会

左半结肠破裂后为避免肠瘘，一般行近端造瘘，二期闭瘘术。近１０年来我院收治左半结肠破裂病人１０例，一期修补后将修补处外置于腹腔外，避免了二期手术，效果良好，报道如下。１ 临床资料 本组男７例，女３例，年龄２５－６２岁，平均４１岁。高处坠落伤２例，其中１例为降结肠末端损伤，裂口长约２．５ｃｍ，另１例为降结肠与乙状结肠交界处破裂，裂口长约２．０ｃｍ，医源性乙状结肠破裂１例，裂口长约１．０ｃｍ、车祸致伤４例，其中２例为降结肠末端破裂，裂口长分别为２．５ｃｍ和２．０ｃｍ。另２例为乙状结肠破裂，裂口长分别为２…     

利多卡因与甘露醇治疗眩晕症40例疗效观察

１９９８年１月～２０００年５月，我院采用利多卡因与甘露醇治疗４０例眩晕症，疗效较好。现报道如下：１资料与方法１．１临床资料：均为住院患者，年龄２５～５５岁，男女各一半，均有头晕、头痛、视物旋转、恶心、呕吐症状，８例同时伴有耳鸣，病程约１～２天，全部患者查体及实验室检查均无异常。１．２ 治疗方法：４０例患者均采用利多卡因 ０．２ｇ加入 １０％葡萄糖液５００ｍｌ 静脉滴注，２小时滴完，２０％甘露醇２５０ｍｌ静脉滴注，每日１次，连用３～４天。１．３ 疗效判断标准：患者眩晕症状消失为痊愈；缓解为好转；症状无…     

盐酸特拉唑嗪胶囊人体生物利用度及药物动力学研究

目的：对盐酸特拉唑嗪胶囊的人体内生物利用度进行研究。方法：单剂量口服盐酸特拉唑嗪胶囊和片剂２ｍｇ。血药浓度采用ＨＰＬＣ测定，数据用３Ｐ８７计算药动学参数。结果：盐酸特拉唑嗪胶囊剂的药动学参数：Ｋａ为８．２±４．０ｈ－１，Ｔ１／２为８．２±２．５ｈ，Ｔｍａｘ为０．６１±０．１１ｈ，Ｃｍａｘ为４３．５±８．５ｎｇ·ｍｌ－１，ＡＵＣ为３６７．４±３４．６ｎｇ·ｈ·ｍｌ－１；盐酸特拉唑嗪片剂的药动学参数：Ｋａ为６．４±７．４ｈ－１，Ｔ１／２为７．４±２．１ｈ，Ｔｍａｘ为０．９±０．４ｈ，Ｃｍａｘ为４３．１±４．８ｎｇ·ｍｌ－１，ＡＵＣ为３７１．３±４４．４ｎｇ·ｈ·ｍｌ－１。结论：两种剂型的药物动力学参数之间差异均无显著性（Ｐ＞０．０５），胶囊剂的相对生物利用度为９９．８８％。     

聚肌胞治疗婴幼儿秋季腹泻

秋季腹泻７５例，其中３０例（男性１６例，女性１４例；年龄１２±４ｍｏ）采用纠正水，电解质及酸碱平衡用药为对照组。另４５例（男性２６例，女性１９例；年龄１２±４ｍｏ）在与对照线相同的一般疗法外加用聚肌胞１－２ｍｇ／次，ｉｍ，ｑｏｄ共２－３次。结果：聚肌胞组业优于对照组（退热时间为１．０±０．７ｄｖｓ１．７±０．８ｄ；止泻时间为２．４±１．１ｄｖｓ４．１±１．２ｄ，Ｐ值均＜０．０１）。     

环丙沙星3种剂型在62名健康志愿者的药物动力学研究

用微生物测定法对环丙沙星３种剂型在６２名男性健康志愿者身上进行药物动力学研究。在１６名受试者静滴环丙沙星注射液（２００ｍｇ／１００ｍｌ）后，０、１、４、１２ｈ的血药浓度分别为３．６８±０．６３、≤１、０．３３～０．４３及０．１μｇ／ｍｌ，药动学参数Ｔ１／２为３．２４ｈ，总清除率３９３．５ｍｌ／ｍｉｎ，ＡＵＣ０～２４６．２１ｈ·μｇ／ｍｌ，Ｖｓｓ１５５．０±３４．２Ｌ。单次口服环丙沙星１００及５００ｍｇ，体内平均药动学参数Ｃｍａｘ分别为２．３１±０．２８及２．４９±０．２４μｇ／ｍｌ，Ｔｍａｘ分别为１．２６±０．１８及１．４７±０．２１ｈ，Ｔ１／２为２．６９±０．４８及３．８７±０．５３ｈ，ＡＵＣ０～２４为１２．８１±０．８５及１５．０２±２．１１ｈ·μｇ／ｍｌ，结果与文献报道相同。此外，对静滴及口服两种给药途径的血药浓度与临床疗效关系以及统计矩法与房室模型在药物动力学研究中的选用进行了讨论。     

盐酸纳洛酮舌下含片在犬体内的药代动力学及绝对生物利用度

本文采用高效液相色谱－电化学检测法研究了盐酸纳洛酮舌下含片在犬体内的药代动力学及绝对生物利用度。雄性犬８只，ｉｖ５ｍｇ盐酸纳洛酮后，血浆药物浓度的经时过程符合二室开放模型，分布半衰期（ｔ１／２α）为１２．０ｍｉｎ，消除半衰期（ｔ１／２β）为１４３．４ｍｉｎ，ＡＵＣ为７．９２ｍｇ（ｍｉｎ／Ｌ。犬给予５ｍｇ盐酸纳洛酮舌下含片后，血浆药物浓度的经时过程符合一级吸收二室开放模型，吸收较快，吸收半衰期（ｔ１／２Ｋａ）为１１．０ｍｉｎ，分布半衰期（ｔ１／２α）为１５．４ｍｉｎ，消除半衰期（ｔ１／２β）为１６４．１ｍｉｎ，达峰时间（Ｔｍａｘ）为２７．７ｍｉｎ，高峰浓度（Ｃｍａｘ）为３４．２ｎｇ／ｍｌ，ＡＵＣ为６．７９ｍｇ．ｍｉｎ／Ｌ，盐酸纳洛酮舌下含片的绝对生物利用度为８６．８（１０．９％。经统计学检验，两种途径给药后的ｔ１／２α、ｔ１／２β、（和（均无显著性差异（Ｐ＞０．０５）。上述结果表明，盐酸纳洛酮舌下含片在犬体内的处置过程与ｉｖ途径是相似的，生物利用度较高，预计在临床能产生较好的疗效     

兔血浆中延胡索乙素药代动力学的研究

延胡索乙素是中药元胡中镇痛作用较强的有效成分，为了解药动学与药效学的关系，本文采用灵敏度高，选择性强的胶束荧光法。研究了延胡索乙素在兔血浆中的药代动力学，实验结果表明，延胡索乙素在兔体内的代谢属于吸收快，消除慢，能保持较长时间内有镇痛作用的药物，其几个主要药动学参数为ｔ１．２（α）为１．９８ｈ，ｔ１／２（β）为１６．７ｈ，ｔ１／２（ｋａ）为０．７２０ｈ，Ｋ２１为０．２３８ｈ＾－＾１，Ｋ１０为０．０     

后牙牙髓塑化治疗后疗效观察

笔者针对本地区患者口腔保健意识差，早期牙髓病变不能及时治疗，从而并发不可复性牙髓炎，急慢性根尖周炎等症。采用牙髓塑化治疗，１年后复查，现将疗效报告如下。１ 资料与方法１．１ 一般资料：患者２９４人，患牙共３０７颗。其中男１５８人，女１３６人，年龄３５～７０岁，所治患牙全部为磨牙、前磨牙。患者为根尖周炎．根尖病变破坏不超过根尖 １／２者；牙髓坏死；残髓炎；逆行性牙髓炎。１．２ 方法：按常规行塑化治疗操作，塑化剂为酚醛树脂，其配方为第二版医学院口腔内科学教材。治疗结束后１年进行复查。２ 结果２．１ 疗效标…     

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.