β-内酰胺酶抑制剂他唑巴坦的合成

目的：合成他唑巴坦。方法：以6－氨基青霉烷酸（6－APA）为原料，经溴化，酯化，氧化并脱溴成亚砜后，与三唑反应，再氧化，脱保护基得他唑巴坦。结果：使用30％双氧水氧化生成亚砜，与2－三甲基硅－1，2，3－三唑反应生成2α－甲基－2β－（1，2，3－三唑－1－基）甲基青霉烷－3α－羧酸二苯甲酯，结论：该方法缩短了反应路线，操作简便，总收率24％。     

青霉素氧化产物的鉴别及其转化方法

用过氧乙酸氧化青霉素Ｇ钾工业直力量以一个不同正常熔点的低熔点氧化产物，薄层层析、高效液相色谱分析，ＩＲ、Ｈ－ＮＭＲ、ＦＡＢ－ＭＳ、热重分析和元素分析的研究结果表明，此氧化产物为带两个结晶水的青霉素Ｇ亚砜。本文对带结晶水的青霉素Ｇ亚砜转化为无水青霉素Ｇ亚砚进行了研究。本文为青霉素Ｇ亚砚中间体质量标准的确定提供依据。确保得到合格的青霉素Ｇ亚砜。     

由硫醚制备亚砜

硫醚于六氟－２－丙醇中，被两倍摩尔比的３０％双氧水溶液室温氧化成亚砜，反应时间为５～２０ｍｉｎ，１０例收率８２％～９９％。该法的选择性与所用溶剂有关，不会形成砜类副产物，对双键无影响。由硫醚制备亚砜@金卫东     

青霉烷酸对甲氧基苄酯—1α—亚砜的合成方法改进

以6－APA为起始原料，经溴化得6，6－溴青霉烷酸，用11％－13％的过氧乙酸氧化，所得的氧化产物3以固体形式直接从溶液中析出，3以对甲氧基溴苄进行羧基保护，经还原合成了β－内酰胺酶抑制剂他唑巴坦的关键中间体青霉烷酸对甲氧基苄酯－1α－亚砜1。本方法操作简便，价格低廉，实施安全，适宜于规模生产。     

青霉烷酸二苯甲酯亚砜合成工艺改进

6－APA经液溴二溴化得到6,6－二溴青霉烷酸; 再由35％－40％过氧乙酸氧化及二苯腙酯化得到6,6－二溴青霉烷酸二苯甲酯亚砜;最后经锌粉脱二溴得到青霉烷酸二苯甲酯亚砜。     

6α—溴—青霉烷酸二苯甲酯亚砜两种异构体的合成

６α－溴－青霉烷酸二苯甲酯以活性二氧化锰或６％￣８％的过氧乙酸氧化,得到６α－溴－１α（或１β）－青霉烷亚砜二苯甲酯。     

硫醚制备亚砜的简便方法

硫醚制备亚砜的简便方法ＦｒｉｎｇｕｅｌｌｉＦ等［ＳｙｎＣｏｍｍｕｎ，１９９３；２３：３１５７］硫醚使用叔丁基化过氧氢，在硫酸水溶液中，选择性地被氧化成亚砜。反应速度快，条件温和，且无污染。９例收率９５％～１００％。［解文波摘］硫醚制备亚砜的简便方法...     

降钙素基因相关肽的合成

降钙素基因相关肽是由３７个氨基酸残基组成，并有一对二硫键的生物活性多肽，本文采用固相合成方法，以Ｆｍｏｃ－氨基酸为原料，经ＨＢＴＵ－ＨＯＢＴ－ＮＭＭ综合合，三氟乙酸－本甲硫醚－三甲基溴硅烷脱保护，分别用铁氰化钾和二甲亚砚氧化形成二硫键，经ＰＲ－ＨＰＬＣ纯化，获得了ＲＰ－ＨＰＬＣ分析为单一峰的目的，目的肽的质谱和氨基酸组成分析结果均与理论值相符，同时具有较强物降血压生理活怀。     

差示分光光度法测定菲咳露中盐酸异丙嗪的含量

盐酸异丙嗪以氧化剂（Ｈ２Ｏ２－ＨＡｃ）氧化后生成亚砜衍生物与未经氧化处理的溶液，在同一波长处存在差示吸收。其差示光谱在３３８ｎｍ波长处有最大吸收，可排除其他２成分的干扰。在１０－５０μｇ／ｍｌ浓度范围内线性关系良好，相关系数ｒ＝０．９９９９，平均回收率为９９．２７％，相对标准偏差为０．３０％。     

硫醚和亚砜用次氯酸钠氧化生成砜

硫醚和亚砜用次氯酸钠氧化生成砜ＫｈｕｒａｒｉａＪＭ等［ＯｒｇＰｒｅｐＰｒｏｃｅｄ，１９９６；２８：２３４］硫醚或亚砜用次氯酸钠在乙腈中氧化，室温搅拌５～６０ｍｉｎ可生成其相应的砜硫醚８例收率５５～９８％，亚砜６例收率７２～９５％。［邓爱凤摘］硫醚和亚...     

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.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.