枯草杆菌二联活菌肠溶胶囊联合地衣芽胞杆菌活菌胶囊治疗老年抗生素相关性腹泻的效果分析

目的探讨枯草杆菌二联活菌肠溶胶囊联合地衣芽胞杆菌活菌胶囊对老年抗生素相关性腹泻的临床疗效。方法收集2013年2月~2014年2月本院老年抗生素相关性腹泻患者120例,根据随机数字表法分为枯草杆菌二联活菌肠溶胶囊组、地衣芽胞杆菌活菌胶囊组、枯草杆菌二联活菌肠溶胶囊和地衣芽胞杆菌活菌胶囊联合组各40例。比较3组的治疗效果。结果联合组1个月内的腹泻治愈率高于枯草杆菌二联活菌肠溶胶囊组及地衣芽胞杆菌活菌胶囊组,差异有统计学意义(χ2=8.26,P=0.02)。联合组未愈患者1个月内的腹泻次数明显低于枯草杆菌二联活菌肠溶胶囊组及地衣芽胞杆菌活菌胶囊组,差异有统计学意义(F=91.03,P=0.00)。结论枯草杆菌二联活菌肠溶胶囊以及地衣芽胞杆菌活菌胶囊均为益生菌类药物,对治疗老年人抗生素相关性腹泻有一定的疗效,但是枯草杆菌二联活菌肠溶胶囊联合地衣芽胞杆菌活菌胶囊对老年抗生素相关性腹泻的疗效更显著,对于临床治疗有一定的协助作用。     

阿莫西林舒巴坦匹酯片工艺研究

目的　对阿莫西林舒巴坦匹酯片进行工艺研究。方法　采用正交试验设计法 ,以片剂溶出度为指标 ,筛选制剂最优处方 ,通过加速试验、长期试验考察工艺的稳定性。结果　最佳处方为微晶纤维素 4 0 %,乳糖 2 0 %,干法制粒压片。通过筛选处方所试制的 3批样品 ,加速试验在 4 0℃± 2℃、RH 75 %± 5 %条件下放置 6个月 ,长期试验在 2 5℃± 2℃、RH6 0 %± 10 %条件下放置 2 4个月 ,考察主要质量指标无明显变化。结论　正交试验设计的处方工艺、质量稳定 ,可用于工业生产。     

地衣芽孢杆菌对Ⅲ/Ⅳ期CapeOX化疗结直肠癌患者胃肠道功能及免疫功能影响

目的:探讨地衣芽孢杆菌活菌胶囊对Ⅲ/Ⅳ期CapeOX化疗结直肠癌患者胃肠道功能及免疫功能的影响.方法:将我院收治的经病历确诊的Ⅲ/Ⅳ期结直肠癌患者100例随机分为2组,每组50例.实验组:采用地衣芽孢杆菌活菌胶囊联合奥沙利铂+卡培他滨(CapeOX)化疗方案.在化疗前1天口服地衣芽孢杆菌活菌胶囊,口服5天.对照组:使用奥沙利铂+卡培他滨(CapeOX)化疗.2组患者在化疗前后分别检测血液中CD3+、CD4+、CD8+、CD4+/CD8+等免疫功能指标以及血液中二胺氧化酶、细菌内毒素等肠道屏障功能指标,以评价2组患者化疗后的胃肠道功能及免疫情况,从而评估地衣芽孢杆菌活菌胶囊对CapeOX化疗的辅助作用.结果:地衣芽孢杆菌活菌胶囊联合CapeOX化疗后血液中CD8+水平、二胺氧化酶、细菌内毒素等指标水平较对照组低(P<0.05);采用地衣芽孢杆菌活菌胶囊对CapeOX化疗后患者血液中CD3+、CD4+水平较对照组明显升高,较化疗前升高,两组具有统计学差异(P<0.05).结论:CapeOX方案化疗对肠道屏障功能具有损伤作用;地衣芽孢杆菌活菌胶囊对结直肠癌患者CapeOX方案化疗后的免疫功能及胃肠道有一定的改善作用.     

四联活菌肠溶胶囊治疗慢性腹泻的疗效研究

目的:临床验证双歧杆菌、肠球菌、乳杆菌和芽孢杆菌四联活菌肠溶胶囊治疗慢性腹泻的疗效及安全性。方法:采用多中心、随机、盲法平行对照研究方法。试验组124例给予双歧杆菌、肠球菌、乳杆菌和芽孢杆菌四联活菌肠溶胶囊治疗,对照组80例给予双歧三联活菌胶囊(含长型双歧杆菌、嗜酸乳杆菌和粪肠球菌)治疗,疗程14d,观察腹泻缓解时间及腹泻伴随症状(腹痛、腹胀、里急后重等)变化。结果:试验组3d时腹泻缓解率为41.13%,优于对照组的11.25%(P<0.05);疗程结束时试验组腹泻缓解率为90.32%,大便成形率为75.81%,腹泻伴随症状明显下降,与对照组比较有显著性差异(P<0.05)。结论:双歧杆菌、肠球菌、乳杆菌和芽孢杆菌四联活菌肠溶胶囊治疗慢性腹泻安全、有效。     

雷贝拉唑钠肠溶胶囊处方研究及稳定性考察

目的：筛选雷贝拉唑钠肠溶胶囊处方进行并考察其稳定性。方法：采用挤出滚圆和流化床包衣工艺制备雷贝拉唑钠肠溶微丸,采用L₉(3₄)正交试验设计进行载药微丸处方优化,按选定的处方制备微丸,进行隔离层和肠溶层包衣,包衣后将微丸灌装胶囊,成10mg规格,对制备的胶囊进行加速试验确定其稳定性。结果：制备的雷贝拉唑钠肠溶胶囊含量,有关物质,释放度较好,加速条件下质量稳定,稳定性较好。 结论：本工艺简单可行,样品稳定性良好,可作为雷贝拉唑钠肠溶胶囊的制备工艺。     

醋酸溴茶碱胶囊的稳定性研究

目的:探讨醋酸溴茶碱胶囊的稳定性与药品质量控制方法.方法:以性状、内容物色泽、含量、降解产物、溶出度、水分等稳定性重点考察项目,进行强光照射、高温、高湿、加速、长期试验等稳定性考察.结果:样品在(4500±500)Lx强光照射、60℃高温10天后内容物为类白色,含量略降低,有关物质增大.室温暴露空气、相对湿度(RH)=75％高湿10天后、RH=92.5％高湿10天后内容物仍为类白色.在(40±2)℃,RH=(75±5)％的条件下放置6个月及在(25±2)℃,RH=(60±10)％的条件下放置12个月,各项指标均无明显变化.结论:醋酸溴茶碱胶囊样品避光密封贮存,模拟有效期2年内内置阴凉处保存稳定性符合胶囊剂要求,本研究方法适用于胶囊剂的稳定性考察.     

流式细胞术和平板计数法用于地衣芽孢杆菌活菌制剂检测的比较研究

目的 考察流式细胞技术和平板计数法2种方法检测地衣芽孢杆菌活菌制剂（片剂、颗粒剂和胶囊剂）中芽孢数的不同。方法 分别采用BD FACSMicroCount全自动微生物分析系统和平板计数法检测不同水浴温度及不同水浴时间处理过的地衣芽孢杆菌活菌胶囊中的芽孢数。同时采用上述2种方法检测3种地衣芽孢杆菌活菌制剂（片剂、颗粒剂和胶囊剂）中的活菌数、芽孢数和芽孢率。结果 流式细胞技术和平板计数法对于检测不同水浴温度及不同水浴时间处理过的地衣芽孢杆菌活菌胶囊中的芽孢数无显著性差异。采用上述2种方法检测的3种地衣芽孢杆菌活菌制剂（片剂、颗粒剂和胶囊剂）中的活菌数、芽孢数和芽孢率的结果比较均无显著性差异。结论 流式细胞技术和平板计数法对于3种地衣芽孢杆菌活菌制剂（片剂、颗粒剂和胶囊剂）检测活菌数、芽孢数和芽孢率无显著性差异。     

基于临床综合评价维度的地衣芽孢杆菌活菌胶囊价值分析

目的:对地衣芽孢杆菌活菌(0.5 g规格)胶囊进行价值分析，为药品供应保障决策和临床合理用药提供一定的信息支持。方法:遵循《药品临床综合评价管理指南(2021年版试行)》推荐的6个评价维度，收集临床诊疗指南(含专家共识)、循证医学研究、药品说明书，以及真实世界药品价格、采购、销售数据，采用定性和定量分析方法进行比较。结果:在腹泻相关疾病、消化性溃疡和便秘等疾病的治疗中，地衣芽孢杆菌活菌(0.5 g规格)胶囊安全性良好，与双歧杆菌三联活菌和枯草杆菌二联活菌相比有一定的有效性优势，其月均药物治疗成本与地衣芽孢杆菌活菌其他剂型、规格品种相比基本一致或偏低，与相关口服益生菌制剂基本处于较低水平；在药品有效期和储存/运输条件、最小制剂单位活菌含量、给药便利性以及菌种适宜性等方面具有良好的临床适宜性，可负担性和可获得性较好；此外，该药作为我国自主研发的微生态活菌制剂具有一定的创新性。结论:地衣芽孢杆菌活菌(0.5 g规格)胶囊具有较好的临床价值，建议进一步丰富该品种在中国真实世界临床使用数据/证据。     

3种微生态制剂对抗菌药物的敏感性检测

目的 检测常用微生态制荆双歧杆菌四联活菌片、地衣芽孢杆菌活菌胶囊、酪酸梭菌活菌片对16种抗菌药物的敏感性.方法 从3种微生态制剂中培养并分离供试菌,用微生物鉴定分析仪和药敏纸片进行药物敏感性检测.结果 双歧杆菌四联活菌片对抗菌药物均敏感;地衣芽孢杆菌活菌胶囊对青霉素类、头孢菌素类、红霉素、克林霉素有不同程度的耐药,对氨基苷类、喹诺酮类等抗菌药物敏感;酪酸梭菌活菌片对头孢菌素类、氨基苷类、复方新诺明耐药,对青霉素类、红霉素、克林霉素、喹诺酮类等抗菌药物敏感.结论 根据药物敏感性试验,地衣芽孢杆菌活菌胶囊、酪酸梭菌活菌片可以与耐药的抗菌药物联用,双歧杆菌四联活菌片与抗菌药物有配伍禁忌,避免联用,必须联用时应错开服用时间.     

四联活菌肠溶胶囊治疗慢性腹泻的疗效评价

目的探讨四联活菌肠溶胶囊（双歧杆菌、乳杆菌、肠球菌、芽孢杆菌）治疗慢性腹泻的临床疗效及安全性。方法将284例慢性腹泻患者随机分为两组,其中观察组142例接受四联活菌肠溶胶囊治疗;对照组142例接受双歧三联活菌肠溶胶囊（长型双歧杆菌、嗜酸乳杆菌、粪肠球菌）治疗。所有患者的疗程均为14d。结果 （1）观察组患者的治疗效果显著优于对照组,两组患者之间治疗效果的比较差异有统计学意义（P〈0.05）。（2）观察组与对照组不良反应发生率分别为9.9%（14/142）、8.5%（12/142）,两组患者的不良反应发生率相比差异无统计学意义（P〉0.05）。结论四联活菌肠溶胶囊治疗慢性腹泻的疗效确切,是治疗慢性腹泻的理想手段。     

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.     

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.     

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.