二甲双胍分别联合西格列汀及吡格列酮对2型糖尿病患者血糖、胰岛β细胞功能和胰岛素抵抗的影响

目的:探讨二甲双胍联合西格列汀及二甲双胍联合吡格列酮分别治疗2型糖尿病对血糖及胰岛素的影响。方法:选取2016年8月—2019年1月于我院内分泌科治疗的2型糖尿病患者90例,随机分为两组(西格列汀组和吡格列酮组),每组45例。西格列汀组行二甲双胍和西格列汀联合治疗,吡格列酮组行二甲双胍和吡格列酮联合治疗,两组均连续治疗6个月。比较分析两组治疗前后空腹血糖、糖化血红蛋白、空腹胰岛素、餐后2 h胰岛素、胰岛素抵抗指数及胰岛β细胞功能指数。结果:治疗后,两组空腹血糖、糖化血红蛋白及胰岛素抵抗指数均降低,且西格列汀组低于吡格列酮组(P<0.05);两组空腹胰岛素、餐后2 h胰岛素及胰岛β细胞功能指数均升高,且西格列汀组高于吡格列酮组(P<0.05)。结论:联合二甲双胍用药,西格列汀治疗2型糖尿病对血糖及胰岛素水平的改善优于吡格列酮。     

二甲双胍联合吡格列酮及磷酸西格列汀治疗2型糖尿病的疗效观察

目的观察二甲双胍分别联合吡格列酮及磷酸西格列汀对治疗2型糖尿病的临床疗效。方法选择30例服用二甲双胍500mg和吡格列酮15mg（卡优平）12周以上的患者,改为每天服用二甲双胍缓释片1g及磷酸西格列汀100mg持续治疗12周。结果二甲双胍联合磷酸西格列汀对空腹血糖（FBG）、糖化血红蛋白（HbAlc）、空腹胰岛素（FINS）、餐后2h血糖（2hBG）及低血糖发生率均显著下降（P〈0．05）。结论二甲双胍联合磷酸西格列汀在血糖控制,低血糖发生率,减少体重增加的风险方面优于二甲双胍联合吡格列酮。     

联合用药治疗2型糖尿病的临床观察

目的探讨比较吡格列酮、二甲双胍二药联用和吡格列酮、二甲双胍、伏格列波糖三药联用治2型糖尿病的疗效及安全性。方法76例对磺脲类+双胍类药物治疗失败后的2型糖尿病患者,随机分为治疗组、对照组各38例,停用磺脲类,治疗组用吡格列酮30 mg/d、伏格列波糖0.6 mg/d、二甲双胍1.5 g/d三药联用,对照组用同样剂量的二甲双胍和吡格列酮,两组均治疗6个月,监测治疗前、后两个时间节点的空腹、餐后2 h血糖、糖化血红蛋白、空腹胰岛素,肝功能、肾功能,计算胰岛素抵抗指数(IR)。结果空腹、餐后2 h血糖、糖化血红蛋白,胰岛素抵抗指数,治疗前两组指标比较差异无统计学意义(P>0.05);治疗后两组指标与治疗前比较差异均有的统计学意义(bP<0.05),治疗组更显著(aP<0.01);治疗后组间指标比较变化差异有统计学意义(cP<0.05)。空腹胰岛素:治疗前后两组指标比较差异无统计学意义(eP>0.05)。没有发现心力衰竭、严重肝肾损害、血尿和骨质疏松等严重不良反应。结论二甲双胍、吡格列酮联用是治疗磺脲类+双胍类药物治疗失败后的2型糖尿病的有效方法,加用伏格列波糖三联合用可取得更好的疗效。     

吡格列酮治疗2型糖尿病的临床疗效观察

目的观察吡格列酮单用及分别与二甲双胍、格列美脲联用治疗2型糖尿病的临床疗效及不良反应。方法 2型糖尿病患者93例,随机分为3组各31例:单用吡格列酮治疗组给予吡格列酮口服控制血糖治疗;吡格列酮联合二甲双胍控制血糖治疗;吡格列酮联合格列美脲控制血糖治疗。观察3组患者在空腹血糖(FBG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)等指标的变化情况及药物不良反应。结果治疗8周后,3组患者在控制FBG、2hPBG、HbA1c各项指标达标率方面均取得较好疗效,联合用药治疗组的指标达标率均高于单用吡格列酮治疗组,但联合用药组不良反应发生率亦较单用吡格列酮治疗组不良反应发生率增高。结论吡格列酮单用能较好的控制2型糖尿病患者的血糖水平,与格列美脲或二甲双胍合用在控制2型糖尿病的血糖方面则取得更好的临床疗效,但合用组易发生低血糖不良反应,尤以吡格列酮与格列美脲联用为明显。     

盐酸吡格列酮联合二甲双胍治疗2型糖尿病的安全性及疗效观察

目的:探究盐酸吡格列酮联合二甲双胍治疗2型糖尿病的安全性及治疗效果。方法:选取2017年4月至2018年4月在我院诊治的16名2型糖尿病患者,将其无规律划分为常规组与实验组,每组8名。常规组服用二甲双胍治疗,而实验组除了服用二甲双胍治疗外,新增口服药物盐酸吡格列酮,比较两组患者用药后的血红蛋白指标与血糖指标。结果:实验组患者用药后的血红蛋白指标(HbAlc)以及空腹血糖(FBG)、餐后2h小时血糖(2hBG)两个血糖指标均明显低于常规组患者,P0.05,有统计学意义。结论:综上所述,盐酸吡格列酮联合二甲双胍治疗2型糖尿病的治疗效果理想,不仅能够降低患者体内血糖水平、还能减少患者发生不良反应的几率,具有令人满意的安全性功能,是值得推广的血糖控制方案。     

2型糖尿病胰岛素抵抗应用吡格列酮和二甲双胍疗效的比较

目的 观察吡格列酮和二甲双胍治疗对2型糖尿病患者胰岛素抵抗(IR)的影响.方法 2型糖尿病患者50例一般治疗方案下,随机分为吡格列酮组及二甲双胍组,治疗疗程为12周.结果 吡格列酮组和二甲双胍组在治疗后空腹和餐后C肽水平均较用药前有明显降低,IR稍有降低,β细胞功能明显改善,吡格列酮在降低餐后胰岛素、改善IR方面优于二甲双胍,两药治疗前后血游离脂肪酸水平未见统计学差异.结论 吡格列酮和二甲双胍均有降低IR和改善β细胞功能,在降IR方面,吡格列酮优于二甲双胍.     

吡格列酮、瑞格列奈和二甲双胍对初发2型糖尿病患者血尿酸及肾功能的影响

目的比较吡格列酮、瑞格列奈和二甲双胍对初发2型糖尿病患者的血糖、血尿酸及肾功能的影响。方法选取75名初发2型糖尿病合并高尿酸血症患者,每组25人,监测、分析3种药物12周治疗前后空腹血糖、餐后2 h血糖、糖化血红蛋白（HbA1c）、血尿酸、尿微量白蛋白（MAU）、尿素氮（BUN）、肌酐（Cr）、总胆固醇（TC）和甘油三酯（TG）。结果吡格列酮组试验后空腹血糖、餐后2 h血糖、HbA1c、血尿酸、MAU、BUN、Cr、TC和TG均较试验前下降（P〈0.05）。瑞格列奈组试验后空腹血糖、餐后2 h血糖、HbA1c均较试验前显著下降（P〈0.05）。二甲双胍组试验后空腹血糖、餐后2 h血糖、HbA1c、TC、TG和MAU较试验前下降（P〈0.05）。瑞格列奈组试验后空腹血糖、餐后2 h血糖和HbA1c均低于吡格列酮组和二甲双胍组（P〈0.05）。吡格列酮组降低血尿酸改善肾功能的作用显著高于瑞格列奈组和二甲双胍组（P〈0.05）。吡格列酮组对尿微量白蛋白的影响比二甲双胍组显著（P〈0.05）。结论瑞格列奈的降糖作用最强。吡格列酮显著降低血尿酸,改善肾功能。2型糖尿病初发患者,同时伴有肾病、高尿酸血症或痛风时,宜选用吡格列酮。     

吡格列酮和二甲双胍对2型糖尿病肥胖患者胰岛素抵抗的影响

目的:观察吡格列酮和二甲双胍对2型糖尿病肥胖患者胰岛素抵抗(IR)的影响。方法:2型糖尿病肥胖患者50例,在饮食和运动治疗基础上随机分为吡格列酮组及二甲双胍组,疗程12周。结果:二甲双胍组和吡格列酮在治疗后空腹和餐后 C 肽水平均较用药前有明显降低、IR 亦有降低、β细胞功能明显改善。吡格列酮在降低餐后胰岛素、改善 IR 方面优于二甲双胍,两药物治疗前后血游离脂肪酸水平未见统计学差异。结论:二甲双胍和吡格列酮都可降低 IR 和改善β细胞功能,在降低 IR 方面,吡格列酮优于二甲双胍。     

二甲双胍联合西格列汀或吡格列酮对肥胖型2型糖尿病的疗效比较

目的：比较西格列汀与吡格列酮分别联用二甲双胍治疗二甲双胍单药控制不佳的肥胖型2型糖尿病的疗效。方法：60例2型糖尿病肥胖患者在服用二甲双胍片的前提下,随机分为西格列汀组（n=30）和吡格列酮组（n=30）,分别给予西格列汀片与吡格列酮片口服,检测入组时和治疗12周后两组糖化血红蛋白、空腹及餐后血糖水平、低血糖例数、体重指数等数据。结果：治疗12周后,西格列汀组患者的糖化血红蛋白、空腹及餐后血糖、体重指数均比吡格列酮组改善明显,两组均无低血糖发生。结论：西格列汀联用二甲双胍片治疗肥胖型2型糖尿病的疗效优于吡格列酮片联用二甲双胍片。     

吡格列酮联用二甲双胍治疗2型糖尿病的疗效及安全性分析

目的:评价吡格列酮联用二甲双胍治疗2型糖尿病的临床疗效及安全性。方法:将102例2型糖尿病患者随机分为2组,治疗组采用吡格列酮联用二甲双胍治疗,对照组单用二甲双胍治疗,比较2组血糖和胰岛素指标的变化。结果:连用6个月后2组空腹血糖(FPG)、餐后2h血糖(P2hBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、餐后2h胰岛素(P2hINS)、稳态胰岛素评价指数(HOMA-IR)水平均明显降低,与治疗前比较差异均有统计学意义(P<0.05);但治疗组治疗后FPG、P2hBG、HbA1c、FINS、P2hINS、HOMA-IR水平明显低于同期对照组水平,2组比较差异有统计学意义(P<0.05);2组不良反应少,均未见严重不良反应。结论:吡格列酮联用二甲双胍治疗2型糖尿病,能够明显降低血糖水平,改善胰岛素状态,且不良反应少。     

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.