糖化血红蛋白、尿微量白蛋白、尿微量白蛋白/尿肌酐比值联合检测在早期糖尿病肾病诊断和治疗中的价值

目的:探讨糖化血红蛋白(Hb A1c)、尿微量白蛋白(Um Alb)、尿微量白蛋白/尿肌酐比值(Um Alb/UCr)联合检测在早期糖尿病肾病诊断和治疗中的价值。方法:选取116例糖尿病患者为观察组和86例健康体检者为对照组(N组)分别检测Hb A1c,Um Alb,Um Alb/UCr,并对观察组治疗前后及对照组应用统计学方法进行分析。将观察组根据Hh AI c的水平分为4组:A组(Hb A1c4.8%±1.0%)B组(Hh Alc6.5%±0.6%)C组(Hb A1c8.1%±1.0%)D组(Hh Alc10.1%±1.3%)。结果:糖尿病患者观察组Hb A1c,Um Alb,Um Alb/UCr较正常对照组显著升高(P<0.05),随着Hb A1c的升高糖尿病患者Um Alb,Um Alb/UCr升高更明显,且三项联合检测阳性率明显高于单项检测阳性率,经治疗后Hb A1c,Um Alb,Um Alb/UCr结果显著降低(P<0.05)。结论:Hb A1c,Um Alb,Um Alb/UCr联合检测提高了早期糖尿病肾病诊断的敏感性,对于早期糖尿病肾病的诊断和治疗有着非常重要的价值.     

百令胶囊联合利拉鲁肽治疗早期糖尿病肾病的疗效观察

目的探讨百令胶囊联合利拉鲁肽治疗早期糖尿病肾病的临床效果。方法选取2014年1月—2015年2月佛山市高明区人民医院内分泌科收治的早期糖尿病肾病患者160例,随机分为对照组和治疗组,每组各80例。对照组皮下注射利拉鲁肽注射液,第1周0.6 mg/d,第2周1.2 mg/d,第3周1.8 mg/d,此后维持1.8 mg/d。治疗组在对照组治疗基础上口服百令胶囊,2粒/次,3次/d。两组均连续治疗2个月。观察两组的临床疗效,同时比较两组治疗前后体质量指数(BMI)、总胆固醇(TC)、三酰甘油(TG)、24 h尿白蛋白定量(Upr)、血尿素氮(BUN)、血肌酐(Scr)、空腹血糖(FBG)、糖化血红蛋白(Hb A1c)、膀胱抑素C(Cys C)、尿微量白蛋白(m Alb)的变化。结果治疗后,对照组和治疗组的总有效率分别为80.00%、91.25%,两组比较差异具有统计学意义(P0.05)。治疗后,两组BMI、TC、Upr、BUN、Scr、Hb A1c、Cys C、m Alb较治疗前显著下降,同组治疗前后差异均有统计学意义(P0.05),且治疗组这些观察指标的改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后两组TG、FBG均显著降低,同组治疗前后差异均有统计学意义(P0.05),但治疗后两组比较差异无统计学意义。对照组和治疗组的不良反应发生率分别为15.00%、3.75%,两组比较差异具有统计学意义(P0.05)。结论百令胶囊联合利拉鲁肽治疗早期糖尿病肾病具有较好的临床效果,能改善患者的脂代谢、糖代谢及肾功能相关指标,且安全性较高,具有一定的临床推广应用价值。     

大补元煎治疗早期糖尿病肾病的疗效观察

目的探讨大补元煎联合西药治疗早期糖尿病肾病的临床疗效。方法将我院2012年3月~2014年9月门诊及住院治疗的122例早期糖尿病肾病患者随机分为对照组和治疗组。对照组57例,给予西药合理控制血糖、血压、血脂等综合治疗。治疗组65例,使用大补元煎联合上述西药治疗。观察两组患者治疗前后的尿微量白蛋白排泄率(UAER)、胱抑素C(Cys C)、血清肌酐(Scr)、糖化血红蛋白(Hb A1c)、甘油三脂(TG)、胆固醇(TC)的变化。所有患者疗程均为60d。结果两组患者治疗后的UAER、Cys C、Scr、Hb A1C、TG、TC水平较治疗前均有改善,治疗前后差异有统计学意义(P0.05)。但是,治疗组疗效明显优于对照组,组间比较差异有显著统计学意义(P0.01)。结论大补元煎联合西药治疗早期糖尿病肾病可以明显提高临床疗效。     

西格列汀对糖尿病合并肾损伤患者肾功能及γ-谷氨酰转移酶的影响

目的观察西格列汀对糖尿病合并肾损害患者肾功能及γ-谷氨酰转移酶(γ-GT)等指标的影响。方法选择早期2型糖尿病合并肾损伤且血糖控制不佳的患者67例,随机分为两组,西格列汀组32例,对照组35例。在原治疗方案的基础上,西格列汀组加用西格列汀片100 mg,每日1次;对照组可增加药物剂量或联合除二肽基肽酶4抑制剂外的降糖药物。观察时间均为12周。治疗前后检测患者空腹血糖(FPG)、糖化血红蛋白(Hb A_(1c))、β_2微球蛋白(β_2-MG)、血尿素氮(BUN)、胱抑素C(Cys C)、血肌酐(Cr)、γ-GT水平,并观察不良反应发生情况。结果治疗前两组各项指标比较差异均无显著意义(P>0.05)。治疗12周后,两组FPG和Hb A1c均下降,与治疗前比较差异显著(P<0.05),组间比较无显著差异(P>0.05)。对照组Cr、BUN、β_2-MG、Cys C、γ-GT无明显变化(P>0.05),而西格列汀组以上指标均降低(P<0.05),且低于对照组(P<0.05)。两组均无明显不良反应发生。结论西格列汀治疗糖尿病合并肾损害患者,可以降低γ-GT等指标,改善肾功能。     

沙格列汀单用或联合替米沙坦对2型糖尿病肾损害患者血清胱抑素C和白细胞介素18水平的影响

目的观察沙格列汀单用或联合替米沙坦对早期2型糖尿病肾病患者血清胱抑素C(Cys C)和白细胞介素18(IL-18)水平的影响。方法 120例早期糖尿病肾病患者随机分为三组,每组40例。在原有生活方式、治疗方案的基础上,沙格列汀组加用沙格列汀片5 mg,po,qd;替米沙坦组加用替米沙坦片40 mg,po,qd;联合用药组加用沙格列汀和替米沙坦片,用法剂量同前;三组疗程均为12周。观察治疗前后各组糖化血红蛋白(HbA1c)、24 h尿白蛋白排泄率(UAER)、血肌酐(Cr)、血尿素(UA)、血清CysC和IL-18水平的变化。结果治疗后,三组患者UAER、Cr、UA及血清Cys C和IL-18水平均较治疗前下降(P<0.05),联合用药组下降幅度大于其他两组(P<0.05),沙格列汀组与替米沙坦组间无显著差异(P>0.05)。沙格列汀组、联合用药组患者治疗后Hb A1c降低(P<0.05),组间无显著差异(P>0.05),替米沙坦组患者Hb A1c无明显变化(P>0.05)。沙格列汀组不良反应发生率2%,替米沙坦组5%,联合用药组10%,组间差异无显著意义(P>0.05)。结论沙格列汀单用或联合替米沙坦均可改善早期2型糖尿病肾病患者的血糖与肾功能,联合应用效果更佳,降低此类患者的血清CysC和IL-18水平可能为其作用机制之一。     

贝那普利联合阿托伐他汀治疗早期糖尿病肾病的临床分析

目的探讨贝那普利联合阿托伐他汀治疗早期糖尿病肾病的临床效果。方法将早期糖尿病肾病患者70例分为对照组与观察组。对照组行贝那普利治疗,观察组加用阿托伐他汀治疗。结果观察组患者治疗有效率为88.57%,高于对照组患者的71.43%;观察组患者不良反应发生率为8.57%,低于对照组的25.71%(P<0.05);治疗前两组患者UAER(尿蛋白排泄率)、ACR(尿白蛋白/肌酐比值)、Hb A1c(血清糖化血红蛋白)、CRP(C反应蛋白)对比无明显差异(P>0.05),治疗后观察组患者UAER、ACR、Hb A1c、CRP改善情况明显优于对照组(P<0.05)。结论贝那普利联合阿托伐他汀治疗早期糖尿病肾病的效果显著。     

健脾通络方联合缬沙坦治疗早期糖尿病肾病临床研究

目的 观察健脾通络方联合缬沙坦治疗早期糖尿病肾病(DN)的临床疗效.方法 60例早期DN患者随机分为治疗组和对照组各30例,治疗组采用健脾通络方联合缬沙坦胶囊治疗,对照组单用缬沙坦胶囊治疗,两组均治疗12周,比较两组治疗前后尿白蛋白排泄率(UAER)、尿β2微球蛋白(β2-GM)、血清肌酐(Scr)、糖化血红蛋白、血脂、平均动脉压(MAP)等变化.结果 治疗后,两组UAER、尿β2-GM、MAP均较治疗前明显下降(t =2.413、2.505、2.815、2.446、2.581、2.769,均P＜0.01),治疗组较对照组下降更为显著(t =2.663、2.410、2.761,均P＜0.01);两组Scr、HbA1c等治疗前后无明显变化(均P＞0.05).结论 健脾通络方联合缬沙坦胶囊治疗早期DN疗效确切,可有效减低DN患者白蛋白尿.     

联合检测尿微量白蛋白/肌酐及血清胱抑素C对2型糖尿病早期肾损伤的临床诊断价值

目的探讨尿微量白蛋白/肌酐和血清胱抑素联合检测对2型糖尿病早期肾损伤的诊断价值。方法研究对象选取为133例2型糖尿病患者及45例健康体检者,其中尿蛋白阴性且合并2型糖尿病患者75例设为A组,尿蛋白弱阳性且合并2型糖尿病患者45例设为B组,健康体检者45例设为C组,对三组受检者的血清尿素氮及肌酐水平进行测定对比。结果 A组和B组U-m Alb/Cr及Cys C水平均明显高于C组(P0.05),且B组与A组比较,差异有统计学意义(P0.05)。A组中通过血清Cys C与U-m Alb/Cr两者联合检测阳性率高达76.0%,明显高于单项检测。结论 U-m Alb/Cr与血清Cys C的水平与2型糖尿病患者早期肾损伤程度密切相关,血清Cys C与U-m Alb/Cr联合检测对于糖尿病肾病的早期诊断、早期治疗及监测有重要的意义。     

西格列汀对初发2型糖尿病患者胰岛B细胞功能的影响

目的研究西格列汀对初发2型糖尿病患者胰岛B细胞功能的影响。方法选择我院门诊2型糖尿病患者69例,随机分为对照组和试验组,对照组35例,试验组34例,对照组予二甲双胍治疗,试验组予二甲双胍、西格列汀治疗,12周后比较治疗前后两组患者空腹血糖(FPG)、餐后2 h血糖(PPG)、糖化血红蛋白(Hb A1c)、体重指数(BMI)、空腹胰岛素(Fins)、餐后2 h胰岛素(Pins)。结果两组治疗前各项指标比较差异无统计学意义(P>0.05),治疗后,两组FPG、PPG、Hb A1c、BMI均较治疗前显著下降(P<0.05)。与对照组相比,试验组FPG、PPG、Hb A1c降低更明显(P<0.05),Fins、Pins水平升高更显著(P<0.05)。结论西格列汀能明显改善初发2型糖尿病患者的胰岛B细胞功能,在临床应用中安全有效。     

卡格列净联合利格列汀治疗早期2型糖尿病肾病的临床研究

目的观察卡格列净片联合利格列汀片治疗早期2型糖尿病肾病的临床疗效。方法选择2020年5月—2020年10月就诊于天津市第二医院的86例早期2型糖尿病肾病患者,采用随机数字表法将所有患者分为对照组和治疗组,每组各43例。对照组早餐前口服利格列汀片,5 mg/次,1次/d;治疗组在对照组治疗的基础上早餐前口服卡格列净片,100 mg/次,1次/d。两组患者均治疗16周。观察两组的临床疗效,同时比较两组治疗前后血糖、糖化血红蛋白(Hb A1c)、血清胱抑素C(Cys-C)、尿β2-微球蛋白(β2-MG)、尿白蛋白肌酐比值(UACR)、尿白蛋白排泄率(UAER)变化。结果治疗后,对照组和治疗组总有效率分别为72.09%、88.37%,两组总有效率比较差异有统计学意义(P0.05)。治疗后,两组患者空腹血糖(FPG)、餐后2小时血糖(2 h PG)、Hb A1c水平均较治疗前明显下降,差异均有统计学意义(P0.05),治疗组患者FPG、2hPG、Hb A1c水平较对照组下降更明显(P0.05)。治疗后,两组患者胱抑素C(Cys-C)、β2-MG、UACR、UAER水平均下降,差异有统计学意义(P0.05),且治疗组患者Cys-C、β2-MG、UACR、UAER水平较对照组下降更明显(P0.05)。结论卡格列净片联合利格列汀片治疗早期2型糖尿病肾病具有较好的临床疗效,可有效降糖、减少尿蛋白。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.

---

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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

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.