预混门冬胰岛素30治疗2型糖尿病疗效观察

目的：观察预混门冬胰岛素30（诺和锐30）治疗2型糖尿病（ T2DM）的疗效。方法将104例口服降糖药血糖控制不佳的T2DM患者随机分为诺和锐30组53例和预混人胰岛素30R（诺和灵30R）组51例。每天早晚餐前皮下注射诺和锐30及诺和灵30R,治疗12周后比较2组空腹血糖（ FPG）、餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）和低血糖发生率。结果治疗前2组FPG、2hPG、HbA1c水平差异无统计学意义（P＞0．05）。治疗后2组FPG、2hPG、HbA1c水平均低于治疗前,且诺和锐30组早餐、晚餐后2hPG和HbA1c水平低于诺和灵30R组,差异均有统计学意义（P＜0．05）。2组治疗后空腹血糖、中餐后2hPG水平差异均无统计学意义（P＞0．05）。诺和锐30组低血糖、严重低血糖发生率均低于诺和灵30R组,差异有统计学意义（P＜0．05）。结论诺和锐30治疗T2DM效果显著,且有良好的安全性,优于诺和灵30R,值得临床推广应用。     

瑞格列奈联合吡格列酮治疗2型糖尿病的临床疗效观察

目的探究瑞格列奈联合吡格列酮治疗2型糖尿病的临床疗效。方法选取2013年6月—2014年5月千岛湖镇社区卫生服务中心收治的102例2型糖尿病患者,随机分为观察组（52例）和对照组（50例）。对照组患者采用瑞格列奈治疗,观察组采用瑞格列奈联合吡格列酮治疗。比较两组患者治疗前后空腹血糖（ FPG）、餐后2h血糖（2hPG）、空腹胰岛素（ FINS）、糖化血红蛋白（ HbA1c ）、三酰甘油（ TG）、低密度脂蛋白胆固醇（ LDL-C）水平及不良反应情况。结果两组患者治疗前FPG、2hPG、FINS、HbA1c、TG、LDL-C比较,差异无统计学意义（ P>0.05）;两组患者治疗后FPG、2hPG、FINS、HbA1c、TG、LDL-C比较,差异有统计学意义（ P<0.05）。两组患者均未发生低血糖以及严重的脏器损害等。结论瑞格列奈联合吡格列酮治疗2型糖尿病的疗效显著,且不良反应少。     

门冬胰岛素联合地特胰岛素对2型糖尿病强化治疗的疗效评价

目的 比较门冬胰岛素联合地特胰岛素与单纯使用门冬胰岛素对新诊断2型糖尿病（T2DM）患者治疗的安全性和有效性.方法 选取2010年9月-2013年5月在我院就诊的新诊断的T2DM 患者100例,随机分两组,A组联合使用门冬胰岛素和地特胰岛素强化治疗,B组单纯使用门冬胰岛素,比较两组治疗前后的静脉空腹血糖（FPG）、FPG达标率、糖化血红蛋白（HbA1c）、HbA1c达标率、静脉餐后2h血糖（2hPG）、2 hPG达标率、低血糖发生率情况.结果 强化治疗后两组FPG、HbA1c、2hPG均下降,A组较B组相关指标下降明显,且A组的FPG达标率增高,差异有统计学意义（P＜0.05）;A组低血糖发生率较B组低.结论 在控制T2DM患者的血糖方面,采用门冬胰岛素联合地特胰岛素的强化治疗方案更为安全有效.     

格列吡嗪联合阿卡波糖治疗2型糖尿病的临床观察

目的：比较格列吡嗪联合阿卡波糖与单用阿卡波糖（商品名拜唐苹）治疗2型糖尿病患者的临床疗效。方法：将65例单纯饮食加运动疗法治疗不满意的2型糖尿病患者随机分为两组,治疗组应用格列吡嗪联合阿卡波糖33例,对照组应用阿卡波糖32例,1个疗程为12周。定期测定并比较两组治疗前后空腹血糖（FPG）、餐后2h血糖（2hPBG）,糖化血红蛋白（HbA1c）,空腹及餐后2h胰岛素（FINS,2hPINS）和血脂。结果：治疗组FPG平均下降幅度大于对照组,两组P值均〈0.01;两种药物对2hPBG均有明显的降低作用（P〈0.01）,且降低程度相似;两组HbA1c均能显著降低,治疗组从（8.81±1.12）%降至（7.01±0.96）%（P〈0.01）,对照组从（8.75±0.71）%降至（6.95±0.92）%（P〈0.01）,两组比较HbA1c降低的幅度差异无统计学意义（P〉0.05）;餐后2h血清胰岛素与治疗前比较,治疗组升高,差异有统计学意义（P〈0.01）,而对照组明显降低（P〈0.01）。结论：两组均有明显降低空腹和餐后血糖以及HbA1c的作用,对以餐后血糖高为主的糖尿病患者更适合选用。格列吡嗪联合阿卡波糖降空腹血糖的作用优于单用阿卡波糖,而且能很好地控制继发失效2型糖尿病患者的血糖。     

罗格列酮联合格列吡嗪治疗2型糖尿病疗效观察

目的观察罗格列酮联合格列吡嗪治疗2型糖尿病（T2DM）的临床疗效及安全性。方法 47例经磺酰脲类或双胍类药物治疗效果不佳[空腹血糖（FPG）〉7.0mmol/L]的T2DM患者,给予罗格列酮联合格列吡嗪治疗,疗程为3个月,观察治疗前、后FPG、餐后2h血糖（2hPG）、糖化血红蛋白（HbA1C）、丙氨酸氨基转移酶（ALT）的变化。结果治疗后患者的FPG、2hPG、HbA1C均较治疗前降低,差异有统计学意义（P〈0.01）。ALT治疗前后无变化,差异无统计学意义（P〉0.05）。结论罗格列酮联合格列吡嗪治疗T2DM疗效显著,且安全性好,值得临床推广应用。     

沙格列汀联合伏格列波糖对老年2型糖尿病患者糖脂代谢的影响

目的:观察沙格列汀联合α-葡萄糖苷酶抑制剂(伏格列波糖)对老年2型糖尿病(T2DM)患者糖脂代谢的影响.方法:选取2018-02～ 2019-05我院90例老年T2DM患者,采用随机数字表法分组,各45例.对照组予以伏格列波糖治疗,观察组在对照组基础上予以沙格列汀治疗.对比两组治疗前后血糖指标[空腹血糖(FBG)、餐后2h血糖(2 hPG)、糖化血红蛋白(HbA1c)]、血脂指标[总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)]、血管内皮细胞功能[一氧化氮(NO)、内皮素-1(ET-1)]水平.结果:治疗3个月后观察组血清FBG、2 hPG、HbA1c、TC、LDL-C水平低于对照组(P＜0.05);观察组血清NO水平高于对照组,血清ET-1水平低于对照组(P＜0.05).结论:沙格列汀联合伏格列波糖治疗老年T2DM患者,不仅能降低血糖,改善糖脂代谢,还可调节血管内皮细胞功能.     

门冬胰岛素治疗妊娠糖尿病的临床效果观察

目的观察门冬胰岛素治疗妊娠糖尿病的临床效果。方法选取60例妊娠糖尿病患者,随机分为对照组与观察组,每组各30例。对照组给予常规人胰岛素三餐前30min皮下注射治疗;治疗组给予门冬胰岛素早晚餐前5min皮下注射治疗。比较两组的FPG、2hPG、HbA1c的控制情况及血糖达标时间、胰岛素日用量、低血糖发生率。结果治疗后,两组的FPG、2hPG、HbA1c均较治疗前明显降低;治疗组FPG、2hPG、HbA1c均低于对照组（P〈0．05）;治疗组血糖达标时间明显短于对照组,胰岛素用量较对照组低,且低血糖发生率较对照组低（P〈0．05）;两组的母婴结局比较,差异无统计学意义（P〉0．05）。结论门冬胰岛素治疗妊娠糖尿病,疗效确切,安全性可靠,对母婴结局有重要的意义。值得临床推广。     

国产混合重组人胰岛素30／70注射液联合二甲双胍治疗初发2型糖尿病疗效观察

目的观察国产混合重组人胰岛素30／70注射液联合二甲双胍治疗初发2型糖尿病（T2DM）的临床疗效。方法将72例初发T2DM患者随机分为治疗组和对照组各36例。对照组采用国产混合重组人胰岛素30／70注射液治疗,治疗组在对照组基础上予二甲双胍口服治疗。观察2组治疗前后体质量、体质量指数（BMI）、腰臀比（WHR）、空腹胰岛素（FINS）、空腹血糖（FPG）、餐后2h血糖（2hPG）、糖代血红蛋白（HbA1c）及三酰甘油（TG）、总胆固醇（TC）、低密度酯蛋白胆固醇（LDL—C）水平和胰岛素抵抗指数（HOMA—IR）。结果治疗后,治疗组各指标均低于治疗前;对照组FPG、HbA1c、TG、TC、LDL-C、HOMA-IR低于治疗前,差异均有统计学意义（P〈0．05）;治疗后,治疗组FPG、HbA1c及HOMA-IR均低于对照组,差异均有统计学意义（P〈0．05）。结论国产混合重组人胰岛素30／70注射液联合二甲双胍治疗T2DM,疗效较满意,值得基层医院推广应用。     

格列美脲与二甲双胍或阿卡波糖联合治疗2型糖尿病临床观察

目的探讨格列美脲与二甲双胍或阿卡波糖联合治疗2型糖尿病对空腹血糖（FPG）的疗效及临床意义。方法 2013年1月-2013年12月收治的格列美脲治疗效果不理想的2型糖尿病患者40例,随机分为治疗组与对照组各20例,2组均予格列美脲2mg常规治疗,治疗组加用二甲双胍0.25g,对照组加用阿卡波糖50mg,均为每天3次,观察其治疗前后的FPG、餐后2h血溏（2hPG）及糖化血红蛋白（HbA1c）变化。结果治疗12周后2组FPG、2hPG、HbA1c均显著下降,且治疗组下降较对照组更为明显,2组比较差异有统计学意义（P〈0.05）。结论格列美脲联合二甲双胍控制FPG效果优于格列美脲联合阿卡波糖。     

糖化血红蛋白与血糖的相关性分析及其对糖尿病诊断敏感性探讨

目的：行糖化血红蛋白（HbA1c）与空腹血糖（FPG）、餐后2h血糖（2hPG）相关性分析,探讨其在糖尿病（DM）诊断中的价值。方法：同时测定150例门诊就诊者FPG、HbA1c、2hPG,将HbA1c按不同切点分组计算各自对DM诊断的灵敏性及特异性。结果：150例就诊患者中确诊109例DM患者,其FPG、HbA1c、2hPG与非DM患者组比较显著增高（P〈0.01）;DM组中,HbA1c与FPG、2hPG正相关;HbA1c对DM诊断的灵敏性较FPG好;HbA1c对DM诊断的最佳切点为6.5%。结论：FBG的波动性较大,2hPG检查繁琐,HbA1c测定对DM的诊断有一定价值及优势。     

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.

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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.

     

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.     

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.     

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.