氯氮平和利培酮对精神分裂症病人体重、瘦素及脂代谢的影响

目的 :观察氯氮平、利培酮对精神分裂症病人体重、瘦素及脂代谢的影响。方法 :6 4例 1mo内未服药的精神分裂症病人分入氯氮平 (n =33)或利培酮组 (n =31)治疗 8wk ,治疗前后测量其身高、体重、腰围、血脂水平及血清瘦素浓度 ,计算其体重指数 (BMI) ,同时评定简明精神症状评定量表(BPRS)。结果 :(1)治疗 8wk后 2组病人体重、腰围及BMI均明显增加 (P <0 .0 5 ) ;体重增加与治疗前体重、治疗前腰围及BPRS减分率无相关 (P >0 .0 5 )。 (2 ) 2组病人均有血三酰甘油 (TG)、总胆固醇 (TC)的升高 (P <0 .0 5 ) ,TG与腰围相关。 (3) 2组病人血清瘦素浓度均升高 ,瘦素浓度与性别及腰围相关。结论 :氯氮平及利培酮均能引起病人体重增加 ,同时引起血清瘦素及血脂的改变。有必要对服用氯氮平或利培酮病人的体重及脂代谢指标进行监测。     

血清瘦素与2型糖尿病胰岛素抵抗的相关性研究

目的　探讨瘦素 (L eptin)与 2型糖尿病 (2型 DM)胰岛素抵抗的相关情况。方法　测定全部受试对象的体重指数 (BMI)及空腹静脉血糖 (FPG)、血清甘油三酯 (TG)、总胆固醇 (TC)及高密度脂蛋白 (HDL)等生化指标。采用放射免疫的方法检测 70例 2型 DM患者和 6 0例健康对照者空腹血清胰岛素 (FINS)及循环 L eptin水平。胰岛素抵抗 (IR)采用自我平衡模型分析法 (HOMA)进行评价 ,HOMA胰岛素抵抗指数 (HOMA- IR) =FPG×FINS/2 2 .5。结果　 2型 DM组及正常对照组 FPG分别为 11.0 3± 4 .89mmol/ l Vs5 .2 0± 1.14 mm ol/ l(P<0 .0 1) ,FINS分别为 11.31± 4 .31m IU/ l Vs 14 .6 7± 4 .96 m IU/ l (P<0 .0 1) ,L eptin分别为 9.17± 5 .0 3ng/ ml Vs 6 .99± 3.39ng/ ml (P<0 .0 5 ) ,HOMA- IR分别为 5 .5 4± 2 .2 5 Vs 3.39± 1.4 8(P<0 .0 1)。 L eptin与 HOMA- IR呈正相关。结论　 L eptin与胰岛素抵抗指数呈正相关 ,L eptin可能通过增加胰岛素抵抗参与糖尿病的发生     

利培酮短期治疗的男性精神分裂症患者催乳素水平对胰岛素敏感性的影响

目的初步探讨利培酮短期治疗的男性精神分裂症患者催乳素水平对胰岛素敏感性的影响。方法将符合入组标准的51例利培酮治疗2⁶周的住院精神分裂症患者依据催乳素水平分为A组(催乳素≥800 mIU·L6周的住院精神分裂症患者依据催乳素水平分为A组(催乳素≥800 mIU·L^(-1))27例和B组(催乳素<800 mIU·L(-1))27例和B组(催乳素<800 mIU·L^(-1))24例,比较两组的胰岛素敏感性指标和体重指数(BMI);依据BMI分为正常体重组(BMI 18.5(-1))24例,比较两组的胰岛素敏感性指标和体重指数(BMI);依据BMI分为正常体重组(BMI 18.5²3.9 kg·m23.9 kg·m^(-2))29例和超重组(BMI≥24 kg·m(-2))29例和超重组(BMI≥24 kg·m^(-2))22例,比较两组的血清催乳素和胰岛素敏感性指标。结果 A、B两组空腹胰岛素(FINS)、稳态模型评估胰岛素抵抗指数(HONA-IR)、定量胰岛素敏感性检测指数(QUICKI)均无显著差异(P>0.05)。正常体重组与超重组的催乳素水平无显著差异(P>0.05);超重组FINS、HOMA-IR高于正常体重组(P<0.01),超重组QUICKI低于正常体重组(P<0.01)。结论利培酮短期治疗后的男性精神分裂症患者中体重超重者胰岛素敏感性降低,而催乳素水平不影响患者的体重及胰岛素敏感性。     

2型糖尿病患者瘦素水平测定及临床意义的研究

目的探讨2型糖尿病患者的血清瘦素水平、瘦素与胰岛素抵抗的关系及临床意义。方法糖尿病组100例,分为糖尿病非肥胖组[体重指数(BMI)<25kg/m2)]与肥胖组(BMI≥25kg/m2),计算BMI、腰臀围比值(WHR),用酶联免疫吸附试验(ELISA)测定人血清瘦素,同时测定空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素原(PI)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)、睾酮。胰岛素敏感性以HOMA模型中胰岛素抵抗指数(HOMA-R)评价。对照组:健康人60名与糖尿病组相匹配,分组和观察指标也相同。结果山西地区人血清瘦素正常值女性为(7.6±3.6)μg/L,男性为(2.1±1.0)μg/L;糖尿病组与对照组肥胖者瘦素水平均明显高于非肥胖者,瘦素水平与性别、体重、BMI、FINS、PI、HOMA-R、FFA显著相关,男性瘦素水平与男性睾酮呈显著负相关。肥胖者多数存在高胰岛素血症,胰岛素不敏感者较胰岛素敏感者瘦素水平增高。多元回归结果显示,糖尿病组性别、BMI、FINS、HOMA-R是瘦素水平的影响因素。结论2型糖尿病患者瘦素水平与非糖尿病无明显差异,瘦素水平与肥胖和胰岛素抵抗关系密切,并对糖尿病患者的防治有一定的临床意义。     

托吡酯对0～8岁癫痫病儿血清瘦素水平及体重指数的影响

目的:探讨托吡酯对0～8a癫痫病儿血清瘦素水平及体重指数(BMI)的影响。方法:对43例服用托吡酯单药治疗的0～8a癫痫病儿随访6mo,采用放射免疫法分别对其用药前及用药后1,3,6mo的血清瘦素水平的进行测定,同时测量身高与体重,以BMI评定体脂情况。结果:托吡酯治疗前病儿血清瘦素水平为(6.5±s2.5)μg·L-1,服用托吡酯1mo后为(7.1±2.6)μg·L-1,3mo后为(9±3)μg·L-1,6mo后为(11±3)μg·L-1。治疗后3mo血清瘦素的水平变化有非常显著差异(P<0.01);BMI的下降在用药后6mo明显降低(P<0.01)。结论:托吡酯能提高癫痫病儿血清瘦素水平,降低BMI。     

胰岛素抵抗与瘦素关系初探

目的　探讨血清瘦素水平与体重指数、胰岛素抵抗指数相互间的关系。方法　测定不同体重指数 (BMI)人群的胰岛素抵抗指数 (Homa IR)血清瘦素浓度 ,分析其间的相关性。结果　胰岛素抵抗指数与BMI呈正相关 ( r=0 .42 5 ,P <0 .0 1) ;男、女血清瘦素浓度均和BMI呈正相关 ( r分别为 0 .2 40和 0 .43 5 ,P <0 .0 5 ) ;瘦素与胰岛素抵抗指数呈正相关 (男性r =0 .44 4,P <0 .0 0 1;女性r =0 .3 81,P <0 .0 5 )。结论　肥胖机体过度表达瘦素 ,在肥胖相关的IR中起着重要作用。通过减低体重降低瘦素水平 ,或许可成为改善胰岛素抵抗的可行方法。     

瘦素抵抗在肥胖2型糖尿病发病中的作用（附96例分析）

目的　探讨瘦素抵抗在肥胖 2型糖尿病发病中的作用。方法　根据体重指数将 96例 2型糖尿病患者分为肥胖 (BMI≥ 2 5 kg/ m2 )和非肥胖 (BMI<2 5 kg/ m2 )两组 ,并测定血浆瘦素和胰岛素、空腹血糖、血脂、糖化血红蛋白等指标 ,测量腰围、臀围、身高、体重 ,计算腰 /臀比值和体重指数。结果　肥胖组的血瘦素和胰岛素水平均显著高于非肥胖组 (P<0 .0 5或 0 .0 1) ,血瘦素水平与体重指数、空腹血胰岛素水平呈显著正相关 (男 :r=0 .6 12、 0 .4 0 3,P<0 .0 1;女 :r=0 .5 86、 0 .4 5 5 ,P<0 .0 1) ,女性的瘦素水平约为男性的 3倍。结论　肥胖 2型糖尿病患者可能存在瘦素抵抗 ,瘦素抵抗在其发病中起一定的作用     

糖耐量减低患者血清瘦素水平与肥胖、血糖及胰岛素的相关性研究

目的　探讨糖耐量减低 (IGT)患者血清瘦素水平与肥胖程度、血糖、胰岛素浓度的关系。方法　测定 6 0例IGT患者的空腹血清瘦素水平 ,并行口服葡萄糖耐量试验 ,测定血浆胰岛素和葡萄糖浓度 ,同时测定身高、体重 ,计算体重指数 (BMI)。结果　血清瘦素水平与BMI呈正相关 (男r=0 6 39,P <0 0 1;女r =0 76 2 ,P <0 0 1) ,女性显著高于男性 (P <0 0 1)。采用多元逐步回归法分析 ,去除BMI等因素的影响后 ,瘦素与胰岛素曲线下面积呈正相关 ,与血糖浓度无相关性。结论　肥胖者空腹血清瘦素升高 ,高瘦素血症与高胰岛素血症的相关性提示 ,瘦素可能在IGT发展成 2型糖尿病 (2型DM )中亦起一定的作用     

糖负荷对原发性高血压患者血清瘦素水平的影响探讨

目的　利用口服葡萄糖耐量试验 (OGTT)中体内血糖和胰岛素浓度的变化 ,探讨原发性高血压患者血糖和胰岛素对瘦素可能存在的即时和短时效应。方法　 33例原发性高血压患者男 16例 ,女 17例 ,其中肥胖 16例 ,非肥胖 17例 ;行 OGTT,测定 0、 30、 6 0、 12 0、 180分钟时相的血清葡萄糖 (GL U )、胰岛素 (INS)和瘦素(L eptin)水平 ;并测量体重指数 (BMI)、腰围、腹围、臀围、血压、心率 ,测定甘油三酯 (TG)、总胆固醇(CHOL )等指标。结果　原发性高血压患者空腹血清瘦素女性为 (12 .80± 1.4 4 ng/ ml) ,男性为 (6 .39± 1.4 3ng/ml) ,P<0 .0 5 ;原发性高血压患者空腹血清瘦素肥胖组为 (11.0 4± 1.13ng/ ml) ,非肥胖组为 (7.0 3± 1.34ng/ ml) ,P<0 .0 5。空腹血清瘦素水平与 BMI呈正相关 (r=0 .4 9,P<0 .0 5 ) ;而与胰岛素敏感性 (ISI)无关 (r=0 .0 2 8,P>0 .0 5 )。与非肥胖组相比 ,肥胖组 OGTT血糖升高明显 ;胰岛素释放曲线呈高峰延迟 ,肥胖组 12 0分钟时相胰岛素水平高于非肥胖组 ;原发性高血压瘦素释放曲线变化不明显 ,肥胖组与非肥胖组之间差别无统计学意义。结论　血清瘦素水平未随着胰岛素浓度的升高而升高 ,提示胰岛素促瘦素分泌的效应 ,未能影响瘦素白天下降的趋势     

2型糖尿病多种脂肪细胞因子水平及罗格列酮干预治疗的影响

目的:观察罗格列酮治疗2型糖尿病对多种脂肪细胞因子水平的影响及其与胰岛素抵抗的关系。方法:糖尿病组2型糖尿病病人56例,男性33例,女性23例,年龄(61±s 7)a,随机分为2组。观察组30例,予罗格列酮4 mg·d-1;对照组26例,予二甲双胍和(或)磺酰脲类降糖药,疗程均为2 mo。并设正常组,健康者54例,男性30例,女性24例,年龄(61±8)a。测定治疗前后各组的血压、抵抗素、脂联素、瘦素、血糖、胰岛素抵抗水平。结果:糖尿病组血压、空腹血糖和胰岛素、胰岛素抵抗指数、抵抗素和瘦素水平均高于正常组,脂联素水平低于正常组。治疗后,观察组抵抗素和瘦素分别降低(1．73±0．22)μg·L-1和(1．4±0．4)mg·L-1,血糖、胰岛素抵抗明显改善,与治疗前及对照组相比,差异有非常显著意义(P<0．01);脂联素升高(0．6±0．6)mg·L-1,与对照组[升高(0．4±0．3)mg·L-1]无显著差异(P>0．05)。抵抗素与空腹胰岛素、脂联素呈负相关(r=-0．386,r=-0．387),与体重指数、三酰甘油和腰臀比呈正相关(r=0．4,r=0．322,r=0．298)。结论:罗格列酮可改善2型糖尿病病人抵抗素、瘦素、脂联素水平,这些脂肪细胞因子的改变可能与2型糖尿病病人胰岛素抵抗的改善有关。     

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.