参芎葡萄糖注射液对急性脑梗死患者炎性因子和脂联素、瘦素水平的影响

目的 :探讨参芎葡萄糖注射液治疗急性脑梗死(acute cerebral infarction,ACI)临床疗效及对患者炎性因子和脂联素、瘦素水平的影响。方法 :收集124例符合纳入标准的ACI患者作为观察对象,随机分为2组,每组各62例。对照组患者给予常规治疗,观察组患者在对照组患者基础上给予参芎葡萄糖注射液辅助治疗。治疗前后,采用美国国立卫生研究院卒中量表(NIHSS)评价患者神经功能情况。疗程结束后,比较对照组和观察组患者临床疗效、NIHSS评分、血清炎性因子及脂联素、瘦素水平。结果:ACI临床疗效显示,观察组患者治疗总有效率高于对照组(93.5%vs 80.6%,P<0.05)。治疗后,与对照组相比,观察组患者NIHSS评分[(11.9±2.4)vs(14.3±3.6)]降低,血清TNF-α[(1.67±0.14)ng·L~(-1) vs(2.01±0.23)ng·L~(-1)]、IL-6水平[(65.75±13.86)ng·L~(-1) vs(83.13±15.21)ng·L~(-1)]均降低,IL~(-1)0水平[(3.57±0.72)ng·m L~(-1) vs(2.96±0.61)ng·m L~(-1)]升高,脂联素水平[(8.02±1.41)mg·L~(-1) vs(6.25±1.23)mg·L~(-1)]升高,瘦素水平[(7.53±1.37)vs(8.12±1.83)ng·m L~(-1)]降低,组间比较均具有统计学差异(P<0.05)。结论 :参芎葡萄糖注射液辅助治疗ACI临床疗效良好,治疗有效率高,能够有效改善神经功能,减轻机体炎性反应,并且能够升高脂联素水平、降低瘦素水平。     

卡维地洛与氢氯噻嗪对原发性高血压患者血管活性物质的影响

目的探讨氢氯噻嗪、卡维地洛单用或联用对轻中度原发性高血压患者血压和血浆肾上腺髓质素(AM)、血管紧张素Ⅱ(AngⅡ)及丙二醛(MDA)水平的影响。方法107例新发现的或不规则服降压药但已停药2 wk以上的轻中度原发性高血压患者随机分为3组,分别服用氢氯噻嗪(12.5～25 mg·d~(-1))、卡维地洛(25～50 mg·d~(-1))、卡维地洛和氢氯噻嗪(分别为12.5 mg·d~(-1)和12.5～25 mg·d~(-1),分别测量治疗前和治疗8 wk后血压和AM、AngⅡ及MDA浓度。结果氢氯噻嗪组、卡维地洛组和卡维地洛/氢氯噻嗪组血浆AM浓度治疗前后分别为(60.41±17.13)ng·L~(-1)vs(51.70±20.35)ng·L~(-1)(P<0.05);(65.41±18.62)ng·L~(-1)vs(49.39±18.55)ng·L~(-1)(P<0.01);(62.08±21.50)ng·L~(-1)vs(47.97±18.71)ng·L~(-1)(P<0.01)。卡维地洛组和卡维地洛/氢氯噻嗪组治疗后较治疗前血浆AngⅡ水平下降(35.51±32.31)ng·L~(-1)vs(18.21±14.61)mg·L~(-1)(P<0.01);(30.81±31.02)ng·L~(-1)vs(17.71±12.85)ng·L~(-1)(P<0.05);同时血浆MDA水平也下降分别为(10.19±3.23)mmol·L~(-1) vs(6.98±2.88)mmol·L~(-1)(P<0.01);(9.79±2.71)mmol·L~(-1)vs(6.61±2.74)mmol·L~(-1)(P<0.01);而氢氯噻嗪组治疗前后血浆AngⅡ、MDA浓度变化差异无统计学意义。结论低剂量氢氯噻嗪和卡维地洛联合应用安全性好,降压效果明确,具有降低血浆AM浓度的作用,起到了协同降压的作用。     

脂必泰胶囊与阿托伐他汀钙对老年血脂异常患者血脂和炎症因子的影响

目的：观察脂必泰胶囊与阿托伐他汀钙对老年血脂异常患者血脂和炎症因子的影响。方法选择老年血脂异常患者64例,随机分为对照组和治疗组,每组32例。对照组患者睡前口服阿托伐他汀钙片10 mg·d-1,治疗组患者在对照组基础上加服脂必泰胶囊(每次240 mg,bid)。均治疗6周。分别于治疗前后检测两组患者血清总胆固醇( TC)、三酰甘油( TG)、低密度脂蛋白胆固醇( LDL-C)、高密度脂蛋白胆固醇( HDL-C)、肿瘤坏死因子-α( TNF-α)和白细胞介素-6(IL-6)水平。结果与对照组治疗后比较,治疗组患者血清TC[(5.18±0.57) mmol·L-1比(5.73±0.65)mmol·L-1]、TG[(1.52±0.43) mmol·L-1比(1.86±0.48)mmol·L-1]、LDL-C[(3.36±0.48) mmol·L-1比(3.85±0.53)mmol·L-1]、TNF-α[(5.37±2.21) ng·L-1比(7.63±2.59)ng·L-1]和IL-6[(12.27±2.75) ng·L-1比(15.63±2.92)ng·L-1]水平均显著降低(均P<0.01),HDL-C[(1.26±0.25) mmol·L-1比(1.13±0.23)mmol·L-1]水平显著升高(P<0.05)。结论脂必泰胶囊联合阿托伐他汀钙治疗老年血脂异常,不仅有调脂作用,还具有降低患者血清TNF-α和IL-6水平、抑制炎症反应作用。     

多巴胺联合氢化可的松治疗感染性休克的疗效及对血清炎性指标的影响

目的探讨多巴胺联合氢化可的松治疗感染性休克的疗效。方法将100例感染性休克患者分为观察组(52例)与对照组(48例)。观察组患者使用多巴胺联合氢化可的松进行治疗,对照组使用氢化可的松。对比研究2组患者的治疗效果。结果 (1)治疗前,2组患者心率(HR)、收缩压(SBP)和尿量无明显差别。治疗后1,4,12,24和72 h观察组HR明显低于对照组(P<0.05),SBP和尿量明显高于对照组(P<0.05)。(2)治疗前,2组患者炎性相关指标[白细胞介素-6(IL-6)、白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)和白细胞(WBC)]无明显差别。治疗后,观察组炎性指标值明显小于对照组(P<0.05)。(3)与对照组比较,观察组患者恢复时间[(3.12±1.18) d vs (5.09±1.86) d]、住院时间[(20.76±3.38) d vs (26.43±4.75) d]更短,多器官功能障碍综合征(MODS)发生率(28.85%vs 66.67%)和病死率(15.38%vs 35.42%)更低。(4) 2组治疗前血清谷氨酸-丙酮酸转氨酶(ALT)、谷草转氨酶(AST)和乳酸(Lac)无明显差别。观察组治疗后上述指标值明显较对照组更低[(ALT:(44.54±14.09) U·L~(-1) vs (67.86±13.64) U·L~(-1);AST:(54.64±10.09) U·L~(-1) vs (70.87±18.65) U·L~(-1);Lac:(2.11±0.82) mmol·L~(-1)vs (3.56±1.03) mmol·L~(-1)]。结论多巴胺联合氢化可的松能明显增加感染性休克患者的尿量及血压,并降低患者炎性反应及血清ALT、AST和Lac水平,可提高患者的生存质量,且疗效显著。     

重组人粒细胞集落刺激因子(rhG-CSF)抑制大鼠脑卒中后的谷氨酸毒性和IL-1β反应

目的:研究重组人粒细胞集落刺激因子(rhG-CSF)对急性脑卒中大鼠脑梗死区域内谷氨酸、IL-1β和IL-6浓度的影响。方法:采用线拴大脑中动脉阻塞(MCAO)法制备急性脑卒中模型,90 min后再灌注。线栓封堵大脑中动脉后,静脉一次性注射rhG-CSF(60 mg·kg~(-1),治疗组,n=10)或0.3mL生理氯化钠溶液(对照组,n=8)。采用微透析法,检测纹状体内谷氨酸浓度;ELISA法分别检测脑组织和血清的IL-1β和IL-6含量。结果:脑卒中发生后0.5～3 h,治疗组梗死侧纹状体内谷氨酸浓度明显低于对照组梗死侧(P<0.01);脑卒中后6 h,治疗组梗死侧脑组织内IL-1β浓度明显低于对照组[(11.38±5.54)vs(21.15±9.57)ng·g~(-1),P<0.01];治疗组血浆内的IL-1β浓度也明显低于对照组[(74.26±26.47)vs(122.88±29.10)ng·mL~(-1),P<0.01]。脑卒中6h后,两组大鼠的血浆和脑组织中均未检测到IL-6。结论:rhG-CSF能明显抑制脑卒中后的谷氨酸毒性和IL-1β反应。     

慢性心力衰竭与白细胞介素-17及白细胞介素-10的相关性研究

目的 探讨慢性心力衰竭与白细胞介素(IL)-17、IL-10的相关性.方法 采用酶联免疫吸附试验(ELISA)检测37例慢性心力衰竭患者(慢性心衰组)和34例健康体检者(对照组)血浆IL-17和IL-10水平,并进行相关性分析.结果 慢性心衰组血浆IL-17水平高于对照组[(46.37±10.57) ng/L vs(32.45±4.55)ng/L],IL-10水平低于对照组[(27.49±4.19) ng/L vs(32.71±4.38) ng/L],差异均有统计学意义(t=7.09,5.46,P＜0.01);慢性心力衰竭患者血浆IL-17与IL-10呈负相关(r=-0.63,P＜0.01).结论 慢性心力衰竭的发病可能与体内IL-17、IL-10的水平失衡存在相关.     

α?硫辛酸对白细胞介素 1β诱导的软骨细胞损伤的保护作用

目的 探讨α-硫辛酸(ALA)调控微小RNA-877(miR-877)/N-myc下游调节基因2(NDRG2)分子轴对白细胞介素1β(IL-1β)诱导的软骨细胞损伤的影响及其机制.方法 本研究于2019年1月至2019年7月在南充市中心医院风湿免疫科实验室完成.分离培养SD大鼠膝关节软骨细胞,按照随机数字表法分为对照(Con)组、IL-1β组、IL-1β+ALA-低剂量(L)组、IL-1β+ALA-中剂量(M)组、IL-1β+ALA-高剂量(H)组、IL-1β+miRNA抑制物阴性对照(anti-miR-NC)组、IL-1β+miR-877抑制物(anti-miR-877)组、IL-1β+空载体质粒(pcDNA)组和IL-1β+NDRG2过表达质粒(pcDNA-NDRG2)组、IL-1β+ALA+miRNA模拟物阴性对照(miR-NC)组和IL-1β+ALA+miR-877组.流式细胞术检测细胞凋亡,酶联免疫吸附测定(ELISA)试剂盒检测白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)的分泌量,蛋白质印记(western blot)法检测NDRG2蛋白的表达水平,实时定量PCR(qRT-PCR)检测miR-877和NDRG2 mRNA的表达水平.双荧光素酶报告基因实验和western blot检测miR-877和NDRG2的靶向调控关系.结果 与Con组比较,IL-1β组软骨细胞IL-6[(3.27±0.31)比(1.06±0.09)ng/L]、TNF-α、IFN-γ的分泌增加,miR-877[(2.65±0.24)比(1.02±0.09)]表达升高,NDRG2[(0.21±0.03)比(0.69±0.06)]表达降低,细胞凋亡率[(0.69±0.06)比(6.24±0.63)％]升高(均P<0.05);与IL-1β组比较,IL-1β+ALA-L组、IL-1β+ALA-M组、IL-1β+ALA-H组软骨细胞IL-6[(2.91±0.25),(2.33±0.23),(1.65±0.16)比(3.27±0.31)ng/L]、TNF-α、IFN-γ的分泌降低,miR-877[(2.21±0.19),(1.96±0.17),(1.43±0.14)比(2.65±0.24)]的表达降低,NDRG2[(0.34±0.03),(0.46±0.04),(0.58±0.05)比(0.21±0.03)]表达升高,细胞凋亡率[(20.13±2.12),(16.32±1.63),(11.04±1.15)比(27.62±2.43)]％降低,差异有统计学意义(P<0.05);与IL-1β+anti-miR-NC组比较,IL-1β+anti-miR-877组软骨细胞IL-6[(1.38±0.14)比(3.34±0.33)ng/L]、TNF-α、IFN-γ的分泌降低,细胞凋亡率[(12.54±1.25)比(27.14±2.73)]％降低,差异有统计学意义(P<0.05);与IL-1β+pcDNA组比较,IL-1β+pcDNA-NDRG2组软骨细胞IL-6[(1.43±0.15)比(3.47±0.34)ng/L]、TNF-α、IFN-γ的分泌降低,细胞凋亡率[(13.55±1.35)比(28.14±2.83)]％降低,差异有统计学意义(P<0.05);与IL-1β+ALA+miR-NC组相比,IL-1β+ALA+miR-877组软骨细胞IL-6[(3.01±0.29)比(1.42±0.13)ng/L]、TNF-α、IFN-γ的分泌升高,细胞凋亡率[(25.47±2.53)比(11.68±1.87)]％增加,差异有统计学意义(P<0.05).结论 α-硫辛酸能够减轻IL-1β诱导的软骨细胞损伤,其机制与调控miR-877/NDRG2通路有关.     

哮喘大鼠肾上腺皮质功能变化与白细胞介素10水平的关系

目的 探讨哮喘大鼠肾上腺皮质功能变化与白细胞介素10(IL-10)水平的关系.方法 卵蛋白致敏方法制备大鼠哮喘模型,随机分为哮喘急性发作期组(A组)、哮喘缓解期组(B组)、正常对照组(C组)、模型对照组(D组),每组6只.放射免疫分析法测定血浆皮质酮(CORT)、促肾上腺皮质激素(ACTH)以及下丘脑促肾上腺皮质激素释放激素(CRH)的含量;ELASA法检测下丘脑组织和血浆IL-10的水平.结果 与C组比较,A组大鼠脑组织和血浆IL-10水平均下降[(15.45±4.06)Pg·mg-1·prot-1 vs.(28.74±8.91) pg·mg-1·prot-1,和(26.62±6.78)pg/ml vs.(54.86±14.32) pg/ml](P＜0.01);CORT、ACTH以及CRH的含量降低[(1.47±0.11) ng·mg-1·prot-1 vs.(1.84±0.12) pg·mg-1·prot-1,(75.55±8.17)pg/ml vs,(108.34±16.57) pg/ml,和(121.69±17.65) ng/ml vs.(162.01±21.21) ng/m1](P＜0.01).哮喘缓解期大鼠脑组织IL-10水平上升,CRH的含量增高.结论 哮喘大鼠存在肾上腺皮质功能减退可能与下丘脑和血中IL-10水平变化有关.     

小剂量沙利度胺与VAD方案治疗多发性骨髓瘤的效果及耐受性

目的 探讨小剂量沙利度胺与VAD方案治疗多发性骨髓瘤(MM)的效果及耐受性,为临床用药提供参考.方法 选取2011年12月至2014年12月本院收治的50例多发性骨髓瘤患者为研究对象,采用随机数字表法分为观察组和对照组,各25例.对照组采取标准VAD化疗方案,观察组在此基础上联合小剂量沙利度胺治疗,两组均以4周为1个疗程.对比分析治疗3个疗程时两组M蛋白、血管内皮生长因子(VEGF)、白细胞介素-6(IL-6)及骨髓浆细胞数,并应用Karnofsky功能状态评分评价两种方案疗效,同时观察两组不良反应如嗜睡、便秘、皮疹、感染等的发生率,比较耐受性.结果 治疗3个疗程,观察组M蛋白[(16.48±9.82) g/L]、VEGF[(251.54±124.69) pg/ml]、IL-6[(16.28±3.04) pg/ml]及骨髓浆细胞数[(4.42±2.18)％]显著低于对照组[(27.33±10.98)g/L、(376.27±123.43)pg/ml、(18.57±3.92)pg/ml、(10.01±3.21)％](P＜0.05),且观察组Karnofsky评分[(94.31±0.05)分]显著高于对照组[(81.24±0.03)分];观察组不良反应发生率与对照组比较,差异无统计学意义(60.0％ vs.44.0％,P＞0.05).结论 VAD方案治疗多发性骨髓瘤有一定疗效,但与小剂量沙利度胺联合治疗多发性骨髓瘤疗效明显较高,不会显著增加不良反应,是临床治疗的较好选择.     

病毒性脑炎病儿脑脊液中微小 RNA-21表达水平与辅助性 T细胞 17/调节性 T细胞平衡的相关性分析

目的 探讨病毒性脑炎病儿脑脊液中微小RNA-21(miR-21)表达水平与辅助性T细胞17(Th17)/调节性T细胞(Treg)平衡的相关性.方法 选取2017年9月至2019年7月在抚顺市中心医院就诊的病毒性脑炎病儿(观察组)108例作为研究对象,其中,轻症病儿(轻症组)57例,重症病儿(重症组)51例,选取同期抚顺市中心医院患病毒性脑炎后已康复的儿童(对照组)110例作为对照组.采集受试者脑脊液,实时荧光定量聚合酶链式反应(qRT-PCR)法检测miR-21相对表达量;酶联免疫(ELI?SA)法检测白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、白细胞介素-17(IL-17)、转化生长因子-β(TGF-β)水平;流式细胞仪分析Treg、Th17细胞水平;Pearson法分析病毒性脑炎病儿脑脊液中miR-21、Th17/Treg水平与IL-6、IL-10、IL-17、TGF-β水平,miR-21水平与Th17/Treg水平的相关性.结果 与对照组比较,观察组脑脊液中miR-21[(3.51±0.74)比(2.27±0.59)]、Th17[(3.14±0.62)％比(2.38±0.37)％]、Th17/Treg[(3.16±0.97)比(1.89±0.55)]、IL-6[(29.63±5.32)ng/L比(22.84±4.36)ng/L]、IL-17[(25.69±4.79)ng/L比(19.44±3.36)ng/L]水平明显升高(P<0.05),Treg[(1.04±0.23)％比(1.37±0.36)％]、IL-10[(29.68±5.22)ng/L比(36.87±6.63)ng/L]、TGF-β[(634.14±63.58)ng/L比(771.62±95.74)ng/L]水平明显降低(P<0.05);与轻症组相比,重症组病毒性脑炎病儿脑脊液中miR-21、Th17、Th17/Treg、IL-6、IL-17水平明显升高(P<0.05),Treg、IL-10、TGF-β水平明显降低(P<0.05);病毒性脑炎病儿脑脊液中miR-21水平、Th17/Treg水平与IL-6、IL-17水平,miR-21水平与Th17/Treg均明显正相关(P<0.05),miR-21水平、Th17/Treg水平与IL-10、TGF-β水平均明显负相关(P<0.05).结论 miR-21表达水平增加与Th17/Treg细胞平衡失衡密切相关,这一相关过程可能有IL-6、IL-10、IL-17、TGF-β的参与,可能均参与了病毒性脑炎的发病及病情加重过程.     

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.

     

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.     

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.     

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.     

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.