发育期镉染毒对小鼠大脑皮质单胺类递质含量的影响

选用出生２～３天的昆明种小鼠，每天腹腔注射镉０．０、０．５、１．０ｍｇ／ｋｇ体重，即对照组、低镉组、高镉组。染毒４５天，每组随机抽取１０只小鼠，雌雄各半，断头后分离出大脑皮质，用高效液相色谱仪进行大脑皮质单胺类递质含量的测定。结果显示，发育期镉染毒对小鼠大脑皮质ＮＥ、ＤＡ及ＤＡ代谢产物含量的作用不明显。低镉组５－ＨＴ含量较对照组明显降低，高镉组没有变化；５－ＨＴ代谢产物５－ＨＩＡＡ含量，低镉组没有明显改变，而高镉组较对照组明显增加。这可能是低剂量镉可阻止５－ＨＴ的合成，而高剂量镉促进了５－ＨＴ合成及转化或阻止了５－ＨＩＡＡ的进一步代谢。     

饲料锌对大鼠单胺类递质和锌,铜,铁含量的影响

为研究缺锌及高锌饲料影响大鼠脑发育和学习记忆的机理，选择断乳１～２天健康雄性Ｗｉｓｔａｒ大鼠，建立缺锌组（ＺＤ）、高锌组（ＺＨ）、对照组（ＡＬ）模型。采用原子分光光度计火焰法测定血清和脑锌、铜、铁含量，用ＨＰＬＣ电化学法测定脑组织单胺类递质的含量。结果表明：缺锌及高锌饲料影响大鼠生长发育、食欲和活动状况；ＺＤ组血清和脑锌、铁含量低于ＡＬ组，而脑铜含量高于ＡＬ组，ＺＨ组则血清锌明显高于ＡＬ组，而血清和脑铜、铁含量均明显低于ＡＬ组；ＺＤ组脑组织５ＴＨ及ＺＨ组脑ＮＥ和５ＴＨ明显低于ＡＬ组，而ＺＤ及ＺＨ组５ＨＩＡＡ则明显高于ＡＬ组。提示，缺锌与高锌时大鼠脑组织单胺类递质的紊乱及血清和脑组织锌、铜、铁水平的异常可能是大鼠脑发育和学习记忆障碍的生化基础之一。     

模拟4000米高原大鼠脑单胺变化研究

本文研究了大鼠在模拟４０００ｍ高原停留４８ｈ脑内单胺类物质，包括５－羟色胺（５-ＨＴ）、５－羟吲哚乙酸（５－ＨＩＡＡ）、去甲肾上腺素（ＮＥ）和多巴胺（ＤＡ）等含量的动态变化。结果表明，动物进入模拟高原后，脑内上述四种单胺类物质含量均有不同程度的增高，其变化机制可能与高原低氧或缺氧有关。     

二硫化碳对大鼠神经递质及其代谢产物的影响

目的探讨二硫化碳ＣＳ２的神经毒作用机理。方法应用高效液相色谱法，观察大鼠染毒ＣＳ２（０、１２００、２４００ｍｇ／ｍ３）２个月后，脑组织单胺类递质、氨基酸类神经递质及其代谢产物的改变。结果ＣＳ２染毒可使大鼠纹状体中３－甲氧－４－羟基扁桃酸含量下降，多巴胺代谢产物３，４－二羟基苯甲酸和高香草酸含量升高，兴奋性氨基酸及其代谢产物（谷氨酰胺、门冬氨酸和门冬酰胺）含量下降，且３－甲氧－４－羟基扁桃酸、门冬氨酸及门冬酰胺含量与动物行为改变之间具有一定的相关性。结论神经递质代谢紊乱在ＣＳ２的神经毒作用机理中起了重要作用。     

铁缺乏对大鼠肝脏及脑组织7种微量元素的影响

通过铁缺乏动物模型，观察了缺铁性贫血的非贫血期实验组和对照组大鼠肝脏及脑组织７种微量元素的变化。结果表明实验组大鼠肝脏、脑组织总铁和锌含量低于对照组，锰和铜含量高于对照组，硒、镉、铅变化不大。说明铁缺乏除可引起铁减少外，还存在其它元素的代谢紊乱。     

915 MHz电磁波对小鼠脑内神经递质含量的影响

目的 研究915MHz电磁波对小鼠脑组织内神经递质含量的影响,探索微波辐射对中枢神经系统影响的机制.方法 将1月龄清洁级健康雄性昆明小鼠随机分为高剂量组(5 mW/cm2)、低剂量组(2 mW/cm2)、对照组(除不进行电磁波辐射外,其余条件均与剂量组相同),每天从9:00开始,依次轮流暴露于915 MHz电磁场中,每组暴露2 h,连续暴露30 d.采用高效液相色谱-电化学法测定脑皮层、海马中的单胺类神经递质[去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)]及其代谢产物[多巴胺的代谢产物:3,4-二羟基苯乙酸(DOPAC),5-羟色胺的代谢产物:5-羟基吲哚乙酸(5-HIAA)]含量,采用碱性羟胺比色法测定剩余脑组织中乙酰胆碱(Ach)含量.结果 不同组别小鼠脑皮层、海马内NE、DA(海马内DA低于仪器检出限,不作比较)、5-HT、DOPAC、5-HIAA含量间比较,经方差分析,差异无统计学意义(P＞0.05).不同组别小鼠脑组织内乙酰胆碱(Ach)含量间比较,经方差分析,差异无统计学意义(P＞0.05).结论 经过915 MHz的电磁辐射,未发现小鼠大脑皮层、海马内的单胺类神经递质及其代谢产物含量以及脑组织内Ach含量发生改变.     

丙烯腈对大鼠脑单胺类神经递质及其代谢产物的影响

目的　评价长期低浓度接触丙烯腈对大鼠脑单胺类神经递质及其代谢产物的影响。方法　雄性SD大鼠 30只,随机分成对照组、低剂量组和高剂量组,每组 10只。通过饮水对大鼠进行丙烯腈染毒,分别给予 0、50和 200mg/L的丙烯腈溶液。染毒时间为 12周。染毒结束后从每组随机选取 7只大鼠迅速分离双侧纹状体和小脑皮层,测定单胺类神经递质及其代谢产物的浓度,并取大脑皮层测定单胺氧化酶活性。结果　随着染毒剂量的增加,低剂量组和高剂量组大鼠纹状体中的多巴胺含量分别降低到 (2 .2±0 .7)和 (3 .2±2 .0)μg/g脑湿重,与对照组的多巴胺含量 ( 9. 0±4.2)μg/g脑湿重比较,差异有统计学意义。3组大鼠小脑中的多巴胺未见减少,其代谢产物 3, 4 双羟苯乙酸分别为(186±41)、(245±90)和(115±65)ng/g脑湿重,低剂量组显著升高。3组染毒大鼠纹状体内的 5 羟色胺含量分别为 (249±34)、(155±95)和 (128±101)ng/g脑湿重,呈逐渐下降趋势,并具有显著的剂量 效应关系,但 3组大鼠小脑中的 5- 羟色胺及其代谢产物含量的变化无统计学意义。3组大鼠脑组织纹状体和小脑中的去甲肾上腺素及其代谢产物以及脑皮层单胺氧化酶活性的改变均无统计学意义。结论　丙烯腈对单胺类神经递质及其代谢产物的影响可能是其神经行为毒性的生物学     

沙棘汁对铅所致小鼠脑脂质过氧化和单胺类神经递质变化的影响

[目的] 研究沙棘汁对醋酸铅所致小鼠脑脂质过氧化、胆碱酯酶及。MAO-A、B活性及单胺类神经递质变化的影响。[方法] 采用硫代巴比妥酸比色法测定脂质过氧化作用中的中间产物MDA；碱性羟胺法测定胆碱酯酶活性；苄胺法测定。MAO-A、B活性；荧光法测定单胺类神经递质含量。[结果] 20d腹腔注射醋酸铅10mg／kg组小鼠，其脑组织MDA含量明显增多，胆碱酯酶活性升高，MAO-A、B活性增高，同时给予20％、40％沙棘汁可以不同程度地缓解这种脑组织神经生化改变。给铅组小鼠脑组织NE、5-HE、5-HIAA含量明显减少，80％沙棘汁能拮抗此种变化，但DA含量未见明显改变。[结论] 20％、40％沙棘汁能拮抗铅致小鼠脑脂质过氧化、胆碱酯酶及MAO-A、B活性及单胺类神经递质含量的改变。     

模拟高原大鼠梭曼中毒血液单胺类递质的变化

本研究采用荧光分光光度仪检测了模拟４０００ｍ高原大鼠复合梭曼中毒后不 清中５－羟色胺（５－ＨＴ）、５－羟吲哚乙酸（５－ＨＩＡＡ）、去甲肾上腺素（ＮＥ）、肾上腺素（Ｅ）和多巴胺（ＤＡ）等５种单胺物质的含量。结果表明：大鼠在模拟高的状态和复合中一道因中单胺物质的含量民平原对照相比，以及７２μｇ／ｋｇ中毒组与５６μｇ／ｋｇ中毒组和高原对照组相比，明显同（Ｐ〈０．０１）。提示高原复合梭曼中体内单胺类物质的     

铅染毒对大鼠神经行为功能及神经化学的影响

作者研究了铅染毒对大鼠神经行为功能、海马中单胺类递质及脑组织脂质过氧化水平的影响。结果显示，１ ３３３．３ｍｇ／ｋｇ剂量组（Ｐｂ－Ｂ为６．２３μｍｏｌ／Ｌ）大鼠学习记忆能力受到影响，２６６．７ｍｇ／ｋｇ（Ｐｂ－Ｂ为４．２０μｍｏｌ／Ｌ）和１３３３．３ｍｇ／ｋｇ剂量组大鼠的运动改变，情绪状态不稳定；海马中多巴胺递质及其代谢产物含量有随染毒剂量增高而降低的趋势，而脑组织中脂质过氧化水平有随染毒剂量升高     

Synthesis and anticancer activities of amphiphilic 5-fluoro-2'-deoxyuridylic acid prodrugs

Amphiphilic anticancer prodrugs of 5'-fluoro-2'-deoxyuridine-5'-monophosphate (5-FdUMP) were synthesized according to the hydrogen phosphonate method by coupling lipophilic cytosine derivatives or a phospholipid with 5-fluoro-2'-deoxyuridine (5-FdU). Studies within the in vitro Anticancer Screen Program of the National Cancer Institute have demonstrated high anticancer activities of the heterodinucleoside phosphates: N4-palmitoyl-2'-deoxycytidylyl-(3' --> 5')-3'-O-acetyl-5-fluoro-2'-deoxyuridine (dC(pam)-5-FdU(Ac), N4-palmitoyl-2',3'-dideoxycytidylyl-(5' --> 5')-3'-O-acetyl-5-fluoro-2'-deoxyuridine (ddC(pam)-(5' --> 5')-5-FdU(Ac), 5-fluoro-2'-deoxyuridylyl-(3' --> 5')-5-fluoro-N4-hexadecyl-2'-deoxycytidine (5-FdU-5-FdC(hex)), and of the new liponucleotide 1-O-octadecyl-rac-glycerylyl-(3 --> 5')-5-fluoro-2'-deoxyuridine (Oct1Gro-(3 --> 5')-5-FdU). The anticancer activities of these prodrugs are comparable to those of 5-FdU and the tumor specificities are modulated by their structures. The highest cytotoxic activity being even superior to 5-FdU was expressed by the dimer 5-FdU-5-FdC(hex).     

Synthesis, stereochemistry, and antimicrobial evaluation of substituted piperidin-4-one oxime ethers

In a wide search program toward new and efficient antimicrobial agents, a series of substituted piperidin-4-one oxime ethers (5a-5k) was synthesized and tested for their in vitro antibacterial and antifungal activities. Also, the structures of these oxime ethers and their relative stereochemistries have been investigated by nuclear magnetic resonance spectroscopy. In all the oxime ethers synthesized, the orientation of the N-O bond of the oxime ether moiety syn to C-5 (E-isomer) was deduced based on (1)H NMR and (13)C NMR spectra. It was found that the sterically less hindered compounds, either C-3 (H) and C-5 (H)- or C-3 (Me) and C-5 (H) -substituted ones 5a, 5c, 5d, 5f, 5g, 5i and 5j prefer chair conformation, whereas the sterically more hindered C-3 (Me) and C-5 (Me) -substituted ones 5b, 5e, 5h, and 5k prefer twist-boat conformation. Among the oxime ethers tested, 1,3,5-trimethyl-2,6-diphenylpiperidin-4-one O-(2-chlorophenylmethyl)oxime (5h) exhibited good antibacterial property against Bacillus subtilis, with minimum inhibitory concentration (MIC) closer to that of reference drug, streptomycin. Compounds, 1,3-dimethyl-2,6-diphenylpiperidin-4-one O-(2-chlorophenylmethyl)oxime (5g) and 1,3-dimethyl-2,6-diphenylpiperidin-4-one O-(2-bromophenylmethyl)oxime (5j) showed potent antifungal activity against Aspergillus flavus and Candida-51, respectively. The later compound 5j is more active than the reference drug while the activity of the former one 5g is similar to that of the reference drug, amphotericin B in terms of MIC. The present results may be used as key steps for the construction of novel chemical entities with better pharmacological profiles than standard drugs.     

Synthesis of some new 5-(2-substituted-1,3-thiazol-5-yl)-2-hydroxy benzamides and their 2-alkoxy derivatives as possible antifungal agents

The 2-hydroxy-5-(1,3-thiazol-5-yl) benzamide (4a), 5-(2-amino-1, 3-thiazol-5-yl)-2-hydroxy benzamide (4b), 2-hydroxy-5-(2-alkyl-1,3-Thiazol-5-yl) benzamide (4c and 4d), 5-(2-[(N-substituted aryl)amino]-1,3-thiazol-5-yl)2-hydroxy benzamides (6a-j) were prepared by reacting 5-(bromoacetyl) salicylamide (2) with thiourea, thioformamide, thioalkylamide (3c-d) and substituted thioureas (5a-j) in absolute ethanol. These compounds were converted to 5-(2-substituted-1,3-thiazol-5-yl)-2-alkoxybenzamides and 5-(2-N-(substituted aryl)-1,3-thiazol-5-yl)-2-alkoxy benzamides (8a-g) by reacting with n-alkylbromides (7a-b) in presence of a base. The newly synthesized compounds were characterized by IR, (1)H-NMR and mass spectral data. Compounds were also screened for their antifungal activity.     

Pharmacokinetics of Sodium and Calcium Salts of (6S)-5-Methyltetrahydrofolic Acid Compared to Folic Acid and Indirect Comparison of the Two Salts

(6S)-5-Methyltetrahydrofolic acid ((6S)-5-Methyl-THF) salts and folic acid may differ in their abilities to raise plasma (6S)-5-Methyl-THF levels. We compared the area under the curve (AUC), C_max, and T_max of plasma (6S)-5-Methyl-THF after intakes of (6S)-5-Methyl-THF-Na salt (Arcofolin^®) and folic acid. Moreover, we compared the AUCs after intakes of (6S)-5-Methyl-THF-Na and the calcium salt, (6S)-5-Methyl-THF-Ca, that were tested against folic acid in two independent studies. The study was randomized, double blind, and cross over. Twenty-four adults (12 men and 12 women) received a single oral dose of 436 µg (6S)-5-Methyl-THF-Na and an equimolar dose of folic acid (400 µg) on two kinetic days with two weeks washout period in between. The plasma concentrations of (6S)-5-Methyl-THF were measured at 9 time points between 0 and 8 h. We found that the AUC_{0–8 h} of plasma (6S)-5-Methyl-THF (mean (SD) = 126.0 (33.6) vs. 56.0 (25.3) nmol/L*h) and C_max (36.8 (10.8) vs. 11.1 (4.1) nmol/L) were higher after administration of (6S)-5-Methyl-THF-Na than after the administration of folic acid (p < 0.001 for both). These differences were present in men and women. Only administration of folic acid resulted in a transient increase in plasma unmetabolized folic acid (2.5 (2.0) nmol/L after 0.5 h and 4.7 (2.9) nmol/L after 1 h). Intake of (6S)-5-Methyl-THF-Na was safe. The ratios of the AUC_{0–8 h} for (6S)-5-Methyl-THF-Na and (6S)-5-Methyl-THF-Ca to the corresponding folic acid reference group and the delta of these AUC_{0–8 h} did not differ between the studies. In conclusion, a single oral dose of (6S)-5-Methyl-THF-Na caused higher AUC_{0–8 h} and C_max of plasma (6S)-5-Methyl-THF compared to folic acid. The Na- and Ca- salts of (6S)-5-Methyl-THF are not likely to differ in their pharmacokinetics. Further studies may investigate whether supplementation of the compounds for a longer time will lead to differences in circulating or intracellular/tissue folate concentrations.     

New potent 5-HT(2A) receptor ligands containing an N'-cyanopicolinamidine nucleus: Synthesis and in vitro pharmacological evaluation

N'-cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to serotonin 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical for affinity to 5-HT(1A) receptors and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT(2A) and moderate to no affinity for other relevant receptors (5-HT(1A), 5-HT(2C), D(1), D(2), α(1) and α(2)). N'-cyano-N-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-picolinamidine (4l) with K(i)=0.000185nM, was the most active and selective derivative for the 5-HT(2A) receptor compared to other serotoninergic, dopaminergic and adrenergic receptors.     

Synthesis and preliminary evaluation of new 5-pyrazolinone derivatives as analgesic agents

New 4-(aroyloxyalkanoyl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one s (5) were cyclized to 4-(2-aryl-5-unsubstituted/substituted oxazol-4-yl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-ones (6) employing the Davidson procedure. Preliminary evaluation of analgesic activity revealed that the effect of 4-(2-phenyl-5-ethyloxazol-4-yl)-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-chlorophenyl)-5-ethyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazoline-5-one on acetic acid induced writhing was superior to that of antypyrine and aminopyrine. 4-[2-(4-Chlorophenyl)-5-methyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-methoxyphenyl)-5-ethyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one were more potent than aminopyrine, whereas 4-(2-phenyl-5-methyloxazol-4-yl)-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-methoxyphenyl)-5-methyl-oxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one were not as active (modified Koster's Test; 0.19-0.21 mmol.kg(-1)). None of the selected entries showed inhibition of formaldehyde-induced paw oedema.     

Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker

OBJECTIVES: The aims were to study the toxicokinetics of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) in blood and urine after exposure to N-methyl-2-pyrrolidone (NMP) and to study the suitability of 5-HNMP as a biomarker for assessing NMP exposure. METHODS: Six male volunteers were exposed for 8 hours to NMP concentrations of 0, 10, 25, and 50 mg/m3. Blood and urine were sampled before, during, and up to 40 hours after exposure. Aliquots of urine and plasma were purified, derivatized, and analyzed for 5-HNMP on a gas chromatograph/mass spectrometer in the electron impact mode. RESULTS: The mean plasma concentration [P-(5-HNMP)] after 8-hour NMP exposure to 10, 25, and 50 mg/m3 was 8.0, 19.6, and 44.4 micromol/l, respectively. The mean urinary concentration [U-(5-HNMP)] for the 2 last hours of exposure was 17.7, 57.3, and 117.3 mmol/mol creatinine, respectively. The maximal P-(5-HNMP)and U-(5-HNMP) concentrations occurred 1 hour and 0-2 hours, respectively, after the exposure. The half-times of P-(5-HNMP) and U-(5-HNMP) were 6.3 and 7.3 hours, respectively. The 5-HNMP urinary concentrations were 58% of the calculated retained dose. There was a close correlation (r) between P-(5-HNMP) (r=0.98) and U-(5-HNMP) (r=0.97) with NMP exposure. CONCLUSIONS: 5-HNMP is an excellent biomarker for assessing exposure to NMP. Its plasma and urinary half-times (6-7 hours), the minimal risk for contamination during sampling in occupational settings, and the close correlation of P-(5-HNMP) and U-(5-HNMP) with NMP exposure makes 5-HNMP suitable for monitoring exposure to NMP. 5-HNMP in plasma is recommended.     

Maternal antibody inhibition of recombinant Newcastle disease virus vectored vaccine in a primary or booster avian influenza vaccination program of broiler chickens

Maternally-derived antibodies (MDA) provide early protection from disease, but may interfere with active immunity in young chicks. In highly pathogenic avian influenza virus (HPAIV)-enzootic countries, broiler chickens typically have MDA to Newcastle disease virus (NDV) and H5 HPAIV, and their impact on active immunity from recombinant vectored vaccines is unclear. We assessed the effectiveness of a spray-applied recombinant NDV vaccine with H5 AIV insert (rNDV-H5) and a recombinant turkey herpesvirus (HVT) vaccine with H5 AIV insert (rHVT-H5) in commercial broilers with MDA to NDV alone (MDA:AIV⁻NDV⁺) or to NDV plus AIV (MDA:AIV⁺NDV⁺) to provide protection against homologous HPAIV challenge. In Experiment 1, chicks were spray-vaccinated with rNDV-H5 at 3 weeks (3w) and challenged at 5 weeks (5w). All sham-vaccinated progeny lacked AIV antibodies and died following challenge. In rNDV-H5 vaccine groups, AIV and NDV MDA had completely declined to non-detectable levels by vaccination, enabling rNDV-H5 spray vaccine to elicit a protective AIV antibody response by 5w, with 70–78% survival and significant reduction of virus shedding compared to shams. In Experiment 2, progeny were vaccinated with rHVT-H5 and rNDV-H5 at 1 day (1d) or 3w and challenged at 5w. All sham-vaccinated progeny lacked AIV antibodies and died following challenge. In rHVT-H5(1d) vaccine groups, irrespective of rNDV-H5(3w) boost, AIV antibodies reached protective levels pre-challenge, as all progeny survived and virus shedding significantly decreased compared to shams. In contrast, rNDV-H5-vaccinated progeny had AIV and/or NDV MDA at the time of vaccination (1d and/or 3w) and failed to develop a protective immune response by 5w, resulting in 100% mortality after challenge. Our results demonstrate that MDA to AIV had minimal impact on the effectiveness of rHVT-H5, but MDA to AIV and/or NDV at the time of vaccination can prevent development of protective immunity from a primary or booster rNDV-H5 vaccine.     

DL- and PO-phosphatidylcholines as a promising learning and memory enhancer

In the water maze test, oral administration with 1,2-dilynoleoyl- sn -glycero-3-phosphocholine (DLPhtCho)(5 mg/kg) alone or DLPhtCho (5 mg/kg) plus 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPhtCho)(5 mg/kg) significantly shortened the prolonged acquisition latency for rats intraperitoneally injected with scopolamine, with more efficient effect than (POPhtCho)(5 mg/kg) alone, arachidonic acid (AA)(5 mg/kg) alone, docosahexaenoic acid (DHA)(5 mg/kg) alone, or 1-palmitoyl-2-linoleil- sn -glycero-3-phosphoserine (PLPhtSer)(5 mg/kg) alone. POPhtCho (5 mg/kg) alone or DLPhtCho (5 mg/kg) plus POPhtCho (5 mg/kg) also significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine, but otherwise no significant effect was obtained with DLPhtCho (5 mg/kg) alone, AA (5 mg/kg) alone, DHA (5 mg/kg) alone, or PLPhtSer (5 mg/kg) alone. Oral co-administration with DLPhtCho (5 mg/kg) and POPhtCho (5 mg/kg) significantly shortened the acquisition latency for rats untreated with scopolamine as compared with the latency for administration with polyethylene glycol (PEG), DLPhtCho alone at doses of 5 and 10 mg/kg, or POPhtCho alone at doses of 5 and 10 mg/kg, while no efficient effect on the retention latency was obtained. To assess the effect of DLPhtCho and POPhtCho on cognitive functions for humans, Mini Mental State Examination (MMSE) test was performed in subjects with cognitive disorders (the average MMSE score, 15). Oral co-intake with DLPhtCho (50 mg) and POPhtCho (45 mg) once after breakfast everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 5 months after intake, and the increase in the score was significantly greater than that for oral intake with DLPhtCho (100 mg/day) alone or POPhtCho (90 mg/kg) alone. Taken together, the results of the present study show that co-intake with DLPhtCho and POPhtCho could enhance learning and memory ability and improve cognitive disorders for both the animals and humans with a promising efficacy.     

Sex-specific differences in mortality after high-titre measles immunization in rural Senegal.

Administration of high-titre measles vaccine (Edmonston-Zagreb (EZ) at > 10(5) plaque-forming units (PFU) per dose) before the age of 9 months has been recommended in areas with high measles mortality before the routine age of immunization after 9 months. The study compares the long-term survival after high-titre measles immunization at 5 months of age with that following routine immunization with standard-titre vaccine at 10 months of age. At 5 months of age the high-titre group received Edmonston-Zagreb (EZ-HT, 5 months) or Schwarz (SW-HT, 5 months) at titres > 10(5) PFU per dose, while the standard-titre group received placebo at 5 months of age and < 10(4) PFU per dose of Schwarz vaccine at 10 months (SW-std, 10 months). All the children were followed up to at least 36 months of age. The mortality ratio (MR) for infants in the EZ-HT, 5 months and SW-HT, 5 months groups was 1.32 (P = 0.089) and 1.45 (P = 0.092), respectively, which did not differ significantly from that of recipients of the SW-std, 10 months. The higher MR among recipients of the high-titre vaccines was due to the significantly lower survival among females compared with the females who received SW-std vaccine (EZ-HT, 5 months MR = 1.76, P = 0.013; SW-HT, 5 months MR = 2.14, P = 0.017). For children aged 5-10 months the high-titre measles vaccine did not increase mortality relative to unvaccinated children who had received placebo.