Sensitization to social anxiolytic effects of ethanol in adolescent and adult Sprague-Dawley rats after repeated ethanol exposure

Ontogenetic studies using a social interaction paradigm have shown that adolescent rats are less sensitive to anxiolytic properties of acute ethanol than their adult counterparts. It is not known, however, whether adaptations to these anxiolytic effects on repeated experiences with ethanol would be similar in adolescents and adults. The present study investigated sensitivity to the anxiolytic effects of ethanol in adolescent and adult male and female Sprague-Dawley rats after 7 days of exposure (postnatal day [P] 27-33 for adolescents and P62-68 for adults) to 1 g/kg ethanol or saline (intraperitoneally]) and in animals left nonmanipulated during this time. Anxiolytic effects of ethanol (0, 0.75, 1.0, 1.25, and 1.5 g/kg for adolescents and 0, 0.25, 0.5, 0.75, 1.0, and 1.25 g/kg for adults in experiments 1 and 2, respectively) were examined 48 h after the last exposure using a modified social interaction test under unfamiliar test circumstances. At both ages, repeated ethanol exposure resulted in the development of apparent sensitization to anxiolytic effects of ethanol, indexed by enhancement of social investigation and transformation of social avoidance into social indifference or preference and expression of tolerance to the socially inhibiting effects induced by higher ethanol doses. Evidence for the emergence of sensitization in adults and tolerance at both ages was seen not only after chronic ethanol but also after chronic saline exposure, suggesting that chronic manipulation per se may be sufficient to alter the sensitivity of both adolescents and adults to socially relevant effects of ethanol.     

Chronic ethanol exposure alters dopaminergic signal transduction processes

A number of data suggest that the chronic ethanol treatment induces derangements of cell membrane structure leading to modifications of membrane related processes. In particular, alterations have been observed in the mechanisms of neurotransmitter recognition and in the coupling of the receptor with the effector system. Phosphorylation of specific proteins by cyclic AMP stimulated protein kinases represent the final step in the biological response in several distinct functional processes. Ethanol neurotoxic action therefore may affect neurotransmitter availability and release as well as receptors effector systems and protein phosphorylation. In this line, chronic ethanol treatment in rats decreases cyclic AMP dependent protein kinase activity in rat striatal membrane fractions. When lysine rich histone type III was used as exogenous substrate, cyclic AMP stimulated 32P incorporation was still decreased in the ethanol group. These data favor the hypothesis of a decreased capability of the enzyme to phosphorylate in response to cAMP.     

Effects of ethanol administration on corticosterone levels in adolescent and adult rats

Adolescent humans and rodents have been shown to consume more alcohol than their adult counterparts. Given that corticosterone (CORT) has been shown to be related to the intake of several drugs of abuse, this study assessed the ontogenetic effects of low-moderate doses of ethanol on CORT increases and recovery. Despite no significant differences in baseline (home cage) CORT levels, CORT responses to ethanol were greater in females than in males and in adult females than in adolescent females; males, however, showed less marked age differences in CORT levels after ethanol consumption. Adolescent blood ethanol concentrations (BECs) were lower than those of adults, although these BEC differences appear insufficient to account for the ontogenetic differences in CORT levels. Collectively, these findings suggest that it is unlikely that age differences in CORT elevations provide a major contribution to the ontogenetic differences in alcohol intake seen between adolescents and adults.     

铅对仔鼠海马蛋白激酶C和钙调蛋白表达的影响

目的 研究慢性铅染毒对不同发育时期仔鼠海马蛋白激酶C(PKC)、钙调蛋白(CaM)表达的影响.方法 孕鼠随机分为蒸馏水对照组、0.2%醋酸铅和1.0%醋酸铅组,从怀孕第0灭起开始通过自由饮水染毒.幼鼠出生后,先通过哺乳接触铅,断乳后则自行饮用与其母鼠浓度相同的含铅水.分别于出生后8、50 d处死仔鼠,原子吸收光谱法测定脑铅含量,Western-blotting法观察各组仔鼠海马PKC、CaM的蛋白表达情况.结果 同一发育时期的染铅组仔鼠脑铅含量明显高于对照组,差异有统计学意义(P＜0.01).同一剂量染铅组出生后50 d仔鼠脑铅含最明显高于出生后8 d,差异有统计学意义(P＜0.01).不同发育时期的染铅组仔鼠海马的PKC、CaM的蛋白表达均相应地下降,与对照组相比,差异有统计学意义(P＜0.05).结论 仔鼠海马PKC、CaM的蛋白表达降低可能是铅致仔鼠学习记忆功能损害的分子机制之一.     

Chronic intermittent ethanol exposure during adolescence: Effects on social behavior and ethanol sensitivity in adulthood

This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45 and P65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later in life.     

Autonomic responses to ethanol in adolescent and adult rats: a dose-response analysis

Athough the exact cause of the increase in ethanol consumption during adolescence is not known, age differences in sensitivity to some of ethanol's effects may play a contributory role. Prior research has shown little difference in the expression of ethanol-induced tachycardia between adolescents and adults following ethanol inhalation. In contrast, there is mounting evidence of ontogenetic differences in ethanol-induced hypothermia, although the nature of the ontogenetic effect observed has been found to vary across studies and even within labs. Relative ontogenetic differences in body temperature (BT) after ethanol administration appear to be driven in part by the amount of experimental perturbation associated with the test protocol, although differing ethanol exposure levels across studies may also have contributed to the variations in ontogenetic patterns that have been observed. To explore the latter possibility, the present study assessed ethanol-induced hypothermia and tachycardia in adolescent and adult male Sprague-Dawley rats examined in their home cages in the presence of their housing partner following intraperitoneal administration of 0.5, 1.5, or 3.0 g/kg ethanol. The results showed that, although adolescents did not show an adult-typical tachycardic effect at any dose, they proved more sensitive than adults to ethanol's hypothermic effects at the two highest doses. These findings suggest that not only the degree of experimental perturbation, but also the amount of ethanol exposure may differentially effect expression of age differences in ethanol-induced hypothermia, with adolescents showing greater hypothermia than adults at higher doses. Together with previous findings, these data contribute to the emerging picture that age differences in autonomic effects of ethanol appear to be particularly sensitive to dosing parameters and experimental protocols, unlike the generally more consistent ontogenetic findings observed across studies when using behavioral measures of ethanol sensitivity.     

Developmental differences in EEG and sleep responses to acute ethanol administration and its withdrawal (hangover) in adolescent and adult Wistar rats

Age-related differences in sensitivity to the acute effects of alcohol may play an important role in the increased risk for the development of alcoholism seen in teens that begin drinking at an early age. The present study evaluated the acute and protracted (hangover) effects of ethanol in adolescent (P33–P40) and adult (P100–P107) Wistar rats, using the cortical electroencephalogram (EEG). Six minutes of EEG was recorded during waking, 15 min after administration of 0, 1.5, or 3.0 g/kg ethanol, and for 3 h at 20 h post ethanol, during the rats' next sleep cycle. Significantly higher overall frontal and parietal cortical power was seen in a wide range of EEG frequencies in adolescent rats as compared to adult rats in their waking EEG. Acute administration of ethanol did not produce differences between adolescents and adults on behavioral measures of acute intoxication. However, it did produce a significantly less intense acute EEG response to ethanol in the theta frequencies in parietal cortex in the adolescents as compared to the adults. At 20 h following acute ethanol administration, during the rats' next sleep cycle, a decrease in slow-wave frequencies (1–4 Hz) was seen and the adolescent rats were found to display more reduction in the slow-wave frequencies than the adults did. The present study found that adolescent rats, as compared to adults, demonstrate low sensitivity to acute ethanol administration in the theta frequencies and more susceptibility to disruption of slow-wave sleep during hangover. These studies may lend support to the idea that these traits may contribute to increased risk for alcohol use disorders seen in adults who begin drinking in their early teenage years.     

A single exposure to voluntary ethanol self-administration produces adaptations in ethanol consumption and accumbal dopamine signaling

In well-trained animals, accumbal dopamine release is stimulated during operant ethanol self-administration, but the time course of development of this dopaminergic response, particularly during the acquisition of ethanol drinking behavior, remains unknown. To examine this, we trained male Long-Evans rats to self-administer 10% ethanol plus 10% sucrose, using a protocol in which the concentration of ethanol was kept constant throughout the study. The animals were required to press the lever four times to gain continuous access to the drinking solution for 20 minutes, and microdialysis was performed on either the first or second day of 10% ethanol plus 10% sucrose self-administration or 10% sucrose as controls. Ethanol and dopamine were both analyzed in the dialysates. All groups (day 1 and 2 ethanol and their corresponding sucrose controls) showed an increase in accumbal dopamine during the transfer from the home cage into the operant chamber. Our main finding was an increase in dopamine in the nucleus accumbens core-shell border during the first 5 minutes of consumption on the second day but not on the first day of ethanol self-administration. Our results suggest that a single exposure to a 10% ethanol plus 10% sucrose drinking solution may be sufficient to learn the association between ethanol cues and its reinforcing properties. Furthermore, we speculate that the dopamine response during ethanol consumption likely reflects the reward-prediction role of the mesolimbic dopamine system.     

Dose-dependent increase and decrease in active glucose uptake in jejunal epithelium of broilers after acute exposure to ethanol

Little is known about the effects of ethanol on gastrointestinal tract of chicken. In this study, we investigated the effects of low levels of ethanol on electrophysiological variables of jejunal epithelium of commercial broilers. Jejunal tissues from 35- to 39-day-old broilers were exposed to either 0 or 0.1% ethanol in Ussing chambers, and electrophysiological variables were monitored for 40 min. After 40 and 60 min of incubation, glucose (20 mM) and carbamoylcholine (200 μM), respectively, were introduced into the chambers. The absolute and percent increase in short-circuit current (I_sc) and potential difference (V_t) induced by glucose were increased significantly with 0.1% ethanol. There was no significant effect of 0.1% ethanol on carbamoylcholine-induced electrophysiological variables. To investigate if higher levels of ethanol have similar effects, we tested the effects of 0, 0.33, and 0.66% ethanol under similar experimental conditions until the glucose-addition step. Contrary to 0.1% ethanol, both the 0.33 and 0.66% ethanol levels significantly decreased the basal and glucose-induced I_sc and V_t. Tissue conductivity remained unaffected in all cases. These results indicate that intestinal epithelia of chicken may be more sensitive to the effects of ethanol as compared with other species. This is the first report indicating dose-dependent increase and decrease in active glucose absorption in intestinal epithelia in the presence of ethanol.     

Effect of acute ethanol and acute allopregnanolone on spatial memory in adolescent and adult rats

The effects of ethanol differ in adolescent and adult rats on a number of measures. The evidence of the effects of ethanol on spatial memory in adolescents and adults is equivocal. Whether adolescents are more or less sensitive to ethanol-induced impairment of spatial memory acquisition remains unclear; with regard to the effects of acute ethanol on spatial memory retrieval there is almost no research looking into any age difference. Thus, we examined the effects of acute ethanol on spatial memory in the Morris Watermaze in adolescents and adults. Allopregnanolone (ALLO) is a modulator of the GABA_A receptor and has similar behavioral effects as ethanol. We sought to also determine the effects of allopreganolone on spatial memory in adolescent and adults. Male adolescent (post natal [PN]28-30) and adult (PN70-72) rats were trained in the Morris Watermaze for 6 days and acute doses of ethanol (saline, 1.5 and 2.0 g/kg) or ALLO (vehicle, 9 and 18 mg/kg) were administered on Day 7. A probe trial followed on Day 8. As expected, there were dose effects; higher doses of both ethanol and ALLO impaired spatial memory. However, in both the ethanol and ALLO conditions adolescents and adults had similar spatial memory impairments. The current results suggest that ethanol and ALLO both impair hippocampal-dependent spatial memory regardless of age in that once learning has occurred, ethanol or ALLO does not differentially impair the retrieval of spatial memory in adolescents and adults. Given the mixed results on the effect of ethanol on cognition in adolescent rats, additional research is needed to ascertain the factors critical for the reported differential results.     

Dietary polyphenols identified as intracellular protein kinase A inhibitors

Background  Dietary plants contain several thousands different polyphenols that can potentially influence normal and pathological cellular processes through modulation of intracellular signaling pathways. A few polyphenols have been shown to be potent inhibitors of protein kinases. Aims of study  To identify possible dietary protein kinase A (PKA) inhibitors we designed a method for screening of substances in crude mixtures of food items for modulation of intracellular PKA activity that enables high-throughput testing of a large number of compounds and extracts. Methods  Luciferase was mutated to render it sensitive to phosphorylation by PKA (luciferase^PKA) and transfected into a human hepatoma cell line (HepG2). Cells were then treated with extracts from dietary plants, including berries, fruits and spices, and intracellular PKA-activity was assessed by change in bioluminescence in live cells by imaging. Results  Several extracts were found to inhibit PKA activity in a 96-well platform high-throughput screen. Green tea, crowberry, clove and cinnamon extracts were found to reduce intracellular cAMP levels consistent with their ability to increase luminescence from luciferase^PKA. Also pomegranate extract inhibited intracellular PKA and was used to estimate cellular association of polyphenols by HPLC and LC–MS. Pomegranate extract contains several anthocyanins, including delphinidin-3 glucoside. Delphinidin aglycone was found to inhibit cellular PKA activity in a concentration dependent manner. The inhibitory activity was found to be structure specific as a closely related compound to delphinidin had no activity. Conclusion  The current work identify phytochemicals in crude extracts which modulate cell signaling through PKA in a way that facilitate high through-put screening to help elucidate how plant based diet reduce risks of chronic diseases.     

Effect of acute and chronic ethanol treatment on renal prostaglandins in the rat

To study the effects of ethanol on renal prostaglandins (PGs), we gave rats a dose of 3.0 g/kg body weight either as a single IP injection (acute treatment) or daily IP injections of the same dose for 23 consecutive days (chronic treatment). The availability of PG precursors was evaluated from the post mortem accumulation of PGF_2α in kidney as determined by gas chromatography—mass spectrometry, and the renal excretion of PGF_2α was measured by radioimmunoassay. Acute ethanol treatment had no dramatic effect on either tissue levels or urinary excretion rate of PGF_2α but chronic ethanol treatment significantly lowered renal PGF_2α levels. In another experiment we employed liquid ethanol diets and a pair feeding technique for 12 days to achieve tolerance and physical dependence on ethanol. The levels of PGF_2α and 6-keto PGF_1α were measured in kidney in rats killed at 2, 6, and 12 days post-treatment. The kidney levels of both prostaglandins were lowered throughout the period of chronic ethanol exposure but returned to normal within five days after withdrawal. Thus, chronic but not acute ethanol treatment leads to a depletion of the renal stores of prostaglandin precursors in the rat.     

Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice

Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared with group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition, experience with CVS early in life results in elevated ethanol intake later in adulthood. Taken together, these results emphasize the important role of early stress experiences that modulate later voluntary ethanol intake during adulthood.     

Role of acute ethanol exposure and TLR4 in early events of sepsis in a mouse model

Sepsis is a major cause of death worldwide. The associated risks and mortality are known to significantly increase on exposure to alcohol (chronic or acute). The underlying mechanisms of the association of acute ethanol ingestion and poor prognosis of sepsis are largely unknown. The study described here was designed to determine in detail the role of ethanol and TLR4 in the pathogenesis of the sepsis syndrome. The effects of acute ethanol exposure and TLR4 on bacterial clearance, spleen cell numbers, peritoneal macrophage numbers, and cytokine production were evaluated using wild-type and TLR4 hyporesponsive mice treated with ethanol and then challenged with a nonpathogenic strain of Escherichia coli. Ethanol-treated mice exhibited a decreased clearance of bacteria and produced lesser amounts of most pro-inflammatory cytokines in both strains of mice at 2 h after challenge. Neither ethanol treatment nor a hyporesponsive TLR4 had significant effects on the cell numbers in the peritoneal cavity and spleen 2 h postinfection. The suppressive effect of acute ethanol exposure on cytokine and chemokine production was more pronounced in the wild-type mice, but the untreated hyporesponsive mice produced less of most cytokines than untreated wild-type mice. The major conclusion of this study is that acute ethanol exposure suppresses pro-inflammatory cytokine production and that a hyporesponsive TLR4 (in C3H/HeJ mice) decreases pro-inflammatory cytokine levels, but the cytokines and other mediators induced through other receptors are sufficient to ultimately clear the infection but not enough to induce lethal septic shock. In addition, results reported here demonstrate previously unknown effects of acute ethanol exposure on leukemia inhibitory factor and eotaxin, and provide the first evidence that interleukin (IL)-9 is induced through TLR4 in vivo.     

西洛他唑及阿斯匹林对老年ACS患者血小板聚集功能及蛋白激酶B活性变化的影响

目的 探讨西洛他唑对老年急性冠状动脉综合征（ACS）患者血小板聚集功能及蛋白激酶B（PKB）活性变化的影响。方法 ACS患者48例，随机分为两组，即西洛他唑（CS）组（26例）和阿斯匹林（AS）组（22例）；26例健康老年人为对照组（NC组）。cs组在常规抗凝治疗的同时给予西洛他唑100mg口服；AS组给予阿斯匹林300mg口服。于用药前10min及用药7d后（从当日晨起服药时开始计时）的3．5、6．0、24．0h分别测定血小板聚集率（PLTAR）。结果 所有老年ACS患者血小板最大聚集率均较NC组明显增加（P〈0．01），胞膜PKB表达较NC组明显增高（P〈0．01），而胞浆PKB表达则显著降低（P〈0．01）。口服CS、AS7d后6．0h血小板最大聚集率较用药前降低最明显（P〈0．01），但24．0h时CS对血小板聚集仍有较强的抑制作用，而AS已不明显。口服CS 7d后6．0hCS组患者血小板胞膜PKB活性较用药前明显下降（P〈0．01）；而胞浆PKB表达则已明显升高。AS组二项指标虽有所变化．但用药前后比较差异无统计学意义。结论 老年ACS患者体内血小板处于活化状态，CS能有效抑制血小板活化．作用优于AS。     

A correlation between voluntary ethanol consumption and brain catalase activity in the rat

The relationship between voluntary ethanol consumption and brain catalase activity was investigated in male Long Evans rats. In the first study, rats which were voluntarily consuming alcohol or water for 25 days were sacrificed by decapitation immediately (group A) or 15 days (group B) following withdrawal of alcohol and their brains analysed for catalase activity. Mean brain catalase activity did not differ among the two groups of rats exposed to ethanol and the ones exposed to water only. Furthermore, there were significant positive correlations between individual voluntary ethanol intake and catalase activity in both groups, (group A:r = .69, p less than or equal to 0.05; group B:r = .54, p less than or equal to 0.05). In the second study, rats were forced to drink high levels of ethanol presented as the only source of fluid for 25 days. Rats were sacrificed and brain, liver, muscle and heart tissue were extracted and analysed for catalase activity. There were no differences in mean brain catalase activity between water and forced ethanol drinking rats indicating that the enzyme was not inducible by high volume ethanol consumption. The results suggest that inherent differences in brain catalase activity may be one of the factors in determining an animal's propensity to voluntarily consume ethanol.     

Effect of pre- and postnatal ethanol exposure on protein tyrosine kinase activity and its endogenous substrates in rat cerebral cortex.

The rat brain contains high levels of tyrosine-specific protein kinases (PTKs) that specifically phosphorylate the tyrosine-containing synthetic peptide poly(Glu4Tyr1). Using this peptide as a substrate, we have measured the protein tyrosine kinase activity in membrane and cytosolic fractions from the cerebral cortices of pre- and postnatal ethanol-exposed rats at time intervals of 8, 30, and 90 days. During the course of development of the cerebral cortex, PTK activity decreased both in the membrane and cytosolic fractions from 8 and 90 days of age. Maximum activity was associated at the age of 8 days and gradually declined in the later ages (30 and 90 days) of postnatal development. However, PTK activity in the ethanol exposed rat cerebral cortex was further decreased when compared to controls in all the ages of postnatal development in membrane as well as in cytosolic fractions. In the presence of vanadate, a specific inhibitor of protein tyrosine phosphatases (PTPs), the PTK activity increased, indicating that the balance between protein tyrosine kinase and protein tyrosine phosphatase might be lost during ethanol exposure. In addition, when using an antibody specific for phosphotyrosine, endogenous substrates for protein tyrosine kinases were identified on an immunoblot of membrane and cytosolic fractions from the ethanol-exposed rat cerebral cortex. The immunoblot showed several phosphotyrosine-containing proteins with molecular weights of 114, 70, 36, 34, 32, 20, and 14 kDa that were present in the cerebral cortex. However, higher levels of immunoreactivity of these proteins were found in the ethanol-exposed membrane fractions when compared to control fractions-particularly at the age of 30 and 90 days. Two phosphotyrosine proteins with molecular weights of 38 and 40 kDa showed decreased immunoreactivity at the age of 90 days in the cytosolic fraction of an ethanol-exposed rat's cerebral cortex. The differences in tyrosine-specific protein kinase activity and in phosphotyrosine-containing proteins observed during pre- and postnatal ethanol exposure may reflect specific functional defects in the cerebral cortex which could possibly underlie the mechanism contributing to fetal alcohol syndrome (FAS).     

工频磁场对应激活化蛋白激酶及上游激酶磷酸化和活力的影响

目的　研究 5 0Hz工频磁场对细胞内应激活化蛋白激酶 (stress activatedproteinkinase,SAPK/JNK)信号转导途径的影响 ,探索工频磁场生物效应相关的细胞信息转导机制。方法　细胞分别经 0 .4、0 .8mT的工频磁场进行不同时间辐照后 ,利用Western印迹方法 ,比较辐照后细胞与对照细胞胞浆中SAPK及SAPK激酶 (SAPK/ERKkinase 1,SEK1/MKK4 )磷酸化程度。随后以固相激酶分析法(solid phasekinaseassay) ,对经 2个强度分别辐照 15min后的细胞SAPK活力进行测定。结果　 0 .4及0 .8mT工频磁场辐照处理可呈时相性增强SAPK磷酸化 ,并且均在 15min时达到最大值 ,SAPK磷酸化分别提高 2 0 %和 17% ;同时SAPK激酶活力也相应增强 ,分别是对照的 (2 .9± 0 .4 )和 (2 .1± 0 .9)倍。然而 ,0 .8mT诱导SAPK磷酸化的时程长于 0 .4mT ,而脱磷酸化的时程短于 0 .4mT。SAPK上游激酶SEK1/MKK4的磷酸化不受工频磁场的影响。结论　工频磁场可以激活SAPK ,但其激活并非通过SEK1/MKK4激酶途径 ;其生物学效应可能与SAPK信息转导途径相关     

西洛他唑及阿斯匹林对老年ACS患者血小板聚集功能及蛋白激酶B活性变化的影响

目的探讨西洛他唑对老年急性冠状动脉综合征(ACS)患者血小板聚集功能及蛋白激酶B(PKB)活性变化的影响。方法ACS患者48例,随机分为两组,即西洛他唑(CS)组(26例)和阿斯匹林(AS)组(22例);26例健康老年人为对照组(NC组)。CS组在常规抗凝治疗的同时给予西洛他唑100mg口服;AS组给予阿斯匹林300mg口服。于用药前10min及用药7d后(从当日晨起服药时开始计时)的3.5、6.0、24.0h分别测定血小板聚集率(PLTAR)。结果所有老年ACS患者血小板最大聚集率均较NC组明显增加(P<0.01),胞膜PKB表达较NC组明显增高(P<0.01),而胞浆PKB表达则显著降低(P<0.01)。口服CS、AS7d后6.0h血小板最大聚集率较用药前降低最明显(P<0.01),但24.0h时CS对血小板聚集仍有较强的抑制作用,而AS已不明显。口服CS7d后6.0hCS组患者血小板胞膜PKB活性较用药前明显下降(P<0.01);而胞浆PKB表达则已明显升高。AS组二项指标虽有所变化,但用药前后比较差异无统计学意义。结论老年ACS患者体内血小板处于活化状态,CS能有效抑制血小板活化,作用优于AS。