乙肝疫苗初免失败婴儿再免疫方法研究

目的探索乙肝疫苗初次全程免疫失败婴儿的再免疫方法.方法对乙肝疫苗全程免疫后乙肝病毒表面抗体(抗-HBs)和乙肝病毒表面抗原(HBsAg)均阴性的144名婴儿,随机分成5组,1组为对照组,其余4组分别采用不同的再免疫方法,观察再免成功率.结果抗-HBs总阳转率为93.79%,抗-HBs几何平均滴度(GMT)为546.97mIU/ml,各组抗-HBs阳转率分别为87.88%、90.91%、100%、96.88%;各组GMT分别为475.34mIU/ml、658.65mIU/ml、625.18mIU/ml、455.90mIU/ml.结论乙肝疫苗初免失败婴儿,再免成功率达93.79%.     

孟根乌森乌日乐对小鼠的急性毒性研究

目的：了解孟根乌森乌日乐的急性毒性作用剂量及给药后的急性毒性反应和死亡分布情况,确定孟根乌森乌日乐的半数致死量（ LD50）。方法用孔氏综合法（改进寇氏法）分为14．30,9．28,6．04,3．92,2．55,1．66 g? kg－16个剂量组,以0．4 mL／10 g的量灌胃给药1次。实验后观察14 d,记录体重变化及不良反应情况。结果孟根乌森乌日乐小鼠半数致死量为5．1597 g? kg－1（95％CI：3．6652～7．2637 g? kg－1）。14 d内未出现明显不良反应症状且体重有增长趋势。结论孟根乌森乌日乐的急性毒性实验的半数致死量为临床用药量的100倍,提示单次口服较为安全。     

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.     

Effects of prenatal nicotine exposure on primate brain development and attempted amelioration with supplemental choline or vitamin C: neurotransmitter receptors, cell signaling and cell development biomarkers in fetal brain regions of rhesus monkeys.

Studies in developing rodents indicate that nicotine is a neuroteratogen that disrupts brain development by stimulating nicotinic acetylcholine receptors (nAChRs) that control neural cell replication and differentiation. We administered nicotine to pregnant Rhesus monkeys from gestational day 30 through 160 by continuous infusion, achieving maternal plasma levels comparable to those in smokers (30 ng/ml). Fetal brain regions and peripheral tissues were examined for nAChR subtypes, other neurotransmitter receptors, and indices of cell signaling and cell damage. Nicotine evoked nAChR upregulation, but with distinct regional disparities indicative of selective stimulatory responses. Similarly, indices of cell loss (reduced DNA), cell size and neuritic outgrowth (protein/DNA and membrane/total protein ratios) were distinct for each region and did not necessarily follow the rank order of nAChR upregulation, suggesting the involvement of additional mechanisms such as oxidative stress. We then attempted to offset the adverse effects of nicotine with standard dietary supplements known to interact with nicotine. By itself, choline elicited nicotine-like actions commensurate with its promotion of cholinergic neurotransmission. When given in combination with nicotine, choline protected some regions from damage but worsened nicotine's effects in other regions. Similarly, Vitamin C supplementation had mixed effects, increasing nAChR responses while providing protection from cell damage in the caudate, the brain region most susceptible to oxidative stress. Our results indicate that nicotine elicits neurodevelopmental damage that is highly selective for different brain regions, and that dietary supplements ordinarily thought to be neuroprotectant may actually worsen some of the adverse effects of nicotine on the fetal brain.     

PBL在病原生物与免疫学教学中的实践

目的探讨病原生物与免疫学教学中开展PBL教学的效果。方法对照组采用传统的教学方法，实验组采用PBL教学方法，通过问卷调查、考试成绩综合分析教学改革效果。结果实验班绝大多数学生接受并欢迎PBL教学模式，并在自学能力、理解能力、分析解决问题能力等方面得到明显的提高。结论PBL教学方法优于传统的教学方法，能有效提高病原生物与免疫学教学质量。     

Cocaine acutely inhibits DNA synthesis in developing rat brain regions: evidence for direct actions

Perinatal exposure to cocaine has been shown to cause morphological and neurobehavioral abnormalities. In the current study, neonatal rats were given an acute injection of cocaine (30 mg/kg s.c.) at 1, 3, 5, 8, 11 or 15 days of age, and [3H]thymidine incorporation into DNA examined over the ensuing 30 min period. Three brain regions were used that differ in their timetables of cell maturation: cerebellum, cerebral cortex and midbrain + brainstem. Cocaine inhibited DNA synthesis in all brain regions, with diminishing impact as the animals matured; by 15 days of age, the effect of cocaine was no longer significant. Inhibition of macromolecule synthesis was selective for DNA, as [3H]leucine incorporation into protein was much less affected by cocaine. Although inhibition of [3H]thymidine incorporation by a single injection of cocaine was short-lived, repeated administration could have cumulative effects: chronic treatment on days 2, 3 and 4 did not desensitize the adverse effect of a subsequent dose administered on day 5. Additionally, with chronic cocaine, the cerebellum displayed a pronounced rebound elevation of DNA synthesis 24 h after the last dose, a characteristic finding in delayed cell maturation. Inhibition of DNA synthesis by cocaine in developing brain was not secondary to ischemia, nor to local anesthesia, as alpha-adrenergic blockade with phenoxybenzamine afforded no protection, and lidocaine could not substitute for cocaine. In contrast, a small amount (15 micrograms) of cocaine injected directly into the central nervous system readily caused inhibition of DNA synthesis; the same dose given systemically had no effect. These data suggest that cocaine damages the developing brain, in part, through direct interference with DNA synthesis.     

Inhibition of DNA synthesis in neonatal rat brain regions caused by acute nicotine administration

Perinatal exposure to nicotine has been shown to cause morphological and neurobehavioral abnormalities in developing brain. In the current study, neonatal rats were given an acute injection of nicotine (3 mg/kg) at 1, 3, 8, 10 or 15 days of age, and [3H]thymidine incorporation into DNA examined over the 30-min period after drug administration. Three brain/regions were used that differ in their timetables of cell maturation and in their concentrations of nicotinic receptors. Nicotine inhibited DNA synthesis in all brain regions but with a rank order of effect corresponding to the concentration of nicotinic receptors, namely midbrain + brainstem greater than or equal to cerebral cortex greater than cerebellum. Superimposed on this hierarchy, periods of rapid cell replication were more sensitive to nicotine, so that drug effects in the cerebellum, which develops last, became significant past the point at which nicotine no longer affected DNA synthesis in the other regions. The inhibitory effect of nicotine was also found in fetal brain on gestational day 20 after injection of nicotine to pregnant rats. Studies with adrenergic and ganglionic blocking agents and with 100% O2 indicated that autonomic and respiratory actions of nicotine, including ischemia, cardiac arrhythmias and hypoxia, could not solely account for the inhibition of DNA synthesis in neonatal brain. In contrast, injection of a small amount (2 micrograms) of nicotine directly into the central nervous system readily caused inhibition; the same small dose given systemically had no effect. These data suggest that nicotine damages the developing brain, in part, through direct actions on cell replication.     

Beta adrenergic control of macromolecule synthesis in neonatal rat heart, kidney and lung: relationship to sympathetic neuronal development

The sympathetic nervous system has been hypothesized to coordinate the timing of cellular development in peripheral tissues. In the current study, we evaluated the relationships among the ontogeny of sympathetic projections to peripheral organs, the patterns of macromolecule synthesis in those organs and the reactivity of synthetic processes to beta adrenergic stimulation by isoproterenol. The major developmental rise in norepinephrine concentration and turnover, as well as in numbers of beta receptors, occurred during the second to fourth postnatal weeks in renal and lung sympathetic pathways and slightly earlier in the cardiac-sympathetic axis. The developmental decline in DNA synthesis in heart, kidney and lung coincided with the maturation of sympathetic projections. Direct stimulation of beta receptors by the in vivo administration of isoproterenol caused acute reductions in DNA synthesis in an age-dependent manner. In the heart, isoproterenol was first able to suppress DNA synthesis at 5 days of age and a maximal effect was seen at 9 days; this early phase was characterized by a rapid time constant of coupling of beta receptors to the DNA effect (maximal effect at 6 h after isoproterenol). Reactivity was lessened by 12 days of age and thereafter displayed a longer time constant (maximal effect at 12-24 h). Reactivity of DNA synthesis to isoproterenol challenge was slightly different in kidney and lung (detectable by 2 days of age), but bore similar developmental characteristics to the pattern in the heart (peak of reactivity at 9 days and a decline in reactivity and lengthening of the time constant after 16 days).(ABSTRACT TRUNCATED AT 250 WORDS)     

淋巴靶向制剂——吸附抗癌药毫微粒活性炭的研究进展

目的介绍新型淋巴靶向制剂———吸附抗癌药毫微粒活性炭的研究进展。方法依据近年来的文献 ,对活性炭的制备工艺及体内外性质等方面进行了综述。结果活性炭具有很强的吸附功能 ,普通市售活性炭仅用作脱色、吸附热原与除味等。以微粒球磨机为粉碎器械 ,可加工制备粒径达1 0 0nm左右的纳米炭微粒 ,具有优越的淋巴趋向性。结论吸附抗癌药毫微粒活性炭在临床治疗癌症方面具有良好的运用前景