ONRAB® oral rabies vaccine is shed from,but does not persist in,captive mammals

ONRAB® is a human adenovirus rabies glycoprotein recombinant vaccine developed to control rabies in wildlife. To support licensing and widespread use of the vaccine, safety studies are needed to assess its potential residual impact on wildlife populations. We examined the persistence of the ONRAB® vaccine virus in captive rabies vector and non-target mammals. This research complements work on important rabies vector species (raccoon, striped skunk, and red fox) but also adds to previous findings with the addition of some non-target species (Virginia opossum, Norway rats, and cotton rats) and a prolonged period of post vaccination monitoring (41 days). Animals were directly inoculated orally with the vaccine and vaccine shedding was monitored using quantitative real-time PCR applied to oral and rectal swabs. ONRAB® DNA was detected in both oral and rectal swabs from 6 h to 3 days post-inoculation in most animals, followed by a resurgence of shedding between days 17 and 34 in some species. Overall, the duration over which ONRAB® DNA was detectable was shorter for non-target mammals, and by day 41, no animal had detectable DNA in either oral or rectal swabs. All target species, as well as cotton rats and laboratory-bred Norway rats, developed robust humoral immune responses as measured by competitive ELISA, with all individuals being seropositive at day 31. Similarly, opossums showed good response (89% seropositive; 8/9), whereas only one of nine wild caught Norway rats was seropositive at day 31. These results support findings of other safety studies suggesting that ONRAB® does not persist in vector and non-target mammals exposed to the vaccine. As such, we interpret these data to reflect a low risk of adverse effects to wild populations following distribution of ONRAB® to control sylvatic rabies.     

大鼠脑组织单胺类递质及其代谢产物的检测方法研究

目的 :研究大鼠脑组织中单胺类递质及其代谢产物的高效液相反相离子对色谱测定法。方法 :采用LiChrosorbC18,10 μm色谱柱 ,流动相为甲醇 :水 (4 0 :60 ) ,含 0 .0 2 8g LEDTANa2 ,0 .15g LSDS ,0 .2ml LH2 SO4(pH 2 .5～ 3 ) ,荧光检测波长 :λEX=2 85 ,λEM=3 3 3。结果 :对 87只大鼠脑组织中 4种单胺类递质及其代谢产物的含量进行了同时测定 ,高香草酸 (HVA) 2 .5 0～ 40 .0 μg ml、去甲肾上腺素 (NE) 0 .0 1～ 0 .5 0 μg ml、多巴胺 (DA)0 .0 5～ 1.0 0 μg ml、5 羟色胺 (5 HT) 0 .0 2 5～ 0 .5 0 μg ml,峰面积与其含量呈良好的线性关系。 结论 :该法操作简便、快速、准确 ,为组织中单胺类递质及其代谢产物检测的一种理想方法 ,并适用于临床相关研究。     

Neuron transplantation into mice hippocampus alters sensitivity to barbital narcosis

The role of several hippocampal innervations in the sensitivity to barbital-induced narcosis was studied in selected mice strains. The outbred and inbred mouse strains HS/Ibg, SABRA/HUC, C57BL, CBA/LAC, and BALB/c were tested for barbital-induced sleep (315 mg/kg). The relatively short sleeping HS/Ibg (HS) and the longest sleeping BALE/c (BALE) were chosen for further investigation. Cholinergic (ACh), serotonergic (5-HT), and noradrenergic (NE) innervations were studied in HS strain; whereas BALE, which possesses both an unusually high sensitivity to barbital and unique NE innervations in the cortex and hippocampus, was employed in a detailed study of the NE innervations. Transplantation of embryonic NE cells from the mouse embryo into the hippocampus of adult HS mice increased barbital narcosis by 65% (p < 0.05), whereas transplantation of 5-HT cells decreased barbital narcosis by 54% (p < 0.001). Transplantation of ACh cells had no significant effect on barbital-induced narcosis. BALB mice were subjected to NE cell transplantation into the hippocampus and cortex. Similarly to HS, BALB receiving NE transplants into their hippocampus slept 34% longer than control after barbital challenge (p < 0.025). Noradrenergic cell transplantation into frontal cortex had no effect on barbital sleep. The results suggest that (a) enhancement by neural grafting of the NE innervation to the hippocampus accentuates and enhancement of the 5-HT innervations attenuates the sensitivity to barbital narcosis, whereas ACh innervations have no effect on the sensitivity to barbital narcosis, and (b) the unusually high sensitivity of BALB mice to barbital may not be related to its unique NE innervations.     

Nucleus A10 dopaminergic neurons in inbred mouse strains: Firing rate and autoreceptor sensitivity are independent of the number of cells in the nucleus

Inbred mouse strains have different numbers of midbrain dopaminergic neurons; for example, BALB/cJ mice have 20–25% more neurons than CBA/J mice. As the number of cells decrease, for example in Parkinson's disease and in animals with midbrain dopaminergic cell lesions, the activity of their remaining cells increases. The purpose of the present experiment was to determine whether the functional properties of dopaminergic neurons in the ventral tegmental area (nucleus A10) differ in inbred mouse strains which possess different numbers of cells. The firing rate and autoreceptor sensitivity of A10 dopaminergic cells were examined in the in vitro slice preparation in BALB/cJ, C3H/HeJ, CBA/J, and DBA/2J mouse strains. It was observed that the autoreceptors on mouse dopaminergic neurons exhibit pharmacological properties of dopamine autoreceptors; activation of the autoreceptor produced a marked inhibition (50–70%) in cell firing rate by quinpirole (10⁻⁸ M), LY-141865 (10⁻⁷ M), (+)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine (10⁻⁶ M), propyl-norapomorphine (10⁻⁵ M) and dopamine (10⁻⁴ M), and this inhibition was blocked or reversed by specific dopamine D2 receptor antagonists [(−) sulphide and spiroperidol, 10⁻⁶ M]. The baseline firing rates of the A10 cells did not differ among the four inbred strains [range 2.5 ± 0.2 (C3H/HeJ)−3.4 ± 0.3 (CBA/J) spikes/s ±SEM], and there was no significant difference in autoreceptor sensitivity among the mouse strains as assessed either by superfused dopamine (inhibitory dose 50% ≈150 μM), or by superfused quinpirole (inhibitory dose 50% ≈10 nM). These data indicate that differences in A10 cell numbers of 30% do not significantly influence the baseline firing rate or autoreceptor sensitivity of the cells.     

Virulence of Candida albicans mutants

Mutant strains of the fungal pathogen Candida albicans blocked in pyrimidine transport and salvage metabolism were tested for virulence in various animal models. The growth rate, germination and proteolytic enzyme production did not correlate with the virulence of the strains. However, a defect in the uridine transport system significantly decreased virulence in murine candidosis, although it had no effect in vaginal candidosis or in a Candida cyst model. It remains unclear whether this is due to the differing host defence mechanisms involved in systemic and superficial mycoses, or to the different requirements of the fungal systems for adherence and tissue invasion in the two types of infection.     

思他宁对人胰腺癌细胞株ASPC-1的生长调控

目的:观察思他宁对人胰腺癌细胞ASPC-1的生长作用.方法:细胞培养,分别加入不同浓度的思他宁.应用MTT法来观察细胞增殖程度;放免法测定细胞内cAMP含量;荧光法测定[Ca2 ]i.结果:不同浓度的思他宁(10-11～10-6mol/L)均能有效地抑制ASPC-1的生长,能抑制ASPC-1细胞内cAMP生成和细胞内钙离子水平,cAMP生成量和细胞内钙离子水平与思他宁浓度呈负相关.结论:思他宁能抑制ASPC-1细胞的生长,经过特异性受体调节.     

广东省结核病流行菌株研究

目的：从分子流行病学的角度探讨广东省结核分支杆菌菌株流行的分布。方法：构建广东省74株临床分离的以RFLP为基础的结核分支杆菌的IS6110 DNA指纹图谱技术，确诊结核分支杆菌菌株的流行分布。结果：24．3％（18／74）的结核菌株的IS6110 DNA指纹相似值在1－0．65之间，鉴定结果为它们均是“北京家族”结核分支杆菌菌株。结论：广东省结核菌株流行主要存在着遗传关系接近，在基因水平上相关程度较高的“北京家族”结核分支杆菌菌株，且该家族菌株正以一定的比例在我省流行。     

The regulation of pulmonary vascular tone

1 The ability to manipulate pharmacologically pulmonary vascular tone independent of effects on systemic blood vessels is a desirable objective. Elucidation of the biochemical mechanisms underlying hypoxia-induced pulmonary vasoconstriction (HPV) may permit preferential targeting of the pulmonary circulation.
2 Here we review our studies of the role of locally synthesized candidate vasoactive factors in HPV. In addition, we present data demonstrating an attenuated pressor response to hypoxia in the pulmonary circulation of Fischer 344 rats compared with the Wistar-Kyoto (WKY) rat strain.
3 We propose that a systematic genome-wide search using the HPV phenotype and a panel of highly informative microsatellite markers will elucidate the genetic loci underlying the difference in susceptibility to HPV in these two rat strains and provide a valuable and novel insight into the factors that determine the HPV response.     

枸杞多糖对运动性骨骼肌疲劳恢复的细胞定量化学分析和电镜观察

通过小鼠实验，用枸杞多糖解除运动性骨骼肌疲劳，以显微分光光度计进行琥珀酸脱氢酶(SDH)和糖原的定性定量分析，并于透射电镜下观察超微结构的变化。结果显示，运动疲劳(B)组糖原含量明显降低，各类肌纤维与对照(A)组比较P<0．001。SDH活性增加，各类肌纤维与A组比较P<0．001。服用枸杞多糖(C)组糖原含量增加，各类肌纤维与A组之较P<0．001；与B组比较P<0．001；SDH反应较B组更深，各类肌纤维与A组比较P<0．001，若与B组比较，则其中Ⅰ(慢肌)型和Ⅱ(中间肌)型P<0．001，而Ⅱ(快肌)型则P>0．05。超微结构显示，B组线粒体增多且体积明显增大，呈肿胀状态，C组全无此类改变，提示服用枸杞多糖后可解除疲劳，其中以Ⅰ(慢肌)型肌纤维效果尤佳。