Adolescent vulnerability to cardiovascular consequences of chronic emotional stress: Review and perspectives for future research

Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. Adolescence has been proposed as a developmental period of vulnerability to stress. This idea has been mainly supported by experimental research in animals demonstrating a higher impact of chronic emotional stress in adolescents compared with adults. Adolescent vulnerability is also based on evidence that stress during this developmental period affects development, so that enduring changes are found in adult animals that experienced stress during adolescence. The purpose of the present review is to discuss experimental research in rodent models that investigated the impact of long-term exposure to stressful events during adolescence on cardiovascular function. The development of cardiovascular function and autonomic activity in rodents is initially reviewed. Then, a discussion of an adolescent vulnerability to cardiovascular effects of chronic stress is presented. From the reviewed literature, perspective for future research is proposed to better elucidate adolescent vulnerability to cardiovascular complications evoked by chronic emotional stress.     

精神分裂症啮齿类动物模型及其行为学检测

精神分裂症是一种常见而严重的精神疾病,给患者及其家人的生活造成极大的危害。由于该疾病发病因素复杂,因此在药物治疗上还存在诸多问题。在候选药物筛选和药物研发的临床前研究中,需要可靠稳定的动物模型。本文对精神分裂症阳性症状、阴性症状和认知相关的啮齿类动物模型以及行为学检测方法做一综述,希望能够为抗精神分裂症药物的筛选和临床前研究提供动物模型的参考。     

黑龙江省逊克县火山熔岩地区啮齿动物携带病原体调查

目的 调查黑龙江省逊克县火山熔岩地区啮齿动物携带病原体状况.方法 2014年4-9月,采集啮齿动物样本107只,解剖取脏器肺、肾、肝、肾和膀胱样本,采用PCR方法分别扩增10种鼠传病原体的特异性核酸片段,通过基因测序进一步鉴定.结果 在107份鼠肺中共检出汉城型汉坦病毒RNA核酸阳性样本5份,感染率为4.67％;107份鼠肾中共检出钩端螺旋体DNA核酸阳性样本6份,感染率为5.61％;107份鼠脾中共检出巴尔通体DNA核酸阳性样本7份,感染率为6.54％,嗜吞噬细胞无形体4份,感染率为3.74％;107份鼠肝、鼠脾中鼠疫菌、巴贝西原虫、斑点热群立克次体、恙虫病立克次体、莫氏立克次体的DNA核酸检测结果均为阴性;107份鼠膀胱中伯氏疏螺旋体的DNA核酸检测结果为阴性;在鼠体内还存在复合感染情况,感染率为2.80％.结论 黑龙江省逊克县火山熔岩地区啮齿动物中存在汉坦病毒、钩端螺旋体、巴尔通体和嗜吞噬细胞无形体的感染.     

广西边境口岸鼠类本底调查及探讨

目的 全面掌握中越边境口岸鼠类的种类和组成,为口岸鼠类科学管理提供基础资料.方法 采用夹夜法和笼夜法捕获鼠类.结果 东兴口岸捕获鼠类4种498只,凭祥口岸捕获14种756只,水口口岸捕获6种75只,龙邦口岸捕获8种173只,褐家鼠为各口岸的优势鼠种.结论 褐家鼠是各口岸重点监测和控制的对象.     

Detection of Leishmania donovani and L. tropica in Ethiopian wild rodents

Human visceral (VL, also known as Kala-azar) and cutaneous (CL) leishmaniasis are important infectious diseases affecting countries in East Africa that remain endemic in several regions of Ethiopia. The transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various Leishmania spp., sand fly vectors, and reservoir animals besides human hosts. Particularly in East Africa, the role of animals as reservoirs for human VL remains unclear. Isolation of Leishmania donovani parasites from naturally infected rodents has been reported in several endemic countries; however, the status of rodents as reservoirs in Ethiopia remains unclear. Here, we demonstrated natural Leishmania infections in rodents. Animals were trapped in 41 localities of endemic and non-endemic areas in eight geographical regions of Ethiopia and DNA was isolated from spleens of 586 rodents belonging to 21 genera and 38 species. Leishmania infection was evaluated by real-time PCR of kinetoplast (k)DNA and confirmed by sequencing of the PCR products. Subsequently, parasite species identification was confirmed by PCR and DNA sequencing of the 18S ribosomal RNA internal transcribed spacer one (ITS1) gene. Out of fifty (8.2%) rodent specimens positive for Leishmania kDNA-PCR and sequencing, 10 were subsequently identified by sequencing of the ITS1 showing that five belonged to the L. donovani complex and five to L. tropica. Forty nine kDNA-positive rodents were found in the endemic localities of southern and eastern Ethiopia while only one was identified from northwestern Ethiopia. Moreover, all the ten ITS1-positive rodents were captured in areas where human leishmaniasis cases have been reported and potential sand fly vectors occur. Our findings suggest the eco-epidemiological importance of rodents in these foci of leishmaniasis and indicate that rodents are likely to play a role in the transmission of leishmaniasis in Ethiopia, possibly as reservoir hosts.     

Modulation of Valpha19 NKT cell immune responses by alpha-mannosyl ceramide derivatives consisting of a series of modified sphingosines

We have demonstrated that analogues of alpha-mannosyl ceramide (alpha-ManCer) consisting of a series of immunosuppressive 2-aminoalcohol derivatives in place of sphingosine promote a greater immune response from mouse invariant Valpha19-Jalpha26 (AV19-AJ33) TCR-bearing NKT (Valpha19 NKT) cells than alpha-ManCer itself. To further characterize the immune responses of Valpha19 NKT cells to the alpha-ManCer analogues, cytokine production by the cells was examined in detail. We found that certain alpha-ManCer derivatives individually induced either Th1- or Th2-dominant cytokine production in culture. The Th1- or Th2-biased immune responses of Valpha19 NKT cells were dependent on MHC class I-like MR1, since they were induced by coculture with the MR1 transfectants previously loaded with the glycolipids and were inhibited in the presence of anti-MR1 antiserum. Presumably, the recognition of the alpha-mannosyl residue of the alpha-ManCer analogues by the invariant TCR is individually modulated, depending on the altered interaction with the groove of the antigen-presenting MR1. Priming of the Valpha19 invariant TCR-transgenic mice in vivo with these glycolipid derivatives resulted in the induction of the Th1- or Th2-biased immune responses. Thus, these alpha-ManCer derivatives are likely to be useful in immunotherapy for either Th1 or Th2 excess autoimmune diseases, modulating the function of Valpha19 NKT cells.     

Preclinical safety evaluation of IQG-607 in rats: Acute and repeated dose toxicity studies

In the present study, we evaluated the safety and the possible toxic effects of IQG-607 after acute and 90-day repeated administrations in rats. Single oral administration of IQG-607 (300 or 2000 mg/kg) on female rats did not result in any mortality. No gross lesions were observed in the animals at necropsy. Ninety-day administration test resulted in 20% of deaths, in both male and female rats administered with the highest dose of IQG-607, 300 mg/kg. Repeated administration of the IQG 607 (25, 100 and 300 mg/kg) did not result in any significant body mass alteration, or changes in food and water consumption. The most important clinical sign observed was salivation in both sexes. Importantly, long-term treatment with IQG-607 did not induce alterations in any hematological (for both sex) and serum biochemical (for female) parameters evaluated, even at the highest dose tested. Treatment of male rats with 100 or 300 mg/kg of IQG-607 decreased total cholesterol levels, while animals treated with 100 mg/kg also presented reduction on triglyceride levels. Of note, no treatment induced significant histopathological alterations in tissues of all organs and glands analyzed, even in that group that received the highest dose of IQG-607.     

Puumala hantavirus genetic variability in an endemic region (Northern Sweden)

Puumala hantavirus (PUUV), naturally harboured and shed by bank voles (Myodes [Clethrionomys] glareolus), is the etiological agent to nephropathia epidemica (NE), a mild haemorrhagic fever with renal syndrome. Both host and virus are found throughout much of the European continent and in northern Sweden NE is the second most prevalent serious febrile viral infection after influenza. The reliability of diagnostics by PCR depends on genetic variability for the detection of viral nucleic acids in unknown samples. In the present study we evaluated the genetic variability of PUUV isolated from bank voles in an area of northern Sweden highly endemic for NE. Genetic variability among bank voles was also investigated to evaluate co-evolutionary patterns. We found that the viral sequence appeared stable across the 80km study region, with the exception of the southernmost sampling site, which differed from its nearest neighbour by 7%, despite a geographical separation of only 10km. The southernmost sampling site demonstrated a higher degree of genetic similarity to PUUV previously isolated 100km south thereof; two locations appear to constitute a separate PUUV phylogenetic branch. In contrast to the viral genome, no phylogenetic variance was observed in the bank vole mtDNA in this study. Previous studies have shown that as a result of terrestrial mammals' postglacial re-colonization routes, bank voles and associated PUUV of a southern and a northern lineage established a dichotomous contact zone across the Scandinavian peninsula approximately 100-150km south of the present study sites. Our observations reveal evolutionary divergence of PUUV that has led to dissimilarities within the restricted geographical scale of the northern host re-colonization route as well. These results suggest either a static situation in which PUUV strains are regionally well adapted, or an ongoing process in which strains of PUUV circulate on a geographical scale not yet reliably described.     

北京市越冬长耳鸮食物中鼠类成分调查

目的分析越冬期长耳鸮食物的构成,评估对不同鼠种捕食强度的时空动态。方法于2003-2006年冬季应用直接观察法,在北京市城区和城郊结合部收集冬季长耳鸮的食团,分析内容物中鼠类的种类和数量构成。结果长耳鸮食团内容物中共发现鼠类7种,城区和郊区的鼠种没有明显差异,褐家鼠与小家鼠均为主要猎物;在越冬期的3个时间段内,被捕食鼠类的总体构成没有明显变化,但褐家鼠、小家鼠与黑线姬鼠的被捕食率有差异。结论褐家鼠与小家鼠构成了越冬期长耳鸮的主要食物资源,鼠类的捕食反映了北京市城区和郊区鼠类构成的空间分布与时间变动特点。     

A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson's disease

Adenosine A(2A) receptors, abundantly expressed on striatal medium spiny neurons, appear to activate signaling cascades implicated in the regulation of coexpressed ionotropic glutamatergic receptors. To evaluate the contribution of adenosinergic mechanisms to the pathogenesis of the response alterations induced by dopaminergic treatment, we studied the ability of the selective adenosine A(2A) receptor antagonist KW-6002 to prevent as well as palliate these syndromes in rodent and primate models of Parkinson's disease. In rats, KW-6002 reversed the shortened motor response produced by chronic levodopa treatment while reducing levodopa-induced hyperphosphorylation at S845 residues on AMPA receptor GluR1 subunits. In primates, KW-6002 evidenced modest antiparkinsonian activity when given alone. Once-daily coadministration of KW-6002 with apomorphine prevented the development of dyskinesias, which appeared in control animals 7-10 days after initiating apomorphine treatment. Animals initially given apomorphine plus KW-6002 for 3 weeks did not begin to manifest apomorphine-induced dyskinesias until 10-12 days after discontinuing the A(2A) antagonist. These results suggest that KW-6002 can attenuate the induction as well as the expression of motor response alterations to chronic dopaminergic stimulation in parkinsonian animals, possibly by blocking A(2A) receptor-stimulated signaling pathways. Our findings strengthen the rationale for developing A(2A) antagonists as an early treatment strategy for Parkinson's disease.