Risk factors for developing human herpesvirus 6 (HHV-6) reactivation after allogeneic hematopoietic stem cell transplantation and its association with central nervous system disorders.

We prospectively evaluated the incidence of human herpesvirus 6 (HHV-6) DNAemia after allogeneic hematopoietic stem cell transplantation (HSCT) using quantitative plasma real-time polymerase chain reaction. Of 46 recipients of bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT) from related (n = 11) or unrelated donors (n = 22), and cord blood transplantation (CBT) from unrelated donors (n = 13), 22 (47.8%) developed HHV-6 DNAemia. HHV-6 DNA levels ranged from 200 to 200,000 copies/mL of plasma, and HHV-6 DNAemia was observed significantly more frequently after CBT than after BMT/PBSCT (92.3% vs 30.3%; P < .001). Multivariate analyses identified CBT (vs BMT/PBSCT), HLA mismatches between recipient and donor, and low anti-HHV-6 IgG titer before transplantation as the only risk factors for developing HHV-6 DNAemia. Three patients developed central nervous system (CNS) disorders with detectable HHV-6 DNA in the cerebrospinal fluid; all of these patients simultaneously developed HHV-6 DNAemia. These results suggest that HHV-6 DNAemia is frequently observed after allogeneic HSCT, especially in patients with the aforementioned risk factors. Thus, together with the assessment of risk factors, monitoring of HHV-6 DNAemia could be a useful asset in diagnosing HHV-6-associated CNS disorders.     

毛菊苣总倍半萜磁性纳米脂质体在小鼠体内组织分布和靶向效果

目的研究毛菊苣总倍半萜有效部位、脂质体和磁性纳米脂质体在小鼠体内的组织分布和靶向效果。方法采用高效液相色谱法,以山莴苣素的含量为评价指标,研究毛菊苣总倍半萜有效部位溶液组、脂质体溶液组和磁性纳米脂质体溶液组(加磁场)在小鼠体内不同组织器官的药物浓度;并以AUC0-12 h、平均滞留时间(MRT)和靶向效率(TE)、相对靶向效率(RTE)、靶向指数(TI)为指标评价不同剂型的靶向作用。结果尾静脉注射给药10 min后,磁性纳米脂质体组在心、肝、脾、肺、肾脏组织中山莴苣素浓度较有效部位组、脂质体组显著提高;在动物的肝部体外施加磁场,磁性纳米脂质体组肝部位的AUC0-12 h明显高于其他部位,MRT明显的延长,差异具有显著性(P0.01);TE仅在肝部有增加,且TI大于10。结论在外加磁场的作用下,毛菊苣总倍半萜磁性纳米脂质体可改变药物在动物体内的分布,延长药物的作用时间,提高药物在肝部位的特异性和靶向性。     

Long term sex-dependent psychoneuroendocrine effects of maternal deprivation and juvenile unpredictable stress in rats

We have analysed the long-term psychoneuroendocrine effects of maternal deprivation (MD) [24 h at postnatal day (PND) 9] and/or exposure to chronic unpredictable stress (CUS) during the periadolescent period (PND 28 to PND 43) in male and female Wistar rats. Animals were tested in the elevated plus maze (EPM, anxiety) at PND 44 and in two memory tests, spontaneous alternation and novel object recognition (NOT) in adulthood. The expression of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors, as well as of synaptophysin, neural cell adhesion molecule and brain-derived neurotrophic factor, was analysed by in situ hybridisation in selected hippocampal regions. Endocrine determinations of leptin, testosterone and oestradiol plasma levels were carried out by radioimmunoassay. Young CUS animals showed decreased anxiety behaviour in the EPM (increased percentage of time and entries in the open arms) irrespective of neonatal treatment. Memory impairments were induced by the two stressful treatments as was revealed by the NOT, with males being most clearly affected. Although each stressful procedure, when considered separately, induced different (always decrements) effects on the three synaptic molecules analysed and affected males and females differently, the combination of MD and CUS induced an unique disruptive effect on the three synaptic plasticity players. MD induced a long-term significant decrease in hippocampal GR only in males, whereas CUS tended to increase MR in males and decrease MR in females. Both neonatal MD and periadolescent CUS induced marked reductions in testosterone and oestradiol in males, whereas MD male animals also showed significantly decreased leptin levels. By contrast, in females, none of the hormones analysed was altered by any of the stressful procedures. Taking our data together in support of the 'two-hit' hypothesis, MD during neonatal life and/or exposure to CUS during the periadolescent period induced a permanent deficit in memory, which was accompanied by a decrement in markers for hippocampal plasticity. The long-term effects on body weight and hormone levels, particularly among males, might reflect sex-dependent lasting metabolic alterations as well as an impaired reproductive function.     

Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats

Exposure to early stressful adverse life events may increase vulnerability to psychopathology in adult life. There are important memory disturbances in stress-related psychiatric disorders. Therefore, there is much interest in understanding the mechanisms responsible for interactions between stress and cognition. Male Wistar rats that experienced 3-h daily separations from the dam during the first 3 weeks of life (maternal separation, MS) showed in adulthood a depressive-like behaviour in the forced swimming test, increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and elevated CRF mRNA in the paraventricular nucleus of the hypothalamus (PVN). In the hippocampus of MS rats, there was a lower glucocorticoid receptor density. MS produced significant learning impairments both in the Morris water maze and in the novel object recognition test (NORT). The glucocorticoid receptor antagonist mifepristone and the beta-adrenoceptor antagonist propranolol were able to completely reverse the increased immobility time in the forced swimming test and the memory deficits in the NORT observed in MS rats. Our data support the hypothesis that elevated secretion of glucocorticoids may be associated to behavioural and cognitive deficits in MS rats. The stress hyperresponsiveness observed in MS rats could be attributed, at least in part, to an impaired feedback sensitivity mediated by hippocampal glucocorticoid receptors. It can also be suggested the possible involvement of the noradrenergic system in cognitive impairments mediated by glucocorticoids in the MS model.     

Polymyositis, pulmonary fibrosis and malignant lymphoma associated with hepatitis C virus infection.

Polymyositis has been associated with various viral infections, and a spectrum of immune-related diseases may occur with hepatitis C (HCV) infection. Both polymyositis and HCV infection may be accompanied by pulmonary fibrosis. An association between polymyositis and malignancy has also been reported. We report a 55-year-old woman accompanied cryoglobulinemia with HCV infection and manifesting polymyositis, pulmonary fibrosis and malignant lymphoma. Steroid therapy was effective to improve interstitial pneumonia, polymyositis, and liver function.