自体骨髓间充质干细胞移植后心肌缝隙连接蛋白43表达与室性心动过速发生的关系

目的:缝隙连接蛋白43对维持心肌细胞的连接通讯功能、电信号传导和正常的节律性收缩起重要作用,其表达和分布的异常是多种室性心律失常的解剖学基础,建立小型猪急性心肌梗死模型.观察自体骨髓间充质干细胞移植后室性心动过速的发生及心肌缝隙连接蛋白43的表达方法:实验于2006-01/2007-01在河北省人民医院导管室完成。①材料:选取8～12月龄小型猪22头,由河北医科大学实验动物中心提供,体质量20～30 kg,随机数字表法分为细胞移植组12头、模型对照组10头.实验过程中对动物的处置符合动物伦理学际准②实验方法:无菌条件下抽取猪双侧股骨骨髓20 mL,percoll法 贴壁法分离培养骨髓间充质干细胞,待细胞生长达75%融合时用胰酶消化传代。将传至第2代细胞加入终浓度为10μmol/L的5-氮胞苷进行诱导,用胶体金标记12 h后继续培养20 d用于移植:两组小型猪均采用球囊堵闭法建立急性心肌梗死模型.心电图监测示相关至少2个导联ST段抬高大于0.2 mV、术后血肌钙蛋白和肌酸磷酸激酶同工酶升高超过正常的两倍为建模成功标准:细胞移植组于造模成功后经OTW球囊于第一对角支远端1 cm处再次阻断血流,注入经胶体金标记的10×10~7个骨髓间充质干细胞。③实验评估:于细胞移植后2 h及4周行电生理程序刺激.观察室性心动过速的发生情况。末次电生理检查后、采用免疫组化染色法检测心肌缝隙连接蛋白43的表达.计算其积分吸光度值。结果:①模型建立指标检测:与术前比较.造模后所有小型猪血肌钙蛋白含量和肌酸磷酸激酶同工酶活性均增高,峰值浓度分别为(21.3±3.6)μg/L和(178.3×41.4)IU/L,术中心电图ST段平均抬高(10.67±1.43)mm.证明急性心肌梗死模型成功建立。②骨髓间充质干细胞移植后室性心动过速的发生情况:与模型对照组诱发出室性心动过速的动物数量比较,术后2 h细胞移植组无明显变化(X~2=0.201,P=0.650),术后4周细胞移植组明显降低(X~2=4.455.P=0.035)。②骨髓间充质干细胞移植后梗死心肌缝隙连接蛋白43的表达:术后4周移植到梗死心肌的骨髓间充质干细胞与宿主心肌生长为一体,移植部位颜色变黑,苏木精-伊红染色示移植细胞的胞浆呈紫红色。细胞移植组心肌梗死区缝隙连接蛋白43积分吸光度值明显高于模型对照组(t=16,82.P=0.00),细胞移植组中未发生室性心动过速小型猪的梗死心肌缝隙连接蛋白43的表达明显高于发生室性心动过速小型猪(t=5.06,P=0.00)。结论:自体骨髓间充质干细胞移植可促进急性心肌梗死猪心肌缝隙连接蛋白43的表达,其表达程度可能与急性心肌梗死室性心动过速的发生有关。     

Exploring telehealth opportunities in domestic violence shelters

PURPOSE: To determine the degree of interest in using a computer for the purpose of accessing services from a nurse practitioner (NP) at domestic violence shelters (DVSs); and to identify issues of privacy and confidentiality that might arise from participation by victims of intimate partner violence (IPV) in a Telehealth intervention. DATA SOURCES: Focus groups with 19 women residing in two DVSs. Interviews were recorded, transcribed and themes were identified that answered the questions posed in the interviews. CONCLUSIONS: Most of the women understood the term NP and were favorably inclined to seek services from one. Over half of the women were not familiar with computer use, but were willing to learn in order to receive health care services, both for episodic needs and for maintenance of chronic conditions. After learning of the method proposed to allow them to access an NP through the internet while still protecting their privacy and confidentiality, the women felt comfortable with this approach to meeting their health care needs. IMPLICATIONS FOR PRACTICE: Results from this study can be used to support the development and testing of Telehealth interventions for these victims of IPV.     

Abnormal Development of the Cerebellar Vermis in Children Prenatally Exposed to Alcohol: Size Reduction in Lobules I–V

Abnormalities of the cerebellar vermis have been well documented in animal models of fetal alcohol syndrome. At this point, it is not known if the same brain region is affected in humans prenatally exposed to alcohol. In this study, the area of the cerebellar vermis was measured from brain magnetic resonance images of 9 children and young adults with prenatal alcohol exposure and 24 control subjects in the same age range. Six of the exposed children met standard criteria for fetal alcohol syndrome. The remaining three subjects had significant histories of prenatal exposure to alcohol, but did not have enough of the classic facial features for the diagnosis. For each subject with a suitable midsagittal section, three vermal areas were circumscribed: anterior vermis (vermal lobules I–V), posterior vermis (vermal lobules VI and VII), and the remaining vermal area (including lobules VIII–X). Statistical analyses revealed that the anterior region of the vermis was significantly smaller in subjects with prenatal alcohol exposure, whereas the posterior region and the remaining vermal area did not differ between groups. Previous findings from an animal model of neonatal alcohol exposure have documented Purkinje cell loss in vermal lobules I–V and IX–X, with notable sparing in lobules VI–VII. Thus, the results of both studies indicate similar patterns of abnormal brain development in the anterior vermal region, with apparent sparing in the posterior vermal region. Our findings, for the first time, suggest that regionally specific Purkinje cell death may also occur in humans prenatally exposed to alcohol.     

Low plasma N-3 fatty acids and dementia in older persons: the InCHIANTI study

BACKGROUND: N-3 fatty acids (FA) have an important role in brain development and function. However, there is conflicting evidence concerning the relationship between n-3 FA and dementia in older persons. METHODS: In the Invecchiare in Chianti (InCHIANTI) study, we measured plasma FA by gas chromatography in 935 community-dwelling older persons randomly extracted from the population of two towns near Florence, Italy. Cognitive impairment was measured using the Mini-Mental Status Examination. Participants who scored 相似文献   

Disease progression after bone marrow transplantation in a model of multiple sclerosis is associated with chronic microglial and glial progenitor response

Multiple sclerosis (MS), the most common nontraumatic cause of neurologic disability in young adults in economically developed countries, is characterized by inflammation, gliosis, demyelination, and neuronal degeneration in the CNS. Bone marrow transplantation (BMT) can suppress inflammatory disease in a majority of patients with MS but retards clinical progression only in patients treated in the early stages of the disease. Here, we applied BMT in a mouse model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE), and investigated the kinetics of reconstitution of the immune system in the periphery and in the CNS using bone marrow cells isolated from syngeneic donors constitutively expressing green fluorescent protein. This approach allowed us to dissect the contribution of donor cells to the turnover of resident microglia and to the pathogenesis of observed disease relapses after BMT. BMT effectively blocked or delayed EAE development when mice were treated early in the course of the disease but was without effect in mice with chronic disease. We found that there is minimal overall replacement of host microglia with donor cells in the CNS and that newly transplanted cells do not appear to contribute to disease progression. In contrast, EAE relapses are accompanied by the robust activation of endogenous microglial and macroglial cells, which further involves the maturation of endogenous Olig2 glial progenitor cells into reactive astrocytes through the cytoplasmic translocation of Olig2 and the expression of CD44 on the cellular membrane. The observed maturation of large numbers of reactive astrocytes from glial progenitors and the chronic activation of host microglial cells have relevance for our understanding of the resident glial response to inflammatory injury in the CNS. Our data indicate that reactivation of a local inflammatory process after BMT is sustained predominantly by endogenous microglia/macrophages.     

Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction and excess

Females and males typically play different roles in survival of the species and would be expected to respond differently to food scarcity or excess. To elucidate the physiological basis of sex differences in responses to energy intake, we maintained groups of male and female rats for 6 months on diets with usual, reduced [20% and 40% caloric restriction (CR), and intermittent fasting (IF)], or elevated (high-fat/high-glucose) energy levels and measured multiple physiological variables related to reproduction, energy metabolism, and behavior. In response to 40% CR, females became emaciated, ceased cycling, underwent endocrine masculinization, exhibited a heightened stress response, increased their spontaneous activity, improved their learning and memory, and maintained elevated levels of circulating brain-derived neurotrophic factor. In contrast, males on 40% CR maintained a higher body weight than the 40% CR females and did not change their activity levels as significantly as the 40% CR females. Additionally, there was no significant change in the cognitive ability of the males on the 40% CR diet. Males and females exhibited similar responses of circulating lipids (cholesterols/triglycerides) and energy-regulating hormones (insulin, leptin, adiponectin, ghrelin) to energy restriction, with the changes being quantitatively greater in males. The high-fat/high-glucose diet had no significant effects on most variables measured but adversely affected the reproductive cycle in females. Heightened cognition and motor activity, combined with reproductive shutdown, in females may maximize the probability of their survival during periods of energy scarcity and may be an evolutionary basis for the vulnerability of women to anorexia nervosa.     

Energy intake and amyotrophic lateral sclerosis

Roy Walford, a physician and scientist who pioneered research on the anti-aging effects of caloric restriction and subjected himself to a low-energy diet, recently died from amyotrophic lateral sclerosis (ALS). Information from his case, epidemiological findings, and recent controlled studies in mouse models of ALS suggest that low-energy diets might render motor neurons vulnerable to degeneration, whereas high-energy diets are ameliorative. This contrasts with the effects of low-energy diets on various neuronal populations in the brain that respond adaptively, activating pathways that promote plasticity and resistance to disease. One reason that motor neurons might be selectively vulnerable to low-energy diets is that they are unable to engage neuroprotective responses to energetic stress response involving the protein chaperones, such as, heat-shock protein-70.