肺不藏魄型失眠模型大鼠相关脏器多巴胺D1、D2受体表达差异研究

目的:探讨肺不藏魄型失眠模型大鼠相关脏器中多巴胺D1、D2受体的表达差异。方法:将16只大鼠用随机数字表法分为对照组和失眠模型组,每组8只。失眠模型组采用小平台水环境法进行造模,造模9 d。造模成功后,取两组大鼠的肺、大肠、脑、心、肝、脾和肾组织,采用HE染色观察肺和脑的病理变化,免疫组化法观察各组织中多巴胺D1、D2受体的表达。结果:失眠模型组肺组织HE染色可见肺泡壁毛细血管轻微扩张充血、纤维结缔组织增生致使肺泡壁增厚、肺泡腔可见巨噬细胞;脑组织未见明显病理改变。与对照组比较,在肺、大肠、脑、心中,失眠模型组D1受体表达明显升高(P<0.05),D2受体表达明显降低(P<0.05)。结论:肺不藏魄型失眠模型大鼠肺、大肠、脑、心中多巴胺D1受体表达明显增加,D2受体表达明显降低,说明D1受体表达增加,D2受体表达降低与肺不藏魄型失眠机制密切相关,是该型失眠模型的失眠机制之一。     

64排CT肾脏、肾上腺、肾动脉三合一扫描在继发性高血压病因筛查中的应用

目的 探讨64排CT肾脏、肾上腺、肾动脉三合一扫描在继发性高血压病因筛查中的应用价值.方法 利用飞利浦64排螺旋CT进行肾脏、肾上腺、肾动脉三合一扫描增强扫描,69例获得原始横断面图像后,采用容积再现(VR)、最大密度投影(MIP)、多平面重建(MPR)技术处理图像,29例行DSA检查或手术治疗.结果 所有病例CT三合一扫描1次检查均获成功,显示肾上腺疾病25例,肾脏实质性病变9例,肾动脉狭窄35例.结论 64排CT一次检查可实现对肾脏、肾上腺、肾动脉的快速联合排查,是继发性高血压病因的有效筛查手段,具有重要临床应用价值.     

Human huntingtin derived from YAC transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotype

Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in exon 1 of a novel gene. The HD protein (huntingtin) plays a critical role in early embryonic development since homozygous targeted disruption of the murine HD gene results in embryonic lethality by day 7.5. To rescue this phenotype by transgene based huntingtin expression it is therefore essential to express the protein early enough in development in the appropriate cells. Since YAC based transgenes are known to be regulated in an appropriate temporal and tissue-specific manner, we sought to rescue the embryonic lethality by breeding YAC transgenic mice expressing human huntingtin with mice heterozygous for the targeted disruption. We generated viable offspring homozygous for the disrupted murine HD gene but expressing human huntingtin derived from the YAC. This result clearly shows that YAC transgene based expression of huntingtin occurs prior to 7.5 days gestation. Additionally, we show that human huntingtin expression in YAC transgenic mice follows an identical tissue distribution and subcellular localisation pattern as that of the murine endogenous protein and that expression levels of 2-3 times endogenous can be achieved. This shows that human huntingtin under the influence of its native promoter, despite differences to the murine protein, is functional in a murine background and can compensate for loss of the murine protein. These results show that YAC transgenic approaches are a particularly promising route to producing an animal model for disorders associated with CAG expansion.      

Comparison of radiographic image quality from four digitization devices as viewed on computer monitors

The objective of this study was to compare the quality of radiographic images digitized from commercial-grade and consumer-grade digital cameras and scanners as viewed on computer monitor. Radiographic images were digitized from hardcopy film using a commercial-grade laser scanner, a consumer-grade desktop flatbed scanner, a commercial-grade digital camera, and a consumer-grade digital camera. The quality of images without and with grayscale histogram adjustment was evaluated subjectively by 10 board-certified radiologists. Optical density response was evaluated objectively using a grayscale test pattern. There was no significant difference in subjective quality among images digitized with the commercial scanner, consumer scanner, and commercial camera. The quality of images digitized with the consumer camera was lower than the other 3. Objective tests showed the commercial scanner to have the most linear optical density response. For the purpose of viewing images on a computer monitor, a consumer-grade desktop scanner can produce images of similar quality to those produced by more expensive laser commercial-grade scanners and digital cameras and provides cost-efficient means to digitize radiographic plain films. A consumer-grade camera may not be optimal for use in this setting.     

Reduced penetrance of the Huntington's disease mutation

Controversy persists concerning the significance of Huntington disease (HD) alleles in the 36-39 repeat range. Although some clinically affected persons have been documented with repeats in this range, elderly unaffected individuals have also been reported. We examined 10 paternal transmissions of HD alleles of 37-39 repeats in collateral branches of families with de novo HD. All 10 descendants, including many who are elderly, are without symptoms of HD. Forty percent of the transmissions were unstable, although none varied by more than one repeat. The observation that individuals with alleles of 37-39 repeats may survive unaffected beyond common life expectancy supports the presence of reduced penetrance for HD among some persons with repeat sizes which overlap the clinical range. Non-penetrance may be increased in the collateral branches of de novo mutation families when compared to penetrance estimates from patient series. There was no CAA-->CAG mutation for the penultimate glutamine in either a de novo expanded 42 repeat allele or the corresponding non-penetrant 38 repeat allele in a family with fresh mutation to HD.      

Hepatitis C virus load and expression of a unique subset of cellular genes in circulating lymphoid cells differentiate non‐responders from responders to pegylated interferon alpha–ribavirin treatment

Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha–ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non‐responders had 3‐ to 10‐fold higher basal levels of interleukin (IL)‐8, IFN‐stimulated gene 15 (ISG15), 2′,5′‐oligoadenylate synthetase (OAS), and Toll‐like receptors (TLR)‐4, ‐5, and ‐7 compared to responders. Non‐responders with similar post‐treatment follow‐ups as responders persistently expressed 6‐ to 20‐fold greater levels of IL‐8, ISG15, and OAS after therapy. Higher expression of IFN‐α, IFN‐γ, and IFN‐λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre‐treatment HCV RNA loads in PBMCs of non‐responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non‐responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR‐4, ‐5, and ‐7 levels, and persistently high levels of IL‐8, ISG15, and OAS were correlated with IFN non‐responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN‐based therapies. J. Med. Virol. 85:441–448, 2013. © 2012 Wiley Periodicals, Inc.     

Stray dog trade fuelled by dog meat consumption as a risk factor for rabies infection in Calabar,southern Nigeria

Background

Rabies is a preventable zoonosis with the highest case fatality of any disease in the world. In the developing world, it is transmitted mainly by dog bites. In parts of southern Nigeria, dog meat is a delicacy.

Objective

To highlight trade in stray dogs as a major risk factor for rabies in animals and humans in south-south Nigeria.

Method

Patients admitted into the University of Calabar Teaching Hospital (UCTH) with a diagnosis of rabies between July and October 2012 were analysed for risk factors, post exposure prophylaxis (PEP), health seeking behaviour and outcome. Focused group interview were also conducted among traders/handlers of stray dogs.

Results

Ten cases of rabies in subjects aged 3 to 52 years were recorded in these five months period. Eight of the cases were male and apparently got infected directly or indirectly through the trade in stray dogs for human consumption. None had proper PEP and all patients died.

Conclusion

Stray dog trade, fuelled by eating of dog meat, is a risk factor for human and animal rabies in Calabar, southern Nigeria. Culling of stray dogs, control of stray dogs'' trade and public enlightenment on PEP is recommended.     

Kinin B<Subscript>2</Subscript>receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice

Background  

Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B₁ and B₂. Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis (MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. The aim of the present study was to evaluate the relevance of B₂ receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG)_35–55-induced EAE in mice.     

Count every newborn; a measurement improvement roadmap for coverage data

Background

The Every Newborn Action Plan (ENAP), launched in 2014, aims to end preventable newborn deaths and stillbirths, with national targets of ≤12 neonatal deaths per 1000 live births and ≤12 stillbirths per 1000 total births by 2030. This requires ambitious improvement of the data on care at birth and of small and sick newborns, particularly to track coverage, quality and equity.

Methods

In a multistage process, a matrix of 70 indicators were assessed by the Every Newborn steering group. Indicators were graded based on their availability and importance to ENAP, resulting in 10 core and 10 additional indicators. A consultation process was undertaken to assess the status of each ENAP core indicator definition, data availability and measurement feasibility. Coverage indicators for the specific ENAP treatment interventions were assigned task teams and given priority as they were identified as requiring the most technical work. Consultations were held throughout.

Results

ENAP published 10 core indicators plus 10 additional indicators. Three core impact indicators (neonatal mortality rate, maternal mortality ratio, stillbirth rate) are well defined, with future efforts needed to focus on improving data quantity and quality. Three core indicators on coverage of care for all mothers and newborns (intrapartum/skilled birth attendance, early postnatal care, essential newborn care) have defined contact points, but gaps exist in measuring content and quality of the interventions. Four core (antenatal corticosteroids, neonatal resuscitation, treatment of serious neonatal infections, kangaroo mother care) and one additional coverage indicator for newborns at risk or with complications (chlorhexidine cord cleansing) lack indicator definitions or data, especially for denominators (population in need). To address these gaps, feasible coverage indicator definitions are presented for validity testing. Measurable process indicators to help monitor health service readiness are also presented. A major measurement gap exists to monitor care of small and sick babies, yet signal functions could be tracked similarly to emergency obstetric care.

Conclusions

The ENAP Measurement Improvement Roadmap (2015-2020) outlines tools to be developed (e.g., improved birth and death registration, audit, and minimum perinatal dataset) and actions to test, validate and institutionalise proposed coverage indicators. The roadmap presents a unique opportunity to strengthen routine health information systems, crosslinking these data with civil registration and vital statistics and population-based surveys. Real measurement change requires intentional transfer of leadership to countries with the greatest disease burden and will be achieved by working with centres of excellence and existing networks.