Can an EASYcare based dementia training programme improve diagnostic assessment and management of dementia by general practitioners and primary care nurses? The design of a randomised controlled trial

Background  

Early diagnosis of dementia benefits both patient and caregiver. Nevertheless, dementia in primary care is currently under-diagnosed. Some educational interventions developed to improve dementia diagnosis and management were successful in increasing the number of dementia diagnoses and in changing attitudes and knowledge of health care staff. However, none of these interventions focussed on collaboration between GPs and nurses in dementia care. We developed an EASYcare-based Dementia Training Program (DTP) aimed at stimulating collaboration in dementia primary care. We expect this program to increase the number of cognitive assessments and dementia diagnoses and to improve attitudes and knowledge of GPs and nurses.     

脱羰青蒿素的抗疟活性

青蒿素(1)是从青蒿(Artemisia annua)中分离得到的一个抗疟化合物。青蒿素的发现改变了以往抗疟药物均为含氮杂环化合物的格式,开创了一类以过氧化合物为特征的、对抗氯喹虫株有效的新型抗疟药物。七十年代青蒿素结构发表以来,国内外在化学、药理以及临床方面均进行了大量工作,成为当今抗疟药方面最活跃的一个研究课题。这里简要报道     

重组人粒细胞-巨噬细胞集落刺激因子乳酸链球菌表达载体的构建

目的:构建重组人粒细胞-巨噬细胞集落刺激因子乳酸链球菌表达载体,为进一步研究人粒细胞-巨噬细胞集落刺激因子在乳链菌的表达及其治疗价值奠定基础。方法:实验于2005-04/2006-03在南方医科大学南方医院消化病研究所完成。①载体pNCSF的构建:将质粒集落刺激因子及含有P59启动子、USP45蛋白信号肽的pNBC1000质粒分别加入BamH Ⅰ和Pst Ⅰ进行双酶切,并用Apa Ⅰ、Sac Ⅰ进行双酶切鉴定,重组质粒命名为pNCSF。②SDGFP的TA克隆及载体pNCSFGFP的构建:将经过优化适合在乳链菌表达的人粒细胞-巨噬细胞集落刺激因子基因克隆于含有P59启动子、USP45蛋白信号肽的pNBC1000载体,得到重组质粒pNCSF;同时设计上下游引物经PCR扩增增强荧光表达蛋白(EGFP),TA克隆后经测序验证,再连接于pNCSF获得重组质粒pNCSFGFP。③载体pTRCSF、pTRCSFGFP的建立:将获得的pNCSF和pNCSFGFP进一步克隆于穿梭载体pTR1001c,以获得人粒细胞-巨噬细胞集落刺激因子乳链菌表达载体pTRCSF及pTRCSFGFP。结果:①载体pNCSF构建结果:酶切鉴定产物经1.0%的琼脂糖凝胶电泳后,发现有(含启动子P59、信号肽USP45、人粒细胞-巨噬细胞集落刺激因子)720bp的目的片段。②SDGFP的TA克隆及载体pNCSFEGFP的构建结果:SDGFP阳性克隆产物经EcoRⅠ酶切鉴定得到775bp目的片段。pNCSFEGFP酶切鉴定产物经1.0%的琼脂糖凝胶电泳后,发现有(含启动子P59、信号肽USP45、人粒细胞-巨噬细胞集落刺激因子、SDGFP)1495bp的目的片段。③穿梭质粒pTRCSF、pTRCSFGFP酶切鉴定结果:经Xba Ⅰ、Sac Ⅰ进行双酶切鉴定,分别得到约717bp、1492bp大小目的片段。结论:获得了人粒细胞-巨噬细胞集落刺激因子乳链菌表达载体pTRCSF及pTRCSFGFP,并经酶切鉴定和测序证实。     

上海市0～6岁小儿佝偻病的现状调查

目的:了解上海市小儿佝偻病的现状及影响因素。方法:2005年春季以整群和分层随机抽样法抽取上海市部分城区0～6岁小儿821名,采取问卷调查方法了解小儿的生活环境、饮食习惯、户外活动、营养状况、既往疾病史及母亲的妊娠情况等。佝偻病的诊断以1996年国家卫生部颁布的"婴幼儿佝偻病防治方案"为诊断标准。结果:取得完整有效资料769名,其中男童396名,女童373名;集居儿童456名,散居儿童313名。①小儿佝偻病患病率为17.3%(133/769),其中男童患病率为17.4%、女童为17.2%。②佝偻病与喂养方式(母乳喂养的患病率为13.0%、混合喂养的患病率为17.5%、人工喂养的患病率为25.2%)、鱼肝油添加(按时添加维生素D的患病率为13.5%、偶加或未加维生素D的患病率为32.5%)、居住环境(居住在市区的患病率为23.6%、居住在郊区的患病率为10.6%;集居儿童患病率为13.8%、散居儿童患病率为22.4%)、户外活动时间(经常户外活动的患病率为12.9%、偶尔户外活动的患病率为31.8%)、反复呼吸道感染(小儿有反复呼吸道感染的患病率为26.9%、无反复呼吸道感染的患病率为12.9%)、母孕期缺钙(母孕期有缺钙的患病率为33.2%、无缺钙的患病率为12.0%)等因素有关(P<0.01)。结论:上海市小儿佝偻病患病率有上升趋势。影响因素与城市环境污染、母乳喂养减少、年轻父母科学育儿知识缺乏等有关。     

激光治疗瘢痕的特征

目的:介绍国内近20年来激光治疗瘢痕的临床研究概况,以期进一步了解激光治疗瘢痕的新进展。资料来源:应用计算机检索Pubmed和中国生物医学文献数据库1983/2006的相关文章,限定文章语言种类为英文和中文,检索词为“cicatrices(瘢痕),laser(激光)”。资料选择:对资料进行初审,选择临床试验研究文献查找全文。纳入标准:①有明确诊断标准。②随机对照实验或对照试验。有无随访,是否采用盲法不限制。③治疗组干预措施为激光或激光联合药物;对照组干预措施为曲安奈德、冷冻联合曲安奈德或不采用药物措施。排除标准:①非对照研究。②治疗组或对照组的干预措施不符合纳入标准。③机制研究。④重复研究。资料提炼:共收集到相关文献120篇,按上述标准纳入31篇,其余文献均被排除。资料综合:31篇文章中11篇为随机对照研究,10篇为对照研究,各研究的研究期为1～6个月。各研究所纳入的病例数量为10～50例。其中6个研究对比了激光与传统药物治疗瘢痕的疗效及安全性,2个研究进行了激光治疗瘢痕基础研究机制比较,10个研究观察了激光结合与单纯药物或单纯激光对瘢痕的疗效,4个研究比较了激光联合西药治疗瘢痕的疗效,2个研究观察了激光治疗瘢痕的副作用。7篇介绍国内或国外瘢痕治疗的研究情况。结论:激光治疗瘢痕的疗效可靠,具有副作用少,方法简单,安全性高,易被患者接受等优势。但由于激光治疗瘢痕还存在着一定的局限性,今后还需要在激光的穿透深度方面研究。     

Protection of mitochondrial function and improvement in cognitive recovery in rats treated with hyperbaric oxygen following lateral fluid-percussion injury

OBJECT: Hyperbaric oxygen (HBO2) has been shown to improve outcome after severe traumatic brain injury, but its underlying mechanisms are unknown. Following lateral fluid-percussion injury (FPI), the authors tested the effects of HBO2 treatment as well as enhanced normobaric oxygenation on mitochondrial function, as measured by both cognitive recovery and cellular adenosine triphosphate (ATP) levels. METHODS: Adult male Sprague-Dawley rats were subjected to moderate lateral FPI or sham injury and were allocated to one of four treatment groups: 1) FPI treated with 4 hours of normobaric 30% O2; 2) FPI treated with 4 hours of normobaric 100% O2; 3) FPI treated with 1 hour of HBO2 plus 3 hours of normobaric 100% O2; and 4) sham-injured treated with normobaric 30% O2. Cognitive outcome was assessed using the Morris water maze (MWM) on Days 11 to 15 after injury. Animals were then killed 21 days postinjury to assess hippocampal neuronal loss. Adenosine triphosphate was extracted from the neocortex and measured using high-performance liquid chromatography. The results showed that injured animals treated with HBO2 or normobaric 100% O2 alone had significantly higher levels of cerebral ATP as compared with animals treated using normobaric 30% O2 (p < or = 0.05). The injured animals treated with HBO2 had significant improvements in cognitive recovery, as characterized by a shorter latency in MWM performance (p < or = 0.05), and decreased neuronal loss in the CA2/3 and hilar regions as compared with those treated with 30% or 100% O2, (p < or = 0.05). CONCLUSIONS: Both hyperbaric and normobaric hyperoxia increased cerebral ATP levels after lateral FPI. In addition, HBO2 treatment improved cognitive recovery and reduced hippocampal neuronal cell loss after brain injury in the rat.     

Valerenic acid derivatives as novel subunit-selective GABAA receptor ligands �Cin vitro and in vivo characterization

BACKGROUND AND PURPOSE

Subunit-specific modulators of γ-aminobutyric acid (GABA) type A (GABA_A) receptors can help to assess the physiological function of receptors with different subunit composition and also provide the basis for the development of new drugs. Valerenic acid (VA) was recently identified as a β_2/3 subunit-specific modulator of GABA_A receptors with anxiolytic potential. The aim of the present study was to generate VA derivatives as novel GABA_A receptor modulators and to gain insight into the structure–activity relation of this molecule.

EXPERIMENTAL APPROACH

The carboxyl group of VA was substituted by an uncharged amide or amides with different chain length. Modulation of GABA_A receptors composed of different subunit compositions by the VA derivatives was studied in Xenopus oocytes by means of the two-microelectrode voltage-clamp technique. Half-maximal stimulation of GABA-induced chloride currents (I_GABA) through GABA_A receptors (EC₅₀) and efficacies (maximal stimulation of I_GABA) were estimated. Anxiolytic activity of the VA derivatives was studied in mice, applying the elevated plus maze test.

KEY RESULTS

Valerenic acid amide (VA-A) displayed the highest efficacy (more than twofold greater I_GABA enhancement than VA) and highest potency (EC₅₀= 13.7 ± 2.3 µM) on α₁β₃ receptors. Higher efficacy and potency of VA-A were also observed on α₁β₂γ_2s and α₃β₃γ_2s receptors. Anxiolytic effects were most pronounced for VA-A.

CONCLUSIONS AND IMPLICATIONS

Valerenic acid derivatives with higher efficacy and affinity can be generated. Greater in vitro action of the amide derivative correlated with a more pronounced anxiolytic effect in vivo. The data give further confidence in targeting β₃ subunit containing GABA_A receptors for development of anxiolytics.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.     

Production of genetically stable high-titer retroviral vectors that carry a human gamma-globin gene under the control of the alpha-globin locus control region

The ability to generate stable high-titer vectors that give rise to high levels of expression of transduced globin genes in erythroid cells is a prerequisite for effective retroviral-mediated globin gene therapy. The human beta-globin gene with its immediate flanking sequences does not contain all the regulatory elements necessary for regulated high-level and position-independent expression in erythroid cells. The regulatory element known as the beta-globin locus control region (BetaLCR) can provide a linked Beta-globin gene with these properties. However, addition of BetaLCR sequences to a retrovirus carrying a beta-globin gene increases its genetic instability. We have developed a new generation of retroviral vectors in which a human gamma- globin gene is placed under the control of the alphaLCR, the major regulatory element of the alpha-globin gene cluster. We demonstrate that these retroviruses are genetically stable in producer cell lines and can be produced at high titers that exceed 5 x 10(6) colony-forming units (CFU)/mL. In addition, we show that the transduced gamma-globin gene can be expressed in the adult erythroid environment of mouse erythroleukemia (MEL) cells at a level comparable to that of a single endogenous Betamaj-globin gene. These retroviruses can also transduce primary murine bone marrow progenitor cells as efficiently as retroviruses that carry the neomycin resistance (neor) gene. This new generation of globin retroviral vectors may prove useful for gene therapy of human beta-globin gene disorders such as sickle cell disease and beta-thalassemia.