Reduced oligomeric and vascular amyloid-β following immunization of TgCRND8 mice with an Alzheimer's DNA vaccine

Immunization with amyloid-β (Aβ) peptide reduces amyloid load in animal studies and in humans; however clinical trials resulted in the development of a pro-inflammatory cellular response to Aβ. Apoptosis has been employed to stimulate humoral and Th2-biased cellular immune responses. Thus, we sought to investigate whether immunization using a DNA vaccine encoding Aβ in conjunction with an attenuated caspase generates therapeutically effective antibodies. Plasmids encoding Aβ and an attenuated caspase were less effective in reducing amyloid pathology than those encoding Aβ alone. Moreover, use of Aβ with an Arctic mutation (E22G) as an immunogen was less effective than wild-type Aβ in terms of improvements in pathology. Low levels of IgG and IgM were generated in response to immunization with a plasmid encoding wild-type Aβ. These antibodies decreased plaque load by as much as 36 ± 8% and insoluble Aβ42 levels by 56 ± 3%. Clearance of Aβ was most effective when antibodies were directed against N-terminal epitopes of Aβ. Moreover, immunization reduced CAA by as much as 69 ± 12% in TgCRND8 mice. Finally, high-molecular-weight oligomers and Aβ trimers were significantly reduced with immunization. Thus, immunization with a plasmid encoding Aβ alone drives an attenuated immune response that is sufficient to clear amyloid pathology in a mouse model of Alzheimer's disease.     

A literature review exploring how healthcare professionals contribute to the assessment and control of postoperative pain in older people

Little research has examined the care older people receive in the acute surgical setting. Although pain assessment and management are judged to be a priority in nursing, often pain, in older people, is undermanaged for a variety of reasons. Factors such as stoicism, communication and ageism can shape both the patients’ and nurses’ attitude towards the perception of pain which subsequently affects pain management. Through a review of the literature, this paper aims to: (i) identify how healthcare professionals contribute to the assessment and control of postoperative pain in older people and (ii) explore potential barriers to achieving more advantageous pain control in this group. It is suggested that to improve pain management there is a need to individualize pain assessment for older people and to assist clinicians with enhancing their education and decision‐making abilities in this field. This may best be achieved by supporting a programme of change to develop the skills of staff and encouraging learning through reflective practice. There is however a need for further research in this area.     

Reliability of DSM-III diagnoses for major depression and generalized anxiety disorder using the structured clinical interview for DSM-III

This study examined the interrater reliability of generalized anxiety disorder (GAD) and major depressive disorder (MDD) diagnoses derived from the Structured Clinical Interview for DSM-III (SCID). Using videotaped interviews, paired raters made independent diagnoses of 75 psychiatric outpatients. The percent agreement of the raters was 82% for MDD and 86% for GAD; the respective kappa values were .72 and .79. The results indicated that the SCID can be employed reliably to differentiate MDD from GAD. The SCID is recommended for further research with these disorders.     

Influence of ethanol on fetal brain cholinergic enzyme activities

Cultured brain cells from rat fetuses of ethanol-treated mothers demonstrated more than 2-fold elevations in choline acetyltransferase (ChAT) activity relative to those of control (saline-exposed) fetal brain cells. When cells from control animals were incubated in vitro for 5 days with 0.1% ethanol, ChAT activity was found to increase more than 4-fold. Brain cells from in utero ethanol-treated animals further exposed to ethanol in vitro for 5 days demonstrated significantly higher ChAT activity compared to cells exposed to ethanol only in vivo. These levels were more than 6 times greater than those of central nervous system cells never exposed to ethanol. Acetylcholinesterase (AChE) activity was significantly elevated (greater than 4-fold) in fetal brain cells when ethanol was present both in vivo and in vitro, but neither treatment alone resulted in any significant changes in AChE. These effects of ethanol on enzymes involved in acetylcholine metabolism may contribute to the different developmental neurologic abnormalities associated with fetal alcohol exposure.     

Similar dose responsiveness of hepatic glycogenolysis and gluconeogenesis to glucagon in vivo

This study was undertaken to determine whether the dose-dependent effect of glucagon on gluconeogenesis parallels its effect on hepatic glycogenolysis in conscious overnight-fasted dogs. Endogenous insulin and glucagon secretion were inhibited by somatostatin (0.8 micrograms X kg-1 X min-1), and intraportal replacement infusions of insulin (213 +/- 28 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1) were given to maintain basal hormone concentrations for 2 h (12 +/- 2 microU/ml and 108 +/- 23 pg/ml, respectively). The glucagon infusion was then increased 2-, 4-, 8-, or 12-fold for 3 h, whereas the rate of insulin infusion was left unchanged. Glucose production (GP) was determined with 3-[3H]glucose, and gluconeogenesis (GNG) was assessed with tracer (U-[14C]alanine conversion to [14C]glucose) and arteriovenous difference (hepatic fractional extraction of alanine, FEA) techniques. Increases in plasma glucagon of 53 +/- 8, 199 +/- 48, 402 +/- 28, and 697 +/- 149 pg/ml resulted in initial (15-30 min) increases in GP of 1.1 +/- 0.4 (N = 4), 4.9 +/- 0.5 (N = 4), 6.5 +/- 0.6 (N = 6), and 7.7 +/- 1.4 (N = 4) mg X kg-1 X min-1, respectively; increases in GNG (approximately 3 h) of 48 +/- 19, 151 +/- 50, 161 +/- 25, and 157 +/- 7%, respectively; and increases in FEA (3 h) of 0.14 +/- 0.07, 0.37 +/- 0.05, 0.42 +/- 0.04, and 0.40 +/- 0.17, respectively. In conclusion, GNG and glycogenolysis were similarly sensitive to stimulation by glucagon in vivo, and the dose-response curves were markedly parallel.     

全科医生札记--布朗医生日记

汽车机械学 Bobby是我的汽车修理师，他有一种我喜欢效仿的工作风格。首先他是一位伟大的诊断专家；如果你告诉他汽车出现了什么问题，他会帮你做出鉴别诊断。“运货车是否发动不着了？发动机是否转动？你是否听到了滴滴答答的声音？”问了几个问题后，他便会做出判断。比如我的发动机供不上汽油了，排除了几种可能性后他认为是由燃油泵造成的。