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Selected Abstracts,-Amyloid immunization approaches for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Bruno P. Imbimbo Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source] Change processes for attractive work in small manufacturing companiesHUMAN FACTORS AND ERGONOMICS IN MANUFACTURING & SERVICE INDUSTRIES, Issue 1 2009Mattias Åteg The article originates from research in interaction between researchers and companies in a network, which has led to an increasing awareness among managers on issues such as reasons behind difficulties in attracting competent labor. Particularly, attention has been directed toward the importance of work environment improvements that increase the attractivity of industrial work. To deal with such challenges, for more than 5 years a number of small engineering companies, with research support, have been engaged in change processes based on the concept of attractive work. The purpose of the article is to develop knowledge and understanding for how small engineering companies can create more attractive work. One goal is to make it possible to draw conclusions about the employees' experiences of changes in the attractivity of industrial work. Efforts in this direction have been conducted through work environment assessments (before and after the changes) and through administration of a questionnaire. The results show that it is possible to analyze how employees experience changes in the attractivity of work. This is most interesting from the perspective that the results can be used for assisting further improvements. © 2008 Wiley Periodicals, Inc. [source] Formal pooling of health risks in sub-Saharan Africa: Reflections on the obstacles encounteredINTERNATIONAL SOCIAL SECURITY REVIEW, Issue 2 2002Bruno Meessen Over the past few years a number of institutional solutions to the pooling of health risks have been advanced in a great number of reform proposals for developing countries. The empirical arguments in favour of such recommendations have the full force of accumulated experience in countries that have long been industrialized. However, rural realities in Africa and Asia naturally have very little to do with past or present realities in western countries. Whereas the technical-cooperation and scientific community has relatively good knowledge of techniques, a number of recent experiences of the introduction of mutual benefit schemes in Africa seem to show that this approach is now enjoying some success. The low levels of membership in particular make it essential to tackle the problem fully. This article tries to identify the various possible explanations for this lack of enthusiasm in sub-Saharan Africa. [source] Challenging the Bioethical Application of the Autonomy Principle within Multicultural SocietiesJOURNAL OF APPLIED PHILOSOPHY, Issue 1 2004Andrew Fagan abstract,This article critically re-examines the application of the principle of patient autonomy within bioethics. In complex societies such as those found in North America and Europe health care professionals are increasingly confronted by patients from diverse ethnic, cultural, and religious backgrounds. This affects the relationship between clinicians and patients to the extent that patients' deliberations upon the proposed courses of treatment can, in various ways and to varying extents, be influenced by their ethnic, cultural, and religious commitments. The principle of patient autonomy is the main normative constraint imposed upon medical treatment. Bioethicists typically appeal to the principle of patient autonomy as a means for generally attempting to resolve conflict between patients and clinicians. In recent years a number of bioethicists have responded to the condition of multiculturalism by arguing that the autonomy principle provides the basis for a common moral discourse capable of regulating the relationship between clinicians and patients in those situations where patients' beliefs and commitments do or may contradict the ethos of biomedicine. This article challenges that claim. I argue that the precise manner in which the autonomy principle is philosophically formulated within such accounts prohibits bioethicists' deployment of autonomy as a core ideal for a common moral discourse within multicultural societies. The formulation of autonomy underlying such accounts cannot be extended to simply assimilate individuals' most fundamental religious and cultural commitments and affiliations per se. I challenge the assumption that respecting prospective patients' fundamental religious and cultural commitments is necessarily always compatible with respecting their autonomy. I argue that the character of some peoples' relationship with their cultural or religious community acts to significantly constrain the possibilities for acting autonomously. The implication is clear. The autonomy principle may be presently invalidly applied in certain circumstances because the conditions for the exercise of autonomy have not been fully or even adequately satisfied. This is a controversial claim. The precise terms of my argument, while addressing the specific application of the autonomy principle within bioethics, will resonate beyond this sphere and raises questions for attempts to establish a common moral discourse upon the ideal of personal autonomy within multicultural societies generally. [source] Review article: possible beneficial effects of coffee on liver disease and functionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2007I. S. H. CADDEN Summary Background Coffee is consumed by 50 percent of Americans every day. After oil, coffee is the second most valuable commodity in the world. In recent years a number of studies have suggested potential health risks associated with coffee consumption; however, the results are controversial. Whilst coffee has been reported to increase cardiovascular risk factors, other investigators have demonstrated its protective effects on diseases ranging from type 2 diabetes to Parkinson's disease. A number of investigators have focused their attention on the relationship between the consumption of coffee and liver disease. Aim, To examine the published literature to date in an attempt to establish the presence of an hepatoprotective effect of coffee. Methods, Using PubMed, we identified published studies and review articles relating to the effect of coffee consumption on diseases of the liver. Conclusion, A number of studies have reported the beneficial effects of coffee on abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. At the present time the mechanism of this effect remains unclear as does the ,,dose'' required to achieve these benefits. [source] | |||||||||||||