Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most signifcant social and health crises which has currently afficted nearly 44 million patients worldwide and about new 7.7 million ...Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most signifcant social and health crises which has currently afficted nearly 44 million patients worldwide and about new 7.7 million cases are reported every year. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus comprehensively addresses Alzheimer’s disease pathophysiology with an insight of underlying multicascade pathway and elaborates possible therapeutic targets- particularly anti-amyloid approaches, anti-tau approaches, acetylcholinesterase inhibitors, glutamatergic system modifiers, immunotherapy, anti-nflammatory targets, antioxidants, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors and insulin. In spite of extensive research leading to identification of newer targets and potent drugs, complete cure of Alzheimer’s disease appears to be an unreached holy grail. This can be attributed to their ineffective delivery across blood brain barrier and ultimately to the brain. With this understanding, researchers are now focusing on development of drug delivery systems to be delivered via suitable route that can circumvent blood brain barrier effectively with enhanced patient compliance. In this context, we have summarized current drug delivery strategies by oral, transdermal, intravenous, intranasal and other miscellaneous routes and have accentuated the future standpoint towards promising therapy ultimately eading to Alzheimer’s disease cure.展开更多
Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes...Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes, genetic factors, environmental impact factors, apoptosis, and so on. Especially, oxidative stress plays an essential role in AD pathogenesis by the function of linking agent. Oxidative stress in AD mainly includes lipid peroxidation, protein oxidation and DNA oxidation. Lipid peroxidation plays a key role in the development and progression of AD. Protein oxidation is an important mechanism in AD. Oxidative damage to DNA may plays an important role in aging and AD.展开更多
Alternatives to the sectoral and public policies and regulations of environmental and water resources＇ protection, and the experiments of integrated management have been rapidly multiplied since the year 1990. Water ...Alternatives to the sectoral and public policies and regulations of environmental and water resources＇ protection, and the experiments of integrated management have been rapidly multiplied since the year 1990. Water constitutes a principal stake of these environmental policies in the majority of the countries and especially in the countries of North Africa as Algeria, where this resource is threatened by repeated dryness and by the impact of the climate change. The integrated water resource management reflects today the world tendency of the governments to exploit and preserve this resource by a way based on a process of governance, which passes by the dialog of diversified actors （various sectors）. According to this policy and to the promulgation of the Algerian National Report on State effective implementation and coordination mechanisms are required. How this principle of integrated water management will be executed with various scenarios in Algeria and what are the main difficulties that can be met？ Or, more exactly, what are the variables that can influence the operation of the local water process governorship？ This analysis will be carried out through the example of the Wadi El K6bir watershed located in the northeast of Algeria, which is real natural area of water supply that feeds the communities, the natural and artificial basins, and preserves the perenniality of the existing natural ecosystems especially the one of the natural park classified by the United Nations Educational Scientific and Cultural Organization （U.N.E.S.C.O） in 1989 as the inheritance of humanity and six other sites classified according to the Ramsar convention as wetlands of international importance to be preserved.展开更多
Objective To learn the effect of omemtum transposition to the brain of patients with Alzheimer’s disease. Methods Ten consecutive patients, aged 58-81 years old, underwent graft of their elongated pedicled omentum on...Objective To learn the effect of omemtum transposition to the brain of patients with Alzheimer’s disease. Methods Ten consecutive patients, aged 58-81 years old, underwent graft of their elongated pedicled omentum onto their left frontal-temperal-parietal cerebral cortex. Those patients, who had more than five years of dementia with low mini mental-state examination (MMSE) scores of 2-15, were diagnosed by a neurologist. All subjects underwent single photon evoked computer tomography (SPECT) pre- and post-operatively. SPECT results were analyzed semi-quantitatively by calculation of the left/right radioactivity counts symmetry index (Si). The patients were followed up to one year. The outcome was evaluated by the neurologist with a modified scale of activities of daily living (mADL) as well as the MMSE. Results Three months following the surgery, the Si of SPECT increased from (98.7±1.9)% to (103.9±2.3)% (P=0.0307). The neurological and neuropsychological testing scores increased insignificantly during the follow-up period. By the one year, the MMSE score rose from 8.7±1.4 to 10.7±1.8(P>0.05), while the mADL from 13.3±1.8 to 16.9±2.0 (P>0.05). One of the patients suffered a heart attack, two had epileptic episodes postoperatively. Conclusion We believe that omental transposition to the brain augments cerebral blood flow, which might be helpful to decelerate the processing of Alzheimer’s disease. However, it is still a potentially risky procedure for the elderly.展开更多
文摘Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most signifcant social and health crises which has currently afficted nearly 44 million patients worldwide and about new 7.7 million cases are reported every year. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus comprehensively addresses Alzheimer’s disease pathophysiology with an insight of underlying multicascade pathway and elaborates possible therapeutic targets- particularly anti-amyloid approaches, anti-tau approaches, acetylcholinesterase inhibitors, glutamatergic system modifiers, immunotherapy, anti-nflammatory targets, antioxidants, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors and insulin. In spite of extensive research leading to identification of newer targets and potent drugs, complete cure of Alzheimer’s disease appears to be an unreached holy grail. This can be attributed to their ineffective delivery across blood brain barrier and ultimately to the brain. With this understanding, researchers are now focusing on development of drug delivery systems to be delivered via suitable route that can circumvent blood brain barrier effectively with enhanced patient compliance. In this context, we have summarized current drug delivery strategies by oral, transdermal, intravenous, intranasal and other miscellaneous routes and have accentuated the future standpoint towards promising therapy ultimately eading to Alzheimer’s disease cure.
文摘Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes, genetic factors, environmental impact factors, apoptosis, and so on. Especially, oxidative stress plays an essential role in AD pathogenesis by the function of linking agent. Oxidative stress in AD mainly includes lipid peroxidation, protein oxidation and DNA oxidation. Lipid peroxidation plays a key role in the development and progression of AD. Protein oxidation is an important mechanism in AD. Oxidative damage to DNA may plays an important role in aging and AD.
文摘Alternatives to the sectoral and public policies and regulations of environmental and water resources＇ protection, and the experiments of integrated management have been rapidly multiplied since the year 1990. Water constitutes a principal stake of these environmental policies in the majority of the countries and especially in the countries of North Africa as Algeria, where this resource is threatened by repeated dryness and by the impact of the climate change. The integrated water resource management reflects today the world tendency of the governments to exploit and preserve this resource by a way based on a process of governance, which passes by the dialog of diversified actors （various sectors）. According to this policy and to the promulgation of the Algerian National Report on State effective implementation and coordination mechanisms are required. How this principle of integrated water management will be executed with various scenarios in Algeria and what are the main difficulties that can be met？ Or, more exactly, what are the variables that can influence the operation of the local water process governorship？ This analysis will be carried out through the example of the Wadi El K6bir watershed located in the northeast of Algeria, which is real natural area of water supply that feeds the communities, the natural and artificial basins, and preserves the perenniality of the existing natural ecosystems especially the one of the natural park classified by the United Nations Educational Scientific and Cultural Organization （U.N.E.S.C.O） in 1989 as the inheritance of humanity and six other sites classified according to the Ramsar convention as wetlands of international importance to be preserved.
文摘Objective To learn the effect of omemtum transposition to the brain of patients with Alzheimer’s disease. Methods Ten consecutive patients, aged 58-81 years old, underwent graft of their elongated pedicled omentum onto their left frontal-temperal-parietal cerebral cortex. Those patients, who had more than five years of dementia with low mini mental-state examination (MMSE) scores of 2-15, were diagnosed by a neurologist. All subjects underwent single photon evoked computer tomography (SPECT) pre- and post-operatively. SPECT results were analyzed semi-quantitatively by calculation of the left/right radioactivity counts symmetry index (Si). The patients were followed up to one year. The outcome was evaluated by the neurologist with a modified scale of activities of daily living (mADL) as well as the MMSE. Results Three months following the surgery, the Si of SPECT increased from (98.7±1.9)% to (103.9±2.3)% (P=0.0307). The neurological and neuropsychological testing scores increased insignificantly during the follow-up period. By the one year, the MMSE score rose from 8.7±1.4 to 10.7±1.8(P>0.05), while the mADL from 13.3±1.8 to 16.9±2.0 (P>0.05). One of the patients suffered a heart attack, two had epileptic episodes postoperatively. Conclusion We believe that omental transposition to the brain augments cerebral blood flow, which might be helpful to decelerate the processing of Alzheimer’s disease. However, it is still a potentially risky procedure for the elderly.
