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Okko T Pyykkö, Ossi Nerg, Hanna-Mari Niskasaari, Timo Niskasaari, Anne M Koivisto, Mikko Hiltunen, Jussi Pihlajamäki, Tuomas Rauramaa, Maria Kojoukhova, Irina Alafuzoff, Hilkka Soininen, Juha E Jääskeläinen, Ville Leinonen
OBJECT: To investigate the incidence, comorbidities, mortality, and causes of death in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A cohort of 536 patients with possible NPH from a defined population with a median follow-up time of 5.1 years, (range 0.04-19.9 years) was included in the study. Patients were evaluated by brain imaging and intraventricular pressure monitoring, with a brain biopsy specimen immunostained against amyloid-β and hyperphosphorylated τ...
April 2018: World Neurosurgery
Neera Raghav, Mamta Singh
Cathepsins have emerged as promising molecular targets in a number of diseases such as Alzeimer's, inflammation and cancer. Elevated cathepsin's levels and decreased cellular inhibitor concentrations have emphasized the search for novel inhibitors of cathepsins. The present work is focused on the design and synthesis of some acetophenone phenylhydrazone based pyrazole derivatives as novel non peptidyl inhibitors of cathepsins B, H and L. The synthesized compounds after characterization have been explored for their inhibitory potency against cathepsins B, H and L...
August 31, 2017: Bioorganic Chemistry
Long Yuan, Yunlin Fu, Duxi Zhang, Yuan-Qing Xia, Qianping Peng, Anne-Françoise Aubry, Mark E Arnold
A sensitive, accurate and rugged UHPLC-MS/MS method was developed and validated for the quantitation of Epothilone D (EpoD), a microtubule stabilizer in development for treatment of Alzeimer's disease, in rat plasma. The ester group in EpoD can be hydrolyzed by esterases in blood or plasma, which creates a stability concern for the bioanalysis of EpoD. Species differences in the stability of EpoD in plasma were observed. Carboxylesterases were identified as the likely esterases responsible for the hydrolysis of EpoD in plasma ex vivo, and the cause of the species different stability...
October 15, 2014: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Heather A Born, Ji-Yoen Kim, Ricky R Savjani, Pritam Das, Yuri A Dabaghian, Qinxi Guo, Jong W Yoo, Dorothy R Schuler, John R Cirrito, Hui Zheng, Todd E Golde, Jeffrey L Noebels, Joanna L Jankowsky
Alzheimer's disease (AD) is associated with an elevated risk for seizures that may be fundamentally connected to cognitive dysfunction. Supporting this link, many mouse models for AD exhibit abnormal electroencephalogram (EEG) activity in addition to the expected neuropathology and cognitive deficits. Here, we used a controllable transgenic system to investigate how network changes develop and are maintained in a model characterized by amyloid β (Aβ) overproduction and progressive amyloid pathology. EEG recordings in tet-off mice overexpressing amyloid precursor protein (APP) from birth display frequent sharp wave discharges (SWDs)...
March 12, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Vildan Enisoğlu Atalay, Safiye Sağ Erdem
Monoamine oxidase (MAO) enzymes regulate the level of neurotransmitters by catalyzing the oxidation of various amine neurotransmitters, such as serotonin, dopamine and norepinephrine. Therefore, they are the important targets for drugs used in the treatment of depression, Parkinson, Alzeimer and other neurodegenerative disorders. Elucidation of MAO-catalyzed amine oxidation will provide new insights into the design of more effective drugs. Various amine oxidation mechanisms have been proposed for MAO so far, such as single electron transfer mechanism, polar nucleophilic mechanism and hydride mechanism...
December 2013: Computational Biology and Chemistry
Jaume Folch, Ignacio Pedrós, Iván Patraca, Nohora Martínez, Francesc Sureda, Antoni Camins
The more common sporadic form of Alzheimer disease (SAD) and the metabolic syndrome are two highly prevalent pathological conditions of Western society due to incorrect diet, lifestyle, and vascular risk factors. Due to the increasing aging of populations, prevalence of AD in western industrialized countries will rise in the near future and, thus, new knowledge in the area of molecular biology and epigenetics will probably help to reverse the neurodegenerative process. Recent data have suggested metabolic syndrome as an independent risk factor for SAD...
2013: Current Pharmaceutical Design
Narendra Singh, Mohit Bhalla, Prashanti de Jager, Marilena Gilca
Withania somnifera (Ashawagandha) is very revered herb of the Indian Ayurvedic system of medicine as a Rasayana (tonic). It is used for various kinds of disease processes and specially as a nervine tonic. Considering these facts many scientific studies were carried out and its adaptogenic / anti-stress activities were studied in detail. In experimental models it increases the stamina of rats during swimming endurance test and prevented adrenal gland changes of ascorbic acid and cortisol content produce by swimming stress...
2011: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
George J Brewer
It is a pleasure and an honor to contribute a paper to a special issue of the Journal of the American College of Nutrition honoring Stanley Wallach and Pearl Small. In this brief review I advance the hypothesis that copper toxicity is the major cause of the epidemic of mild cognitive impairment and Alzheimer's disease engulfing our aging population. This epidemic is recent, exploding in the last 50-60 years. The disease was virtually unknown 100 years ago. And it involves only developed countries that use copper plumbing...
June 2009: Journal of the American College of Nutrition
Aron D Mosnaim, Vasant V Ranade, Marion E Wolf, Javier Puente, M Antonieta Valenzuela
The chemical structure of phenothiazine provides a most valuable molecular template for the development of agents able to interact with a wide variety of biological processes. Synthetic phenothiazines (with aliphatic, methylpiperazine, piperazine-ethanol, piperazine-ethyl, or piperidine side-chain) and/or phenothiazine-derived agents e.g., thioxanthenes, benzepines, imonostilbenes, tricyclic antidepressants, dimetothiazine, and cyproheptadine have been effective in the treatment of a number of medical conditions with widely different etiology...
May 2006: American Journal of Therapeutics
L Emilsson, P Saetre, E Jazin
Regulator of G-protein signaling 4 (RGS4) showed decreased mRNA levels in Alzheimer's disease in a large collection of human brain autopsies from prefrontal cortex. The expression levels of three RGS4 splice variants were examined in the same samples, and the association between RGS4 gene expression and/or the disease with single nucleotide polymorphisms located in this gene was explored. We show that all splice variants are down-regulated in patients. We also demonstrate that one rare haplotype (ATAG) is associated with decreased mRNA levels in both cases and controls...
March 1, 2006: Synapse
S Santosh Kumar, K Indira Priyadarsini, Krishna B Sainis
Several neurodegenerative diseases such as Alzeimer's and Parkinson's as well as septic shock and inflammation involve formation of reactive oxygen and nitrogen species that include peroxynitrite (PON). PON can also react with endogenous antioxidants. Therefore, dietary supplementation with antioxidants may help in these diseases. An exogenous antioxidant, vanillin (4-hydroxy-3-methoxybenzaldehyde), used widely as a food flavoring agent, was evaluated for its ability to scavenge PON and inhibit PON-mediated reactions...
January 14, 2004: Journal of Agricultural and Food Chemistry
M F Collen
OBJECTIVES: Significant changes in mortality patterns are part of the changing population demographics. This paper explores their implications for health evaluation and screening programs. METHODS: A review of selected age-adjusted mortality rates from the National Vital Statistics Reports of the USA was undertaken and their change over the last five decades analyzed. RESULTS: The review shows a continued decline in mortality rates from leading causes of death, such as heart disease, cancer, stroke, pneumonia and influenza, and a sharp rise in the death rates from Alzheimer's disease...
2002: Methods of Information in Medicine
Dean G Tang, Arthur T Porter
Apoptosis is a cell suicide program characterized by distinct morphological (cell shrinkage, membrane blebbing, pyknosis, chromatin margination, denser cytoplasmic images) and biochemical (e.g., DNA fragmentation into distinct ladders; degradation of apoptotic markers such as PARP and nuclear lamins) features. It is involved in multiple physiological processes examplified by involution of mammary tissues, embryonic development, homeostatic maintenance of tissues and organs, and maturation of the immune system, as well as in many pathological conditions represented by neurologic degeneration (Alzeimer's disease), autoimmune and inflammatory diseases, etiology of atherosclerosis, AIDS, and oncogenesis and tumor progression...
1996: Pathology Oncology Research: POR
H L Hu, R J Forsey, T J Blades, M E Barratt, P Parmar, J R Powell
Elderly humans have altered cellular redox levels and dysregulated immune responses, both of which are key events underlying the progression of chronic degenerative diseases of ageing, such as atherosclerosis and Alzeimer's disease. Poorly maintained cellular redox levels lead to elevated activation of nuclear transcription factors such as NFkB and AP-1. These factors are co-ordinately responsible for a huge range of extracellular signalling molecules responsible for inflammation, tissue remodelling, oncogenesis and apoptosis, progessess that orchestrate many of the degenerative processess associated with ageing...
December 20, 2000: Mechanisms of Ageing and Development
P Eikelenboom, R Veerhuis
A variety of inflammatory mediators including complement activation products, protease inhibitors, and cytokines are colocalized with beta-amyloid (A beta) deposits in the Alzeimer's disease (AD) brain. Activation products of the early complement components C1, C4, and C3 are always found in neuritic plaques and to a lesser extent in varying numbers of diffuse plaques. In contrast to these findings, no immunohistochemical evidence was obtained for the presence of the late complement components C7 and C9 and the complement membrane attack complex in the neuropathological lesions in AD brains...
September 1996: Neurobiology of Aging
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