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Gvido Cebers, Robert C Alexander, Samantha Budd Haeberlein, David Han, Ronald Goldwater, Larry Ereshefsky, Tina Olsson, Naidong Ye, Laura Rosen, Muir Russell, Justine Maltby, Susanna Eketjäll, Alan R Kugler
AZD3293 (LY3314814) is a promising new potentially disease-modifying BACE1 (β-secretase) inhibitor in Phase III clinical development for the treatment of Alzheimer's disease. Reported here are the first two Phase I studies: (1) a single ascending dose study evaluating doses of 1-750 mg with a food-effect component (n = 72), and (2) a 2-week multiple ascending dose study evaluating doses of 15 or 50 mg once daily (QD) or 70 mg once weekly (QW) in elderly subjects (Part 1, n = 31), and 15, 50, or 150 mg QD in patients with mild to moderate Alzheimer's disease (Part 2, n = 16)...
October 19, 2016: Journal of Alzheimer's Disease: JAD
Alze Pereira Dos Santos Tavares, Carolina Paparelli, Carolina Sassaki Kishimoto, Silvia Avo Cortizo, Karen Ebina, Mariana Sarkis Braz, Sandra Regina Gonçalves Mazutti, Marcio José Cristiano Arruda, Bárbara Antunes
BACKGROUND: Gathering clinical evidence data on patients' palliative care needs is paramount to identify changes in outcomes over time and maintaining on-going quality improvement. Implementation of patient-centred outcome measures has been widely recommended. The routine use of these instruments in daily practice is challenging and not widespread. AIM: To implement a patient-centred outcome measure in daily practice and fulfil one quality indicator: improve pain during the 72 h after admission, in at least 75% of patients...
July 6, 2016: Palliative Medicine
Masoud Soheili, Mostafa Rezaei Tavirani, Mahmoud Salami
OBJECTIVES: Neurodegenerative Alzheimer's disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area...
November 2015: Iranian Journal of Basic Medical Sciences
Yuhai Zhao, Peter N Alexandrov, Walter J Lukiw
Overview- One hundred and ten years since its first description Alzheimer's disease (AD) still retains its prominent status: (i) as the industrialized world's number one cause of age-related intellectual impairment and cognitive decline; (ii) as this country's most rapidly expanding socioeconomic and healthcare concern; and (iii) as an insidious, progressive and lethal neurological disorder of the human central nervous system (CNS) for which there is currently no adequate treatment or cure (Alzheimer, 1991; Alzheimer et al...
2016: Frontiers in Neuroscience
Rebecca Davis, Jennifer Ohman
AIM: To report a study protocol that examines the impact of adding salient cues in a virtual reality simulation of a senior residential building on wayfinding for older adults with and without Alzheimer's disease. BACKGROUND: An early symptom of Alzheimer's disease is the inability to find one's way (wayfinding). Senior residential environments are especially difficult for wayfinding. Salient cues may be able to help persons with Alzheimer's disease find their way more effectively so they can maintain independence...
July 2016: Journal of Advanced Nursing
David T Liebers, Mehdi Pirooznia, Fayaz Seiffudin, Katherine L Musliner, Peter P Zandi, Fernando S Goes
Cognitive impairment is a common feature of the major psychotic disorders, with deficits often present in at risk individuals and unaffected first-degree relatives. Previous studies have suggested that polygenic risk scores (PRS) for schizophrenia (SCZ) are associated with cognitive deficits, but there has been little examination of this association in longitudinal datasets, or comparison with other disorders. We used mixed models to study the association between PRS for 4 adult onset psychiatric disorders with cross-sectional cognitive performance and longitudinal cognitive decline in 8616 older adults from the Health and Retirement Study (HRS), followed for an average of 10 years...
July 2016: Schizophrenia Bulletin
K Kremeike, C Juergens, H Alz, D Reinhardt
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common form of paediatric cancer. Maintenance therapy as last treatment phase includes oral chemotherapy with methotrexate (MTX) and mercaptopurine (6-MP), self- or parent-administered at home, given for about 1 ½ years, and qualified as decisive for an optimum therapy outcome. The aim of our study was to analyze factors influencing the adherence of patients with ALL undergoing maintenance therapy and their families. METHODS: A multi-method study was undertaken between 11/2011 and 10/2014 with patients surveyed by the Hannover Medical School outpatient clinic, including a questionnaire survey and qualitative interviews with parents as well as blood samples of the patients...
November 2015: Klinische Pädiatrie
G O André, W R Politano, S Mirza, T R Converso, L F C Ferraz, L C C Leite, M Darrieux
Streptococcus pneumoniae is a common colonizer of the human nasopharynx, which can occasionally spread to sterile sites, causing diseases such as otitis media, sinusitis, pneumonia, meningitis and bacteremia. Human apolactoferrin (ALF) and lysozyme (LZ) are two important components of the mucosal innate immune system, exhibiting lytic effects against a wide range of microorganisms. Since they are found in similar niches of the host, it has been proposed that ALF and LZ could act synergistically in controlling bacterial spread throughout the mucosa...
December 2015: Microbial Pathogenesis
Rafael Arcesio Delgado-Ruíz, Gerardo Gomez Moreno, Antonio Aguilar-Salvatierra, Aleksa Markovic, Jose Eduardo Mate-Sánchez, José Luis Calvo-Guirado
OBJECTIVES: To measure the lateral surface area of microgrooved zirconia implants, to evaluate the cell geometry and cell density of human fetal osteoblasts seeded on zirconia microgrooved implants, to describe the surface roughness and chemistry, and to evaluate the activity of human fetal osteoblasts seeded on zirconia microgrooved disks. MATERIALS AND METHODS: This experimental in vitro study used 62 zirconia implants and 130 zirconia disks. Two experimental groups were created for the implants: 31 non-microgrooved implants (Control) and 31 microgrooved implants (Test); two experimental groups were created for the disks: 65 non-microgrooved disks (Control) and 65 microgrooved disks (Test)...
March 25, 2015: Clinical Oral Implants Research
Eva Machová, Jana Korcová, Alžbeta Cížová, Slavomír Bystrický
A new approach to obtain broadly cross-reactive antisera against important yeast pathogens by intensive hyperimmunization with polysaccharide-protein conjugates is described here. Surface mannan of Candida albicans and capsular galactoglucoxylomannan of Cryptococcus laurentii were isolated and chemically linked to human serum albumin. Antisera elicited by a 7-week vigorous immunization of rabbits with the conjugates showed effective cross-reactive growth inhibition of different representatives of Candida spp...
July 2015: Journal of Microbiology and Biotechnology
Paola Flores-Rodríguez, Miguel A Ontiveros-Torres, María C Cárdenas-Aguayo, Juan P Luna-Arias, Marco A Meraz-Ríos, Amparo Viramontes-Pintos, Charles R Harrington, Claude M Wischik, Raúl Mena, Benjamin Florán-Garduño, José Luna-Muñoz
We previously demonstrated that, in the early stages of tau processing in Alzheimer's disease, the N-terminal part of the molecule undergoes a characteristic cascade of phosphorylation and progressive misfolding of the proteins resulting in a structural conformation detected by Alz-50. In this immunohistochemical study of AD brain tissue, we have found that C-terminal truncation of tau at Asp-421 was an early event in tau aggregation and analyzed the relationship between phospho-dependent tau epitopes located at the C-terminus with truncation at Glu-391...
2015: Frontiers in Neuroscience
A L Z Marinho, C Vila-Verde, M V Fogaça, F S Guimarães
The infralimbic (IL) and prelimbic (PL) regions of the prefrontal cortex are involved in behavioral responses observed during defensive reactions. Intra-PL or IL injections of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, result in opposite behavioral effects in the contextual fear conditioning (CFC) paradigm. The intra-PL effects of CBD are mediated by 5HT1A receptors and depend on previous stressful experiences but the mechanisms and effects of intra-IL CBD injected are unknown...
June 1, 2015: Behavioural Brain Research
M Marufuzzaman, M B I Reaz, M A M Ali, L F Rahman
OBJECTIVES: The goal of smart homes is to create an intelligent environment adapting the inhabitants need and assisting the person who needs special care and safety in their daily life. This can be reached by collecting the ADL (activities of daily living) data and further analysis within existing computing elements. In this research, a very recent algorithm named sequence prediction via enhanced episode discovery (SPEED) is modified and in order to improve accuracy time component is included...
2015: Methods of Information in Medicine
Zhouxian Bai, Guangchun Han, Bin Xie, Jiajia Wang, Fuhai Song, Xing Peng, Hongxing Lei
Alzheimer's disease (AD) affects a significant portion of elderly people worldwide. Although the amyloid-β (Aβ) cascade hypothesis has been the prevailing theory for the molecular mechanism of AD in the past few decades, treatment strategies targeting the Aβ cascade have not demonstrated effectiveness as yet. Thus, elucidating the spatial and temporal evolution of the molecular pathways in AD remains to be a daunting task. To facilitate novel discoveries in this filed, here, we have integrated information from multiple sources for the better understanding of gene functions in AD pathogenesis...
January 2016: Molecular Neurobiology
Matthew L Hughes, Deborah A Lowe, Hannah E Shine, Brian D Carpenter, Steve Balsis
BACKGROUND: The purpose of the current study was to investigate whether an informative Web site is effective at producing higher scores for an individual's knowledge of Alzheimer's disease (AD) relative to those who do not visit a Web site. METHODS: A total of 552 participants completed the study on Amazon's Mechanical Turk; half were randomly assigned to visit, while a control group did not. Both groups were given the AD Knowledge Scale (ADKS) to assess their knowledge of AD...
February 2015: American Journal of Alzheimer's Disease and Other Dementias
Sylvie Bonin-Guillaume, Gaëlle Martin, Joseline Zafack, Gaétan Gentile, Véronique Allaria-Lapierre, Vincent Sciortino, Xavier Thirion, Joëlle Micallef
AIM: The aim of the study was to identify and to characterize patients with Alzheimer's disease or related dementia describing antipsychotics and other psychotropic expositions. METHODS: The study was performed, in 2010, based on Provence-Alpes-Côte d'Azur region (PACA)-Corse Alz cohort included patients with dementia, with chronic condition 'Alzheimer disease or related disease' and/or had at least one delivery of Alzheimer's specific treatment, registered in the General Health Care System...
May 2014: Thérapie
Xuemei Feng, Zhouxian Bai, Jiajia Wang, Bin Xie, Jiya Sun, Guangchun Han, Fuhai Song, Peter J Crack, Yong Duan, Hongxing Lei
The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing disease mechanism at the gene expression level. However, thousands of genes have been reported to be dysregulated in AD brains in existing studies, and the consistency or discrepancy among these studies has not been thoroughly examined. Toward this end, we conducted a comprehensive survey of the brain transcriptome datasets for AD and other neurological diseases. We first demonstrated that the frequency of observed dysregulation in AD was highly correlated with the reproducibility of the dysregulation...
2014: Journal of Alzheimer's Disease: JAD
Yuji Ishii, Shinji Takasu, Ken Kuroda, Kohei Matsushita, Aki Kijima, Takehiko Nohmi, Kumiko Ogawa, Takashi Umemura
DNA adductome analysis using liquid chromatography-tandem mass spectrometry is a promising tool to exhaustively search DNA modifications. Given that the molecular weight of chemical-specific adducts is determined by the total molecular weights of the active form and nucleotide bases, we developed a new method of comprehensive analysis for chemical-specific DNA adducts based on the principle of adductome analysis. The actual analytical mass range was 50 mass units up or down from the average molecular weight of the four DNA bases plus the molecular weight of the expected active form of the chemical...
April 2014: Analytical and Bioanalytical Chemistry
Tamotsu Kiyoshima, Hiroaki Fujiwara, Kengo Nagata, Hiroko Wada, Yukiko F Ookuma, Maho Shiotsuka, Makiko Kihara, Kana Hasegawa, Hirotaka Someya, Hidetaka Sakai
Previous studies have shown that the recombination of cells liberated from developing tooth germs develop into teeth. However, it is difficult to use human developing tooth germ as a source of cells because of ethical issues. Previous studies have reported that thymosin beta 4 (Tmsb4x) is closely related to the initiation and development of the tooth germ. We herein attempted to establish odontogenic epithelial cells from non-odontogenic HaCaT cells by transfection with TMSB4X. TMSB4X-transfected cells formed nodules that were positive for Alizarin-red S (ALZ) and von Kossa staining (calcium phosphate deposits) when cultured in calcification-inducing medium...
January 2014: Stem Cell Research
Bhupinder Singh, Sandeep Sharma, Naveen Dubey, Ashish Dwivedi, Rama S Lokhandae
BACKGROUND: The use of anti-histaminic agents has been increased significantly from last decades and till now no method is available for quantitation of ALZ in human plasma which can be applied in a bioequivalence study using LC-MS/MS. OBJECTIVE: The present study is concerned with the development and validation of ALZ in human plasma by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). MATERIALS AND METHODS: Sample preparation involved the extraction with liquid-liquid extraction method by using ethyl acetate as an organic solvent...
2013: Journal of Pharmacy & Bioallied Sciences
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