Sano M

References (28)

Title : Racial\/ethnic disparities in initiation and persistent use of anti-dementia medications - Zhu_2022_Alzheimers.Dement__
Author(s) : Zhu CW , Neugroschl J , Barnes LL , Sano M
Ref : Alzheimers Dement , : , 2022
Abstract : BACKGROUND: Racial/ethnic disparities in anti-dementia medications use in longitudinally followed research participants are unclear. METHODS: The study included initially untreated participants followed in National Alzheimer's Coordinating Center Uniform Data Set who were <=65 at baseline with Alzheimer's disease dementia. OUTCOMES: Outcomes for acetylcholinesterase inhibitor (AChEI) treatment included (1) any new AChEI treatment during follow-up, and (2) persistence of treatment during follow-up categorized into: intermittent treatment (< 50% follow-ups reporting treatment), persistent (<=50% follow-ups), and always treated. Outcomes for memantine treatment were similarly constructed. RESULTS: Controlling for participant characteristics, Black and Hispanic participants remained less likely than White participants to report any new AChEI or memantine treatment during follow-up. Among those who reported new treatment during follow-up, both Black and Hispanic participants were less likely than White participants to be persistently treated with AChEI and memantine. DISCUSSION: Substantial racial/ethnic treatment disparities remain in controlled settings of longitudinal research in which participants have access to dementia experts, suggesting wider disparities in the larger community.
ESTHER : Zhu_2022_Alzheimers.Dement__
PubMedSearch : Zhu_2022_Alzheimers.Dement__
PubMedID: 35218291

Title : Neuropsychiatric Symptoms and Caregiver Burden in Individuals With Alzheimer's Disease: The TEAM-AD VA Cooperative Study - Chen_2018_J.Geriatr.Psychiatry.Neurol__891988718783897
Author(s) : Chen P , Guarino PD , Dysken MW , Pallaki M , Asthana S , Llorente MD , Love S , Vertrees JE , Schellenberg GD , Sano M
Ref : J Geriatr Psychiatry Neurol , :891988718783897 , 2018
Abstract : OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms (NPS) in mild-to-moderate Alzheimer disease (AD) and their association with caregiver burden. METHODS: Secondary analyses of baseline data from the Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD) (N=613). Neuropsychiatric Inventory were used to measure severity of NPS and caregiver activity survey to measure caregiver burden. RESULTS: A total of 87% of patients displayed at least 1 NPS; 70% displayed clinically meaningful NPS. The most common symptoms were apathy (47%), irritability (44%), agitation (42%), and depression (40%). Those with moderate AD had more severe NPS than those with mild AD ( P = .03). Neuropsychiatric symptoms were significantly associated with caregiver time after adjusting for age, education, cognitive function, and comorbidity ( P-value < .0001) with every point increase in NPS associated with a 10-minute increase in caregiver time. CONCLUSION: Neuropsychiatric symptoms were prevalent in both mild and moderate AD, even in patients receiving treatment with an acetylcholinesterase inhibitors, and were more severe in moderate AD and associated with greater caregiver time.
ESTHER : Chen_2018_J.Geriatr.Psychiatry.Neurol__891988718783897
PubMedSearch : Chen_2018_J.Geriatr.Psychiatry.Neurol__891988718783897
PubMedID: 29966477

Title : 5-Bromoindirubin 3'-(O-oxiran-2-ylmethyl)oxime: A long-acting anticancer agent and a suicide inhibitor for epoxide hydrolase - Ichimaru_2017_Bioorg.Med.Chem_25_4665
Author(s) : Ichimaru Y , Fujii T , Saito H , Sano M , Uchiyama T , Miyairi S
Ref : Bioorganic & Medicinal Chemistry , 25 :4665 , 2017
Abstract : Indirubin 3'-oxime (Indox (1b)) suppresses cancer cell growth (IC50: 15muM towards HepG2 cells) and inhibits cell cycle-related kinases such as cyclin-dependent kinases and glycogen synthase kinase-3beta. We have previously reported that the conjugation of 1b with oxirane, a protein-reactive component, enhanced the cytotoxic activity of Indox as determined from the IC50 value (1.7muM) of indirubin 3'-(O-oxiran-2-ylmethyl)oxime (Epox/Ind (1c)). Here we prepared Epox/Ind derivatives with one or two halogen atoms or a methoxy group on the aromatic ring(s) of an Indox moiety and studied the structure-activity relationships of the substituent(s). We found that bromine-substitution at the 5-position on 1c or any Epox/Ind derivative(s) having bromine on the aromatic ring except Epox/6'-Br-Ind was efficient to improving anticancer activity. Of the 22 Epox/Ind derivatives, 5-bromoindirubin 3'-(O-oxiran-2-ylmethyl)oxime (Epox/5-Br-Ind (2c)) was the best anticancer agent in both short- (24h) (IC50: 0.67muM) and extended-duration (72h) cultures. The high anticancer activity of 2c was partly due to it being a poor substrate and a suicide inhibitor for epoxide hydrolase as epoxide hydrolase was identified as the enzyme primarily responsible for the metabolism of 2c.
ESTHER : Ichimaru_2017_Bioorg.Med.Chem_25_4665
PubMedSearch : Ichimaru_2017_Bioorg.Med.Chem_25_4665
PubMedID: 28743492

Title : Increased enzyme production under liquid culture conditions in the industrial fungus Aspergillus oryzae by disruption of the genes encoding cell wall alpha-1,3-glucan synthase - Miyazawa_2016_Biosci.Biotechnol.Biochem__1
Author(s) : Miyazawa K , Yoshimi A , Zhang S , Sano M , Nakayama M , Gomi K , Abe K
Ref : Biosci Biotechnol Biochem , :1 , 2016
Abstract : Under liquid culture conditions, the hyphae of filamentous fungi aggregate to form pellets, which reduces cell density and fermentation productivity. Previously, we found that loss of alpha-1,3-glucan in the cell wall of the fungus Aspergillus nidulans increased hyphal dispersion. Therefore, here we constructed a mutant of the industrial fungus A. oryzae in which the three genes encoding alpha-1,3-glucan synthase were disrupted (tripleDelta). Although the hyphae of the tripleDelta mutant were not fully dispersed, the mutant strain did form smaller pellets than the wild-type strain. We next examined enzyme productivity under liquid culture conditions by transforming the cutinase-encoding gene cutL1 into A. oryzae wild-type and the tripleDelta mutant (i.e. wild-type-cutL1, tripleDelta-cutL1). A. oryzae tripleDelta-cutL1 formed smaller hyphal pellets and showed both greater biomass and increased CutL1 productivity compared with wild-type-cutL1, which might be attributable to a decrease in the number of tripleDelta-cutL1 cells under anaerobic conditions.
ESTHER : Miyazawa_2016_Biosci.Biotechnol.Biochem__1
PubMedSearch : Miyazawa_2016_Biosci.Biotechnol.Biochem__1
PubMedID: 27442340

Title : Genome sequence of Aspergillus luchuensis NBRC 4314 - Yamada_2016_DNA.Res_23_507
Author(s) : Yamada O , Machida M , Hosoyama A , Goto M , Takahashi T , Futagami T , Yamagata Y , Takeuchi M , Kobayashi T , Koike H , Abe K , Asai K , Arita M , Fujita N , Fukuda K , Higa KI , Horikawa H , Ishikawa T , Jinno K , Kato Y , Kirimura K , Mizutani O , Nakasone K , Sano M , Shiraishi Y , Tsukahara M , Gomi K
Ref : DNA Research , 23 :507 , 2016
Abstract : Awamori is a traditional distilled beverage made from steamed Thai-Indica rice in Okinawa, Japan. For brewing the liquor, two microbes, local kuro (black) koji mold Aspergillus luchuensis and awamori yeast Saccharomyces cerevisiae are involved. In contrast, that yeasts are used for ethanol fermentation throughout the world, a characteristic of Japanese fermentation industries is the use of Aspergillus molds as a source of enzymes for the maceration and saccharification of raw materials. Here we report the draft genome of a kuro (black) koji mold, A. luchuensis NBRC 4314 (RIB 2604). The total length of nonredundant sequences was nearly 34.7 Mb, comprising approximately 2,300 contigs with 16 telomere-like sequences. In total, 11,691 genes were predicted to encode proteins. Most of the housekeeping genes, such as transcription factors and N-and O-glycosylation system, were conserved with respect to Aspergillus niger and Aspergillus oryzae An alternative oxidase and acid-stable alpha-amylase regarding citric acid production and fermentation at a low pH as well as a unique glutamic peptidase were also found in the genome. Furthermore, key biosynthetic gene clusters of ochratoxin A and fumonisin B were absent when compared with A. niger genome, showing the safety of A. luchuensis for food and beverage production. This genome information will facilitate not only comparative genomics with industrial kuro-koji molds, but also molecular breeding of the molds in improvements of awamori fermentation.
ESTHER : Yamada_2016_DNA.Res_23_507
PubMedSearch : Yamada_2016_DNA.Res_23_507
PubMedID: 27651094
Gene_locus related to this paper: 9euro-a0a146f3d2

Title : Draft Genome Sequence of Potassium-Dependent Alkaliphilic Bacillus sp. Strain TS-2, Isolated from a Jumping Spider - Fujinami_2014_Genome.Announc_2_e00458
Author(s) : Fujinami S , Takeda K , Onodera T , Satoh K , Sano M , Narumi I , Ito M
Ref : Genome Announc , 2 : , 2014
Abstract : The potassium-dependent alkaliphilic Bacillus sp. strain TS-2 was isolated from the mashed extract of a jumping spider, and its draft genome sequence was obtained. Comparative genomic analysis with a previously sequenced sodium-dependent alkaliphilic Bacillus species may reveal potassium-dependent alkaline adaptation mechanisms.
ESTHER : Fujinami_2014_Genome.Announc_2_e00458
PubMedSearch : Fujinami_2014_Genome.Announc_2_e00458
PubMedID: 24855304
Gene_locus related to this paper: 9baci-x0rr90 , 9baci-x0rp53

Title : Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease - Hager_2014_Neuropsychiatr.Dis.Treat_10_391
Author(s) : Hager K , Baseman AS , Nye JS , Brashear HR , Han J , Sano M , Davis B , Richards HM
Ref : Neuropsychiatr Dis Treat , 10 :391 , 2014
Abstract : BACKGROUND: Currently available treatments for Alzheimer's disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD.
METHODS: In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the 'last observation carried forward' approach, in an analysis of covariance model.
RESULTS: In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (-2.14 [4.34]) compared with the galantamine group (-1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (-10.81 [18.27]) versus the galantamine group (-8.16 [17.25]) (P=0.002). Incidences of treatment-emergent adverse events were 54.0% for the galantamine and 48.6% for the placebo group. CONCLUSION: Long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients. IDENTIFICATION: This study is registered at (NCT00679627).
ESTHER : Hager_2014_Neuropsychiatr.Dis.Treat_10_391
PubMedSearch : Hager_2014_Neuropsychiatr.Dis.Treat_10_391
PubMedID: 24591834

Title : Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial - Dysken_2014_JAMA_311_33
Author(s) : Dysken MW , Sano M , Asthana S , Vertrees JE , Pallaki M , Llorente M , Love S , Schellenberg GD , McCarten JR , Malphurs J , Prieto S , Chen P , Loreck DJ , Trapp G , Bakshi RS , Mintzer JE , Heidebrink JL , Vidal-Cardona A , Arroyo LM , Cruz AR , Zachariah S , Kowall NW , Chopra MP , Craft S , Thielke S , Turvey CL , Woodman C , Monnell KA , Gordon K , Tomaska J , Segal Y , Peduzzi PN , Guarino PD
Ref : Jama , 311 :33 , 2014
Abstract : IMPORTANCE: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures.
RESULTS: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. TRIAL REGISTRATION: Identifier: NCT00235716.
ESTHER : Dysken_2014_JAMA_311_33
PubMedSearch : Dysken_2014_JAMA_311_33
PubMedID: 24381967

Title : Comparative genomic characterization of three Streptococcus parauberis strains in fish pathogen, as assessed by wide-genome analyses - Nho_2013_PLoS.One_8_e80395
Author(s) : Nho SW , Hikima J , Park SB , Jang HB , Cha IS , Yasuike M , Nakamura Y , Fujiwara A , Sano M , Kanai K , Kondo H , Hirono I , Takeyama H , Aoki T , Jung TS
Ref : PLoS ONE , 8 :e80395 , 2013
Abstract : Streptococcus parauberis, which is the main causative agent of streptococcosis among olive flounder (Paralichthys olivaceus) in northeast Asia, can be distinctly divided into two groups (type I and type II) by an agglutination test. Here, the whole genome sequences of two Japanese strains (KRS-02083 and KRS-02109) were determined and compared with the previously determined genome of a Korean strain (KCTC 11537). The genomes of S. parauberis are intermediate in size and have lower GC contents than those of other streptococci. We annotated 2,236 and 2,048 genes in KRS-02083 and KRS-02109, respectively. Our results revealed that the three S. parauberis strains contain different genomic insertions and deletions. In particular, the genomes of Korean and Japanese strains encode different factors for sugar utilization; the former encodes the phosphotransferase system (PTS) for sorbose, whereas the latter encodes proteins for lactose hydrolysis, respectively. And the KRS-02109 strain, specifically, was the type II strain found to be able to resist phage infection through the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system and which might contribute valuably to serologically distribution. Thus, our genome-wide association study shows that polymorphisms can affect pathogen responses, providing insight into biological/biochemical pathways and phylogenetic diversity.
ESTHER : Nho_2013_PLoS.One_8_e80395
PubMedSearch : Nho_2013_PLoS.One_8_e80395
PubMedID: 24260382
Gene_locus related to this paper: 9stre-f1yze3

Title : Draft Genome Sequence of Sodium-Independent Alkaliphilic Microbacterium sp. Strain TS-1 - Fujinami_2013_Genome.Announc_1_e01043
Author(s) : Fujinami S , Takeda K , Onodera T , Satoh K , Sano M , Narumi I , Ito M
Ref : Genome Announc , 1 : , 2013
Abstract : Alkaliphilic Microbacterium sp. strain TS-1, newly isolated from the jumping spider, showed Na(+)-independent growth and motility. Here, we report the draft genome sequence of this bacterium, which may provide beneficial information for Na(+)-independent alkaline adaptation mechanisms.
ESTHER : Fujinami_2013_Genome.Announc_1_e01043
PubMedSearch : Fujinami_2013_Genome.Announc_1_e01043
PubMedID: 24356828
Gene_locus related to this paper: 9mico-u2xlj2 , 9mico-u2xbp1 , 9mico-u2xhz2

Title : Draft Genome Sequence of Agarivorans albus Strain MKT 106T, an Agarolytic Marine Bacterium - Yasuike_2013_Genome.Announc_1_e00367
Author(s) : Yasuike M , Nakamura Y , Kai W , Fujiwara A , Fukui Y , Satomi M , Sano M
Ref : Genome Announc , 1 :e00367 , 2013
Abstract : Agarivorans albus is a Gram-negative, strictly aerobic, and agar-hydrolyzing marine bacterium. We present the draft genome sequence of the A. albus strain MKT 106(T), which is composed of 67 contigs (>500 bp) totaling 4,734,285 bp and containing 4,397 coding DNA sequences (CDSs), four rRNAs, and 64 tRNA sequences.
ESTHER : Yasuike_2013_Genome.Announc_1_e00367
PubMedSearch : Yasuike_2013_Genome.Announc_1_e00367
PubMedID: 23868120
Gene_locus related to this paper: agaal-r9psh6 , agaal-r9pnu7 , agaal-r9ptw5 , agaal-r9pkj2 , agaal-r9ptp8

Title : Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer's disease - Zhu_2013_Alzheimers.Dement_9_733
Author(s) : Zhu CW , Livote EE , Scarmeas N , Albert M , Brandt J , Blacker D , Sano M , Stern Y
Ref : Alzheimers Dement , 9 :733 , 2013
Abstract : OBJECTIVES: To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time.
METHODS: The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores >/= 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score </= 10) and functional (Blessed Dementia Rating Scale score >/= 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval.
RESULTS: ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points.
CONCLUSIONS: Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects.
ESTHER : Zhu_2013_Alzheimers.Dement_9_733
PubMedSearch : Zhu_2013_Alzheimers.Dement_9_733
PubMedID: 23332671

Title : Utilization of antihypertensives, antidepressants, antipsychotics, and hormones in Alzheimer disease - Zhu_2011_Alzheimer.Dis.Assoc.Disord_25_144
Author(s) : Zhu CW , Livote EE , Kahle-Wrobleski K , Scarmeas N , Albert M , Brandt J , Blacker D , Sano M , Stern Y
Ref : Alzheimer Disease & Associated Disorders , 25 :144 , 2011
Abstract : This study explores the longitudinal relationship between patient characteristics and use of 4 drug classes (antihypertensives, antidepressants, antipsychotics, and hormones) that showed significant changes in use rates over time in patients with Alzheimer disease. Patient/caregiver-reported prescription medication usage was categorized by drug class for 201 patients from the Predictors Study. Patient characteristics included use of cholinesterase inhibitors and/or memantine, function, cognition, living situation, baseline age, and sex. Assessment interval, year of study entry, and site were controlled for. Before adjusting for covariates, useage increased for antihypertensives (47.8% to 62.2%), antipsychotics (3.5% to 27.0%), and antidepressants (32.3% to 40.5%); use of hormones decreased (19.4% to 5.4%). After controlling for patient characteristics, effects of time on the use of antidepressants were no longer significant. Antihypertensive use was associated with poorer functioning, concurrent use of memantine, and older age. Antipsychotic use was associated with poorer functioning and poorer cognition. Antidepressant use was associated with younger age, poorer functioning, and concurrent use of cholinesterase inhibitors and memantine. Hormone use was associated with being female and younger age. Findings suggest accurate modeling of the Alzheimer disease treatment paradigm for certain subgroups of patients should include antihypertensives and antipsychotics in addition to cholinesterase inhibitors and memantine.
ESTHER : Zhu_2011_Alzheimer.Dis.Assoc.Disord_25_144
PubMedSearch : Zhu_2011_Alzheimer.Dis.Assoc.Disord_25_144
PubMedID: 20975515

Title : Longitudinal medication usage in Alzheimer disease patients - Zhu_2010_Alzheimer.Dis.Assoc.Disord_24_354
Author(s) : Zhu CW , Livote EE , Kahle-Wrobleski K , Scarmeas N , Albert M , Brandt J , Blacker D , Sano M , Stern Y
Ref : Alzheimer Disease & Associated Disorders , 24 :354 , 2010
Abstract : This study examined in detail patterns of cholinesterase inhibitors (ChEIs) and memantine use and explored the relationship between patient characteristics and such use. Patients with probable Alzheimer disease AD (n=201) were recruited from the Predictors Study in 3 academic AD centers and followed from early disease stages for up to 6 years. Random effects logistic regressions were used to examine effects of patient characteristics on ChEIs/memantine use over time. Independent variables included measures of function, cognition, comorbidities, the presence of extrapyramidal signs, psychotic symptoms, age, sex, and patient's living situation at each interval. Control variables included assessment interval, year of study entry, and site. During a 6-year study period, rate of ChEIs use decreased (80.6% to 73.0%) whereas memantine use increased (2.0% to 45.9%). Random effects logistic regression analyses showed that ChEI use was associated with better function, no psychotic symptoms, and younger age. Memantine use was associated with better function, poorer cognition, living at home, later assessment interval, and later year of study entry. Results suggest that high rate of ChEI use and increasing memantine use over time are consistent with current practice guidelines of initiation of ChEIs in mild-to-moderate AD patients and initiation of memantine in moderate-to-severe patients.
ESTHER : Zhu_2010_Alzheimer.Dis.Assoc.Disord_24_354
PubMedSearch : Zhu_2010_Alzheimer.Dis.Assoc.Disord_24_354
PubMedID: 20625271

Title : Current Alzheimer's disease clinical trials: methods and placebo outcomes - Schneider_2009_Alzheimers.Dement_5_388
Author(s) : Schneider LS , Sano M
Ref : Alzheimers Dement , 5 :388 , 2009
Abstract : BACKGROUND: Eighteen-month-long randomized, placebo-controlled clinical trials are common for phase II and phase III drug development for Alzheimer's disease (AD). Yet, no 18-month trial has shown statistically significant outcomes favoring the test drug. We examined characteristics and underlying assumptions of these trials by assessing the placebo groups. METHODS: We searched the registry for randomized, placebo-controlled clinical trials for AD of at least 18-month duration and extracted demographic, clinical, and trials characteristics, and change in main outcomes from the placebo groups. We obtained additional information from presentations, abstracts, publications, and sponsors. RESULTS: Of 23 trials identified, 11 were completed and had baseline data available; nine had follow-up data available; 17 were phase III. General inclusion criteria were very similar except that minimum Mini-Mental State Examination (MMSE) scores varied from 12 to 20. Sample sizes ranged from 402 to 1,684 for phase III trials and 80 to 400 for phase II. Cholinesterase inhibitor use was from 53% to 100%, and memantine use was from 13.5% to 78%. The AD Assessment Scale-cognitive (ADAS-cog) was the co-primary outcome in all trials; and activities of daily living, global severity, or global change ratings were the other co-primaries. APOE epsilon4 genotype carriers ranged from 58% to 67%; mean baseline ADAS-cog was 17.8 to 24.2. ADAS-cog worsening in the placebo groups during 18 months ranged from 4.34 to 9.10, with standard deviations from 8.17 to 9.39, increasing during 18 months. CONCLUSIONS: Inclusion criteria are essentially similar to earlier 6-month and 12-month trials in which cholinesterase inhibitors were not allowed, as were mean ADAS-cog rates of change. Yet increasing variability and relatively little change overall in the ADAS-cog placebo groups, eg, about 25% of patients do not worsen by more than 1 point, might make it more unlikely than previously assumed that a modestly effective drug can be reliably recognized, especially when the drug might work only to attenuate decline in function and not to improve function. These observations would be strengthened by pooling individual trials data, and pharmaceutical sponsors should participate in such efforts.
ESTHER : Schneider_2009_Alzheimers.Dement_5_388
PubMedSearch : Schneider_2009_Alzheimers.Dement_5_388
PubMedID: 19751918

Title : Preventing Alzheimer's disease : separating fact from fiction - Sano_2008_CNS.Drugs_22_887
Author(s) : Sano M , Grossman H , Van Dyk K
Ref : CNS Drugs , 22 :887 , 2008
Abstract : Alzheimer's disease is an ever-increasing health concern among the aging population, and as we research new and existing treatments for this disease we begin to uncover possibilities for its prevention. Observational studies and animal models have provided promising findings and generated excitement, but placebo-controlled clinical trials are required to demonstrate true efficacy for these treatments.In the past two decades, clinical trials have led to the approval of symptomatic treatments for Alzheimer's disease, including cholinesterase inhibitors and, more recently, an NMDA receptor antagonist. Clinical trials have also examined antioxidants, NSAIDs, hormone replacement, nutritional supplements and nonpharmacological interventions for the treatment and prevention of Alzheimer's disease. While the results of many of these trials have been disappointing, new mechanisms targeting the hallmark pathology of Alzheimer's disease are currently under investigation, including immunotherapy and secretase modulation, targeted at reducing the amyloid burden, for which we await the results. We review the evidence from completed trials, support for ongoing studies and propose directions for future research.
ESTHER : Sano_2008_CNS.Drugs_22_887
PubMedSearch : Sano_2008_CNS.Drugs_22_887
PubMedID: 18840031

Title : Lack of evidence for endocrine disrupting effects in rats exposed to fenitrothion in utero and from weaning to maturation - Okahashi_2005_Toxicology_206_17
Author(s) : Okahashi N , Sano M , Miyata K , Tamano S , Higuchi H , Kamita Y , Seki T
Ref : Toxicology , 206 :17 , 2005
Abstract : Fenitrothion is a broad-spectrum organophosphate insecticide. Recently, it has been reported to exert androgenic or anti-androgenic activity in in vitro and in vivo screening assays, although the effects appear equivocal in vivo. To provide a conclusive and comprehensive evaluation of fenitrothion, especially regarding its anti-androgenic activity in the reproductive and endocrine systems, we conducted a one-generation reproductive toxicity study at appropriately toxic dose levels with a number of sensitive endpoints for endocrine disruption. Fenitrothion was administered to Crj:CD(SD)IGS parental animals (P) at concentrations of 10, 20, and 60 ppm in the diet for 10 weeks prior to mating, and throughout mating, gestation and lactation. Their offspring (F1) were exposed from weaning until maturation at the age of 10 weeks. In the P generation, brain cholinesterase activity was remarkably reduced in the 60 ppm males and in the 20 and 60 ppm females. Reproductive performance, organ weights, histopathology, and sperm analytical parameters were not affected. In the F1 generation, no general toxicity or effects on anogenital distance, retention of areolae/nipples, onset of puberty, organ weights, histopathological findings, and sperm parameters were observed. In conclusion, fenitrothion had no effects on the reproductive or endocrine systems of the P and F1 generations, even at toxic doses that markedly suppressed brain cholinesterase activity in P animals. The results suggest that fenitrothion at in-use levels in the environment is unlikely to cause disruption of human endocrine systems.
ESTHER : Okahashi_2005_Toxicology_206_17
PubMedSearch : Okahashi_2005_Toxicology_206_17
PubMedID: 15590106

Title : Genome sequencing and analysis of Aspergillus oryzae - Machida_2005_Nature_438_1157
Author(s) : Machida M , Asai K , Sano M , Tanaka T , Kumagai T , Terai G , Kusumoto K , Arima T , Akita O , Kashiwagi Y , Abe K , Gomi K , Horiuchi H , Kitamoto K , Kobayashi T , Takeuchi M , Denning DW , Galagan JE , Nierman WC , Yu J , Archer DB , Bennett JW , Bhatnagar D , Cleveland TE , Fedorova ND , Gotoh O , Horikawa H , Hosoyama A , Ichinomiya M , Igarashi R , Iwashita K , Juvvadi PR , Kato M , Kato Y , Kin T , Kokubun A , Maeda H , Maeyama N , Maruyama J , Nagasaki H , Nakajima T , Oda K , Okada K , Paulsen I , Sakamoto K , Sawano T , Takahashi M , Takase K , Terabayashi Y , Wortman JR , Yamada O , Yamagata Y , Anazawa H , Hata Y , Koide Y , Komori T , Koyama Y , Minetoki T , Suharnan S , Tanaka A , Isono K , Kuhara S , Ogasawara N , Kikuchi H
Ref : Nature , 438 :1157 , 2005
Abstract : The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.
ESTHER : Machida_2005_Nature_438_1157
PubMedSearch : Machida_2005_Nature_438_1157
PubMedID: 16372010
Gene_locus related to this paper: aspor-Q2U722 , aspfn-b8mvx2 , aspfn-b8mwk1 , aspfn-b8n1a4 , aspfn-b8n5l3 , aspfn-b8n7y0 , aspfn-b8n829 , aspfn-b8ncj5 , aspfn-b8nhj9 , aspfn-b8njx6 , aspfn-b8nsk2 , aspfu-q4wj61 , aspor-axe1 , aspor-CPI , aspor-cutas , aspor-cuti2 , aspor-DPPIV , aspor-faec , aspor-MDLB , aspor-ppme1 , aspor-q2tw11 , aspor-q2tw16 , aspor-q2tw28 , aspor-q2twc4 , aspor-q2twg0 , aspor-q2twj3 , aspor-q2twv2 , aspor-q2twv4 , aspor-q2tx21 , aspor-q2txq8 , aspor-q2tya1 , aspor-q2tyh6 , aspor-q2tyn9 , aspor-q2typ0 , aspor-q2tyq4 , aspor-q2tyv8 , aspor-q2tz03 , aspor-q2tzh3 , aspor-q2tzr5 , aspor-q2tzv9 , aspor-q2u0k7 , aspor-q2u0q2 , aspor-q2u0r6 , aspor-q2u1a5 , aspor-q2u1a6 , aspor-q2u1k0 , aspor-q2u1k8 , aspor-q2u1m8 , aspor-q2u2a1 , aspor-q2u2a4 , aspor-q2u3a3 , aspor-q2u3a6 , aspor-q2u3k5 , aspor-q2u3l6 , aspor-q2u4a0 , aspor-q2u4e0 , aspor-q2u4f6 , aspor-q2u4g6 , aspor-q2u4h9 , aspor-q2u4w9 , aspor-q2u4y8 , aspor-q2u5f5 , aspor-q2u5n3 , aspor-q2u5y8 , aspor-q2u6h7 , aspor-q2u6j5 , aspor-q2u6m8 , aspor-q2u6m9 , aspor-q2u6n6 , aspor-q2u7i2 , aspor-q2u7v0 , aspor-q2u8j8 , aspor-q2u8r1 , aspor-q2u8r4 , aspor-q2u8t5 , aspor-q2u8z3 , aspor-q2u9a1 , aspor-q2u9n5 , aspor-q2u144 , aspor-q2u161 , aspor-q2u185 , aspor-q2u199 , aspor-q2u212 , aspor-q2u331 , aspor-q2u348 , aspor-q2u400 , aspor-q2u453 , aspor-q2u489 , aspor-q2u704 , aspor-q2u728 , aspor-q2u798 , aspor-q2u822 , aspor-q2u854 , aspor-q2u875 , aspor-q2u908 , aspor-q2ua10 , aspor-q2ua48 , aspor-q2uab6 , aspor-q2uak9 , aspor-q2uaq4 , aspor-q2ub32 , aspor-q2ub76 , aspor-q2uba1 , aspor-q2ubd6 , aspor-q2ubm2 , aspor-q2ubr2 , aspor-q2uc28 , aspor-q2uc65 , aspor-q2uc77 , aspor-q2uc98 , aspor-q2uck0 , aspor-q2ucy7 , aspor-q2ud03 , aspor-q2ud06 , aspor-q2ud08 , aspor-q2ud23 , aspor-q2udn5 , aspor-q2udr0 , aspor-q2uec1 , aspor-q2uef3 , aspor-q2uf10 , aspor-q2uf27 , aspor-q2uf48 , aspor-q2ufd8 , aspor-q2ufe5 , aspor-q2ufm4 , aspor-q2ufr3 , aspor-q2ufz8 , aspor-q2ug78 , aspor-q2ugd6 , aspor-q2uge1 , aspor-q2ugg7 , aspor-q2ugi2 , aspor-q2ugl2 , aspor-q2ugy9 , aspor-q2uh24 , aspor-q2uh73 , aspor-q2uhe4 , aspor-q2uhf0 , aspor-q2uhj6 , aspor-q2uhn1 , aspor-q2uhq0 , aspor-q2ui56 , aspor-q2uib2 , aspor-q2uib5 , aspor-q2uie9 , aspor-q2uih1 , aspor-q2uii1 , aspor-q2uik9 , aspor-q2uiq0 , aspor-q2uiu1 , aspor-q2uix9 , aspor-q2uiy5 , aspor-q2uiz4 , aspor-q2uj89 , aspor-q2uja2 , aspor-q2uju3 , aspor-q2uk31 , aspor-q2uk42 , aspor-q2ukb6 , aspor-q2ukq7 , aspor-q2ul81 , aspor-q2uli9 , aspor-q2ulr2 , aspor-q2ulv7 , aspor-q2umf3 , aspor-q2umv2 , aspor-q2umx6 , aspor-q2unw5 , aspor-q2up23 , aspor-q2up89 , aspor-q2upe6 , aspor-q2upi1 , aspor-q2upl1 , aspor-q2upw4 , aspor-q2uq56 , aspor-q2uqb4 , aspor-q2uqm7 , aspor-q2ur58 , aspor-q2ur64 , aspor-q2ur80 , aspor-q2ur83 , aspor-q2ure7 , aspor-q2urf3 , aspor-q2urg5 , aspor-q2urq0 , aspor-q2urt4 , aspor-q2uru5 , aspor-q2usi0 , aspor-q2usp7 , aspor-q2usq8 , aspor-q2usv6 , aspor-q2uta5 , aspor-q2uu89 , aspor-q2uub4 , aspor-q2uux8 , aspor-q2uv29 , aspor-TGLA , aspor-q2ue03 , aspor-q2uj83 , aspno-a0a0l1j1c9

Title : Economic effect of cholinesterase inhibitor therapy: implications for managed care - Sano_2004_Manag.Care.Interface_17_44
Author(s) : Sano M
Ref : Manag Care Interface , 17 :44 , 2004
Abstract : The growing elderly population is at great risk for Alzheimer's disease (AD). In 1997, annual costs associated with AD were 100 billion dollars. Cholinesterase inhibitor (ChEI) therapy is most commonly used to manage patients with AD, but the economic implications arising from their use are not well known. A review of studies assessing the cost effectiveness of ChEIs suggests that ChEI therapy provides benefit at every stage of disease, with better outcomes resulting from persistent, uninterrupted treatment. The cost savings range from 73 dollars over two years to 3891 dollars over one year, depending on the type of study, drug evaluated, and economic model employed in the evaluation.
ESTHER : Sano_2004_Manag.Care.Interface_17_44
PubMedSearch : Sano_2004_Manag.Care.Interface_17_44
PubMedID: 15471110

Title : Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D - Matsuzaki_2004_Nature_428_653
Author(s) : Matsuzaki M , Misumi O , Shin IT , Maruyama S , Takahara M , Miyagishima SY , Mori T , Nishida K , Yagisawa F , Yoshida Y , Nishimura Y , Nakao S , Kobayashi T , Momoyama Y , Higashiyama T , Minoda A , Sano M , Nomoto H , Oishi K , Hayashi H , Ohta F , Nishizaka S , Haga S , Miura S , Morishita T , Kabeya Y , Terasawa K , Suzuki Y , Ishii Y , Asakawa S , Takano H , Ohta N , Kuroiwa H , Tanaka K , Shimizu N , Sugano S , Sato N , Nozaki H , Ogasawara N , Kohara Y , Kuroiwa T
Ref : Nature , 428 :653 , 2004
Abstract : Small, compact genomes of ultrasmall unicellular algae provide information on the basic and essential genes that support the lives of photosynthetic eukaryotes, including higher plants. Here we report the 16,520,305-base-pair sequence of the 20 chromosomes of the unicellular red alga Cyanidioschyzon merolae 10D as the first complete algal genome. We identified 5,331 genes in total, of which at least 86.3% were expressed. Unique characteristics of this genomic structure include: a lack of introns in all but 26 genes; only three copies of ribosomal DNA units that maintain the nucleolus; and two dynamin genes that are involved only in the division of mitochondria and plastids. The conserved mosaic origin of Calvin cycle enzymes in this red alga and in green plants supports the hypothesis of the existence of single primary plastid endosymbiosis. The lack of a myosin gene, in addition to the unexpressed actin gene, suggests a simpler system of cytokinesis. These results indicate that the C. merolae genome provides a model system with a simple gene composition for studying the origin, evolution and fundamental mechanisms of eukaryotic cells.
ESTHER : Matsuzaki_2004_Nature_428_653
PubMedSearch : Matsuzaki_2004_Nature_428_653
PubMedID: 15071595
Gene_locus related to this paper: cyam1-m1vi61 , cyam1-m1vhh9

Title : The effects of galantamine treatment on caregiver time in Alzheimer's disease - Sano_2003_Int.J.Geriatr.Psychiatry_18_942
Author(s) : Sano M , Wilcock GK , Van Baelen B , Kavanagh S
Ref : Int J Geriatr Psychiatry , 18 :942 , 2003
Abstract : AIM: The aim of the study was to determine whether the clinical benefits of galantamine for patients with Alzheimer's disease lead to benefits for caregivers.
METHODS: Data were pooled from two concurrent, multi-centre, randomized, double-blind, placebo-controlled, 6-month trials. Time caregivers spent assisting with activities of daily living (ADL) and time patients could be left unsupervised each day were assessed using the Allocation of Caregiver Time Survey. In total, 825 patients with mild-to-moderate Alzheimer's disease were included.
RESULTS: At endpoint, caregivers of galantamine-treated patients were more likely to report reductions (41% vs 37%), maintenance (19% vs 14%) or smaller increases (26% vs 34% reporting an increase >30 minutes) in time assisting with ADL compared with the placebo group (p=0.026; Wilcoxon rank-sum test). The mean daily time difference was 32 minutes (p=0.011). Among patients with moderate Alzheimer's disease, caregivers of galantamine-treated patients were even more likely to report reductions (46% vs 37%), maintenance (15% vs 6%) or smaller increases (25% vs 42% for increases >30 min) vs placebo (p=0.004), with a mean daily time saving of 53 minutes (p=0.021). Caregivers of galantamine-treated patients were more likely to report increases (22% vs 18%), maintenance (45% vs 43%) or smaller reductions (30% vs 37% for reductions >30 minutes) in time the patient could be left unsupervised compared with placebo (p=0.027). Mean daily time saving was 27 minutes. Among patients with moderate Alzheimer's disease, the treatment effect was greater (p=0.029), with caregivers in the galantamine group reporting the change in time left unsupervised as 68 minutes longer each day than caregivers of patients receiving placebo. CONCLUSION: The clinical benefits of galantamine for patients with Alzheimer's disease are also associated with benefits to caregiving.
ESTHER : Sano_2003_Int.J.Geriatr.Psychiatry_18_942
PubMedSearch : Sano_2003_Int.J.Geriatr.Psychiatry_18_942
PubMedID: 14533127

Title : Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial - Aisen_2003_JAMA_289_2819
Author(s) : Aisen PS , Schafer KA , Grundman M , Pfeiffer E , Sano M , Davis KL , Farlow MR , Jin S , Thomas RG , Thal LJ
Ref : Jama , 289 :2819 , 2003
Abstract : CONTEXT: Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease. OBJECTIVE: To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications. SETTING: Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium. PARTICIPANTS: Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled. INTERVENTIONS: Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo. MAIN OUTCOME MEASURES: The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death).
RESULTS: The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group. CONCLUSION: The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.
ESTHER : Aisen_2003_JAMA_289_2819
PubMedSearch : Aisen_2003_JAMA_289_2819
PubMedID: 12783912

Title : The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins - Dehal_2002_Science_298_2157
Author(s) : Dehal P , Satou Y , Campbell RK , Chapman J , Degnan B , De Tomaso A , Davidson B , Di Gregorio A , Gelpke M , Goodstein DM , Harafuji N , Hastings KE , Ho I , Hotta K , Huang W , Kawashima T , Lemaire P , Martinez D , Meinertzhagen IA , Necula S , Nonaka M , Putnam N , Rash S , Saiga H , Satake M , Terry A , Yamada L , Wang HG , Awazu S , Azumi K , Boore J , Branno M , Chin-Bow S , DeSantis R , Doyle S , Francino P , Keys DN , Haga S , Hayashi H , Hino K , Imai KS , Inaba K , Kano S , Kobayashi K , Kobayashi M , Lee BI , Makabe KW , Manohar C , Matassi G , Medina M , Mochizuki Y , Mount S , Morishita T , Miura S , Nakayama A , Nishizaka S , Nomoto H , Ohta F , Oishi K , Rigoutsos I , Sano M , Sasaki A , Sasakura Y , Shoguchi E , Shin-I T , Spagnuolo A , Stainier D , Suzuki MM , Tassy O , Takatori N , Tokuoka M , Yagi K , Yoshizaki F , Wada S , Zhang C , Hyatt PD , Larimer F , Detter C , Doggett N , Glavina T , Hawkins T , Richardson P , Lucas S , Kohara Y , Levine M , Satoh N , Rokhsar DS
Ref : Science , 298 :2157 , 2002
Abstract : The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.
ESTHER : Dehal_2002_Science_298_2157
PubMedSearch : Dehal_2002_Science_298_2157
PubMedID: 12481130
Gene_locus related to this paper: cioin-141645 , cioin-147959 , cioin-150181 , cioin-154370 , cioin-ACHE1 , cioin-ACHE2 , cioin-cxest , cioin-f6qcp0 , cioin-f6r8z1 , cioin-f6u176 , cioin-f6vac9 , cioin-f6x584 , cioin-f6xa69 , cioin-f6y403 , cioin-h2xqb4 , cioin-H2XTI0 , cioin-F6T1M3 , cioin-H2XUP7 , cioin-CIN.7233 , cioin-F6V269 , cioin-Cin16330 , cioin-h2xua2 , cioin-f6vaa5 , cioin-f6v9x6 , cioin-f6swc9 , cioin-f7amz2 , cioin-f6s021 , cioin-h2xxq9 , cioin-h2xne6 , cioin-f6ynr2

Title : New acetylcholinesterase inhibitor (donepezil) treatment for Alzheimer's disease in a chronic dialysis patient - Suwata_2002_Nephron_91_330
Author(s) : Suwata J , Kamata K , Nishijima T , Yoshikawa T , Sano M
Ref : Nephron , 91 :330 , 2002
Abstract : The new-generation acetylcholinesterase inhibitor, donepezil, is useful in the treatment of mild-to-moderate Alzheimer's disease. A 72-year-old male chronic hemodialysis patient was diagnosed as having moderate Alzheimer's disease. We administered donepezil at 3 mg/day orally to the patient. After 1 month's treatment, the patient improved to a controllable psychiatric condition and was discharged from the hospital. The 24-hour plasma concentration profile of donepezil following the 3-mg once-daily dose varied from 11.1 to 18.2 ng/ml. The through level of donepezil was reduced from 12.4 to 10.9 ng/ml over a 3-month period. We did not experience any episodes of drug toxicity or adverse effects in this chronic dialysis patient. Donepezil treatment might have a beneficial impact on patients with severe renal dysfunction.
ESTHER : Suwata_2002_Nephron_91_330
PubMedSearch : Suwata_2002_Nephron_91_330
PubMedID: 12053074

Title : Treatment of Alzheimer's disease -
Author(s) : Mayeux R , Sano M
Ref : N Engl J Med , 341 :1670 , 1999
PubMedID: 10572156

Title : First International Pharmacoeconomic Conference on Alzheimer's Disease: report and summary - Whitehouse_1998_Alzheimer.Dis.Assoc.Disord_12_266
Author(s) : Whitehouse PJ , Winblad B , Shostak D , Bhattacharjya A , Brod M , Brodaty H , Dor A , Feldman H , Forette F , Gauthier S , Hay J , Henke C , Hill S , Mastey V , Neumann P , O'Brien B , Pugner K , Sano M , Sawada T , Stone R , Wimo A
Ref : Alzheimer Disease & Associated Disorders , 12 :266 , 1998
Abstract : The First International Pharmacoeconomic Conference on Alzheimer's Disease (AD) was held in Amsterdam in July 1998. The meeting was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines (http:\/\/, bringing together academics, clinicians, purchasers, and representatives from industry. Presentations were given on the methodology of pharmacoeconomic studies in AD, particularly focusing on caregiver burden, quality of life (QOL), and resource utilization. Three economic models of AD were presented based on data from the United States, Canada, and the United Kingdom. In two studies, these data were then used to model the cost-effectiveness and effect on cost of treatment with donepezil. Both studies suggested a possible cost advantage for the use of donepezil, when compared with no placebo or treatment, particularly when donepezil is used appropriately in mild-to-moderate AD. These data need to be interpreted with care, as none of the cost or utility information were collected during the clinical trials. Additional data from a 2-year clinical trial of selegiline and vitamin E suggest that cognitive measures may be poor predictors of economic outcome, which is better measured directly. Both economic models of donepezil rely on short-term cognitive data to predict long-term outcome, a methodf that may not be useful in predicting economic savings. The issues facing pharmacoeconomists, researchers, clinicians, and families in the future were addressed in a series of workshops using a method of strategic futuring. The workshops attempted to see 7 years into the future for a range of areas, including consumer and caregiver use of pharmacoeconomic data; early detection and prevention; Japanese perspectives; activities of daily life and what will be daily life activities; caregiver burden; QOL at the end of life; new uses for new information and communication technology in clinical research; and physicians' use of pharmacoeconomic data. A range of exciting futures were predicted, although common themes that arose when considering barriers to achieving these futures included cost, education, political will, confidentiality, privacy, and ethics. The first conference was deemed to have been a success, having attracted more than 160 delegates and many distinguished speaker. A second conference is planned for the year 2000. Over the next 2 years, research needs to be broadened particularly in the methodological areas of resource utilization, QOL, and caregiver burden. Data from clinical trials with relevant economic and QOL outcomes will be needed by purchasers if drug treatments for dementia are to gain widespread use. It is also hoped that the models described at the meeting may become more freely available to politicians, purchasers, clinicians, and caregivers to help them make better decisions about treatment.
ESTHER : Whitehouse_1998_Alzheimer.Dis.Assoc.Disord_12_266
PubMedSearch : Whitehouse_1998_Alzheimer.Dis.Assoc.Disord_12_266
PubMedID: 9876955

Title : Tacrine and nursing home placement -
Author(s) : Thal LJ , Thomas RG , Sano M
Ref : Neurology , 49 :897 , 1997
PubMedID: 9305370

Title : Studies on new, centrally active and reversible acetylcholinesterase inhibitors - Arnal_1990_Neurochem.Res_15_587
Author(s) : Arnal F , Cote LJ , Ginsburg S , Lawrence GD , Naini A , Sano M
Ref : Neurochem Res , 15 :587 , 1990
Abstract : We have synthesized the tertiary amines of pyridostigmine and neostigmine, 3-pyridinol dimethylcarbamate (norpyridostigmine) and 3-dimethylaminophenol dimethylcarbamate (norneostigmine) respectively, and we have tested their abilities to cross the blood-brain barrier and inhibit mouse brain AChE activity. The in vivo inhibition of AChE activity by norpyridostigmine reaches 72% at 10 minutes which is comparable to that seen with physostigmine (73% at 10 minutes). Inhibition by norneostigmine is less effective (50% at 10 minutes) and approaches that obtained with tetrahydroaminoacridine (57% at 10 minutes). These data show that both norpyridostigmine and norneostigmine cross the blood-brain barrier and that they are effective inhibitors of mouse brain AChE activity. These drugs could be useful in the treatment of memory impairment associated with Alzheimer's disease, and other memory disorders.
ESTHER : Arnal_1990_Neurochem.Res_15_587
PubMedSearch : Arnal_1990_Neurochem.Res_15_587
PubMedID: 2215850