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Author Report for: Jones RW

Title: Souvenaid(R): a new approach to management of early Alzheimer's disease
Ritchie CW, Bajwa J, Coleman G, Hope K, Jones RW, Lawton M, Marven M, Passmore P
Ref: J Nutr Health Aging, 18:291, 2014 : PubMed
Abstract


ESTHER: Ritchie_2014_J.Nutr.Health.Aging_18_291
PubMedSearch: Ritchie 2014 J.Nutr.Health.Aging 18 291
PubMedID: 24626757

Abstract

Synaptic loss correlates closely with cognitive deficits in Alzheimer's disease and represents a new target for intervention. Souvenaid(R) is the first medical nutrition product to be designed to support synapse formation and function in early Alzheimer's disease, and has undergone an extensive, 12-year development programme. The relatively large amount of clinical data available for Souvenaid(R) is unusual for a medical nutrition product. Souvenaid(R) contains omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid), uridine (as uridine monophosphate) and choline which are nutritional precursors required for synaptic membrane phospholipid synthesis, together with phospholipids and other cofactors. Souvenaid(R) has demonstrated cognitive benefits in patients with mild Alzheimer's disease but not in patients with mild-to-moderate Alzheimer's disease. Two randomised, double-blind, controlled trials (duration 12 and 24 weeks) in patients with mild Alzheimer's disease untreated with acetylcholinesterase inhibitors and/or memantine have demonstrated that Souvenaid(R) is well tolerated and improves episodic memory performance. The daily intake of Souvenaid(R) has not been associated with any harmful effects or interactions with medications and none are anticipated. The ongoing, 24-month, European Union-funded LipiDiDiet trial in subjects with prodromal Alzheimer's disease is evaluating the potential benefits of Souvenaid(R) on memory and in slowing progression to Alzheimer's dementia. If Souvenaid(R) induces synaptogenesis and improved synaptic function, it may provide benefits in other clinical conditions characterised by neurodegeneration. A number of trials are ongoing and planned to evaluate the potential wider benefits of Souvenaid(R).



        

Title: Trends in the prevalence of antipsychotic drug use among patients with Alzheimer's disease and other dementias including those treated with antidementia drugs in the community in the UK: a cohort study
Martinez C, Jones RW, Rietbrock S
Ref: BMJ Open, 3:, 2013 : PubMed
Abstract


ESTHER: Martinez_2013_BMJ.Open_3_
PubMedSearch: Martinez 2013 BMJ.Open 3
PubMedID: 23299113

Abstract

OBJECTIVE: To investigate the pattern and trends of use of antipsychotics, antidepressants, hypnotics and anxiolytics in Alzheimer's disease and other dementias and in patients treated with antidementia medications. DESIGN: Cohort study with dementia patients formed in the UK Clinical Practice Research Datalink. Participants Patients with incident dementia, between 1995 and 2011 and a reference non-dementia cohort matched on age, gender and date of dementia diagnosis. Two subcohorts included new users of acetylcholinesterase inhibitors (AChEIs) and memantine. The study endpoint was use of antipsychotics, antidepressants, hypnotics and anxiolytics up to 10 years before and 4 years after dementia diagnosis, and for up to 5 years before and 1 year after first use of AChEI or memantine.
RESULTS: 50 349 patients with incident dementia diagnosis and 50 349 matched controls, 10 794 first-time users of AChEI and 669 of memantine. The mean prevalence of antipsychotic use from 1995 to 2011 on diagnosis of dementia was 12.5%, decreasing from 19.9% in 1995 to 7.4% in 2011. There was an increase in antidepressant use (10.7-26.3%) and a small increase in anxiolytic use. The matched cohort showed a lower use of antipsychotics and anxiolytics but a rise in antidepressants (5.9-13.4%). Both groups showed a decrease in hypnotic use. 10.6% of AChEI and 26.3% of memantine users were prescribed antipsychotics, 34.1% and 26.3% antidepressants, 13.2% and 4.1% anxiolytics and 18.4% and 8.3% hypnotics. The slopes for monthly use of antipsychotics were positive in the year leading up to AChEI and memantine use; after treatment initiation the slope for AChEI users continued to increase but at a reduced rate whereas antipsychotic use declined for memantine users.
CONCLUSIONS: The marked reduction in antipsychotic use in dementia is to be welcomed while there was a steady increase in antidepressant use. There was a decline in antipsychotic use after the initiation of memantine.



        

Title: Rationale for combining glutamatergic and cholinergic approaches in the symptomatic treatment of Alzheimer's disease
Francis PT, Parsons CG, Jones RW
Ref: Expert Rev Neurother, 12:1351, 2012 : PubMed
Abstract


ESTHER: Francis_2012_Expert.Rev.Neurother_12_1351
PubMedSearch: Francis 2012 Expert.Rev.Neurother 12 1351
PubMedID: 23234396

Abstract

A total of 40 years of biochemical, clinical and neuropathological research have revolutionized our understanding of the pathophysiology of Alzheimer's disease, yet at the present moment the only drugs licensed for treatment are targeted essentially at symptoms. Some disease-modifying drugs remain in clinical trials, but many that have used similar approaches have failed. It is therefore of considerable interest to examine the optimal way of using existing medications for the benefit of patients. This article looks at the rationale behind the combined use of acetylcholinesterase inhibitors and the N-methyl-d-aspartate-receptor antagonist, memantine, from both preclinical and clinical perspectives.



        

Title: A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors
Jones RW
Ref: Int J Geriatr Psychiatry, 25:547, 2010 : PubMed
Abstract


ESTHER: Jones_2010_Int.J.Geriatr.Psychiatry_25_547
PubMedSearch: Jones 2010 Int.J.Geriatr.Psychiatry 25 547
PubMedID: 20049770

Abstract

OBJECTIVE: Alzheimer's disease (AD) is prevalent among elderly people, who often have comorbid conditions, and may be prescribed multiple medications. Drug safety and tolerability is paramount in maximising efficacy and optimising patient and carer quality of life, as patients are vulnerable to adverse events (AEs) and/or compliance difficulties. The two principal categories of drug used in the treatment of AD are the acetylcholinesterase inhibitors (AChEIs) and the NMDA-receptor antagonist, memantine. This paper reviews the most recent safety data for memantine in comparison with the AChEIs. DESIGN: Review of most recent safety/tolerability data for memantine and AChEIs, derived from meta-analyses, pooled analyses, European SPCs and EMEA publications. RESULTS: Memantine was found to have a favourable tolerability profile when used as monotherapy or in combination with other agents. AChEIs were found to be fairly well tolerated. All treatments commonly or very commonly produce dizziness and/or headache. AChEIs are associated with many more types of AEs than memantine, particularly in the gastrointestinal category. Agitation is a less common AE when comparing memantine treatment to placebo, but just as common when comparing AChEI treatment to placebo. Withdrawals in memantine-treated groups are comparable to placebo, and more common in AChEI-treated groups compared to placebo. Overall, drug-drug interactions, contraindications and warnings were fewer for memantine than AChEIs. CONCLUSIONS: In both the clinical and naturalistic setting, memantine displays a safety and tolerability profile that is favourable and distinct from that of AChEIs. Safety and tolerability profiles should be given careful consideration when selecting treatment for AD patients.



        

Title: Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
Haas BJ, Kamoun S, Zody MC, Jiang RH, Handsaker RE, Cano LM, Grabherr M, Kodira CD, Raffaele S and Nusbaum C <86 more author(s)> Haas BJ, Kamoun S, Zody MC, Jiang RH, Handsaker RE, Cano LM, Grabherr M, Kodira CD, Raffaele S, Torto-Alalibo T, Bozkurt TO, Ah-Fong AM, Alvarado L, Anderson VL, Armstrong MR, Avrova A, Baxter L, Beynon J, Boevink PC, Bollmann SR, Bos JI, Bulone V, Cai G, Cakir C, Carrington JC, Chawner M, Conti L, Costanzo S, Ewan R, Fahlgren N, Fischbach MA, Fugelstad J, Gilroy EM, Gnerre S, Green PJ, Grenville-Briggs LJ, Griffith J, Grunwald NJ, Horn K, Horner NR, Hu CH, Huitema E, Jeong DH, Jones AM, Jones JD, Jones RW, Karlsson EK, Kunjeti SG, Lamour K, Liu Z, Ma L, Maclean D, Chibucos MC, McDonald H, McWalters J, Meijer HJ, Morgan W, Morris PF, Munro CA, O'Neill K, Ospina-Giraldo M, Pinzon A, Pritchard L, Ramsahoye B, Ren Q, Restrepo S, Roy S, Sadanandom A, Savidor A, Schornack S, Schwartz DC, Schumann UD, Schwessinger B, Seyer L, Sharpe T, Silvar C, Song J, Studholme DJ, Sykes S, Thines M, van de Vondervoort PJ, Phuntumart V, Wawra S, Weide R, Win J, Young C, Zhou S, Fry W, Meyers BC, van West P, Ristaino J, Govers F, Birch PR, Whisson SC, Judelson HS, Nusbaum C (- 86)
Ref: Nature, 461:393, 2009 : PubMed
Abstract


ESTHER: Haas_2009_Nature_461_393
PubMedSearch: Haas 2009 Nature 461 393
PubMedID: 19741609
Gene_locus related to this paper: phyin-ENDO2, phyin-q2m440, phyin-q58g92, phyit-d0mqp1, phyit-d0mqp2, phyit-d0mt75, phyit-d0muv1, phyit-d0mv34, phyit-d0mv35, phyit-d0mwf9, phyit-d0mxu5, phyit-d0n935, phyit-d0nax9, phyit-d0nfs3, phyit-d0nhj2, phyit-d0nhj4, phyit-d0nhj8, phyit-d0ni28, phyit-d0nj14, phyit-d0nj53, phyit-d0nj54, phyit-d0njf2, phyit-d0nkm4, phyit-d0nr53, phyit-d0nrb1, phyit-d0nrk9, phyit-d0nrl4, phyit-d0ns26, phyit-d0ns42, phyit-d0ns43, phyit-d0nsr8, phyit-d0nu41, phyit-d0nvt3, phyit-d0nwb6, phyit-d0nwm8, phyit-d0nzc0, phyit-d0nzc1, phyit-d0p0z1, phyit-d0p3z2, phyit-kex1, phyit-d0n6q6, phyit-d0n4i8, phyit-d0mqf7, phyit-d0n5g6

Abstract

Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $$6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.



        

Title: The Atorvastatin/Donepezil in Alzheimer's Disease Study (LEADe): design and baseline characteristics
Jones RW, Kivipelto M, Feldman H, Sparks L, Doody R, Waters DD, Hey-Hadavi J, Breazna A, Schindler RJ, Ramos H
Ref: Alzheimers Dement, 4:145, 2008 : PubMed
Abstract


ESTHER: Jones_2008_Alzheimers.Dement_4_145
PubMedSearch: Jones 2008 Alzheimers.Dement 4 145
PubMedID: 18631958

Abstract

BACKGROUND: Growing evidence suggests that elevated cholesterol levels in mid-life are associated with increased risk of developing Alzheimer's disease (AD), and that statins might have a protective effect against AD and dementia. The Lipitor's Effect in Alzheimer's Dementia (LEADe) study tests the hypothesis that a statin (atorvastatin 80 mg daily) will provide a benefit on the course of mild to moderate AD in patients receiving background therapy of a cholinesterase inhibitor (donepezil 10 mg daily).
METHODS: This is an international, multicenter, double-blind, randomized, parallel-group study with a double-blind randomized withdrawal phase of patients with mild to moderate AD (Mini-Mental State Examination [MMSE] score, 13 to 25). Inclusion criteria included age 50 to 90 years, receiving donepezil 10 mg for at least 3 months before randomization, and low-density lipoprotein cholesterol levels (LDL-C) 2.5 to 3.5 mmol/L (95 to 195 mg/dL). Co-primary end points are changes in AD Assessment Scale-cognitive subscale (ADAS-cog) and AD Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale scores. A confirmatory end point is rate of change in whole brain and hippocampal volumes in patients who enrolled in the magnetic resonance imaging substudy.
RESULTS: Enrollment of 641 subjects is complete. The baseline mean data are age 74 +/- 8 years, 53% women, MMSE 22 +/- 3, ADAS-cog 23 +/- 10, AD Functional Assessment and Change Scale (ADFACS) 13 +/- 9, Neuropsychiatric Inventory (NPI) 10 +/- 11, and Clinical Dementia Rating-Sum of Boxes (CDR-SB) 6 +/- 3. Mean prior donepezil treatment was 409 +/- 407 days. Mean baseline lipid levels are total cholesterol 5.8 +/- 0.8 mmol/L (224 +/- 33 mg/dL), LDL-C 3.7 +/- 0.7 mmol/L (143 +/- 26 mg/dL), triglycerides 1.5 +/- 0.7 mmol/L (132 +/- 64 mg/dL), and high-density lipoprotein cholesterol 1.6 +/- 0.5 mmol/L (64 +/- 18 mg/dL).
CONCLUSIONS: LEADe will report in 2008 and is expected to provide a more definitive evaluation of the potential for statins in the treatment of people with AD.



        

Title: Donepezil for the treatment of agitation in Alzheimer's disease
Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, Burns AS, Holmes C, Jacoby R and Rodger M <8 more author(s)> Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, Burns AS, Holmes C, Jacoby R, Johnson T, Knapp M, Lindesay J, O'Brien JT, Wilcock G, Katona C, Jones RW, DeCesare J, Rodger M (- 8)
Ref: N Engl J Med, 357:1382, 2007 : PubMed
Abstract


ESTHER: Howard_2007_N.Engl.J.Med_357_1382
PubMedSearch: Howard 2007 N.Engl.J.Med 357 1382
PubMedID: 17914039

Abstract

BACKGROUND: Agitation is a common and distressing symptom in patients with Alzheimer's disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for behavioral disturbances are unclear.
METHODS: We randomly assigned 272 patients with Alzheimer's disease who had clinically significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day (128 patients) or placebo (131 patients) for 12 weeks. The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory (CMAI) (on a scale of 29 to 203, with higher scores indicating more agitation) at 12 weeks.
RESULTS: There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks (estimated mean difference in change [the value for donepezil minus that for placebo], -0.06; 95% confidence interval [CI], -4.35 to 4.22). Twenty-two of 108 patients (20.4%) in the placebo group and 22 of 113 (19.5%) in the donepezil group had a reduction of 30% or greater in the CMAI score (the value for donepezil minus that for placebo, -0.9 percentage point; 95% CI, -11.4 to 9.6). There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory, the Neuropsychiatric Inventory Caregiver Distress Scale, or the Clinician's Global Impression of Change.
CONCLUSIONS: In this 12-week trial, donepezil was not more effective than placebo in treating agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00142324 [ClinicalTrials.gov].).



        

Title: Safety and tolerability of once-daily versus twice-daily memantine: a randomised, double-blind study in moderate to severe Alzheimer's disease
Jones RW, Bayer A, Inglis F, Barker A, Phul R
Ref: Int J Geriatr Psychiatry, 22:258, 2007 : PubMed
Abstract


ESTHER: Jones_2007_Int.J.Geriatr.Psychiatry_22_258
PubMedSearch: Jones 2007 Int.J.Geriatr.Psychiatry 22 258
PubMedID: 17243195

Abstract

OBJECTIVE: To assess the safety and tolerability of three different dosing schedules of memantine in patients with moderate to severe Alzheimer's disease (AD). METHOD: This 12-week, randomised, double-blind study, investigated three dosing schedules of memantine: OD1 (20 mg once daily with a 1-step up-titration); OD3 (20 mg once daily with a 3-step up-titration); and BID3 (10 mg twice daily with a 3-step up-titration as currently recommended in the memantine labelling). The study comprised 78 patients with moderate to severe AD (DSM-IV-TR criteria; MMSE score < or = 18), 70% of whom were on stable dosing of acetylcholinesterase inhibitor (AChEI) initiated > or = 3 months prior to study start. Safety and tolerability were assessed by the number of withdrawals, adverse events (AEs) and monitoring of vital signs. RESULTS: The number of patient withdrawals was low: 3 of 27 in OD1, 1 of 25 in OD3 and 2 of 26 in BID3. One or more AEs were reported in 9 patients in OD1, 7 patients in OD3 and 12 patients in BID3. Most AEs were mild or moderate, and typical for the population studied; no clinically important differences in AEs or vital signs were observed between the different dosing schedules. There were no between-group differences in efficacy, as assessed by clinical global severity and clinical global change. These results are consistent with the good safety profile of memantine observed in larger studies. CONCLUSIONS: Although relatively small in size, the study indicates that once-daily dosing and twice-daily dosing of memantine are similar in terms of safety and tolerability.



        

Title: How can we best assess the quality of life of people with dementia? the Bath Assessment of Subjective Quality of Life in Dementia (BASQID)
Trigg R, Skevington SM, Jones RW
Ref: Gerontologist, 47:789, 2007 : PubMed
Abstract


ESTHER: Trigg_2007_Gerontologist_47_789
PubMedSearch: Trigg 2007 Gerontologist 47 789
PubMedID: 18192632

Abstract

PURPOSE: The study aim was to develop a measure of self-reported quality of life (QoL) for people with mild to moderate dementia based on their views-the Bath Assessment of Subjective Quality of Life in Dementia (BASQID). DESIGN AND
METHODS: We developed the measure through multiple stages. Two field tests of the measure (ns = 60 and 150) enrolled people with dementia from a memory clinic, and we used the data to analyze the psychometric properties of the scale. Nested within this was a longitudinal investigation of 36 Alzheimer's disease patients prescribed with acetylcholinesterase inhibitors.
RESULTS: The BASQID contains 14 items assessing a range of QoL issues. Results showed that the BASQID satisfies the criteria of a valid, reliable, and acceptable assessment of subjective QoL. Scores were responsive to changes in QoL over 3 months. Low association between the BASQID and the Mini-Mental State Examination indicates that cognitive function may influence QoL but is an indirect measure of the QoL experienced during dementia. IMPLICATIONS: The BASQID provides a means of better understanding the experiences, perceptions, and beliefs of people with dementia. It does this through acknowledgement of the many influences on QoL over and above health status. Practitioners and researchers can use the BASQID alongside objective assessments of dementia to obtain a complete appraisal of a person's QoL.



        

Title: Alpha7 nicotinic acetylcholine receptor expression in Alzheimer's disease: receptor densities in brain regions of the APP(SWE) mouse model and in human peripheral blood lymphocytes
Jones IW, Westmacott A, Chan E, Jones RW, Dineley K, O'Neill MJ, Wonnacott S
Ref: Journal of Molecular Neuroscience, 30:83, 2006 : PubMed
Abstract


ESTHER: Jones_2006_J.Mol.Neurosci_30_83
PubMedSearch: Jones 2006 J.Mol.Neurosci 30 83
PubMedID: 17192639

Abstract

The brains of people with Alzheimer's disease (AD) display several characteristic pathological features, including deposits (plaques) of beta-amyloid 1-42 (Abeta1-42), intraneuronal accumulations (tangles) of hyperphosphorylated tau, degeneration of the basal forebrain cholinergic pathway, and gliosis. Abeta1-42 plaques develop in specific brain regions, including hippocampus and cortex, as well as in the vasculature. Abeta1-42 might promote neurodegeneration through the induction of free radicals and disruption of Ca2+ homeostasis, giving rise to the symptoms of AD. Abeta1-42 interacts with the alpha7 subtype of the nicotinic acetylcholine receptor (alpha7 nAChR), which is widely expressed throughout the central and peripheral nervous systems, as well as in several nonneuronal loci, such as epithelial cells, lymphoid tissues, and peripheral blood lymphocytes. Western blot and autoradiographic analyses indicate that the alpha7 nAChR subunit protein is up-regulated in human brain samples from Alzheimer patients, as well as in animal models of AD (Dineley et al., 2001; Bednar et al., 2002), and might be involved in nicotine-mediated reduction of Abeta1-42 deposition (Hellstrom et al., 2004), although the nature of this relationship remains ill-defined. We have undertaken a semiquantitative histological evaluation of alpha7 nAChR expression in a mouse model of AD pathology, as well as a comparison of alpha7 nAChR levels in lymphocytes from AD patients and control subjects.



        

Title: Phytophthora genome sequences uncover evolutionary origins and mechanisms of pathogenesis
Tyler BM, Tripathy S, Zhang X, Dehal P, Jiang RH, Aerts A, Arredondo FD, Baxter L, Bensasson D and Boore JL <43 more author(s)> Tyler BM, Tripathy S, Zhang X, Dehal P, Jiang RH, Aerts A, Arredondo FD, Baxter L, Bensasson D, Beynon JL, Chapman J, Damasceno CM, Dorrance AE, Dou D, Dickerman AW, Dubchak IL, Garbelotto M, Gijzen M, Gordon SG, Govers F, Grunwald NJ, Huang W, Ivors KL, Jones RW, Kamoun S, Krampis K, Lamour KH, Lee MK, McDonald WH, Medina M, Meijer HJ, Nordberg EK, Maclean DJ, Ospina-Giraldo MD, Morris PF, Phuntumart V, Putnam NH, Rash S, Rose JK, Sakihama Y, Salamov AA, Savidor A, Scheuring CF, Smith BM, Sobral BW, Terry A, Torto-Alalibo TA, Win J, Xu Z, Zhang H, Grigoriev IV, Rokhsar DS, Boore JL (- 43)
Ref: Science, 313:1261, 2006 : PubMed
Abstract


ESTHER: Tyler_2006_Science_313_1261
PubMedSearch: Tyler 2006 Science 313 1261
PubMedID: 16946064
Gene_locus related to this paper: phyrm-h3ga89, phyrm-h3gbl6.1, phyrm-h3gbl6.2, phyrm-h3gbl7, phyrm-h3gdd4, phyrm-h3gl36, phyrm-h3gq42, phyrm-h3gx86, phyrm-h3gyi2, phyrm-h3gyi3, phyrm-h3gyi4, phyrm-h3h292, phyrm-h3h293, phyrm-h3h967, phyrm-h3hcf9, physp-g4ynp3, physp-g4yut6, physp-g4yut8, physp-g4yw23, physp-g4zis3, physp-g4zqe3, physp-g4zqe4, physp-g4zqf0, physp-g4zqn9, physp-g4zwy9, physp-g5a582, physp-g5a583, physp-g5aav9, phyrm-h3g9e7, physp-g4zwu9, phyrm-h3ggp1, physp-g4ztq5, physp-g4zwu8, physp-g4zwv7, physp-g4zwv6, physp-g4zwv0, physp-g4zwv8, phyrm-h3gp95, phyrm-h3g6r5, physp-g4zwv9, physp-g5a510, phyrm-h3glu3, physp-g5aci1, phyrm-h3h2d0, physp-g4ztb2, physp-g4yg47, phyrm-h3h2c9, physp-g4ztb3, phyrm-h3gvj3, phyrm-h3gy62, physp-g4yg46, physp-g4zdt9, phyrm-h3gdh5, physp-g4zm41, physp-g5abj7, phyrm-h3gz76, physp-g5a425, phyrm-h3h080, physp-g4ytv0, phyrm-h3gcw7

Abstract

Draft genome sequences have been determined for the soybean pathogen Phytophthora sojae and the sudden oak death pathogen Phytophthora ramorum. Oomycetes such as these Phytophthora species share the kingdom Stramenopila with photosynthetic algae such as diatoms, and the presence of many Phytophthora genes of probable phototroph origin supports a photosynthetic ancestry for the stramenopiles. Comparison of the two species' genomes reveals a rapid expansion and diversification of many protein families associated with plant infection such as hydrolases, ABC transporters, protein toxins, proteinase inhibitors, and, in particular, a superfamily of 700 proteins with similarity to known oomycete avirulence genes.



        

Title: Have cholinergic therapies reached their clinical boundary in Alzheimer's disease?
Jones RW
Ref: Int J Geriatr Psychiatry, 18:S7, 2003 : PubMed
Abstract


ESTHER: Jones_2003_Int.J.Geriatr.Psychiatry_18_S7
PubMedSearch: Jones 2003 Int.J.Geriatr.Psychiatry 18 S7
PubMedID: 12973745

Abstract

The cholinergic hypothesis suggests that Alzheimer's disease (AD) results from a selective loss in cholinergic neurons with decreased acetylcholine levels. Treatments that increase the level of acetylcholine would be expected to provide clinical benefit. Clinical trials of dietary precursors of acetylcholine and muscarinic receptor agonists have been unsuccessful. Further research is needed to confirm whether nicotine or nicotinic agonists are of value. The most successful approach has been to increase acetylcholine levels by inhibiting cholinesterase function. A number of cholinesterase inhibitors (ChEI) show clinical efficacy including phyostigmine but it is poorly tolerated. Tacrine, the first ChEI to be licensed for AD, needs frequent administration and causes a specific reversible hepatotoxicity. Three ChEI, donepezil, rivastigmine and galantamine are widely available. They are effective in mild to moderate (and possibly severe) AD. Tolerability is improved by slow dose titration and there are a significant number of non-responders. Donepezil appears to be effective, the simplest to use and the best tolerated. Rivastigmine is effective but less well tolerated: galantamine is also very effective with intermediate tolerability. Although there are pharmacological differences between the three compounds, it remains uncertain whether these are clinically relevant. There are still unanswered questions. It is difficult to predict who will respond to the drugs and it is unclear how long treatment benefits last. At present there are little data to support the suggestion of activity beyond symptomatic benefit. Trials are also being conducted in Mild Cognitive Impairment, other dementias and other conditions where cognitive impairment is a problem.



        

Title: Advertisements for donepezil. Prices charged for private prescriptions for donepezil show huge variation
Jones RW, Mann JB, Saunders SA
Ref: BMJ, 315:1624, 1997 : PubMed
Abstract


ESTHER: Jones_1997_BMJ_315_1624
PubMedSearch: Jones 1997 BMJ 315 1624
PubMedID: 9437306
Inhibitor(s) related to this paper: Aricept~Donepezil~E2020