806 articles - 10.09.10
1: Biochem Biophys Res Commun. 2010 Jul 23;398(2):212-6. Epub 2010 Jun 18.
Chen J, Yu H, Sun K, Song W, Bai Y, Yang T, Song Y, Zhang Y, Hui R.
Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education, FuWai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.
Angiopoietin-2 has been reported to regulate the inflammation process, which is associated with recurrence of stroke. The purpose of this study was to test the hypothesis that plasma levels of angiopoietin-2 and variants of angiopoietin-2 will confer risk of stroke recurrence. The association of plasma angiopoietin-2 (determined by using ELISA) and the variants in angiopoietin-2 promoter with stroke recurrence was tested in 1735 patients with stroke of three subtypes, lacunar infarct (n=475), atherothrombotic (n=794) and hemorrhage (n=466), for a period of following-up 4.5 years (mean), the association was evaluated by using Kaplan-Meier analysis and the Cox regression models. We found that angiopoietin-2 levels were associated with risk of stroke recurrence in lacunar infarct patients. Taking the lowest quartile as reference, the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for stroke recurrence was 1.48 (0.74-2.95) for the second quartile, 2.56 (1.35-4.86) for the third and 2.15 (1.11-4.17) for the fourth. Allele T of rs3739391 in angiopoietin-2 promoter was associated with elevated angiopoietin-2 levels and increased risk of stroke recurrence in patients with lacunar infarct with HR 1.67 (1.06-2.63) relative to the allele C, but neither in those with atherothrombotic nor in those with hemorrhagic stroke. Our results indicate that both angiopoietin-2 and allele T of rs3739391 might be the risk marker for stroke recurrence in the patients with lacunar infarction. These findings may help to improve future prevention or therapy strategies for stroke. Even some conventional risk factors have been identified responsible for stroke recurrence, but these factors could not fully explain all the recurrent stroke events. Our study opens a new page for the first time that angiopoietin/tie2 pathway has a potential role in lacunar stroke recurrence. Since several strategies are available for blocking or neutralizing plasma angiopoietin-2, especially eicosapentaenoic acid rich in sea food. Our finding obviously has its clinical implication if it was proved by large, prospective clinical studies. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20599737&dopt=ExternalLink
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PMID: 20599737 [PubMed - indexed for MEDLINE]2: Psychiatr Danub. 2010 Jun;22(2):286-8.
Skocic M, Dujmovic J, Jevtovic S, Jakovljevic M.
Department of Psychiatry, University Hospital Centre Zagreb, 10000 Zagreb, Croatia. milena.skocic@gmail.com
Huntington's disease (HD) is a neurodegenerative, autosomal dominant disease that manifests with a triad of symptom clusters including movement disorder, cognitive impairment and psychiatric symptoms. We present a patient with HD who, prior to developing neurological signs and symptoms, had been exposed to war trauma and had developed posttraumatic stress disorder. Fifteen years later he manifested with dysarthria, difficulties with swallowing and involuntary movement. What brought him to psychiatrist was a heteroanamnestically noticed change in personality with irritable mood, impulsivity, aggressive outbursts in behavior and delusional ideation. Therapy was stared with haloperidol, but patient developed severe extrapiramidal side effects. Subsequent treatment with olanzapine, diazepam and omega 3 fatty acids lead to mood stabilization and better impulse control with even some improvement in motoric symptoms. To our knowledge, this is the first case report on combat related PTSD as psychiatric disorder manifested prior to HD. We discuss a possible influence of psychological stress disorder on severity of psychiatric symptoms in the HD. The importance of personalized approach in both psychopharmacological and psychotherapeutical treatment of patients with HD is emphasized. If the influence of environmental stress on the psychiatric phenotype of the disease should be confirmed by clinical trials and further studies, both screening methods and interventions aimed to reduce psychological stress in carriers of Huntington gene could be considered.
Publication Types: Case Reports
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PMID: 20562764 [PubMed - indexed for MEDLINE]3: J Vasc Surg. 2010 Jul;52(1):62-8.
Mahe G, Ronziere T, Laviolle B, Golfier V, Cochery T, De Bray JM, Paillard F.
Laboratory of Vascular investigations, Centre National de la Recherche Scientifique UMR6214/INSERM Unite 771, Rennes, France.
OBJECTIVE: Ischemic strokes represent more than 80% of total strokes in Western countries. The influence of dietary factors on ischemic stroke risk is debated mainly because available data are limited. Our objective was to compare the dietary pattern of symptomatic ischemic stroke patients under 65 years old with control subjects using a validated 14-item food frequency questionnaire (FFQ). We also compared symptomatic ischemic stroke patients with carotid atherosclerosis with those without according to the presence or the absence of carotid plaque defined by duplex scanning. METHODS: This was a case-control multi-center study that took place in one University hospital and two general hospitals in France. One hundred twenty-four symptomatic ischemic stroke patients (confirmation by a neurologist and imaging; 66% smokers) and 50 controls (34% smokers) without any known cardiovascular disease or previous nutritional advice were included. The main outcome measure(s) were intake scores for saturated (SFA), monounsaturated (MUFA), Omega-3 polyunsaturated (Omega-3 PUFA), and Omega-6 polyunsaturated fatty acids (Omega-6PUFA). Fruit and vegetables and an overall cardiovascular dietary score were evaluated with the FFQ. The overall cardiovascular score is calculated as (MUFA + Omega-3 PUFA + fruits and vegetables) - (SFA) scores. RESULTS: Compared with controls, ischemic stroke patients had a higher SFA score (6.6 +/- 3.0 vs 4.9 +/- 2.7; P < .001), lower scores of MUFA (0.8 +/- 0.9 vs 1.5 +/- 1.2; P < .001), Omega-3 PUFA (1.7 +/- 1.6 vs 2.2 +/- 1.5; P = .013), Omega-6PUFA (2.6 +/- 2.5 vs 3.9 +/- 2.7; P = .002), fruit and vegetables (2.9 +/- 1.7 vs 3.8 +/- 1.6; P = .005), and a lower overall dietary score (-1.2 +/- 5.0 vs 2.5 +/- 4.4; P < .001). These results remained statistically significant after adjustment for age, gender, and smoking status. Ischemic stroke patients with carotid atherosclerosis (n = 54) had a worse overall cardiovascular dietary score than those without (n = 68): -2.2 +/- 4.4 vs -0.2 +/- 5.2; P = .024. CONCLUSION: Compared with controls, ischemic stroke patients, especially those with carotid atherosclerosis, have an unfavorable dietary pattern (high SFA, low fruit and vegetables, and Omega-3 PUFA consumptions) that may have been a facilitating condition of the ischemic stroke. Dietary recommendations of a healthy diet should be useful in ischemic stroke prevention, especially in patients with cardiovascular risk factors. Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Publication Types: Multicenter Study
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PMID: 20537496 [PubMed - indexed for MEDLINE]4: Am J Clin Nutr. 2010 Aug;92(2):416-21. Epub 2010 Jun 9.
Gopinath B, Flood VM, Rochtchina E, McMahon CM, Mitchell P.
Centre for Vision Research, Department of Ophthalmology, and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
BACKGROUND: Identification of modifiable risk factors that could prevent or slow the development of age-related hearing loss (presbycusis) would be valuable. Dietary polyunsaturated fatty acid (PUFA) intake may be related to age-related hearing loss. OBJECTIVE: We aimed to determine the association between dietary intakes of omega-3 (n-3) PUFAs and fish and the risk of presbycusis. DESIGN: The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss (1997-1999 to 2002-2004). We collected dietary data by using a semiquantitative food-frequency questionnaire and calculated PUFA and fish intakes. In 2956 participants (aged > or =50 y), we measured presbycusis, which we defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz >25 decibels of hearing loss. RESULTS: There was an inverse association between total n-3 PUFA intake and prevalent hearing loss [odds ratio (OR) per SD increase in energy-adjusted n-3 PUFAs: 0.89; 95% CI: 0.81, 0.99]. There was an inverse association between long-chain n-3 PUFAs and incident hearing loss (OR per SD increase in long-chain n-3 PUFAs: 0.76; 95% CI: 0.60, 0.97). Participants who had > or =2 servings of fish/wk compared with participants who had <1 serving of fish/wk had a significantly reduced risk (42%) of developing presbycusis at follow-up (multivariate-adjusted OR: 0.58; 95% CI: 0.35, 0.95). There was an association between consumption of > or =1 to <2 servings/wk of fish and a reduced risk of a progression of hearing loss (OR: 0.53; 95% CI: 0.32, 0.88). CONCLUSIONS: There was an inverse association between higher intakes of long-chain n-3 PUFAs and regular weekly consumption of fish and hearing loss. Dietary intervention with n-3 PUFAs could prevent or delay the development of age-related hearing loss.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20534742&dopt=ExternalLink
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PMID: 20534742 [PubMed - indexed for MEDLINE]5: Biol Pharm Bull. 2010;33(6):1070-2.
Nakamoto K, Nishinaka T, Mankura M, Fujita-Hamabe W, Tokuyama S.
Department of Clinical Pharmacy, Kobe Gakuin University, School of Pharmaceutical Sciences, Kobe, Japan.
Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (n-3 PUFAs), is an essential polyunsaturated fatty acid in the central nervous system, and possesses many physiological functions in neurodegenerative diseases. Previously, there are some reports that n-3 PUFAs contribute to pain relief. As the antinociceptive effect of DHA alone has not been reported, this study examined the antinociceptive effect of DHA on various pain stimuli. To evaluate the antinociceptive effect of DHA on thermal and chemical nociception, we employed the tail flick test, acetic acid writhing test and formalin test in mice. DHA was orally administrated at 5, 15 and 25 mmol/kg at 30 min before measurement. DHA administration dose-dependently exerted an antinociceptive effect against thermal and chemical stimulation in comparison to the control olive oil administration. These effects of DHA were abolished when mice were pretreated with naloxone, an opioid receptor antagonist. These findings suggest that DHA has opiod receptor-mediated pain control activities, and may provide valuable information towards an advanced therapeutic approach for pain control.
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PMID: 20522981 [PubMed - in process]6: Prim Care. 2010 Jun;37(2):213-36.
Larzelere MM, Campbell JS, Robertson M.
Department of Family Medicine, Louisiana State University Health Sciences Center, 200 West Esplanade Avenue, Suite 409, Kenner, LA 70065, USA. mlarze@lsuhsc.edu
Evidence on the use of complementary and alternative medicine (CAM) modalities in the treatment of depression, anxiety, sleep disorders, and attention-deficit/hyperactivity disorder (ADHD) is reviewed. There is strong evidence to support the use of St. John's wort (SJW) in depression, and growing support for the use of omega-3 fatty acids and S-adenosyl-l-methionine as potential adjuncts to conventional therapies. Evidence is insufficient to support the antidepressant benefit of dehydroepiandrosterone, inositol, folate, and saffron. Only kava has high-quality evidence for use in the treatment of anxiety disorders, and its use is discouraged because of safety concerns. There is preliminary supportive evidence for valerian and inositol treatment of anxiety, but SJW and passionflower have achieved little research support. Melatonin is likely to be useful in treating delayed sleep phase, jet lag, or shift work, but there is little evidence for the benefit of valerian compared with placebo. There are currently no evidence-supported CAM treatments for ADHD (zinc and omega-3 fatty acids are reviewed). Copyright 2010 Elsevier Inc. All rights reserved.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20493333&dopt=ExternalLink
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PMID: 20493333 [PubMed - indexed for MEDLINE]7: Expert Rev Clin Immunol. 2010 May;6(3):381-95.
Yadav V, Shinto L, Bourdette D.
Department of Neurology L226, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. yadavv@ohsu.edu
Multiple sclerosis (MS) is a chronic disabling disease of the CNS that affects people during early adulthood. Despite several US FDA-approved medications, the treatment options in MS are limited. Many people with MS explore complementary and alternative medicine (CAM) treatments to help control their MS and treat their symptoms. Surveys suggest that up to 70% of people with MS have tried one or more CAM treatment for their MS. People with MS using CAM generally report deriving some benefit from the therapies. The CAM therapies most frequently used include diet, omega-3 fatty acids and antioxidants. There is very limited research evaluating the safety and effectiveness of CAM in MS. The most promising among CAM therapies that warrant further investigation are a low-fat diet, omega-3 fatty acids, lipoic acid and vitamin D supplementation as potential anti-inflammatory and neuroprotective agents in both relapsing and progressive forms of MS. There is very limited research evaluating the safety and effectiveness of CAM in MS. However, in recent years, the NIH and the National MS Society have been actively supporting the research in this very important area.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20441425&dopt=ExternalLink
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PMID: 20441425 [PubMed - indexed for MEDLINE]8: Curr Psychiatry Rep. 2010 Jun;12(3):255-64.
Sher Y, Lolak S, Maldonado JR.
Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, 401 Quarry Road, Suite 2336, Stanford, CA 94305, USA.
Depression and heart disease affect millions of people worldwide. Studies have shown that depression is a significant risk factor for new heart disease and that it increases morbidity and mortality in established heart disease. Many hypothesized and studied mechanisms have linked depression and heart disease, including serotonergic pathway and platelet dysfunction, inflammation, autonomic nervous system and hypothalamic-pituitary-adrenal axis imbalance, and psychosocial factors. Although the treatment of depression in cardiac patients has been shown to be safe and modestly efficacious, it has yet to translate into reduced cardiovascular morbidity and mortality. Understanding the impact and mechanisms behind the association of depression and heart disease may allow for the development of treatments aimed at altering the devastating consequences caused by these comorbid illnesses.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20425289&dopt=ExternalLink
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PMID: 20425289 [PubMed - indexed for MEDLINE]9: J Nutr Health Aging. 2010;14(5):347-51.
Dullemeijer C, Verhoef P, Brouwer IA, Kok FJ, Brummer RJ, Durga J.
Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, the Netherlands. Carla.Dullemeijer@wur.nl
OBJECTIVES: Age-related hearing loss is a common social and health problem in the older adult population. Up until now, very little scientific attention has been given to the potential role of fatty acids in age-related hearing loss. In this study we investigated whether plasma very long-chain n-3 polyunsaturated fatty acids (PUFAs) are associated with age-related hearing loss over three years. DESIGN: Cross-sectional and 3-year longitudinal analyses. SETTING: Wageningen, the Netherlands. PARTICIPANTS: 720 men and postmenopausal women (50-70 years of age) without middle ear dysfunction or unilateral hearing loss. MEASUREMENTS: Fatty acid proportions were measured in plasma cholesteryl esters. Hearing thresholds (in decibels, dB) at baseline and after three years were measured with pure-tone audiometry. Hearing loss was calculated as the increase in mean hearing thresholds in the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies over three years. RESULTS: Subjects in the highest quartile of plasma very long-chain n-3 PUFA had less hearing loss in the low frequencies over three years than subjects in the lowest quartile (p < 0.01, ANCOVA, difference in mean adjusted hearing thresholds= -1.2 dB). There were no significant differences between the quartiles of plasma very long-chain n-3 PUFA in hearing loss in the high frequencies (p=0.49, ANCOVA). These associations are adjusted for baseline mean hearing thresholds, age, sex, level of education and alcohol consumption. CONCLUSION: This study is the first to show an inverse association between plasma very long-chain n-3 PUFAs and age-related hearing loss. These results are encouraging, but require confirmation from future studies.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20424800&dopt=ExternalLink
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PMID: 20424800 [PubMed - indexed for MEDLINE]10: Expert Rev Neurother. 2010 May;10(5):693-702.
Sobow T.
Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Czechoslowacka 8/10, Lodz, Poland. tomasz.sobow@umed.lodz.pl
Currently approved medications to treat cognitive deficits in Alzheimer's disease are targeting relatively late neurotransmission alterations and, thus, new approaches are needed to improve the observed modest efficacy. Employing various combinations of existing drugs is one way to achieve this aim. We can attempt to boost the clinical effects by adding drugs with different modes of action, or by adding a compound that is not neurotransmitter-based and not directly symptomatic, which may result in achieving disease progression modification. Recent studies with add-on therapies in Alzheimer's disease, apart from expanding our clinical knowledge, have also provided some new insights to guide future studies and therapeutic approaches. One such lesson is the critical necessity for precise characterization of subjects recruited to the studies, preferably with the use of biomarkers. Currently, even the best studied combination (memantine with a cholinesterase inhibitor) still requires further detailed trials to elucidate its usefulness at different disease stages, in patients with comorbidities, with or without the use of other concomitant medications.
Publication Types: Review
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PMID: 20420490 [PubMed - indexed for MEDLINE]11: J Alzheimers Dis. 2010;20(3):737-47.
Morley JE, Banks WA.
GRECC, VA Medical Center and Saint Louis University School of Medicine, St. Louis, MO, USA.
Cholesterol, omega-3 fatty acids, and triglycerides have been postulated to play roles in affecting cognition in Alzheimer's disease (AD), the elderly, and obesity. Animal, human epidemiological, and in vitro studies each suggest an important role for cholesterol in the regulation of amyloid-beta (Abeta) protein and the pathogenesis of AD. In contrast, well controlled studies have failed to show an effect of cholesterol lowering with statins on cognition, indicating that the cholesterol effect is spurious or indirect, possibly mediated through other lipids. Administration of diedocosahexanoic acid (DHA), a dietary omega-3 fatty acid derived primarily from fish and plants, improves cognition and reduces lipid peroxidation in animals, including in mouse models of AD. DHA also blocks Abeta-mediated tau phosphorylation. In humans, fish consumption or administration of DHA has been associated with cognitive improvement in many, but not all, studies. Both human and animal studies show that obesity is associated with cognitive impairments and that lowering triglycerides improves cognition. Administration of triglycerides to mice decreases learning and memory and impairs long-term potential. The effect of triglycerides may be mediated in part by inducing resistance to positive cognitive features of gastrointestinal hormones such as leptin. Overall, these studies strongly suggest that some lipids affect cognition in AD, the elderly, and obesity through a variety of mechanisms yet to be fully defined.
Publication Types: Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20413879&dopt=ExternalLink
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PMID: 20413879 [PubMed - indexed for MEDLINE]12: J Alzheimers Dis. 2010;20(3):915-24.
Middleton LE, Yaffe K.
Heart and Stroke Foundation Centre for Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. Middleton l@hotmail.com
The prevalence of dementia is expected to increase dramatically over the upcoming decades due to the aging population. Since treatment is still short of a cure, preventative strategies are of the utmost importance. Stimulating activity (cognitive, physical, and social), vascular risk factors, and diet may be important in preventative strategies. Dementia risk may be modified by participation in stimulating activities. One study suggested that the cognitive, physical, and social components of activity were of equal importance to cognitive outcomes. However, while exercise interventions appear to benefit global cognition, the benefits from cognitive training appear to be domain specific. People with vascular risk factors (hypertension, diabetes, dyslipidemia, and obesity) appear to be at higher risk for dementia than those without in observational and clinical trials. Controlled trials suggest that vascular risk management via some pharmaceutical interventions may benefit cognition, though results are inconsistent. Finally, people who adhere to a Mediterranean diet or who have high intake of antioxidants and omega-3 fatty acids have reduced likelihood of dementia in observational studies. However, supplementation in controlled trials has not generally proved successful at improving cognitive outcomes. A single supplement may be insufficient to prevent dementia; it may be that the overall diet is more important. Future large randomized controlled studies should examine whether interventions can reduce the risk of dementia and whether combining cognitive, physical, and social activity, vascular risk reduction, and dietary interventions might have additive or multiplicative effects.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20413867&dopt=ExternalLink
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PMID: 20413867 [PubMed - indexed for MEDLINE]13: BMC Dermatol. 2010 Apr 22;10:3.
Klokk M, Gotestam KG, Mykletun A.
Department of Adult Psychiatry, Aalesund Hospital, Helse Sunnmore HF, N-6026 Aalesund, Norway. ma-klokk@online.no
BACKGROUND: The association between anxiety and depression, and eczema is well known in the literature, but factors underlying this association remain unclear. Low levels of omega-3 fatty acids and female gender have been found to be associated with both depression and eczema. Somatization and health anxiety are known to be associated with anxiety and depression, further, somatization symptoms and health anxiety have also been found in several dermatological conditions. Accordingly, omega-3 fatty acid supplement, female gender, somatization and health anxiety are possible contributing factors in the association between anxiety and depression, and eczema. The aim of the study is to examine the relevance of proposed contributing factors for the association between anxiety and depression, and eczema, including, omega-3 fatty acid supplement, female gender, health anxiety and somatization. METHODS: Anxiety and depression was measured in the general population (n = 15715) employing the Hospital Anxiety and Depression Scale (HADS). Information on eczema, female gender, omega-3 fatty acid supplement, health anxiety and somatization was obtained by self-report. RESULTS: Somatization and health anxiety accounted for more than half of the association between anxiety/depression, and eczema, while the other factors examined were of minor relevance for the association of interest. CONCLUSIONS: We found no support for female gender and omega-3 fatty acid supplement as contributing factors in the association between anxiety/depression, and eczema. Somatization and health anxiety accounted for about half of the association between anxiety/depression, and eczema, somatization contributed most. The association between anxiety/depression, and eczema was insignificant after adjustment for somatization and health anxiety. Biological mechanisms underlying the mediating effect of somatization are yet to be revealed.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20412596&dopt=ExternalLink
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PMID: 20412596 [PubMed - indexed for MEDLINE]14: Clin Interv Aging. 2010 Apr 7;5:45-61.
Jicha GA, Markesbery WR.
University of Kentucky, Alzheimer's Disease Center and the Sanders-Brown Center on Aging University of Kentucky College of Medicine, Lexington, KY 40536-0230, USA. gajich2@email.uky.edu
Omega-3 fatty acids are essential for brain growth and development. They play an important role throughout life, as critical modulators of neuronal function and regulation of oxidative stress mechanisms, in brain health and disease. Docosahexanoic acid (DHA), the major omega-3 fatty acid found in neurons, has taken on a central role as a target for therapeutic intervention in Alzheimer's disease (AD). A plethora of in vitro, animal model, and human data, gathered over the past decade, highlight the important role DHA may play in the development of a variety of neurological and psychiatric disorders, including AD. Cross sectional and prospective cohort data have demonstrated that reduced dietary intake or low brain levels of DHA are associated with accelerated cognitive decline or the development of incipient dementia, including AD. Several clinical trials investigating the effects of omega-3 fatty acid supplementation in AD have been completed and all failed to demonstrate its efficacy in the treatment of AD. However, these trials produced intriguing data suggesting that the beneficial effects of omega-3 fatty acid supplementation may depend on the stage of disease, other dietary mediators, and apolipoprotein E status.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20396634&dopt=ExternalLink
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PMID: 20396634 [PubMed - indexed for MEDLINE]15: Arch Neurol. 2010 Jun;67(6):699-706. Epub 2010 Apr 12.
Gu Y, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N.
The Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
OBJECTIVE: To assess the association between food combination and Alzheimer disease (AD) risk. Because foods are not consumed in isolation, dietary pattern (DP) analysis of food combination, taking into account the interactions among food components, may offer methodological advantages. DESIGN: Prospective cohort study. SETTING: Northern Manhattan, New York, New York. PATIENTS OR OTHER PARTICIPANTS: Two thousand one hundred forty-eight community-based elderly subjects (aged > or = 65 years) without dementia in New York provided dietary information and were prospectively evaluated with the same standardized neurological and neuropsychological measures approximately every 1.5 years. Using reduced rank regression, we calculated DPs based on their ability to explain variation in 7 potentially AD-related nutrients: saturated fatty acids, monounsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E, vitamin B(12), and folate. The associations of reduced rank regression-derived DPs with AD risk were then examined using a Cox proportional hazards model. Main Outcome Measure Incident AD risk. RESULTS: Two hundred fifty-three subjects developed AD during a follow-up of 3.9 years. We identified a DP strongly associated with lower AD risk: compared with subjects in the lowest tertile of adherence to this pattern, the AD hazard ratio (95% confidence interval) for subjects in the highest DP tertile was 0.62 (0.43-0.89) after multivariable adjustment (P for trend = .01). This DP was characterized by higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter. CONCLUSION: Simultaneous consideration of previous knowledge regarding potentially AD-related nutrients and multiple food groups can aid in identifying food combinations that are associated with AD risk.
Publication Types: Research Support, N.I.H., Extramural
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20385883&dopt=ExternalLink
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PMID: 20385883 [PubMed - indexed for MEDLINE]16: Pharmazie. 2010 Mar;65(3):231-2.
Du J, Zhang L, Liu S, Wang Z.
Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing, P.R. China.
Previous results show that treatment with saturated fatty acids, such as palmitic acid (PA), induces the pathology of Alzheimer's disease (AD), while treatment with polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), protects against AD pathology. However, the pharmacological mechanism underlying these opposite effects of fatty acids on AD is not well understood. Here, we show that PA treatment significantly reduced the expression of insulin-degrading enzyme (IDE), an important protease responsible for the degradation of amyloid-beta (A beta) in neural cells, while incubation with DHA up-regulated IDE levels in primary hippocampal neurons. Moreover, pre-incubation with PA attenuated the DHA-induced IDE expression. Taken together, these results suggest the opposite effects of saturated fatty acids and polyunsaturated fatty acids on the expression of IDE, indicating a novel mechanism underlying the pharmacological function of fatty acids in AD intervention.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20383947&dopt=ExternalLink
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PMID: 20383947 [PubMed - indexed for MEDLINE]17: Nat Med. 2010 May;16(5):592-7, 1p following 597. Epub 2010 Apr 11.
Xu ZZ, Zhang L, Liu T, Park JY, Berta T, Yang R, Serhan CN, Ji RR.
Department of Anesthesiology, Sensory Plasticity Laboratory, Pain Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Inflammatory pain, such as arthritis pain, is a growing health problem. Inflammatory pain is generally treated with opioids and cyclooxygenase (COX) inhibitors, but both are limited by side effects. Recently, resolvins, a unique family of lipid mediators, including RvE1 and RvD1 derived from omega-3 polyunsaturated fatty acid, have shown marked potency in treating disease conditions associated with inflammation. Here we report that peripheral (intraplantar) or spinal (intrathecal) administration of RvE1 or RvD1 in mice potently reduces inflammatory pain behaviors induced by intraplantar injection of formalin, carrageenan or complete Freund's adjuvant (CFA), without affecting basal pain perception. Intrathecal RvE1 injection also inhibits spontaneous pain and heat and mechanical hypersensitivity evoked by intrathecal capsaicin and tumor necrosis factor-alpha (TNF-alpha). RvE1 has anti-inflammatory activity by reducing neutrophil infiltration, paw edema and proinflammatory cytokine expression. RvE1 also abolishes transient receptor potential vanilloid subtype-1 (TRPV1)- and TNF-alpha-induced excitatory postsynaptic current increases and TNF-alpha-evoked N-methyl-D-aspartic acid (NMDA) receptor hyperactivity in spinal dorsal horn neurons via inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway. Thus, we show a previously unknown role for resolvins in normalizing the spinal synaptic plasticity that has been implicated in generating pain hypersensitivity. Given the potency of resolvins and the well-known side effects of opioids and COX inhibitors, resolvins may represent new analgesics for treating inflammatory pain.
Publication Types: Research Support, N.I.H., Extramural
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20383154&dopt=ExternalLink
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PMID: 20383154 [PubMed - indexed for MEDLINE]18: Expert Opin Drug Metab Toxicol. 2010 May;6(5):555-70.
Tengstrand EA, Miwa GT, Hsieh FY.
Nextcea, Inc., 600 West Cummings Park, #6375, Woburn, MA 01801, USA.
IMPORTANCE TO THE FIELD: Drug-induced phospholipidosis (PL) is a phospholipid storage disorder characterized by the accumulation of multi-lamellar bodies (myeloid bodies) in tissues. A major unanswered question is whether PL represents a benign adaptive response, symptom or early event in drug toxicity. The absence of a non-invasive biomarker to monitor tissue PL has made it difficult to determine the prevalence and implications of PL in the clinic. As a result, the interpretation of PL in risk assessment remains uncertain in preclinical and clinical drug development. AREAS COVERED IN THIS REVIEW: This review describes the rationale for bis(monoacylglycerol)phosphate (BMP) as a biomarker of PL and explores the potential links between PL and the toxicities of drugs. WHAT THE READER WILL GAIN: The similarities between the hypothesized roles of BMP in PL and Niemann-Pick type C disease are discussed. The potential implications of PL for cellular function are described in the context of drug-induced QT prolongation, myopathy and renal toxicity. TAKE HOME MESSAGE: A specific species of BMP, di-docosahexaenoyl-BMP, should be investigated further as a non-invasive biomarker to monitor the onset and time course of PL and to better understand the functional consequences which could contribute to the toxicities of drugs.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20370598&dopt=ExternalLink
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PMID: 20370598 [PubMed - indexed for MEDLINE]19: Acta Pol Pharm. 2010 Mar-Apr;67(2):129-36.
Marszalek R, Pisklak M, Jankowski W, Lukaszkiewicz J, Horsztynski D, Wawer I.
Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warszawa, Poland.
1H HR MAS (high resolution magic angle spinning) NMR is a promising tool in the in vitro characterisation of brain tumors. Brain tissue samples were collected from patients with intracranial tumors during surgery, frozen and lyophilized. The analysis of solid samples was performed by high-speed rotation (33 kHz) H MAS NMR. The most intense resonances arise from lipids (methylene mid-chain and methyl carbons of fatty acids). 1H MAS spectra obtained from the same histological type of brain tumors are similar; spectra of glioblastomas were different from those of meningiomas. 1H and 13C NMR solution spectra of lipid extracts confirmed the presence of aliphatic chains fatty acids and cholesterol as major constituents. Biochemical information on liberated fatty acid composition was obtained by gas-chromatography (GC). The glioma content of the linoleic acid (18:2n6) was found to be greater, whereas the level of docosahexaenoic acid (22:6n3) was significantly reduced.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20369789&dopt=ExternalLink
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PMID: 20369789 [PubMed - indexed for MEDLINE]20: Am J Obstet Gynecol. 2010 May;202(5):469.e1-6. Epub 2010 Mar 31.
Berman DR, Liu YQ, Barks J, Mozurkewich E.
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI.
OBJECTIVE: Lipopolysaccharide pretreatment potentiates hypoxic ischemic injury. We hypothesized that docosahexaenoic acid pretreatment would improve function and reduce brain volume loss in this rat model of perinatal brain injury and inflammation. STUDY DESIGN: Seven-day-old rats were divided into 3 groups: intraperitoneal docosahexaenoic acid 1 mg/kg and lipopolysaccharide 0.1 mg/kg, 25% albumin and lipopolysaccharide, and normal saline. Injections were given 2.5 hours before carotid ligation, followed by 90 minutes 8% O2. Rats underwent sensorimotor function testing and brain volume loss assessment on postnatal day 14. RESULTS: Docosahexaenoic acid pretreatment improved vibrissae forepaw placing scores compared with albumin/lipopolysaccharide (mean+/-standard deviation weighted score/20: 17.72+/-0.92 docosahexaenoic acid/lipopolysaccharide vs 13.83+/-0.82 albumin/lipopolysaccharide; P<.007). Albumin/lipopolysaccharide rats scores were worse than those of the normal saline/normal saline rats (13.83+/-0.82 vs 17.21+/-0.71; P=.076). No significant differences in brain volume loss were observed among groups. CONCLUSION: Lipopolysaccharide inflammatory stimulation in conjunction with hypoxic ischemic resulted in poorer function than hypoxic ischemic alone. Docosahexaenoic acid pretreatment had significantly improved function in neonatal rats exposed to lipopolysaccharide and hypoxic ischemic. Copyright (c) 2010 Mosby, Inc. All rights reserved.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20356570&dopt=ExternalLink
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PMID: 20356570 [PubMed - indexed for MEDLINE]