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Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women  [PDF]
Erin McGlade, Allison Locatelli, Julia Hardy, Toshikazu Kamiya, Masahiko Morita, Koji Morishita, Yoichiro Sugimura, Deborah Yurgelun-Todd
Food and Nutrition Sciences (FNS) , 2012, DOI: 10.4236/fns.2012.36103
Abstract: Objectives: The present study assessed the potential cognitive-enhancing effects of citicoline, a dietary supplement, in healthy adult women. Specifically, it was hypothesized that citicoline supplementation would be associated with improved attention compared to placebo. Methods: The investigation was a double-blind, randomized, placebo-controlled three-arm study. Sixty healthy adult women ages 40 - 60 completed a clinical screening visit, including a medical exam. After study enrollment each subject was randomly assigned to one of three groups: a daily oral dose of 250 mg citicoline, 500 mg citicoline, or placebo for 28 days. Participants were evaluated with the Continuous Performance Test II (CPT-II), a measure sensitive to attentional function, during a baseline visit and 28 days after baseline. Results: All 60 participants were included in the analyses, which included an ANOVA with Tukey’s post-hoc tests and t-tests. After 28 days of supplementation, individuals in the 250 mg group made fewer omission (p = 0.04) and commission (p = 0.03) errors compared to those in the placebo group. Individuals in the 500 mg group made significantly fewer commission errors compared to those in the placebo group (p = 0.03) and trended toward making fewer omission errors (p = 0.07). Conclusion: After 28 days of daily citicoline supplementation, participants who were administered either the 250 mg or the 500 mg citicoline doses showed significantly better ability to produce correct responses on the CPT-II, likely due to improved cognitive inhibition. Our findings suggest that citicoline may improve attentional performance in middle-aged women and may ameliorate attentional deficits associated with central nervous system disorders.
Malipatil S.M
International Journal of Pharmaceutical Research and Development , 2010,
Abstract: Two simple and sensitive spectrophotometric methods in UV and visible region were developed for the estimation of Citicoline in pharmaceutical dosage forms. Method A is showing absorption maximum at 272 nm in distilled water. Method B is based on the reaction of 3-methyl-2-benzothiazolin-2-one hydrazone (MBTH) with Citicoline in presence of ferric chloride solution to yield a yellow orange colour. This colour has a characteristic light absorption in the visible region with absorption maximum at 625 nm. These methods obey Beer's law in the concentration range of 10-70 μg/ml and 50-250 μg/ml respectively. The proposed method is precise, accurate and reproducible. It can be extended to the analysis of Citicoline in tablet formulations.
Role of Citicoline in Ischaemic Stroke
S.K Gupta,Anupriya Gupta, Deeraj Gondhotra, Ajay Gupta, Shruti Gupta
JK Science : Journal of Medical Education & Research , 2008,
Abstract: Stroke or cerebrovascular accident is the thirdcommonest cause of death and the leading cause of longtermdisability in the world. Citicoline is a neuroprotectiveagent that serves as a choline donor and intermediate inthe biosynthesis of phospholipids. Citicoline reducesischaemic injury in the CNS by preserving membranephospholipids, chiefly phosphatidylcholine. Citicoline isfound to be a drug of choice due to its proven safety andefficacy in patients with stroke.However, the clinicalexperience will help to establish its clinical supermacy inthe coming times.
Therapeutic Applications of Citicoline and Piracetam as Fixed Dose Combination
R. C. Doijad
Asian Journal of Biomedical and Pharmaceutical Sciences , 2012,
Abstract: Combination of citicoline and piracetam is available in market as fixed dosecombination in film coated tablet with dose of citicoline 500 mg andpiracetam 800 mg. It has been approved by DCGI in the year 2010. Thiscombination is chemically and pharmalogically safe. The combination isgenerally prescribed for memory enhancement, neurological and cognitivedisorder, Parkinsonism and Alzheimer disorder. These drugs are nutrientsand acts as cognition enhancing supplements, and are recommended as partof treatment regimens at some aging clinics. Citicoline has been shown toimprove memory and other cognitive functions in patients with chroniccerebrovascular disease or dementia and in old people suffering frommemory deficit. Piracetam is a drug which enhances cognition and memory,slows brain aging, increases oxygen and blood flow to the brain, improvesAlzheimer's and aids in stroke recovery and related conditions. Piracetam andciticoline stimulate thought without peripheral nervous system stimulation.Citicoline alone gives a lift and then a depression but not when taken alongwith piracetam. Whereas piracetam induced headache is reduced whentaken along with citicoline. This review highlights need for combination ofciticoline and piracetam their pharmacological and therapeutic issues andapplication.
G. Raveendra babu*
International Journal of Pharmacy and Technology , 2010,
Abstract: A validated, specific, stability indicating reversed-phase liquid chromatographic method has been developed for quantitative analysis of citicoline and its related substances in oral drops formulation. Forced degradation studies were performed using acidic, basic and oxidizing conditions, and thermal and photolytic stress, to show the stability indicating power of the method. The method was optimized by analysis of the samples generated during the forced degradation studies and sample solutions spiked with the impurities.Good resolution between the analyte peak and peaks corresponding to process related impurities and degradation products was achieved on a Whatman Partisil SAX C18 (250X4.6mm, 10μm) column with amobile phase constituted of phosphate buffer and acetonitrile (40:60 % v/v) and further comprises of 1gm of 1-hexane sulphonic acid sodium salt. The pH of the mobile phase was adjusted to 3.4 with ortho phosphoric acid. Detection was performed at 280 nm. Citicoline sodium was subjected to stress conditions of hydrolysis (acid, base), oxidation, photolysis and thermal degradations. The method was validated in accordance with ICH guidelines and the validation data showed that the assay is sensitive, specific and reproducible for the determination of citicoline in the presence of related substances and degradation products.
Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study
Cotroneo AM, Castagna A, Putignano S, Lacava R, Fantò F, Monteleone F, Rocca F, Malara A, Gareri P
Clinical Interventions in Aging , 2013, DOI: http://dx.doi.org/10.2147/CIA.S38420
Abstract: tiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study Original Research (3198) Total Article Views Authors: Cotroneo AM, Castagna A, Putignano S, Lacava R, Fantò F, Monteleone F, Rocca F, Malara A, Gareri P Video abstract presented by Pietro Gareri Views: 164 Published Date February 2013 Volume 2013:8 Pages 131 - 137 DOI: http://dx.doi.org/10.2147/CIA.S38420 Received: 22 September 2012 Accepted: 14 November 2012 Published: 05 February 2013 Antonino Maria Cotroneo,1 Alberto Castagna,2 Salvatore Putignano,3 Roberto Lacava,2 Fausto Fantò,4 Francesco Monteleone,5 Filomena Rocca,2 Alba Malara,6 Pietro Gareri2 1ASL 2 Turin, Piedmont, 2Elderly Health Care, Ambulatory Center for Dementia, ASP Catanzaro, Calabria, 3ASL Napoli 1, Campania, 4University Hospital Orbassano, Turin, Piedmont, 5Regina Margherita Hospital, Rome, 6Nursing Home S Domenico Lamezia Terme, ASP Catanzaro, Calabria, Italy Background: The studio di intervento nel decadimento vascolare lieve (IDEALE study) was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment. Methods: The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age ≥ 65 years, Mini-Mental State Examination (MMSE) score ≥ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67–90) years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales, mood was assessed by the Geriatric Depression Scale (GDS), and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0), after 3 months (T1), and after 9 months (T2, ie, 6 months after T1). The main outcomes were an improvement in MMSE, ADL, and IADL scores in the study group compared with the control group. Side effects were also investigated. The study group was administered oral citicoline 500 mg twice a day throughout the study. Results: MMSE scores remained unchanged over time (22.4 ± 4 at T0; 22.7 ± 4 at T1; 22.9 ± 4 at T2), whereas a significant difference was found between the study and control groups, both in T1 and in T2. No differences were found in ADL and IADL scores between the two groups. A slight but not statistically significant difference was found in GDS score be
Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells through pathways involving ERK1/2 and insulin receptor substrate-1
Krupinski Jerzy,Abudawood Manal,Matou-Nasri Sabine,Al-Baradie Raid
Vascular Cell , 2012, DOI: 10.1186/2045-824x-4-20
Abstract: Background Citicoline is one of the neuroprotective agents that have been used as a therapy in stroke patients. There is limited published data describing the mechanisms through which it acts. Methods We used in vitro angiogenesis assays: migration, proliferation, differentiation into tube-like structures in Matrigel and spheroid development assays in human brain microvessel endothelial cells (hCMEC/D3). Western blotting was performed on protein extraction from hCMEC/D3 stimulated with citicoline. An analysis of citicoline signalling pathways was previously studied using a Kinexus phospho-protein screening array. A staurosporin/calcium ionophore-induced apoptosis assay was performed by seeding hCMEC/D3 on to glass coverslips in serum poor medium. In a pilot in vivo study, transient MCAO in rats was carried out with and without citicoline treatment (1000 mg/Kg) applied at the time of occlusion and subsequently every 3 days until euthanasia (21 days). Vascularity of the stroke-affected regions was examined by immunohistochemistry. Results Citicoline presented no mitogenic and chemotactic effects on hCMEC/D3; however, it significantly increased wound recovery, the formation of tube-like structures in Matrigel and enhanced spheroid development and sprouting. Citicoline induced the expression of phospho-extracellular-signal regulated kinase (ERK)-1/2. Kinexus assays showed an over-expression of insulin receptor substrate-1 (IRS-1). Knock-down of IRS-1 with targeted siRNA in our hCMEC/D3 inhibited the pro-angiogenic effects of citicoline. The percentage of surviving cells was higher in the presence of citicoline. Citicoline treatment significantly increased the numbers of new, active CD105-positive microvessels following MCAO. Conclusions The findings demonstrate both a pro-angiogenic and protective effect of citicoline on hCMEC/D3 in vitro and following middle cerebral artery occlusion (MCAO) in vivo.
Simple diffusion delivery via brain interstitial route for the treatment of cerebral ischemia
HongBin Han,ZuoLi Xia,He Chen,Chao Hou,WeiBo Li
Science China Life Sciences , 2011, DOI: 10.1007/s11427-011-4141-6
Abstract: Delivering pharmacologic agents directly into the brain has been proposed as a means of bypassing the blood brain barrier. However, despite 16 years of research on a number of central nervous system disorders, an effective treatment using this strategy has only been observed in the brain tumor glioblastoma multiforme. Within this study we propose a novel system for delivering drugs into the brain named the simple diffusion (SDD) system. To validate this technique, rats were subjected to a single intracranial (at the caudate nucleus), or intraperitoneal injection, of the compound citicoline, followed two hours later by a permanent middle cerebral artery occlusion (pMCAO). Results showed that 12 h after pMCAO, with 0.0025 g kg 1 citicoline, an infarct volume 1/6 the size of the intraperitoneal group was achieved with a dose 1/800 of that required for the intraperitoneal group. These results suggest that given the appropriate injection point, through SDD a pharmacologically effective concentration of citicoline can be administered.
Retrospective and observational study to assess the efficacy of citicoline in elderly patients suffering from stupor related to complex geriatric syndrome
Putignano S, Gareri P, Castagna A, Cerqua G, Cervera P, Cotroneo AM, Fiorillo F, Grella R, Lacava R, Maddonni A, Marino S, Pluderi A, Putignano D, Rocca F
Clinical Interventions in Aging , 2012, DOI: http://dx.doi.org/10.2147/CIA.S29366
Abstract: rospective and observational study to assess the efficacy of citicoline in elderly patients suffering from stupor related to complex geriatric syndrome Original Research (3195) Total Article Views Authors: Putignano S, Gareri P, Castagna A, Cerqua G, Cervera P, Cotroneo AM, Fiorillo F, Grella R, Lacava R, Maddonni A, Marino S, Pluderi A, Putignano D, Rocca F Published Date May 2012 Volume 2012:7 Pages 113 - 118 DOI: http://dx.doi.org/10.2147/CIA.S29366 Received: 21 December 2011 Accepted: 06 February 2012 Published: 23 May 2012 Salvatore Putignano, Pietro Gareri, Alberto Castagna, Giuliano Cerqua, Pasquale Cervera, Antonino Maria Cotroneo, Francesco Fiorillo, Roberto Grella, Roberto Lacava, Antonio Maddonni, Saverio Marino, Alice Pluderi, Daria Putignano, Filomena Rocca Associazione Geriatri Extraospedalieri – Geriatria Italiana Territoriale, Tenore 17, Naples, Italy Abstract: A significant percentage of elderly subjects (50%–80%) suffering from sub-acute ischemic cerebrovascular disease, with or without moderate or severe cognitive memory decline and with or without associated behavioral and psychological symptoms, shows a complex syndrome. This syndrome is related to the progressive impairment of health conditions and/or stressing events (ie, hospitalization), characterized by confusion and/or stupor, which are consequently difficult to manage and require a great deal of care. Geriatric patients often suffer from multiple chronic illnesses, may take numerous medications daily, exhibit clinical instability, and may experience worsening of medical conditions following cerebral ischemic events and thus have an increased risk of disability and mortality. There are several studies in literature which demonstrate the efficacy of citicoline, thanks to its neuroprotective function, for the recovery and in postischemic cerebral rehabilitation. It has been shown that, even soon after an ischemic stroke, administration of oral citicoline (500–4000 mg/day) improves the general conditions evaluated with the Rankin scale and the National Institute of Health Stroke Scale 12. In particular, it has been shown that the CDP-choline improves the cognitive and mental performance in Alzheimer's dementia and vascular dementia. We have evaluated the administration of citicoline in geriatric patients following a protocol of intravenous study on improvement of individual performances.
The Role of Citicoline in Neuroprotection and Neurorepair in Ischemic Stroke
José álvarez-Sabín,Gustavo C. Román
Brain Sciences , 2013, DOI: 10.3390/brainsci3031395
Abstract: Advances in acute stroke therapy resulting from thrombolytic treatment, endovascular procedures, and stroke units have improved significantly stroke survival and prognosis; however, for the large majority of patients lacking access to advanced therapies stroke mortality and residual morbidity remain high and many patients become incapacitated by motor and cognitive deficits, with loss of independence in activities of daily living. Therefore, over the past several years, research has been directed to limit the brain lesions produced by acute ischemia (neuroprotection) and to increase the recovery, plasticity and neuroregenerative processes that complement rehabilitation and enhance the possibility of recovery and return to normal functions (neurorepair). Citicoline has therapeutic effects at several stages of the ischemic cascade in acute ischemic stroke and has demonstrated efficiency in a multiplicity of animal models of acute stroke. Long-term treatment with citicoline is safe and effective, improving post-stroke cognitive decline and enhancing patients’ functional recovery. Prolonged citicoline administration at optimal doses has been demonstrated to be remarkably well tolerated and to enhance endogenous mechanisms of neurogenesis and neurorepair contributing to physical therapy and rehabilitation.
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