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MedWorm: CilostazolCilostazol Trumps Aspirin in Secondary Stroke Prevention A large randomized controlled trial suggests that the phosphodiesterase inhibitor cilostazol is more effective for the prevention of secondary stroke and has a superior safety profile. Medscape Medical News (Source: Medscape Today Headlines) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. ASA: Antiplatelet Tops Aspirin for Secondary Stroke Prevention (CME/CE) Cilostazol, an antiplatelet agent used in the U.S. to treat intermittent claudication, was better than aspirin at preventing recurrent stroke from noncardiogenic sources, a randomized trial conducted in Japan showed. (Source: MedPage Today Cardiovascular) Antiplatelet Drug May Be Better Than Aspirin In Preventing Recurrent Strokes This study demonstrated for the first time that cilostazol significantly reduces the risk of recurrent ischemic [blood-clot caused] stroke and the incidence of serious cerebral hemorrhage, compared to aspirin," said Yukito Shinohara, M.D... (Source: Health News from Medical News Today) Antiplatelet Drug May Be Better Than Aspirin In Preventing Recurrent Strokes The antiplatelet drug cilostazol used in the United States to treat leg pain associated with peripheral vascular disease was more effective and safer than aspirin at preventing recurrent strokes in a Japanese trial presented as late-breaking science at the American Stroke Association's International Stroke Conference 2010... (Source: Stroke / Neuroprotection News From Medical News Today) Cilostazol in the Management of Atherosclerosis. Authors: Sallustio F, Rotondo F, Di Legge S, Stanzione P The burden of atherosclerosis is particularly high in western countries in terms of mortality and disability. The cerebral arteries (stroke or transient ischemic attack [TIA]), coronary arteries (myocardial infarction [MI]) and peripheral arteries (intermittent claudication [IC], ischemic limb) can be affected. Atherosclerosis may involve different mechanisms such as inflammation, platelet activation, endothelial damage, balance between proliferation and apoptosis of smooth muscle cells and oxidative stress. Research is focused to counteract each of these aspects. Many antithrombotic drugs are currently available and most of them act as inhibitors of platelet function. Aspirin, ticlopidine, clopidogrel and the combination of aspi... The goal of the trial was to evaluate three regimens of antiplatelet therapy after stenting for acute myocardial infarction (AMI): 1) cilostazol plus standard-dose clopidogrel, 2) high-dose clopidogrel, or 3) standard-dose clopidogrel. (Source: Cardiosource) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Cilostazol enhances neovascularization in the mouse hippocampus after transient forebrain ischemia Cilostazol is known to be a specific type III phosphodiesterase inhibitor, which promotes increased intracellular cAMP levels. We assessed the effect of cilostazol on production of angioneurins and chemokines and recruitment of new endothelial cells for vasculogenesis in a mouse model of transient forebrain ischemia. Pyramidal cell loss was prominently evident 3-28 days postischemia, which was markedly ameliorated by cilostazol treatment. Expression of angioneurins, including endothelial nitric oxide synthase, vascular endothelial growth factor, and brain-derived neurotrophic factor, was up-regulated by cilostazol treatment in the postischemic hippocampus. Cilostazol also increased Sca-1/vascular endothelial growth factor receptor-2 positive cells in the bone marrow and circulating periphe... Conclusions Thus, the comparative analysis revealed that the efficacy of Cilostazole is more than the Pentoxifylline and Placebo in increasing the ICD and ACD in patients of occlusive peripheral arterial disease. In addition, Cilostazole also lowers Triglyceride and LDL levels and increases High Density Lipid (HDL) levels which was not observed with Pentoxifylline and Placebo. Content Type Journal ArticleCategory Original ArticlesDOI 10.1007/s12055-009-0042-8Authors Surjit Singh, Govt Medical College Department of Cardiothoracic and Vascular Surgery and Pharmacology Jammu IndiaHarbinder Singh, Govt Medical College Department of Cardiothoracic and Vascular Surgery and Pharmacology Jammu IndiaArvind Kohli, Govt Medical College Department of Cardiothoracic and Vascular S... Aspirin is widely used for the prevention of recurrent stroke in patients with transient ischaemic attack (TIA) and ischaemic stroke of arterial origin, because it is effective and inexpensive. Clopidogrel and the combination of aspirin and extended-release dipyridamole are more effective than aspirin, but are also much more expensive. No other antithrombotic regimens provide significant advantages over aspirin, although cilostazol and the novel platelet protease activated receptor-1 antagonist, SCH 530348, are currently being evaluated. For patients with TIA and ischaemic stroke of cardiac origin due to atrial fibrillation, vitamin K antagonists (VKAs) are highly effective in preventing recurrent ischaemic stroke but have important limitations and are thus underused. Antiplatelet therapy ... Whilst high pro-coagulant activity is reported in sickle cell disease (SCD), the precise role of platelets (PLTs) in SCD inflammatory and vaso-occlusive processes is unclear. Adhesion of PLTs from healthy controls (CON), SCD individuals (SCD) and SCD patients on hydroxycarbamide (SCDHC) to fibrinogen (FB) was compared using static adhesion assays. PLT adhesion molecules and intraplatelet cyclic adenosine monophosphate (icAMP) were observed by flow cytometry and enzyme-linked immunosorbent assay. SCD-PLTs demonstrated significantly greater adhesion than CON-PLTs to FB. Participation of the [alpha]IIb[beta]3-integrin in SCD-PLT adhesion was implicated by increased [alpha]IIb[beta]3 activation and data showing that an [alpha]IIb[beta]3-function-inhibiting antibody significantly diminished SCD... Intrinsic Sex-Specific Differences in Microvascular Endothelial Cell Phosphodiesterases. We reported previously sex-differences in microvessel permeability (Ps) responses to adenosine that were mediated by the cAMP signaling pathway. The two cyclic nucleotides, cAMP and cGMP, central to the regulation of vascular barrier integrity are hydrolyzed by phosphodiesterases (PDE). We hypothesized that microvascular endothelial cells (EC) would retain intrinsic and inheritable sexually dimorphic genes with respect to the PDEs modulating EC barrier function. Primary cultured microvascular EC from skeletal muscles isolated from male and female rats, respectively, were used. SRY (a sex-determining region Y gene) mRNA expression was observed exclusively in male, not female, cells. The predominant isoform among PDE1-5 present in both XY and XX EC, was PDE4. Expression mRNA levels of PDE1A ... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Review: Combination antithrombotic therapies Source: Circulation Area: News This review summarises the role of combination antiplatelet therapies in the treatment and prevention of atherothrombosis. The following topics and drug combinations are discussed: . Pathophysiology of atherothrombosis . Aspirin . Aspirin dose and bleeding . Thienopyridines . Aspirin monotherapy vs. thienopyridine monotherapy . Thienopyridine plus aspirin: stenting . Clopidogrel plus aspirin and vs. aspirin monotherapy for acute coronary syndromes, primary and secondary prevention . clopidogrel plus aspirin vs. clopidogrel monotherapy: TIA and stroke . Limitations of clopidogrel plus aspirin . Overcoming clopidogrel non-esponsiveness o Higher doses o Prasugrel plus asp... Authors: Kim MS, Kim JS, Hwang SJ The aim of this study was to improve wettability and dissolution rate of a poorly water-soluble drug, cilostazol, using the supercritical antisolvent (SAS) process. The solid state of particles precipitated from dichloromethane containing additives, including poloxamer 188, poloxamer 407, TPGS 1000, Gelucire((R)) 44/14 and Gelucire((R)) 50/13, in supercritical CO(2) medium were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), FT-IR, particle size analysis, contact angle, and dissolution. Interestingly, the morphology of SAS particles processed with TPGS 1000, Gelucire((R)) 44/14 and Gelucire((R)) 50/13 changed to plate- or leaflet-shaped. Furthermore, the particle sizes of cilostazol processed with Gelucire((R)... Conclusions: Triple antiplatelet therapy significantly reduced 12-month risks of stent thrombosis and MI after DES implantation compared with dual antiplatelet therapy without increased risk of bleeding complications. The longer duration of triple therapy after DES implantation was associated with the lower risk of stent thrombosis and MI. (Source: American Heart Journal) Conclusion and implications: Our results demonstrate that suppression of the NF-[kappa]B, ERK, JNK signalling pathways may inhibit LPS-induced NO and PGE2 production. Therefore, cilostazol may have therapeutic potential for neurodegenerative diseases by inhibiting pro-inflammatory mediators and cytokine production in activated microglia. (Source: British Journal of Pharmacology) Protein kinases A and C regulate receptor-mediated increases in cAMP in rabbit erythrocytes Activation of the β-adrenergic receptor (β-AR) or the prostacyclin receptor (IPR) results in increases in cAMP and ATP release from erythrocytes. cAMP levels depend on a balance between synthesis via adenylyl cyclase and hydrolysis by phosphodiesterases (PDEs). Previously, we reported that cAMP increases associated with activation of the β-AR and IPR in rabbit and human erythrocytes are tightly regulated by distinct PDEs (1). Importantly, inhibitors of these PDEs potentiated both increases in cAMP and ATP release. It has been shown that increases in protein kinase (PK) activity can activate PDE3 and PDE4. Both PKA and PKC are present in the erythrocyte and can phosphorylate and activate these PDEs. Here we investigate the hypothesis that PKA regulates PDE activity associated... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Triple, Dual Restenosis Prevention Therapies Studied Antiplatelet therapy including aspirin, clopidogrel and cilostazol helps prevent late stenosis following stent placement better than standard therapy with only aspirin and clopidogrel, according to a study in the Jan. 15 issue of the American Journal of Cardiology. (Source: Modern Medicine) Authors: Liu CQ, Wong SL, Leung FP, Tian XY, Lau CW, Lu L, Yao X, Chen ZY, Yao T, Huang Y Activation of the thromboxane prostanoid (TP) receptor produces potent vasoconstriction, which contributes to the increased vascular tone and blood pressure. The present study was designed to examine the hypothesis that stimulation of prostanoid TP receptors impairs endothelium-independent relaxations to cyclic AMP-elevating agents via increasing the activity of phosphodiesterases (PDEs). Rat carotid arteries without endothelium were isolated and suspended in myograph for the measurement of changes in isometric tension; the tissue content of cyclic AMP was assayed by enzyme immunoassay kit; and prostanoid TP receptor was detected in vascular wall by immunohistochemistry and Western blot. In phenyl... Authors: Jennings DL, Kalus JS The purpose of this study is to evaluate the effect of adding cilostazol to dual antiplatelet therapy (aspirin and thienopyridine) on rates of restenosis after coronary artery stenting. A meta-analysis is conducted of randomized, controlled trials comparing 3 drug regimens (cilostazol, thienopyridine, aspirin [triple therapy]) with dual anti-platelet therapy to reduce restenosis after coronary stenting. A total of 5 studies are included for analysis. The analysis reveals that triple therapy is used in 796 patients, whereas dual therapy is used in 801 patients. Approximately 56% of patients receive a drug-eluting stent. The 6-month restenosis rates are significantly lower with triple versus dual antiplatelet therapy (12.7% vs 21.9%; odds ratio 0.5; 95% con... To assess the effects of cilostazol in inhibiting proliferation and enhancing apoptosis in synovial cells from patients with rheumatoid arthritis (RA).Synovial cell proliferation was measured by MTT assay. The expression of NF-[kappa]B, I[kappa]B[alpha], Bcl-2, Bax, heme oxygenase 1 (HO-1), and Nrf2 was determined by Western blotting.Cilostazol suppressed synovial cell proliferation by arresting the G2/M phases of the cell cycle, and this was reversed by KT5720, an inhibitor of protein kinase A. Cilostazol increased the number of TUNEL-positive cells, with increased cytochrome c release and apoptosis-inducing factor translocation as well as increased caspase 3 activation. Cilostazol (10 [mu]M) and cobalt protoporphyrin IX (CoPP) increased HO-1 messenger RNA and protein expression. These ef... Conclusion: This study found that in these patients with femoropopliteal lesions in peripheral artery disease who were undergoing hemodialysis, those treated with cilostazol 100 mg BID after PTA had a higher mean rate of cumulative patency after PTA than those in the control group. PMID: 20171408 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Protein Kinases A and C Regulate Receptor-Mediated Increases in cAMP in Rabbit Erythrocytes. Authors: Adderley SP, Sridharan M, Bowles EA, Stephenson AH, Ellsworth ML, Sprague RS Activation of the beta-adrenergic receptor (betaAR) or the prostacyclin receptor (IPR) results in increases in cAMP and ATP release from erythrocytes. cAMP levels depend on a balance between synthesis via adenylyl cyclase and hydrolysis by phosphodiesterases (PDEs). Previously we reported that cAMP increases associated with activation of the betaAR and IPR in rabbit and human erythrocytes are tightly regulated by distinct PDEs. Importantly, inhibitors of these PDEs potentiated both increases in cAMP and ATP release. It has been shown that increases in protein kinase (PK) activity can activate PDEs 3 and 4. Both PKA and PKC are present in the erythrocyte and can phosphorylate and activate these PDEs. H... In conclusion, compared to the standard group, initial benefit in decreases of 9-month TLRs and MACEs in the triple group was sustained at 2 years with no differences in death or MI. Triple antiplatelet therapy decrease of 2-year TLR was favorable in all subgroups, especially in patients with high-risk profiles. (Source: The American Journal of Cardiology) Cilostazol Increases Tissue Blood Flow in Contracting Rabbit Gastrocnemius Muscle. Conclusions: Cilostazol increases blood flow in the gastrocnemius muscle during contraction and it is this effect that may be partially responsible for the improved walking distance in IC patients. PMID: 19966507 [PubMed - as supplied by publisher] (Source: Circulation Journal) In conclusion, a PDE-3 inhibitor ameliorates murine ileitis through attenuating migration of monocytes to the intestinal mucosa, suggesting a potential usefulness of antiplatelet drugs for treatment of Crohn's disease. (Source: AJP: Gastrointestinal and Liver Physiology) New evidence; conclusions changed for: Cilostazol One systematic review added, including RCTs already reported in this Clinical Evidence review. Evidence re-evaluated. Categorisation changed from Trade-off between benefits and harms to Likely to be beneficial. New evidence; conclusion confirmed for: Antiplatelet agents One systematic review added, reporting that antiplatelet agents (aspirin or aspirin plus dipyridamole) reduced arterial occlusion of both venous and artificial peripheral bypass grafts versus placebo at 12 months. It found no significant difference in GI adverse effects, or major bleeding between groups. One RCT added, reporting lower MI rates with clopidogrel plus aspirin versus placebo plus aspirin after 26 m... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusions: Although this was a negative study, our findings disclosed a trend toward enhanced antiplatelet effects when cilostazol was added to aspirin in ischaemic stroke patients. Combination of aspirin and cilostazol might be a treatment option in the ischaemic stroke patients with AR. (Source: European Journal of Neurology) (Source: Reactions) In this study, we prepared liposomes containing the platelet aggregation inhibitor Cilostazol (Cil-L). The objective of this study was to investigate the effect of this Cil-L on platelet aggregation and complex formation with murine 4T1 breast cancer cells in vitro and to determine their anti-metastatic potency in a spontaneous metastasis model of 4T1 breast cancer. Cil-L significantly inhibited the aggregation of platelets by up to 78% and completely abolished the complex formation of 4T1 tumor cells in the presence of activated platelets in vitro. Intravenous (i.v.) injection of Cil-L into mice significantly reduced the aggregability of mouse platelets by 60% measured ex vivo. To gain deeper insight into the mode of metastasis formation in a spontaneous metastasis model, 4T1 breast... The Effect of Cilostazol to Arterial Stiffness in the Hypertensive patient Cilostazol is a potent antiplatelet agent that selectively inhibits phosphodiesterase III, and also it has beneficial effect to peripheral arterial disease, like intermittent claudication, by direct vasodilative action. But the effect of cilostazol on arterial stiffness is unclear. We investigated the effect of cilostazol on arterial stiffness by using Pulse Wave Velocity (PWV) which is most common and non-invasive measure technique. (Source: Artery Research) Cilostazol reduces restenosis after carotid artery stenting Conclusions: Although this study was retrospective and nonrandomized, the results suggest that cilostazol administration improves long-term patency after CAS due to its inhibitory effect on smooth muscle cell growth. (Source: Journal of Vascular Surgery) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Cilostazol induces metallothionein expression in vascular cells. We examined the induction of MT synthesis by cilostazol, an antiplatelet drug, in several vascular component cells to find a new pharmacological effect of cilostazol in vascular system. In human coronary artery endothelial cells, cilostazol significantly increased MT-IX and MT-IIA mRNA levels after the treatment for 6 h and endogenous MT-I/II protein levels after the treatment for 24 and 48 h. In addition, cadmium cytotoxicity was prevented by cilostazol in this endothelial cells. Moreover, cilostazol increased MT-IX and MT-IIA mRNA levels in human coronary artery smooth muscle cells, human brain microvascular endothelial cells, human brain microvascular pericytes and human colon carcinoma Caco-2 cells after the treatment for 6 h. Interestingly, cilostazol also increased MT-III mRNA level ... Prescriber compliance with black box warnings in older adult patients. CONCLUSIONS: Administrative claims analysis identified low rates of prescriber compliance with BBWs in managing patients age >or=65 years. Claims analysis may be a cost-effective strategy to monitor prescriber compliance with BBWs in older patients at higher risk. PMID: 19895180 [PubMed - in process] (Source: The American Journal of Managed Care) Conclusions: This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk. (Source: Journal of Stroke and Cerebrovascular Diseases) Peripheral arterial disease in women Abstract: Peripheral arterial disease (PAD) is chronic arterial occlusive disease of the lower extremities caused by atherosclerosis whose prevalence increases with age. Only one-half of women with PAD are symptomatic. Symptomatic and asymptomatic women with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Modifiable risk factors that predispose women to PAD include active cigarette smoking, passive smoking, diabetes mellitus, hypertension, dyslipidemia, increased plasma homocysteine levels and hypothyroidism. With regard to management, women who smoke should be encouraged to quit and referred to a smoking cessation program. Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism require treatment. Statins re... In conclusion, a PDE-3 inhibitor ameliorates murine ileitis through attenuating migration of monocytes to the intestinal mucosa, indicating a potential usefulness of anti-platelet drugs for treatment of Crohn's disease. PMID: 19815627 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Authors: Hideki Ito, Ayako Hashimoto, Yutaka Matsumoto, Hiroshi Yao & Goro Miyakoda (Source: Journal of Cerebral Blood Flow) Sirolimus: Stent thrombosis following cilostazol withdrawal in an elderly patient: case report (Source: Reactions) CONCLUSION: Our results demonstrate that intravenous administration of both cilostazol and nimodipine significantly attenuates cerebral vasospasm after SAH. PMID: 19847758 [PubMed - in process] (Source: Turkish Neurosurgery) Conclusions: Nitinol stent implantation for TASC II A/B FPA lesions is suitable and durable in sustaining freedom from restenosis through 4 years of follow-up. PMID: 19724155 [PubMed - as supplied by publisher] (Source: Circulation Journal) Abstract We previously reported that acute cigarette smoking can cause a dysfunction of endothelium-dependent vasodilation in cerebral vessels, and that a reduction of oxidative stress by agents such as valsartan, fasudil, or apocynin prevented this impairment. Here, our aim was to investigate the comparative effects of two antiplatelet drugs used for stroke-prevention [a phosphodiesterase-3 inhibitor (cilostazol) and a cyclooxygenase inhibitor (aspirin)] on smoking-induced endothelial dysfunction in cerebral arterioles. In Sprague-Dawley rats, we used a closed cranial window preparation to measure the changes in pial vessel diameters induced by topical application of acetylcholine (ACh) following intraperitoneal injection of 0.5% carboxymethyl cellulose sodium salt (CMC; ... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Lithium Fails to Show Efficacy for Mild Alzheimer's DiseaseStudy Finds Important Differences Between Young and Old Bipolar Manic PatientsMirtazapine-Induced HyponatremiaIncreased Dementia Risk Linked to Long-Term Benzodiazepine UseAcetylcholinesterase Inhibitors Studied in a Real-World SettingEditorial Weighs in on Lithium and Alzheimer'sCombination Cilostazol and Donepezil Treatment for ADAdjunctive Valproate and Pleural EffusionBlack Box Warnings for Bupropion and VareniclineAtomoxetine Safety Labeling Changes (Source: The Brown University Geriatric Psychopharmacology Update) Authors: Hayashi H, Sudo T Elevating intracellular cAMP has been shown to inhibit platelet function. cAMP interferes with platelet-activating signals which lead to aggregation inhibition, but the precise mechanism is unclear. The present study examined if cAMP-elevating agents inhibited phosphatidylinositol 3-kinase (PI3-kinase) signaling in rat platelets by immunoblotting. Akt is one of the key molecules downstream of PI3K, and is phosphorylated by collagen stimulation. The phosphodiesterase-3 (PDE3) inhibitors cilostamide and cilostazol, and the adenylate cyclase activator forskolin, inhibited collagen-induced Akt phosphorylation at Ser473. The inhibitory effects of these cAMP-elevating agents on Akt phosphorylation were unchanged in the presence of the PKA (cyclic AMP-dependent prot... CONCLUSION: The DES and cobalt-chromium BMS placed in large coronary arteries showed equally favorable 6-month clinical outcomes, although the 6-month angiographic results appeared more favorable in the DES group than in the BMS group. PMID: 19632529 [PubMed - in process] (Source: Journal of Cardiology) Conclusion: In patients with intermittent claudication secondary to femoropopliteal disease, cilostazol reduces restenosis and repeat revascularization after endovascular therapy. (Source: Journal of Vascular Surgery) We examined whether cilostazol inhibits PAI-1 expression in vascular smooth muscle cells (VSMCs) and neointimal hyperplasia. We found that cilostazol effectively inhibits angiotensin II-, high glucose- and TGF-β-stimulated PAI-1 expression in vivo and in vitro. Cilostazol attenuated PAI-1 expression in neointimal regions and inhibited neointimal hyperplasia after balloon injury. Cilostazol inhibited PAI-1 expression by multiple mechanisms including downregulation of TGF-β, JNK and p38 signaling pathways. Cilostazol also inhibited transactivating activity at the PAI-1 promoter by Smad3, leading to a suppression of PAI-1 gene transcription. Taken together with its antiproliferative effect on VSMCs, this may explain how cilostazol exerts its antithrombogenic effects after angioplasty and st... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Cilostazol therapy attenuates monocrotaline-induced pulmonary arterial hypertension in rat model Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance caused by a proliferation of vascular endothelial and smooth muscle cells, resulting in occlusion of the lumen of small pulmonary arteries. Cilostazol, with its antiproliferative effects on vascular endothelial and smooth muscle cells, may ameliorate monocrotaline (MCT)-induced PAH in rats. (Source: Cardiovascular Revascularization Medicine) In this study, we have investigated if GB can potentiate the antiplatelet effects of cilostazol to explore the utility of combination therapy of cilostazol and GB against peripheral occlusive vascular diseases. GB or cilostazol was evaluated alone or in combination for the antiplatelet activity using in vitro and in vivo models. In addition, potential bleeding side effect of the combinative therapy was assessed by measuring bleeding time, prothrombin time (PT) and activated partial thromboplastin time (aPTT) in vivo after oral administration. In in vitro assays using freshly isolated human platelets, the combination of cilostazol and GB showed superior inhibition of both the shear and the collagen-induced platelet aggregation to those of each drug alone. In accordance with these enhanced i... Conclusion: Modified Danggui Sini Decoction can improve clinical symptoms in patients with diabetic foot ulcers of Wagner grade 0 and it shows therapeutic effects on diabetes complicated with vascular diseases. PMID: 19615315 [PubMed - in process] (Source: Zhong xi yi jie he xue bao : Journal of Chinese Integrative Medicine.) Silence of the Limbs Pharmacological Symptomatic Treatment of Intermittent Claudication. Authors: De Backer T, Stichele RV, De Buyzere M, De Backer G, Van Bortel L Several oral "vasoactive" drugs claim to increase walking capacity in patients with intermittent claudication (IC). Naftidrofuryl, cilostazol, buflomedil, and pentoxifylline are the most studied molecules. Although spanning several decades, several studies underlying these claims were not properly designed, underpowered or showed clinically doubtful outcomes. The evidence for these "vasoactive" drugs has always been received with scepticism, creating the need for systematic reviews and meta-analyses. This brief review discusses the benefit-risk assessment of vasoactive drugs, by applying a systematic review to evaluate randomized, placebo-controlled trials. Oral naftidrofuryl and cilostazol have an acceptable sa... Enhancement of oral bioavailability of cilostazol by forming its inclusion complexes. Authors: Patel SG, Rajput SJ The study was designed to investigate the effect of cyclodextrins (CDs) on the solubility, dissolution rate, and bioavailability of cilostazol by forming inclusion complexes. Natural CDs like beta-CD, gamma-CD, and the hydrophilic beta-CD derivatives, DM-beta-CD and HP-beta-CD, were used to prepare inclusion complexes with cilostazol. Phase solubility study was carried out and the stability constants were calculated assuming a 1:1 stoichiometry. Solid cilostazol complexes were prepared by coprecipitation and kneading methods and compared with physical mixtures of cilostazol and cyclodextrins. Prepared inclusion complexes were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studie... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Medscape Medical News (Source: Medscape Medical News Headlines) Conclusions: Sirolimus and everolimus induce endothelial senescence involving down-regulation of Sirt1. In contrast, the development of endothelial senescence by paclitaxel involves a Sirt1-independent pathway. Because sirolimus and everolimus are involved in Sirt1 modulation, cilostazol rescues HUVEC from sirolimus- or everolimus-induced senescence. These results may have therapeutic implications in the clinical sequelae after DES implantation. (Source: Journal of the American College of Cardiology) Recent studies have demonstrated a high post-treatment platelet activity (HPPR) with clopidogrel as predictive of adverse outcomes after percutaneous coronary intervention (PCI), including stent thrombosis. HPPR can partially be overcome with a higher loading (LD) or maintenance dose (MD) of clopido. . . (Source: Cardiosource) Cerebrovasc Dis 2009;28:135-142 (DOI:10.1159/000223439) (Source: Cerebrovascular Diseases) Cilostazol: Collagenous colitis (first report) in an elderly patient: case report (Source: Reactions) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Peripheral arterial disease: Pathophysiology, risk factors, diagnosis, treatment, and prevention Peripheral Artery Disease (PAD) is a strong predictor of MI, stroke and death due to vascular causes. PAD affects 8-12 million people in the United States. As the population lives longer with chronic diseases, researchers estimate that the incidence of PAD will increase, likely increasing myocardial infarction, stroke and death.This paper reviews the epidemiology, pathophysiology, risk factors, treatment and management of PAD. With improved understanding of the disease process, risk factors and treatment, clinicians will be able to detect PAD earlier, provide diagnosis, treat and manage this disease.PAD is associated with reduced quality of life, and persons with PAD are also at risk of developing coronary artery disease and cerebrovascular disease. Better clinical evaluation and routine s... CONCLUSIONS: Cilostazol protects HUVECs against LPS-induced apoptosis by suppressing mitochondria-dependent apoptotic signaling. Activation of ERK1/2 and p38 MAPKs, and subsequent stimulation of CREB phosphorylation and Bcl-2 expression, may be responsible for the cellular signaling mechanism of cilostazol-mediated protection. PMID: 19543489 [PubMed - in process] (Source: The Korean Journal of Internal Medicine) Cilostazol: Collagenous colitis (first report) in an elderly patient: case report. Page: 16 (Source: Reactions Weekly) Activation of the G protein Gs results in increases in cAMP, a necessary step in the pathway for ATP release from rabbit and human erythrocytes. In all cells, the level of cAMP is the product of its synthesis by adenylyl cyclase and its hydrolysis by phosphodiesterases (PDEs). Both iloprost (Ilo), a PGI2 analog, and isoproterenol (Iso), a β-agonist, stimulate receptor-mediated increases in cAMP in rabbit and human erythrocytes. However, the specific PDEs associated with each of these signaling pathways in the erythrocyte have not been fully characterized. Previously, we reported that PDE3B is present in rabbit and human erythrocyte membranes and that PDE3 inhibitors potentiate Ilo-induced increases in cAMP. Here we report that inhibitors of either PDE2 or PDE4, erythro-9-(2-hydroxy-3-... Background: Cilostazol has proven efficacy in increasing walking distance in claudicants, but it has not been demonstrated to be more effective than placebo in secondary cardiovascular prevention. The direct effect of exercise on platelet function remains less well defined. We have investigated the effect of combination treatment with aspirin and cilostazol on platelet activity in claudicants subjected to repeated treadmill exercise. (Source: Journal of Vascular Surgery) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. The vascular and biochemical effects of cilostazol in patients with peripheral arterial disease Conclusion: Cilostazol is a well-tolerated, safe, and efficacious treatment for PAD patients. It not only improves patients' symptomatology and quality of life but also appears to have beneficial effects on arterial compliance, possibly through its lipid-lowering property. (Source: Journal of Vascular Surgery) Abstract: Background: Cilostazol has proven efficacy in increasing walking distance in claudicants, but it has not been demonstrated to be more effective than placebo in secondary cardiovascular prevention. The direct effect of exercise on platelet function remains less well defined. We have investigated the effect of combination treatment with aspirin and cilostazol on platelet activity in claudicants subjected to repeated treadmill exercise.Methods: Nineteen claudicants completed a double-blind, randomised, controlled, cross-over trial. Each subject received a 2-week course of aspirin (75mg) and placebo and aspirin and cilostazol (100mg twice daily). Following each 2-week treatment period, patients participated in a standardised treadmill test (3.2kmh−1, 10° incline) walking to maxima... Conclusions: Cilostazol is a well-tolerated and efficacious treatment, which improves claudication distances in diabetic PAD patients with further benefits in arterial compliance, lipid profiles, and QoL. (Source: Vascular and Endovascular Surgery) CONCLUSIONS: For patients with acute coronary syndromes, triple-antiplatelet therapy consisting of cilostazol, aspirin, and clopidogrel reduced long-term cardiac and cerebral events after PCI, especially for patients with high-risk profiles. PMID: 19332203 [PubMed - in process] (Source: American Heart Journal) Triple Therapy Reduces Restenosis After PCI NEW ORLEANS — Adding cilostazol to a standard, dual-antiplatelet regimen following the placement of either drug-eluting or bare-metal stents led to less restenosis, late loss, and need for revascularization in a meta-analysis of eight small, randomized trials. (Source: Internal Medicine News) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Authors: Arai H, Takahashi T PMID: 19307864 [PubMed - in process] (Source: Am J Geriatr Psychia...) Conclusions Adjunctive cilostazol reduces the rate of HPPR and intensifies platelet inhibition as compared with a high-MD clopidogrel of 150 mg/day. (Source: Journal of the American College of Cardiology) CONCLUSIONS: Combination treatment with aspirin and cilostazol results in suppression of platelet activation and reduces the effect of exercise on platelets. The benefit seen may be a result of cilostazol enhancing the inhibitory effect of aspirin on the cyclo-oxygenase pathway. PMID: 19297212 [PubMed - as supplied by publisher] (Source: European Journal of Vascular and Endovascular Surgery) Conclusions: Cilostazol can decrease hs-CPR and sCD40L levels and increase that of adiponectin, and then delay the progression of atherogenesis and chronic inflammation in type 2 diabetics, especially those with PAOD. PMID: 19282610 [PubMed - as supplied by publisher] (Source: Circulation Journal) This study examined the effect of cilostazol for alleviating CVC through manipulation of transforming growth factor-beta(1) and type 1 plasminogen activator inhibitor as well as their relation to cAMP was also studied. This was achieved in rats through administration of l-NAME (0.1mg/ml) for two weeks, and then followed by i.p. single dose of streptozotocin (65mg/kg). Rats were classified to three groups; normal rats, control diabetic hypertensive rats and the third group were treated with cilostazol (1.8mg daily, orally) for six weeks. Cilostazol improved serum cAMP level and increased plasma NO concentration leading to dilation of blood vessels. Moreover, cilostazol treatment confirmed the positive correlation between serum TGF-beta(1) and plasma PAI-1 activity which is beneficial in red... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Cilostazol suppresses neointimal hyperplasia in canine vein grafts Conclusion Cilostazol suppressed the development of intimal hyperplasia in canine autogenous vein grafts. Thus, it may be associated with the modulation of cell proliferation and apoptosis. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00595-008-3819-2Authors Fabio A. Kudo, Hokkaido University School of Medicine Department of Cardiovascular Surgery Sapporo, Hokkaido JapanYuka Kondo, Yale University School of Medicine New Department of Vascular Surgery Haven CT USAAkihito Muto, Yale University School of Medicine New Department of Vascular Surgery Haven CT USAKeiko Miyazaki, Hokkaido University School of Medicine Department of Cardiovascular Surgery Sapporo, Hokkaido JapanAlan Dardik, Yale University School of Medicine New Department of Vascular Surge... Conclusions Cilostazol reduced restenosis and repeat revascularization after EVT in patients with intermittent claudication due to femoropopliteal disease. (Source: Journal of the American College of Cardiology) CONCLUSIONS: Cilostazol significantly improves ACD, in addition to attenuating exercise-induced ischaemia-reperfusion injury, in PAD patients. PMID: 19112032 [PubMed - as supplied by publisher] (Source: European Journal of Vascular and Endovascular Surgery) Conclusions Despite extensive animal-based evidence that cilostazol attenuates neuropathic symptomatology, our results do not support this effect in human diabetic PAD patients. (Source: Angiology) Safety and Efficacy of Percutaneous Nephrostolithotomy in Patients on Anticoagulant Therapy Conclusions: With careful perioperative regulation of anticoagulation therapy and clotting parameters, percutaneous nephrostolithotomy can be performed safely and efficiently in properly selected patients requiring long-term anticoagulation. (Source: The Journal of Urology) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Page: 6 (Source: Reactions Weekly) (Source: Reactions) CILOSTAZOL TABLETStablet [Roxane Laboratories, Inc.] Updated Date: Dec 2, 2008 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) Deep Venous Thrombosis in Stroke Patients during Rehabilitation Phase. Conclusion: Incidence of DVT in the rehabilitation phase following stroke was not low, which was predominant as distal DVT on the hemiparetic side. Lower limb paresis, gait disturbance, calf muscle spasticity and use of AFO contributed to occurrence of DVT. It is likely that micro-injuries in the venous endothelium due to spasticity and AFO might cause DVT. Cilostazol seems effective for protecting against venous endothelial damage following DVT. PMID: 19110532 [PubMed - as supplied by publisher] (Source: The Keio Journal of Medicine) Influence of selective inhibitors of phosphodiesterase 3 and 4 on cough and airway reactivity. Authors: Mokry J, Mokra D, Nosalova G, Beharkova M, Feherova Z As the administration of many antitussive drugs is often associated with adverse effects, new alternatives are evaluated in experimental and clinical conditions. The aim of this study was to assess the influence of selective inhibitors of PDE3 (cilostazol) and PDE4 (citalopram) on cough and airway reactivity. The number of cough efforts, specific airway resistance, in vitro airway reactivity, and differential blood cells count were measured in healthy and in ovalbumin-sensitized guinea pigs before and after administration of cilostazol or citalopram (1 mg/kg). Cilostazol significantly suppressed citric acid induced cough only in healthy guinea pigs, whereas citalopram in both healthy and ovalbumin-sensitized animals. Both P... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Authors: Kim JY, Lee K, Shin M, Ahn M, Choe H, Yoo BS, Yoon J, Choe KH, Lee SH The publisher would like to point out to readers at that Hyunmin Choe's position was incorrect, and Wonju College of Medicine, Yonsei University should be changed into Ilsan Paik Hospital, Inje University College of Medicine. (Circ J 2007; 71: 1867 - 1872). PMID: 19029764 [PubMed - in process] (Source: Circulation Journal) This study investigated the effects of cilostazol on NCV and blood flow in acute and chronic cauda equina compression. Cilostazol improved the reduction of NCV and blood flow following cauda equina compression.Page: 2605DOI: 10.1097/BRS.0b013e31818917e9Authors: Sekiguchi, Miho MD, PhD; Aoki, Yoshihito MD, PhD; Konno, Shin-ichi MD, PhD; Kikuchi, Shin-ichi MD, PhD (Source: Spine) Outcomes of Partial Nephrectomy in Patients on Chronic Oral Anticoagulant Therapy We report our experience with patients requiring long-term anticoagulation therapy who underwent open or laparoscopic partial nephrectomy for renal tumors at our institution. We compared outcomes with those in a control group undergoing partial nephrectomy with no anticoagulation requirements.Materials and Methods: We retrospectively reviewed the records of 1,031 patients who underwent laparoscopic or open partial nephrectomy from 2000 to 2005. Since 2000, 31 open and 16 laparoscopic partial nephrectomies were performed in patients on chronic warfarin, clopidogrel or cilostazol. Anticoagulation was appropriately discontinued perioperatively. The 47 anticoagulated cases were compared with 47 nonanticoagulated controls that were carefully matched for surgical approach, partial nephrectomy de... Management of lower extremity peripheral arterial disease. Authors: Gardner AW, Afaq Z Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis, is a significant health problem. It manifests in lower extremities as intermittent claudication, limb ischemia, or gangrene and other locations as stroke, renal failure, or mesenteric ischemia. Fontaine and Rutherford classifications are the 2 commonly used classifications to stage the severity of PAD. The diagnostic tools include ankle-brachial index, a valuable tool in diagnosing lower extremity PAD, and a treadmill test. Other useful diagnostic tools include the San Diego Claudication Questionnaire to screen patients for symptoms and imaging modalities such as duplex scan, angiogram, computer tomographic angiogram, and magnetic resonance angiogram. Medical management of PAD in... Enhanced Platelet Inhibition With Cilostazol for Diabetics With CAD on Antiplatelet Therapy Patients with type 2 diabetes and coronary artery disease (CAD) get a greater degree of platelet inhibition with cilostazol added to clopidogrel and aspirin. Reuters Health Information (Source: Medscape Diabetes Headlines) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusion: Antiplatelet agents, especially cilostazol, offer the promise of becoming key agents for the treatment of NAFLD. (Source: Gut) Peripheral arterial disease may lead to lower limb claudication and increased risk of systemic vascular dysfunction. In this article, the authors have investigated the peripheral vascular dysfunction evaluating forearm blood flow using venous occlusion plethysmography, lipid profile, and C-reactive protein in 60 patients with moderate intermittent claudication treated during 20 weeks with placebo (n = 16), cilostazol (200 mg/d; n = 17), or pentoxifylline (1200 mg/d; n = 15) in a randomized double-blinded clinical trial, taking into account smoking. Forearm blood flow after reactive hyperemia response (FBFh ) or oral nitroglycerine spray to evaluate endothelial-dependent and endothelial-independent vasodilation, respectively, pain-free and maximal walking distance, levels of C-reactive prot... Authors: Matsumoto T, Noguchi E, Ishida K, Nakayama N, Kobayashi T, Kamata K Diabetes mellitus impairs endothelial function, an effect that can be considered a hallmark of the development of cardiovascular diseases in diabetics. Cilostazol, a selective phosphodiesterase 3 inhibitor, is currently used to treat patients with diabetic vascular complications. However, the effects of cilostazol on responses mediated by endothelium-derived relaxing [in particular, nitric oxide (NO) and hyperpolarizing factors (EDHF)] and contracting factors remain unclear. Here, we hypothesized that cilostazol could improve endothelial dysfunctions in mesenteric arteries isolated from type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Using cilostazol-treated (100 mg/kg/day for 4 weeks) or -untr... Conclusion The antiplatelet effects of cilostazol intake could be evaluated by measuring VASP phosphorylation levels and maximal aggregation rates in platelets by ex vivo treatment with a low concentration of PGE(1). PMID: 18832777 [PubMed - as supplied by publisher] (Source: Circulation Journal) Authors: Lee JH, Shin HK, Park SY, Kim CD, Lee WS, Hong KW In the present study, cerebral ischemia was induced by a 10 min transient bilateral common carotid artery occlusion in rats combined with arterial blood pressure lowering to 37-42 mm Hg during occlusion. When histologically evaluated at 7 and 28 days after the forebrain ischemia (DAI) by staining with cresyl violet and Fluoro-Jade, the hippocampal CA1 region was most prominently damaged. At 7 DAI, treatment with cilostazol (60 mg/kg/day, orally) significantly reduced the neuronal damage in the CA1 region. The number of surviving neurons, visualized by NeuN immunostaining, in the CA1 region significantly increased at 7 and 28 DAI in the cilostazol-treated groups. To elucidate whether cilostazol enhances hippocampal neurogenesis ... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Vitamin B for treating peripheral neuropathy. CONCLUSIONS: There are only limited data in randomised trials testing the efficacy of vitamin B for treating peripheral neuropathy and the evidence is insufficient to determine whether vitamin B is beneficial or harmful. One small trial in alcoholic peripheral neuropathy reported slightly greater improvement in vibration perception threshold with oral benfotiamine for eight weeks than placebo. In another small study, a higher dose of oral vitamin B complex for four weeks was more efficacious than a lower dose in reducing symptoms and signs. Vitamin B administered by various routes for two to eight weeks was less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in short-term improvement of clinical and nerve conduction study outcomes. Vitamin B is generally well-toler... Cilostazol and peripheral arterial disease Expert Opinion on Pharmacotherapy , October 2008, Vol. 9, No. 15, Pages 2683-2690. Peripheral arterial disease is both common and disabling. Contemporary management of peripheral arterial disease is multimodal, encompassing both medical and interventional treatments. Cilostazol (Pletalâ„¢), a 2-oxoquinolone derivative, is currently ... (Source: Expert Opinion: Expert Opinion on Pharmacotherapy: Table of Contents) Conclusion Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy enhances inhibition of platelet P2Y12 signalling. (Source: European Heart Journal) In conclusion, PDMP levels as measured by ELISA were increased in patients with chronic cerebral infarction regardless of the anti-platelet therapy. This methodology may be a useful strategy of assessing platelet function in chronic cerebral infarction patients. PMID: 18772609 [PubMed - in process] (Source: Kobe J Med Sci) Authors: Barta J, Sanganalmath SK, Kumamoto H, Takeda N, Edes I, Dhalla NS Antiplatelet agents, sarpogrelate (SAR), a 5-hydroxy tryptamine 2A receptor antagonist and cilostazol (CIL), a phosphodiesterase-III inhibitor, were observed to be beneficial in attenuating cardiac remodeling and improving cardiac function in congestive heart failure due to myocardial infarction in rats; however, CIL increased ventricular tachycardia and mortality. In order to study the effects of these antiplatelet agents on arrhythmias, Sprague-Dawley rats were pretreated with either SAR or CIL (5 mg/kg/day) for 2 weeks and were then either injected cumulative doses of epinephrine (Epi) or subjected to coronary occlusion. Saline-treated animals served as controls. Electrocardiographic analysis revealed that SA... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusion: In light of these findings, we suggest that cilostazol might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF-kappaB following AMPK activation. PMID: 18703532 [PubMed - as supplied by publisher] (Source: Cardiovascular Research) (Source: Reactions) Page: 12 (Source: Reactions Weekly) Authors: Varanasi VS, Veeraraghavan S, Potharaju S, Thappali RS, Raghavan R, Vakkalanka VS A high performance liquid chromatographic (HPLC) method for simultaneous determination of rosiglitazone, CAS 122320-73-4, RSG), cilostazol (CAS 73963-72-1, CLZ) and its active metabolite 3, 4-dehydro-cilostazol (DCLZ), using pioglitazone (PIO) as internal standard (IS), in rat plasma is described. The plasma was extracted with methyl t-butyl ether, the dry extract was reconstituted in mobile phase and the aliquot was injected. The eluent drugs were detected by UV at dual wavelength of 226 nm (RSG and DCLZ) and 257 nm (CLZ). The mobile phase consisting of acetonitrile:potassium di-hydrogen phosphate buffer (35:65 v/v) was used at the flow rate of 1.2 ml/min on a reverse phase C18 column. The absol... Increases in the second messenger cAMP are associated with receptor-mediated ATP release from erythrocytes. In other signaling pathways, cAMP-specific phosphodiesterases (PDEs) hydrolyze this second messenger and thereby limit its biological actions. Although rabbit and human erythrocytes possess adenylyl cyclase and synthesize cAMP, their PDE activity is poorly characterized. It was reported previously that the prostacyclin analog iloprost stimulated receptor-mediated increases in cAMP in rabbit and human erythrocytes. However, the PDEs that hydrolyze erythrocyte cAMP synthesized in response to iloprost were not identified. PDE3 inhibitors were reported to augment increases in cAMP stimulated by prostacyclin analogs in platelets and pulmonary artery smooth muscle cells. Additionally, PDE3... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Peripheral arterial disease: diagnosis and management. Authors: Arain FA, Cooper LT Peripheral arterial disease is a common but underdiagnosed and undertreated disorder with substantial morbidity and mortality. The pathophysiology of peripheral arterial disease and the risk factors for developing it are similar to those for atherosclerotic disease occurring at other sites. Peripheral arterial disease can be diagnosed accurately with simple, noninvasive, office-based tests that measure the severity of the disease and provide valuable prognostic information. Optimal medical therapy includes a supervised exercise program, tobacco cessation, and modification of treatable risk factors. Cilostazol can improve pain-free and peak walking distances in patients with intermittent claudication. As a general rule, patients with lifestyle-limiting claud... Conclusion: The results of this study suggest that combined therapy with aspirin + cilostazol is more effective than aspirin monotherapy in reducing platelet aggregation in patients after OPCAB. This combination therapy may represent a new therapeutic option for an anti-thrombotic regimen in patients after OPCAB. PMID: 18818572 [PubMed - in process] (Source: Annals of Thoracic and Cardiovascular Surgery) Cilostazol may be useful after PCI, based on meta-analysis (Source: Inpharma) Cilostazol may be useful after PCI, based on meta-analysis. Page: 14 (Source: Inpharma Weekly) This study shows that BB-MRI is a useful and less invasive method for the evaluation of DCV, and cilostazol may be effective on DCV. PMID: 18675358 [PubMed - as supplied by publisher] (Source: Neurobiology of Disease) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Conclusion Although dual antiplatelet therapy effectively inhibited its pharmacological targets, thrombin generation, inhibition of fibrinolytic activity, and endothelial dysfunction were determined by other clinical backgrounds. Our data suggested that some patients remain at risk of thrombotic complications after PCI and that these may benefit from anticoagulant treatment despite adequate dual antiplatelet therapy. (Source: European Heart Journal) Authors: Lee JH, Park SY, Shin HK, Kim CD, Lee WS, Hong KW Cilostazol increases intracellular cyclic adenosine monophosphate (cyclic AMP) levels by inhibiting type III phosphodiesterase. It was approved by the Food and Drug Administration for the treatment of intermittent claudication. Its principal actions include inhibition of platelet aggregation, antithrombotic action in cerebral ischemia, and vasodilation, mediated by increased cyclic AMP levels. In a multicenter, randomized, placebo-controlled, double-blind clinical trial, cilostazol has been shown to protect patients from recurrent cerebral infarction. It has been recently suggested that cilastozol could be useful in the treatment of transient focal cerebral ischemic injury. Beneficial effects of cilostazol in cerebral ischemic ... Tissue-specific expression of PPAR mRNAs in diabetic rats and divergent effects of cilostazol. In conclusion, mRNA expression of PPARs is tissue-specific in diabetes and may be differently affected by cilostazol, possibly because of its tissue-specific effects on cAMP content. PMID: 18641696 [PubMed - in process] (Source: Canadian Journal of Physiology and Pharmacology) Authors: Hanson MS, Stephenson AH, Bowles EA, Sridharan M, Adderley S, Sprague RS Increases in the second messenger cAMP are associated with receptor-mediated ATP release from erythrocytes. In other signaling pathways, cAMP-specific phosphodiesterases (PDEs) hydrolyze this second messenger and thereby limit its biological actions. Although rabbit and human erythrocytes possess adenylyl cyclase and synthesize cAMP, their PDE activity is poorly characterized. It was reported previously that the prostacyclin analog iloprost stimulated receptor-mediated increases in cAMP in rabbit and human erythrocytes. However, the PDEs that hydrolyze erythrocyte cAMP synthesized in response to iloprost were not identified. PDE3 inhibitors were reported to augment increases in cAMP stimulated by prostacy... Hydrolytic degradation profile and RP-HPLC estimation of cilostazol in tablet dosage form Basniwal PK, Shrivastava PK, Jain DeeptiIndian Journal of Pharmaceutical Sciences 2008 70(2):222-224 (Source: Indian Journal of Pharmaceutical Sciences) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. We report a case of DES thrombosis after cilostazol withdrawal for colonoscopic polypectomy in a patient previously treated with triple antiplatelet therapy. The patient presented with acute myocardial infarction but survived after successful emergency coronary revascularization. We discuss a plausible mechanism for DES thrombosis in the described case. PMID: 18582963 [PubMed - as supplied by publisher] (Source: International Journal of Cardiology) CONCLUSION: With triple antiplatelet therapy, the prevalence of clopidogrel resistance can be attenuated in patients undergoing PCI with DES. PMID: 18579227 [PubMed - as supplied by publisher] (Source: International Journal of Cardiology) Authors: Inoue Y, Sugano N, Jibiki M, Kudo T, Iwai T Problems associated with prosthetic graft replacement are stenosis at the anastomosis site and thrombus formation on the inner surface. Cilostazol is known to have antiplatelet activity and inhibit vascular smooth muscle cell proliferation and neointima thickening. A cilostazol derivative, (-)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]-propoxy]-2-(1H)-quinolinone (K-134), has more potent anti-platelet activity and anti-neointimal thickening activity than cilostazol in the in-vitro platelet aggregation and in-vivo anti-hyperplastic activity assay. The aim of this study was to investigate effects of cilostazol and K-134 on thrombus formation and neointimal thickening at the site of prosthetic graft replacement. Beagle d... CONCLUSIONS: Our results indicated that cilostazol exerted protective effects against endothelial senescence and dysfunction, and enhancement of NO production is a key mediator in upregulation of Sirt1. PMID: 18556572 [PubMed - as supplied by publisher] (Source: Arteriosclerosis, Thrombosis and Vascular Biology) Journal of the American Geriatrics Society, Volume 56, Issue 6, Page 1153-1154, June 2008. (Source: Journal of the American Geriatrics Society) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. CONCLUSIONS: Cilostazol appears effective and safe in reducing the risk of restenosis and repeat revascularization after PCI, but available evidence is limited by small study effects. Awaiting larger RCTs, this inexpensive treatment can be envisaged in selected patients in which drug-eluting stents are contraindicated or when there is a need for neointimal hyperplasia inhibition. PMID: 18513523 [PubMed - in process] (Source: American Heart Journal) Antiplatelet Cilostazol Is Beneficial in Diabetic and/or Hypertensive Ischemic Stroke Patients Cerebrovasc Dis 2008;26:63-70 (DOI:10.1159/000135654) (Source: Cerebrovascular Diseases) Cilostazol(Cilostazol) Tablet [TEVA PHARMACEUTICALS USA] Updated Date: May 22, 2008 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) Epidemiology, classification, and modifiable risk factors of peripheral arterial disease Nicolas W ShammasMidwest Cardiovascular Research Foundation, Cardiovascular Medicine, PC, Davenport, IA, USAAbstract: Peripheral arterial disease (PAD) is part of a global vascular problem of diffuse atherosclerosis. PAD patients die mostly of cardiac and cerebrovascular-related events and much less frequently due to obstructive disease of the lower extremities. Aggressive risk factors modification is needed to reduce cardiac mortality in PAD patients. These include smoking cessation, reduction of blood pressure to current guidelines, aggressive low density lipoprotein lowering, losing weight, controlling diabetes and the use of oral antiplatelet drugs such as aspirin or clopidogrel. In addition to quitting smoking and exercise, cilostazol and statins have been shown to reduce claudication... Management of peripheral arterial disease in the elderly: focus on cilostazol Travis M Falconer1, John W Eikelboom2, Graeme J Hankey3, Paul E Norman11School of Surgery, University of Western Australia, Fremantle Hospital, Western Australia; 2Department of Medicine, McMaster University, Hamilton, Canada; 3Department of Neurology, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western AustraliaAbstract: Symptomatic and asymptomatic peripheral arterial disease (PAD) is a common problem in the elderly. The management of PAD includes the prevention of cardiovascular events and relief of symptoms – most commonly intermittent claudication (IC). Both require treatment of the causes and consequences of atherothrombosis, but some strategies are more effective for prevention of cardiovascular events and others are more effective for the relief o... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Cilostazol as Effective as Aspirin in Prevention of Recurrent Stroke Results of a randomized pilot trial suggest that cilostazol, a PDE3 inhibitor, is as effective as aspirin in preventing recurrent stroke, with significantly lower rates of bleeding. Medscape Medical News (Source: Medscape Cardiology Headlines) Pletal(Cilostazol) Tablet [OTSUKA AMERICA PHARMACEUTICAL, INC.] Updated Date: May 7, 2008 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) Cilostazol trial holds promise for safer antiplatelet agent Cilostazol has similar efficacy to aspirin in stroke patients, but causes fewer hemorrhages, pilot study results suggest. (Source: MedWire News - Stroke) A Safer Alternative To Aspirin? A study in China has shown that the antiplatelet* drug cilostazol is as effective as aspirin at preventing recurrent stroke, but causes less bleeding events. The results suggest cilostazol could be a safer alternative to aspirin post-stroke for Chinese patients, and warrant both phase III trials and studies in other populations. These are the conclusions of authors of an Article published early Online and in the June edition of The Lancet Neurology. (Source: Pain / Anesthetics News From Medical News Today) Cilostazol as an alternative to aspirin after ischaemic stroke? The Lancet Neurology has published the CASISP study early online (cilostazol versus aspirin for secondary ischaemic stroke prevention), which evaluated the safety and efficacy of cilostazol in comparison with aspirin for the long-term prevention of the recurrence of ischaemic stroke in Chinese patients. The prospective, multicentre, double-blind, study included patients (mean age 60.2 years) who had had an ischaemic stroke within the previous 1–6 months. Patients were randomised to receive aspirin 100mg per day (n= 359) or cilostazole 100mg twice daily (n=360). The primary endpoint was defined as any occurrence of stroke, including ischaemic stroke, cerebral haemorrhage, or subarachnoid haemorrhage. The combined endpoints were defined as more than one of recurrent stroke, new myocardia... MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. A Safer Alternative to Aspirin? LONDON, May 4, 2008-A study in China has shown that the antiplatelet* drug cilostazol is as effective as aspirin at preventing recurrent stroke, but causes less bleeding events. The results suggest cilostazol could be a safer alternative to aspirin... (Source: Drugs.com - Clinical Trials) Cilostazol found may be safer than aspirin post-stroke KABUL (Reuters) - The anti-platelet drug cilostazol is as effective as aspirin at preventing recurrent stroke and appears to be linked to fewer bleeding events, a study in China has shown. (Source: Reuters: Health) Cilostazol shows promise as an alternative to aspirin for patients with ischaemic stroke. Authors: Hankey GJ PMID: 18456559 [PubMed - as supplied by publisher] (Source: Lancet Neurology) Authors: Huang Y, Cheng Y, Wu J, Li Y, Xu E, Hong Z, Li Z, Zhang W, Ding M, Gao X, Fan D, Zeng J, Wong K, Lu C, Xiao J, Yao C, BACKGROUND: Most patients who have had a stroke are given aspirin; however, aspirin-related cerebral haemorrhage is a complication that is currently of concern, particularly in China where there is a high incidence of cerebral haemorrhage in secondary prevention programmes and within the community. Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, is an alternative to aspirin that works through a different mechanism. This trial aimed to compare the efficacy and safety of cilostazol with that of aspirin for the long-term prevention of the recurrence of ischaemic stroke. METHODS: 720 patients (mean age 60.2 years, SD 9.86) who had had an ischaemic stroke withi... Is triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol) more effective than dual antiplatelet therapy for reducing late restenosis in diabetic patients undergoing DES placement? Journal of the American College of Cardiology (Source: Medscape Critical Care Headlines) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Horm Metab ResDOI: 10.1055/s-2008-1065348AbstractCilostazol, an antiplatelet drug, and probucol, a cholesterol-lowering drug, are reported to ameliorate atherosclerosis in animal models. However, their combined effect on atherosclerosis is unclear. We therefore evaluated their combined effect on atherosclerotic lesions in LDL receptor-deficient mice. Male LDL receptor-deficient mice were fed a high fat diet with or without cilostazol alone, probucol alone, or with cilostazol and probucol in combination, for 8 weeks. Body weight and plasma lipid levels were measured before and during treatment. At the end of treatment, the size distribution of plasma lipoproteins was analyzed by HPLC and then plasma HDL cholesterol levels and en face aortic atherosclerotic lesion areas were measured. Probuc... In this study, we tested the hypothesis that both SAR and CIL prevent cardiac remodeling and improve cardiac function in congestive heart failure (CHF) due to myocardial infarction (MI). Post-MI rats (3 weeks after the occlusion of coronary artery) received either vehicle (MI+V, n = 36), SAR (MI+SAR; 5 mg xc kg(-1) x day(-1), n = 35) or CIL (MI+CIL; 5 mg x kg(-1) x day(-1), n = 34) from day 21 to day 56. Sham-operated rats (n = 29) served as controls. Electrocardiographic, echocardiographic, and hemodynamic parameters were measured on day 56. Treatment of infarcted animals with SAR or CIL significantly improved the left ventricular (LV) dimensions, LV fractional shortening, cardiac output, stroke volume, mean arterial pressure, LV diastolic function, and LV systolic pressure, as well as ra... Cilostazol Activates AMP-activated Protein Kinase and Restores Endothelial Function in Diabetes. ConclusionsOur findings suggest that the beneficial effects of cilostazol on endothelial function may be due to AMPK activation. Restoration of endothelial dysfunction in diabetic rats by cilostazol is at least partly attributed to amelioration of biopterin metabolism in the aorta.American Journal of Hypertension (2008) doi:10.1038/ajh.2007.96American Journal of Hypertension (2008); 21 4. 451-457 doi:10.1038/ajh.2008.6. PMID: 18369362 [PubMed - in process] (Source: American Journal of Hypertension) Cilostazol(Cilostazol) Tablet [COREPHARMA LLC.] Updated Date: Mar 25, 2008 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) Cilostazol(Cilostazol) Tablet [Sandoz Inc.] Updated Date: Mar 19, 2008 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Cilostazol Reduces Restenosis in Diabetics Treated With Drug-Eluting Stents Treatment with cilostazol following implantation of a drug-eluting stent helps prevent late restenosis in diabetic patients treated with standard antiplatelet therapy, according to a report in the Journal of the American College of Cardiology for March 25. Reuters Health Information (Source: Medscape Diabetes Headlines) Conclusions Triple antiplatelet therapy after DES implantation decreased angiographic restenosis and extent of late loss, resulting in a reduced risk of 9-month TLR compared with dual antiplatelet therapy in diabetic patients. (Source: Journal of the American College of Cardiology) Optimal management of platelet function after coronary stenting Opinion statement Coronary stenting elicits vessel wall damage, and subsequent activation of platelets is implicated as a major component of complications such as acute, subacute, and late stent thrombosis. As such, dual antiplatelet therapy using aspirin and clopidogrel has become a routine adjunct to coronary stenting. Use of aspirin and clopidogrel with or without glycoprotein IIb/IIIa inhibitors after coronary stenting reduces the complication rate and improves long-term outcomes. Dual antiplatelet therapy using aspirin and clopidogrel is recommended for at least 4 weeks with bare metal stents, and for 3 to 6 months with drug-eluting stents for prevention of major adverse cardiac events. After coronary stenting, 1 year of dual antiplatelet therapy is recommended for pr... Cilostazol + aspirin prevents in-stent restenosis in diabetics (Source: Inpharma) Cilostazol reduces adverse outcome risk in atherothrombosis (Source: Inpharma) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Cilostazol + aspirin prevents in-stent restenosis in diabetics. Page: 10 (Source: Inpharma Weekly) Cilostazol reduces adverse outcome risk in atherothrombosis. Page: 12 (Source: Inpharma Weekly) To examine whether cilostazol, a selective phosphodiesterase type III inhibitor, protects rat articular chondrocytes against nitric oxide (NO)-induced apoptosis and prevents cartilage destruction in mono-iodoacetate-induced osteoarthritis (OA) in a rat model in which inducible nitric oxide synthase (iNOS) is expressed.The NO donor sodium nitroprusside was administered to rat articular chondrocytes that had been pretreated with cilostazol. Induction of apoptosis was evaluated by DNA electrophoresis and pulsed-field gel electrophoresis. The expression level and the subcellular location of apoptosis-associated factors were examined by Western blot analysis and confocal microscopy, respectively. Protein kinase CK2 (PKCK2) activity was also assayed. To examine whether orally administered cilost... Cilostazol(Cilostazol) Tablet [COREPHARMA LLC.] Updated Date: Feb 15, 2008 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) Cilostazol(Cilostazol) Tablet [Actavis Totowa LLC] Updated Date: Feb 15, 2008 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST)) MedWorm Message: Get the very latest Swine Flu news via the MedWorm Swine Flu RSS news feed - updated hourly from thousands of authoritative health and news sources. Clopidogrel Desensitization: Case Report and Review of Published Protocols We describe a 58-year-old man who developed a generalized diffuse rash along his abdomen within 2 weeks of exposure to clopidogrel after drug-eluting stent placement. Clopidogrel was discontinued, and ticlopidine was begun. The rash resolved within 3 days of clopidogrel discontinuation. Using the Naranjo adverse drug reaction probability scale, we determined that the probability of clopidogrel causing the rash was probable (score of 8). Ticlopidine was subsequently discontinued due to severe diarrhea. Because of the patient's implanted stent and high risk for possible thrombosis, an 8-hour clopidogrel desensitization protocol was devised and successfully used in this patient, who continued to receive clopidogrel over the next year without rash recurrence. Based on our experience and the li... Pharmacopsychiatry 2008; 41: 37-39DOI: 10.1055/s-2007-993208AbstractIn our search of a new augmentation therapy for geriatric patients with intractable depression, we administered cilostazol, an antiplatelet agent, in addition to conventional antidepressants to a patient with persistent major depressive disorder showing deep white matter hyperintensities on a T2-weighted magnetic resonance image and evaluated cerebral blood flow before and after the administration of cilostazol by Tc-ethyl-cysteinate dimer single photon emission computed tomography. This patient showed improvements of depressive symptoms as well as an increase in cerebral blood flow. These findings suggest a potential efficacy of cilostazol as a new drug for use in augmentation therapy for depressed patients with deep whit... Antiplatelet Therapy Attenuates Subcellular Remodeling in Congestive Heart Failure. Authors: Sanganalmath SK, Babick AP, Barta J, Kumamoto H, Takeda N, Dhalla NS Antiplatelet agents, sarpogrelate (SAR), a 5-HT(2A) receptor antagonist, and cilostazol (CIL), a phosphodiesterase III inhibitor, are used for the treatment of peripheral vascular disease. We tested whether these agents affect cardiac function and subcellular remodeling in congestive heart failure (CHF) induced by myocardial infarction (MI). Three weeks after MI, rats were treated daily with 5 mg/kg SAR or CIL as well as vehicle for 5 weeks. Sham-operated animals served as controls. At end of the treatment period, hemodynamic measurements were performed and the left ventricle was processed for the determination of sarcoplasmic reticulum (SR) Ca(2+)-uptake and -release activities, and expression of SR Ca(2+)-p... (Source: J Neuropsychiatry Clin Neurosci) |
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