Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cilostazol, a selective phosphodiesterase type III inhibitor, has vasodilatory, antiplatelet, and antithrombotic actions, as well as being the first-choice drug for the intermittent claudication due to peripheral vascular disease. Main researches have demonstrated significant improvement for this situation, including patients with diabetes mellitus, concerning pain-free walking distance and quality-of-life, not rising the bleeding event risk. It does not affect the glucose metabolism even in patients suffering from diabetes. This paper aims to present a review on the discoveries of various studies, most of them experimental, on the prevention and treatment of diabetes mellitus complications, such as nephropathy and neuropathy, through the use of cilostazol, which demonstrated satisfactory results on the improvement in neural blood flow, on sodium-potassium ATPase activity, on insulin resistance, and microalbuminuria. However, strict controlling of glucose plasma levels, hypertension, and smoking habits, as well as more extended investigations on the matter are required to the better comprehension.
...
PMID:[Potential therapeutic approaches for prevention and treatment of diabetic nephropathy and neuropathy: evidences of cilostazol]. 1820 97

Cilostazol and ligands of peroxisome proliferator-activated receptors (PPARs) have been effectively used to alleviate diabetic complications, but the common and tissue-specific expression patterns of PPARs in different tissues in diabetic patients and those treated with cilostazol have not been reported. Here, we aimed to assess the effects of diabetes and cilostazol on mRNA expression of PPARalpha and PPARgamma in the aorta, renal cortex, and retina of diabetic rats treated with cilostazol for 8 weeks. PPARalpha mRNA expression showed uniform downregulation in all these tissues in diabetic rats, and this effect was reversed by cilostazol treatment. Surprisingly, PPARgamma mRNA expression was reduced in the renal cortex and retina, yet increased in the aorta of diabetic rats, although cilostazol still reversed these changes. Interestingly, cilostazol, a well-known phosphodiesterase 3 inhibitor and cAMP elevator, augmented cAMP content only in the aorta, but showed no significant effects in the renal cortex of diabetic rats. 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:Tissue-specific expression of PPAR mRNAs in diabetic rats and divergent effects of cilostazol. 1864 96

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 -untreated OLETF and control (Long Evans Tokushima Otsuka) rats, we examined the acetylcholine-induced endothelium-dependent responses and the cell-permeant cyclic adenosine monophosphate (cAMP) analog-induced relaxations in the superior mesenteric artery. We also determined blood parameters in these animals. In OLETF rats, chronic treatment with cilostazol reduced the blood levels of triglyceride, non-esterified fatty acids, and leptin, and increased antioxidant capacity, but did not alter the blood glucose or insulin levels. In studies on mesenteric arteries from cilostazol-treated OLETF animals, the cilostazol treatment improved: (a) the acetylcholine-induced EDHF-mediated relaxation and (b) the cAMP-mediated relaxation. However, cilostazol did not alter the NO-mediated relaxation or the endothelium-derived contracting factor-mediated contraction. These results suggest that cilostazol improves endothelial functions in OLETF mesenteric arteries by increasing EDHF signaling, and that it normalizes some metabolic abnormalities in OLETF rats. On that basis, cilostazol may prove to be a potent drug for the clinical treatment of diabetic vasculopathy.
...
PMID:Cilostazol improves endothelial dysfunction by increasing endothelium-derived hyperpolarizing factor response in mesenteric arteries from Type 2 diabetic rats. 1893 Jul 28

Peripheral arterial disease (PAD) is a common manifestation of atherosclerotic vascular disease. Its incidence increases with age and in the presence of known cardiovascular risk factors (eg, smoking and diabetes). PAD frequently coexists with coronary and/or cerebrovascular disease, probably because of common risk factors. Asymptomatic PAD of the lower limbs (defined as an ankle-brachial index of less than 0.9) is believed to be approximately three to four times more common than symptomatic PAD. Both symptomatic and asymptomatic diseases are associated with high risk of cardiovascular mortality and morbidity. Therefore, patients with PAD are candidates for preventive strategies for cardiovascular events. Platelet activation and aggregation is believed to significantly contribute to atherothrombotic events. Thus, patients with PAD can benefit from antiplatelet therapy. Both acetylsalicylic acid and clopidogrel decrease serious cardiovascular events in patients with PAD. However, acetylsalicylic acid is the preferred agent because of its low cost and wide availability. Cilostazol is recommended for use in patients with severe and disabling symptoms but not for asymptomatic or less disabling disease. Currently, there is insufficient evidence to recommend routine use of newer agents such as picotamide in patients with PAD.
...
PMID:Medical management and cardiovascular risk reduction in peripheral arterial disease. 1934 25

Increased expression of plasminogen activator inhibitor-1 (PAI-1) in vascular tissues is a potential factor linking diabetes to restenosis after percutaneous coronary intervention. Recent studies have shown that cilostazol, a selective type 3 phosphodiesterase inhibitor, prevents neointimal hyperplasia and in-stent thrombosis in patients with diabetes after coronary angioplasty and stent implantation. However, the molecular mechanism of this drug has not been fully elucidated. 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-beta-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-beta, 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 stent implantation.
...
PMID:Cilostazol inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor expression in artery wall and neointimal region after vascular injury. 1958 29

Although cilostazol has decreased restenosis and target lesion revascularization (TLR) after drug-eluting stent implantation, it is not known if this effect is durable at 2 years. We analyzed 2 randomized studies (Drug-Eluting stenting followed by Cilostazol treatment reduces LAte REstenosis in patients with DIABETES mellitus and Drug-Eluting Stenting Followed by Cilostazol treatment reduces LAte REstenosis in patients with LONG native coronary lesions trials) in which 900 patients were randomly assigned to triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol; triple group, n = 450) and dual antiplatelet therapy (aspirin and clopidogrel; standard group, n = 450) for 6 months in patients with diabetes or long lesions receiving drug-eluting stents. We evaluated 2-year major adverse cardiac events (MACEs) including death, myocardial infarction (MI), and TLR. Nine-month TLRs and MACEs were significantly decreased in the triple versus standard group. At 2 years, the triple group sowed significantly decreased TLRs (4.2% vs 9.1%, hazard ratio 0.45, 95% confidence interval 0.26 to 0.78, p = 0.004) and MACEs (5.6% vs 10.4%, hazard ratio 0.52, 95% confidence interval 0.32 to 0.84, p = 0.008) compared to the standard group with no differences in death and MI. In subgroup analysis, triple antiplatelet therapy decrease of 2-year TLR was favorable in all subgroups, especially in patients with paclitaxel-eluting stents, diabetes mellitus, small vessels, long lesions, and left anterior descending coronary artery lesions. 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.
...
PMID:Comparison of Triple antiplatelet therapy and dual antiplatelet therapy in patients at high risk of restenosis after drug-eluting stent implantation (from the DECLARE-DIABETES and -LONG Trials). 2010 13

Pharmacologic therapy for intermittent claudication in patients with peripheral artery disease (PAD) is limited. We aimed to determine the durability of cilostazol treatment response over time, treatment effects in various subpopulations, and long-term safety. This analysis pooled original data from nine randomized, controlled trials evaluating cilostazol in intermittent claudication, including 1258 subjects treated with cilostazol 100 mg bid. Analysis of covariance was used to compare differences in walking distance, and a pooled random-effects weighted mean difference in maximal walking distance (MWD) was determined. Temporal effects were analyzed by compiling data at 4-week intervals in studies of 24 weeks in duration. Cilostazol was associated with a 50.7% improvement from baseline in MWD compared with placebo (24.3%), with an absolute improvement of 42.1 meters greater than the improvement with placebo (p < 0.001) over a mean follow-up period of 20.4 weeks. Continued increases were demonstrated over the 24-week treatment period. These benefits were seen in all subgroups, after stratifying by age, sex, smoking status, duration of PAD, diabetes, hypertension, prior myocardial infarction, or beta-blocker use. Cilostazol did not increase the risk of all-cause mortality (RR 0.95 [0.68-1.35]). In conclusion, treatment with cilostazol achieves benefits in walking distance that are sustained at 24 weeks and observed irrespective of baseline clinical characteristics. Cilostazol demonstrated no increased risk of all-cause mortality.
...
PMID:A pooled analysis of the durability and predictors of treatment response of cilostazol in patients with intermittent claudication. 2038 11

Diabetic nephropathy is characterized as the progressive development of renal insufficiency in a setting of hyperglycemia. Previous studies indicate that reactive oxygen species (ROS) play an important role in high glucose-induced renal injury. Cilostazol was reported to lower the production of superoxide significantly in situ. We hypothesized that cilostazol administration in streptozotocin-induced diabetic rats exerts effects via improving oxidative stress. Male Sprague-Dawley rats were fed with cilostazol (5 mg/kg or 25 mg/kg) for 12 weeks after streptozotocin-induced diabetes mellitus. The results showed that cilostazol decreased reactive oxygen species activity significantly in the kidneys of diabetic rats and improved the urine albumin/creatinine ratio. Cilostazol can also improve the levels of serum cholesterol, triglyceride, and LDL-cholesterol. Additionally, diabetes-caused increased glomerular size, TGF-beta, and NF-kappaB decreased under treatment with cilostazol in diabetic rats. Our results indicate that cilostazol has beneficial effects in early diabetic nephropathy.
...
PMID:Cilostazol ameliorates nephropathy in type 1 diabetic rats involving improvement in oxidative stress and regulation of TGF-Beta and NF-kappaB. 2062 54

Cilostazol is a platelet inhibitor which when added to aspirin and clopidogrel has shown to reduce the risk of recurrent ischaemic events without an increase in bleeding. These clinical benefits have shown to be more pronounced in patients with diabetes mellitus (DM). However, it remains unknown whether cilostazol exerts different pharmacodynamic effects in patients with and without DM. This was a randomised, double-blind, placebo-controlled, cross-over pharmacodynamic study comparing platelet function in patients with and without DM on aspirin and clopidogrel therapy. Patients (n=111) were randomly assigned to either cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment for another 14 days. Platelet function was performed at baseline, 14 days post-randomisation, and 14 days post-cross-over. Functional testing to assess P2Y12 signalling included flow cytometric analysis of phosphorylation status of vasodilator-stimulated phosphoprotein measured by P2Y12 reactivity index (PRI), light transmittance aggregometry and VerifyNow. Thrombin generation processes were also studied using thrombelastography. Significantly lower PRI values were observed following treatment with cilostazol compared with placebo both in DM and non-DM groups (p < 0.0001). The absolute between-treatment differences of PRI between groups was a 35.1% lower in patients with DM (p=0.039). Similar results were obtained using all other functional measures assessing P2Y12 signalling. Thrombin generation was not affected by cilostazol. Cilostazol reduces platelet reactivity both in patients with and without DM, although these pharmacodynamic effects are enhanced in patients with DM. Despite the marked platelet inhibition, cilostazol does not alter thrombin-mediated haemostatic processes, which may explain its ischaemic benefit without the increased risk of bleeding.
...
PMID:Impact of adjunctive cilostazol therapy on platelet function profiles in patients with and without diabetes mellitus on aspirin and clopidogrel therapy. 2161 14

Patients with peripheral arterial disease (PAD) are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Smoking should be stopped and hypertension, dyslipidemia, diabetes mellitus, and hypothyroidism treated. Statins decrease the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia. The serum low-density lipoprotein cholesterol should be reduced to <70 mg/dL. Antiplatelet drugs such as aspirin or clopidogrel, angiotensin-converting enzyme (ACE) inhibitors, and statins should be given to patients with PAD. Beta blockers should be given if coronary artery disease is present. Cilostazol improves exercise time until intermittent claudication. Exercise rehabilitation programs should be used. Revascularization should be performed if indicated. Patients with an infrarenal or juxtarenal abdominal aortic aneurysm (AAA) measuring 5.5 cm or larger should undergo repair to eliminate the risk of rupture. Patients with an infrarenal or juxtarenal AAA measuring 4.0 to 5.4 cm in diameter should be monitored by ultrasound or computed tomographic scans every 6 to 12 months to detect expansion. Patients with an AAA should undergo intensive risk factor modification, be treated with ACE inhibitors, statins, and beta blockers, and undergo surgery if indicated.
...
PMID:Peripheral arterial disease and abdominal aortic aneurysm in elderly people. 2219 80


<< Previous 1 2 3 4 5 Next >>

---