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Antiplatelet therapy in diabetic ischemic stroke patients: associated factors and outcomes

Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH

Int J Clin Pharmacol Ther, 2011 Oct;49(10):605-13.
PMID: 21961485 DOI: 10.5414/cp201574

BACKGROUND: Patients with diabetes mellitus (DM) are more prone to develop atherosclerotic complications including stroke. Moreover, as a primary and secondary prevention of stroke, antiplatelet therapy is recommended by clinical guidelines for patients with DM.

AIMS: This study aimed to determine the prevalence of antiplatelet therapy use prior to current stroke in diabetic ischemic stroke patients, to examine the factors associated with the use of this important therapy and to assess the impact of the previous use of antiplatelet therapy on ischemic stroke outcomes.

METHODS: An observational study of diabetic acute ischemic stroke patients attending a Malaysian hospital during a 1-year period was carried out. Demographic information, risk factors, previous antiplatelet use and variables used to assess stroke outcomes were collected from medical records.

RESULTS: Overall, 295 diabetic stroke patients were analyzed. The prevalence of previous antiplatelet use among diabetic patients was 38.3%. The independent variables associated with the previous use of antiplatelet medication were previous stroke attack (p < 0.001) and ischemic heart disease (p < 0.001). Better outcomes as measured by a minor Glasgow Coma Scale at admission (p = 0.032), and a higher Modified Barthel index at discharge (p = 0.027) were observed among patients on previous antiplatelet therapy.

CONCLUSION: Our data suggest that antiplatelet therapy is under prescribed among such diabetic stroke patients, particularly in primary prevention. Effective methods to increase antiplatelet use and to enhance the adherence of clinical practice guidelines should be considered at the national and community level.

Matched MeSH terms: Diabetic Angiopathies/drug therapy*
Fulltext Boldine Ameliorates Vascular Oxidative Stress and Endothelial Dysfunction: Therapeutic Implication for Hypertension and Diabetes

Lau YS, Ling WC, Murugan D, Mustafa MR

J Cardiovasc Pharmacol, 2015 Jun;65(6):522-31.
PMID: 25469805 DOI: 10.1097/FJC.0000000000000185

Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, are a rich source of antioxidants. Boldine [(S)-2,9-dihydroxy-1,10-dimethoxy-aporphine], an aporphine alkaloid, is a potent antioxidant found in the leaves and bark of the Chilean boldo tree. Boldine has been extensively reported as a potent "natural" antioxidant and possesses several health-promoting properties like anti-inflammatory, antitumor promoting, antidiabetic, and cytoprotective. Boldine exhibited significant endothelial protective effect in animal models of hypertension and diabetes mellitus. In isolated thoracic aorta of spontaneously hypertensive rats, streptozotocin-induced diabetic rats, and db/db mice, repeated treatment of boldine significantly improved the attenuated acetylcholine-induced endothelium-dependent relaxations. The endothelial protective role of boldine correlated with increased nitric oxide levels and reduction of vascular reactive oxygen species via inhibition of the nicotinamide adenine dinucleotide phosphate oxidase subunits, p47 and nicotinamide adenine dinucleotide phosphate oxidase 2, and angiotensin II-induced bone morphogenetic protein-4 oxidative stress cascade with downregulation of angiotensin II type 1 receptor and bone morphogenetic protein-4 expression. Taken together, it seems that boldine may exert protective effects on the endothelium via several mechanisms, including protecting nitric oxide from degradation by reactive oxygen species as in oxidative stress-related diseases. The present review supports a complimentary therapeutic role of the phytochemical, boldine, against endothelial dysfunctions associated with hypertension and diabetes mellitus by interfering with the oxidative stress-mediated signaling pathway.

Matched MeSH terms: Diabetic Angiopathies/drug therapy*
Dual l-Carnosine/Aloe vera Nanophytosomes with Synergistically Enhanced Protective Effects against Methylglyoxal-Induced Angiogenesis Impairment

Darvishi B, Dinarvand R, Mohammadpour H, Kamarul T, Sharifi AM

Mol Pharm, 2021 09 06;18(9):3302-3325.
PMID: 34297586 DOI: 10.1021/acs.molpharmaceut.1c00248

Microvascular complications are among the major outcomes of patients with type II diabetes mellitus, which are the consequences of impaired physiological functioning of small blood vessels and angiogenic responses in these patients. Overproduction and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl byproduct of glycolysis pathway, has been acclaimed as the main inducer of impaired angiogenic responses and microvascular dysfunction in diabetic patients with uncontrolled hyperglycemia. Hence, an effective approach to overcome diabetes-associated microvascular complications is to neutralize the deleterious activity of enhanced the concentration of MGO in the body. Owing to the glycation inhibitory activity of Aloe vera whole extract, and capability of l-carnosine, an endogenous dipeptide, in attenuating MGO's destructive activity, we examined whether application of a combination of l-carnosine and A. vera could be an effective way of synergistically weakening this reactive dicarbonyl's impaired angiogenic effects. Additionally, overcoming the poor cellular uptake and internalization of l-carnosine and A. vera, a nanophytosomal formulation of the physical mixture of two compounds was also established. Although l-carnosine and A. vera at whole studied combination ratios could synergistically enhance viability of human umbilical vein endothelial cells (HUVECs) treated with MGO, the 25:1 w/w ratio was the most effective one among the others (27 ± 0.5% compared to 12 ± 0.3 to 18 ± 0.4%; F (4, 15) = 183.9, P < 0.0001). Developing dual nanophytosomes of l-carnosine/A. vera (25:1) combination ratio, we demonstrated superiority of the nanophytosomal formulation in protecting HUVECs against MGO-induced toxicity following a 24-72 h incubation period (17.3, 15.8, and 12.4% respectively). Moreover, 500 μg/mL concentration of dual l-carnosine/A. vera nanophytosomes exhibited a superior free radical scavenging potency (63 ± 4 RFU vs 83 ± 5 RFU; F (5, 12) = 54.81, P < 0.0001) and nitric oxide synthesizing capacity (26.11 ± 0.19 vs 5.1 ± 0.33; F (5, 12) = 2537, P < 0.0001) compared to their physical combination counterpart. Similarly, 500 μg/mL dual l-carnosine/A. vera nanophytosome-treated HUVECs demonstrated a superior tube formation capacity (15 ± 3 vs 2 ± 0.3; F (5, 12) = 30.87, P < 0.001), wound scratch healing capability (4.92 ± 0.3 vs 3.07 ± 0.3 mm/h; F (5, 12) = 39.21, P < 0.0001), and transwell migration (586 ± 32 vs 394 ± 18; F (5, 12) = 231.8, P < 0.001) and invasion (172 ± 9 vs 115 ± 5; F (5, 12) = 581.1, P < 0.0001) activities compared to the physical combination treated ones. Further confirming the proangiogenic activity of the dual l-carnosine/A. vera nanophytosomes, a significant shift toward expression of proangiogenic genes including HIF-1α, VEGFA, bFGF, KDR, and Ang II was reported in treated HUVECs. Overall, dual l-carnosine/A. vera nanophytosomes could be a potential candidate for attenuating type II DM-associated microvascular complications with an impaired angiogenesis background.

Matched MeSH terms: Diabetic Angiopathies/drug therapy*
Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study

Rahman S, Ismail AA, Ismail SB, Naing NN, Abdul Rahman AR

Eur J Clin Pharmacol, 2007 Aug;63(8):733-41.
PMID: 17565489 DOI: 10.1007/s00228-007-0315-3

OBJECTIVE: To investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT).

METHODS: In this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.

RESULTS: Rosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period.

CONCLUSIONS: Rosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.

Matched MeSH terms: Diabetic Angiopathies/drug therapy
Treatment for diabetic ulcer wounds using a fern tannin optimized hydrogel formulation with antibacterial and antioxidative properties

Lai JC, Lai HY, Nalamolu KR, Ng SF

J Ethnopharmacol, 2016 08 02;189:277-89.
PMID: 27208868 DOI: 10.1016/j.jep.2016.05.032

ETHNOPHARMACOLOGICAL RELEVANCE: Blechnum orientale Linn. (B. orientale) is a fern traditionally used by the natives as a poultice to treat wounds, boils, ulcers, blisters, abscesses, and sores on the skin.
AIM OF THE STUDY: To investigate the wound healing ability of a concentrated extract of B. orientale in a hydrogel formulation in healing diabetic ulcer wounds.
MATERIALS AND METHODS: The water extract from the leaves of B. orientale was separated from the crude methanolic extract and subjected to flash column chromatography techniques to produce concentrated fractions. These fractions were tested for phytochemical composition, tannin content, antioxidative and antibacterial activity. The bioactive fraction was formulated into a sodium carboxymethylcellulose hydrogel. The extract-loaded hydrogels were then characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. Wound size was measured for 14 days. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. All possible mean values were subjected to statistical analysis using One-way ANOVA and post-hoc with Tukey's T-test (P<0.05).
RESULTS: One fraction exhibited strong antioxidative and antibacterial activity. The fraction was also highly saturated with tannins, particularly condensed tannins. Fraction W5-1 exhibited stronger antioxidant activity compared to three standards (α-Tocopherol, BHT and Trolox-C). Antibacterial activity was also present, and notably bactericidal towards Methicillin-resistant Staphylococcus aureus (MRSA) at 0.25mg/ml. The extract-loaded hydrogels exhibited shear-thinning properties, with high moisture retention ability. The bioactive fraction at 4% w/w was shown to be able to close diabetic wounds by Day 12 on average. Other groups, including controls, only exhibited wound closure by Day 14 (or not at all). Histopathological studies had also shown that extract-treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis.
CONCLUSION: The ethnopharmacological effects of using B. orientale as a topical treatment for external wounds was validated and was also significantly effective in treating diabetic ulcer wounds. Thus, B. orientale extract hydrogel may be presented as a potential treatment for diabetic ulcer wounds.

Matched MeSH terms: Diabetic Angiopathies/drug therapy*