Diabetes and pregnancy can be associated in two ways: pregnancy that occurs in women who are already diabetic (diabetes of pre-gestational origin); and diabetes that occur in women who are already pregnant [gestational diabetes mellitus (GDM) (O'sullivan 1961)]. Patients with previous GDM history have higher risk of developing diabetes outside of pregnancy. Accumulating literature had suggested that adiponectin plays a role in the pathophysiology of this metabolic syndrome, and several of the common single nucleotide polymorphisms (SNP) in adiponectin gene have been identified in type 2 diabetes. Thus, one of the commonly found SNP was studied to determine its association with GDM.
Coronary atherothrombotic diseases such as coronary artery disease, peripheral vascular disease, cerebrovascular disease, and heart failure are the serious concerns of the thrombus formed in blood vessels. Anticoagulant and antiplatelet drugs are the cornerstones of the management of these diseases. To prevent the recurrence of these diseases, double antiplatelet drugs such as aspirin and clopidogrel has been the standard management in most hospitals. However, aspirin resistance and clopidogrel inefficient effects due to noncompliance with double drugs regimen can cause a sinister effect on patients. Medicinal plants serve as a greater resource for new medication and their potential currently became a topic of interest to the researchers all over the world. Traditionally, certain herbs have been used as a treatment for heart diseases but have been investigated for their antiplatelet properties. This current review explained few traditional antithrombotic herbals and their antiplatelet properties in vitro and in vivo and this is to be deeply discussed in further research.
Acute myeloid leukemia (AML) constitutively express growth factors and cytokines for survival. Chemotherapy alters these signals to induce cell death. However, drug resistance in AML remains a major hindrance to successful treatment and early warning is unavailable. Modulation of signaling pathways during chemotherapy may provide a window to detect response and predict treatment outcome. Blood samples collected from AML patients before and at day-3 of induction therapy were compared for changes in expression of CD117, CD34, pro-inflammatory cytokines and mediators of Akt and MAPK pathways, using multi-color flow cytometry. Nine patients were diagnosed as drug-resistant and seven sensitive to chemotherapy. Twelve were paired. Average percentages of CD34 (66.8 ± 11.7% vs. 26.2 ± 5.8%, p = 0.033) and pBAD (66.9 ± 8.2% vs. 28.9 ± 8.2%, p = 0.016) were significantly increased in chemo-resistant (N = 9) compared to chemo-sensitive (N = 5) samples. Percentages of CD34 were strongly correlated with pBAD (R = 0.785; p = 0.001; N = 14) and pFKHR (R = 0.755; p = 0.002; N = 14) at day-3 induction. Chemo-sensitive cases expressed significantly higher percentages of IL-18Rα (71.9 ± 9.6% vs. 29.8 ± 5.8%, p = 0.016). Though not significantly different in the outcome, IL-1β was strongly associated with activated Akt-S473, IL-6 with phosphorylated JNK and FKHR while TNF-α appeared to trigger Bim, in treated samples. These preliminary results suggested AML cells resistant to chemotherapy increased expression of CD34 and may signal through pBAD while cells sensitive to chemotherapy-induced IL18Rα expression. These were observed early during induction therapy. Identifying CD34 is interesting as it is a convenient marker to monitor drug-resistance in AML patients. Inhibition of CD34 and pBAD signaling may be important in treating drug-resistant AML.
Caffeine is therapeutically effective for treating apnea, cellulite formation, and pain management. It also exhibits neuroprotective and antioxidant activities in different models of Parkinson's disease and Alzheimer's disease. However, caffeine administration in a minimally invasive and sustainable manner through the transdermal route is challenging owing to its hydrophilic nature. Therefore, this study demonstrated a transdermal delivery approach for caffeine by utilizing hydrogel microneedle (MN) as a permeation enhancer. The influence of formulation parameters such as molecular weight (MW) of PMVE/MA (polymethyl vinyl ether/maleic anhydride) copolymer and sodium bicarbonate (NaHCO3) concentration on the swelling kinetics and mechanical integrity of the hydrogel MNs was investigated. In addition, the effect of different MN application methods and needle densities of hydrogel MN on the skin insertion efficiency and penetration depth was also evaluated. The swelling degree at equilibrium percentage (% Seq) recorded for hydrogels fabricated with Gantrez S-97 (MW = 1,500,000 Da) was significantly higher than formulation with Gantrez AN-139 (MW = 1,080,000 Da). Increasing the concentration of NaHCO3 also significantly increased the % Seq. Moreover, a 100% penetration was recorded for both the applicator and combination of applicator and thumb pressure compared with only 11% for thumb pressure alone. The average diameter of micropores created by the applicator method was 62.94 μm, which was significantly lower than the combination of both applicator and thumb pressure MN application (100.53 μm). Based on histological imaging, the penetration depth of hydrogel MN increased as the MN density per array decreased. The hydrogel MN with the optimized formulation and skin insertion parameters was tested for caffeine delivery in an in vitro Franz diffusion cell setup. Approximately 2.9 mg of caffeine was delivered within 24 h, and the drug release profile was best fitted to the Korsmeyer-Peppas model, displaying Super Case II kinetics. In conclusion, a combination of thumb and impact application methods and reduced needle density improved the skin penetration efficiency of hydrogel MNs. The results also show that hydrogel MNs fabricated from 3% w/w NaHCO3 and high MW of copolymer exhibit optimum physical and swelling properties for enhanced transdermal delivery.
Coronary artery disease is the leading cause of mortality and morbidity worldwide. The pathogenesis is mainly due to atherosclerosis, plaque rupture, and platelet thrombus formation. The main risk factors for coronary artery disease include obesity, hypercholesterolemia, smoking, diabetes, and high blood pressure. As a part of disease management, treatment options using anticoagulant and antiplatelet drugs can be applied with addition to lipid-lowering medication. However, medicinal plants comprising antiatherothrombotic effects can be used as options to combat the disease rather than drug therapies with lesser adverse effects. Therefore, the haematological effect of Berberis vulgaris L., Teucrium polium L., and Orthosiphon stamineus Benth extracts was studied using in vitro model to prevent and to treat coronary atherothrombotic disease. The aqueous, methanol, and polysaccharide extracts of B. vulgaris, T. polium, and O. stamineus, respectively, were studied for their anticoagulant and antiplatelet effect on human whole blood. Extracts were subjected to the prothrombin time (PT) and activated partial thromboplastin time (APTT) test for anticoagulant activity. The antiplatelet activity was investigated using an electrical impedance method. B. vulgaris aqueous extract (BVAE), B. vulgaris polysaccharide extract (BVPE), T. polium aqueous extract (TPAE), and T. polium polysaccharide extract (TPPE) significantly prolonged the coagulation time in a concentration-dependent manner (p<0.05). The administration of BVAE demonstrated the most effective antiplatelet activity against platelet aggregation caused by arachidonic acid (AA) and collagen. These antiplatelet activities may correspond to the presence of higher total phenolic compound, which thus inhibit the platelet aggregation activity. In conclusion, these findings provide strong evidence on the antiatherothrombotic effect of BVAE and TPAE.
Melastoma malabathricum Linn. is a perennial traditional medicine plants that grows abundantly throughout Asian countries. In this study, M. malabathricum Linn. leaf hot water crude extract with anticoagulant activity was purified through solid phase extraction cartridge and examined for the bioactive chemical constituents on blood coagulation reaction. The SPE purified fractions were, respectively, designated as F1, F2, F3, and F4, and each was subjected to the activated partial thromboplastin time (APTT) anticoagulant assay. Active anticoagulant fractions (F1, F2, and F3) were subjected to chemical characterisation evaluation. Besides, neutral sugar for carbohydrate part was also examined. F1, F2, and F3 were found to significantly prolong the anticoagulant activities in the following order, F1 > F2 > F3, in a dose dependent manner. In addition, carbohydrate, hexuronic acid, and polyphenolic moiety were measured for the active anticoagulant fractions (F1, F2, and F3). The characterisation of chemical constituents revealed that all these three fractions contained acidic polysaccharides (rhamnogalacturonan, homogalacturonan, and rhamnose hexose-pectic type polysaccharide) and polyphenolics. Hence, it was concluded that the presence of high hexuronic acids and polysaccharides, as well as polyphenolics in traditional medicinal plant, M. malabathricum, played a role in prolonging blood clotting in the intrinsic pathway.