Browsing by Author "Deepa, D"

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    Evidence for an exclusive association of matrix metalloproteinase-9 with dysfunctional high-density lipoprotein: A novel finding
    (Atherosclerosis, 2014-09) Sini, S; Deepa, D; Harikrishnan, S; Jayakumari, N
    OBJECTIVE: High-density lipoprotein is a heterogeneous class of lipoprotein with diverse antiatherogenic functions. However, these antiatherogenic properties of HDL can be compromised in atherosclerotic conditions. We have recently identified dysfunctionality in HDL even among healthy subjects, during systemic inflammation. This study was carried out with the objective of examining whether dysfunctional HDL is associated with pro-inflammatory proteins other than the acute phase proteins as reported earlier. METHODS: Serum HDL was isolated by three different methods-density gradient ultracentrifugation, PEG precipitation and electroelution. The antioxidant property of HDL was assessed as change in oxidation of LDL based on Dichloro-dihydro-fluorescein diacetate assay. HDL was subjected to gelatin zymography and western blot for assessment of MMP 9 activity. RESULTS: Dysfunctional HDL did not prevent the auto-oxidation of LDL. On the contrary the oxidation was enhanced. The zymogram data indicated enhanced MMP-9 activity selectively in dysfunctional HDL, irrespective of HDL isolation methods. This was confirmed by western blot of HDL probed with antibody specific to MMP 9. We also observed that dysfunctional HDL induced inflammatory response in monocyte/macrophages as evidenced by enhanced TNF-α and decreased IL-10 production. Further, invitro incubation of functional HDL with MMP-9 provided direct evidence for the association of MMP-9 with HDL and the role of MMP-9 in HDL dysfunction. CONCLUSION: A remarkable finding in the present study is the previously unrecognized association of MMP-9 with dysfunctional HDL and its proinflammatory property, indicating a novel molecular connection that can enhance the risk of cardiovascular disease in subjects with dysfunctional HDL.
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    Oxidative stress is increased in women with epilepsy: Is it a potential mechanism of anti-epileptic drug-induced teratogenesis
    (ANNALS OF INDIAN ACADEMY OF NEUROLOGY, 2012) Deepa, D; Jayakumari, N; Thomas, SV
    Context: Oxidative stress can be a final common pathway for AED-induced teratogenesis. Aims: To compare the oxidative stress of women with epilepsy (WWE) and unfavorable pregnancy outcome (fetal malformation or spontaneous abortion - group EM) with that of WWE with normal pregnancy outcome (group ENM) and healthy women with normal pregnancy outcome (group C). Materials and Methods: We identified WWE under group EM (n = 43) and group ENM (n = 22) from the Kerala Registry of Epilepsy and Pregnancy (KREP). Group C was constituted of healthy volunteers (N = 20). Oxidative stress was assessed by estimating serum levels of malondialdehyde (MDA) and isoprostane (ISP). The antioxidant profile was evaluated as activity of superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT), total antioxidant status (TAO), and glutathione (GSH) content. Results: The MDA and ISP levels for group EM (3.46 0.82 and 17.77 3.0) were higher than that of group ENM (3.07 1.02 and 14.0 5.3), and both were significantly higher than that of group C (2.42 0.51 and 10.77 4.1). Their levels of SOD (146.82 42.64 vs. 175.81 42.61) and GSH (0.98 0.98 vs. 1.55 1.3) were significantly lower than those of controls. No significant changes were seen in TAO and GR. WWE on polytherapy showed significant increase in MDA when compared to monotherapy group. Conclusion: WWE (group EM and ENM) had higher oxidative stress and reduced antioxidant activity. The subgroup of WWE with unfavorable pregnancy outcome (group EM) had higher oxidative stress. Excess oxidative stress can be a final common pathway, by which AEDs exert teratogenic effects.
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