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Sridevi Devaraj

Publications and source records attributed to Sridevi Devaraj.

58 records · Page 4Linked to original sources
PubMed2002

Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha.

Diabetes is a major risk factor for premature atherosclerosis, and oxidative stress appears to be an important mechanism. Previously, we showed that diabetic monocytes produce increased superoxide anion (O(2)(-)), and alpha-tocopherol (AT) supplementation decreases this. The aim of this study was to elucidate the mechanism(s) of O(2)(-) release and inhibition by AT under hyperglycemic (HG) conditions in monocytes. O(2)(-) release, protein kinase C (PKC) activity, and translocation of PKC-alpha and -betaII and p47phox were increased in THP-1 cells (human monocytic cell line) under HG (15 mmol/l glucose) conditions, whereas AT supplementation inhibited these changes. AT, NADPH oxidase inhibitors (apocynin and diphenyleneiodonium chloride [DPI]), and an inhibitor to PKC-alpha and other isoforms (2,2',3,3',4,4'-hexahydroxy-1,1'-biphenyl-6,6'-dimethanol dimethyl ether [HBDDE]) but not PKC-beta II (LY379196) decreased O(2)(-) release and p47phox translocation. Antisense oligodeoxynucleotides to PKC-alpha and p47phox but not to PKC-betaII inhibited HG-induced O(2)(-) release and p47phox translocation in THP-1 cells. Under HG conditions, reactive oxygen species release from monocytes was not inhibited by agents affecting mitochondrial metabolism but was inhibited in human endothelial cells. We conclude that under HG conditions, monocytic O(2)(-) release is dependent on NADPH oxidase activity but not the mitochondrial respiratory chain; HG-induced O(2)(-) release is triggered by PKC-alpha, and AT inhibits O(2)(-) release via inhibition of PKC-alpha.

Acetophenones↗
PubMed2002

alpha-Tocopherol supplementation decreases plasminogen activator inhibitor-1 and P-selectin levels in type 2 diabetic patients.

OBJECTIVE: Type 2 diabetic subjects have an increased propensity to premature atherothrombosis. alpha-Tocopherol (AT), a potent antioxidant, has anti-inflammatory properties at high doses. The aim of the study was to test the effect of natural (RRR)-AT supplementation (1,200 IU/day) on markers of thrombosis, plasminogen activator inhibitor-1 (PAI-1), and soluble P-selectin (sP-selectin) in type 2 diabetic patients with and without macrovascular complications (MVCs) compared with matched control subjects. RESEARCH DESIGN AND METHODS: The volunteers comprised type 2 diabetic patients with (n=23) and without (n=24) MVCs and matched control subjects (n=25). Plasma levels of PAI-1 and P-selectin were assayed at baseline, after 3 months of supplementation, and after a 2-month washout phase. RESULTS: Both diabetic groups had significantly increased levels of PAI-1 compared with control subjects (P < 0.025), whereas only type 2 diabetic patients with MVCs had significantly elevated levels of sP-selectin compared with control subjects. AT supplementation significantly lowered levels of PAI-1 and sP-selectin in all three groups. The reduction in PAI-1 levels with AT supplementation was significantly greater in type 2 diabetic patients with MVCs than in those without MVCs (P=0.005). CONCLUSIONS: Thus, AT therapy decreases markers of thrombosis in diabetic patients and control subjects and could be an adjunctive therapy in the prevention of atherosclerosis.

Antioxidants↗
PubMedDate not supplied

Anemia associated with new-onset diabetes: improvement with blood glucose control.

OBJECTIVE: To evaluate the mild normochromic normocytic anemia associated with new-onset diabetes in young, otherwise healthy patients. METHODS: We undertook a retrospective review of medical records of patients with new-onset diabetes and unexplained anemia. Anemia was defined as a hemoglobin concentration of less than 12.5 g/dL in women and less than 14 g/dL in men. Patients with obvious causes of anemia, such as renal insufficiency, infection, pancreatitis, deficiency of glucose-6-phosphate dehydrogenase, hemolysis, or acute or chronic blood loss, were excluded from the study. RESULTS: In 16 otherwise seemingly healthy patients with new-onset diabetes, a normochromic normocytic anemia (mean corpuscular volume, 86.4 +/- 4 fL) was diagnosed at initial assessment. These 16 patients (8 men and 8 women) had a mean age of 33 +/- 10 years. At diagnosis, the mean glycated hemoglobin (HbA1c) was 15.5 +/- 3.4%, the mean hemoglobin concentration was 12.5 +/- 0.6 g/dL, and the mean hematocrit was 36.2 +/- 2%. All patients were treated with insulin. After a mean follow-up of 10.8 +/- 17 months, insulin treatment resulted in a decline in HbA1c to 7.7 +/- 1.7% (P<0.001; confidence interval [CI], 5.7 to 9.8). The hemoglobin concentration increased to 14.3 +/- 0.9 g/dL (P<0.001; CI, 1.22 to 2.38), and the hematocrit increased to 42.1 +/- 1.9% (P<0.001; CI, 3.59 to 7.04). All patients had hemoglobin AA and normal levels of hemoglobin A2. Men and women had equal improvement in hematologic variables after improvement in glycemic control. CONCLUSION: Some patients with new-onset diabetes have a mild normochromic normocytic anemia that is not attributable to usual causes, such as infection, pancreatitis, or blood loss. Improvement in glycemic control tends to be associated with normalization of hemoglobin levels. The cause of such cases of anemia may be either direct "glucose toxicity" to erythrocyte precursors in the bone marrow or perhaps oxidative stress to mature erythrocytes.

Adult↗