ABSTRACT
AIM: Angiotensin II receptor blockers (ARB) have been shown to lower insulin resistance in obese diabetic animal models and to reduce the risk of new-onset diabetes in hypertensive patients. In the present study, we studied whether telmisartan, an ARB with partial peroxisome proliferator-activated receptor-gamma (PPARgamma) activity, can exert a direct effect against fatty-acid-induced oxidative stress in pancreatic beta-cells. METHODS: The effect of telmisartan on lipotoxicity was evaluated using mouse insulin-secreting clonal MIN6 and isolated mouse pancreatic islet cells. Reactive oxygen species, protein kinase-C (PKC) activity and NAD(P)H oxidase activity were examined to clarify the underlying mechanisms. RESULT: Telmisartan decreased the accumulation of palmitate-induced reactive oxygen species in MIN6 cells by 25% and in mouse islet cells by 55%. Telmisartan also decreased palmitate-induced PKC activity by 36% and NAD(P)H oxidase activity by 32% in MIN6 cells. CONCLUSION: These findings indicate that telmisartan attenuated fatty-acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells. Our observations pave the way to the possible use of ARB as a means of protecting beta-cell survival and preserving insulin secretion capacity in patients with diabetes mellitus.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Benzimidazoles/pharmacology , Benzoates/pharmacology , Insulin-Secreting Cells/drug effects , NADPH Oxidases/metabolism , Oxidative Stress/drug effects , Animals , Clone Cells , Female , Glucose/administration & dosage , Glucose/metabolism , In Vitro Techniques , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/ultrastructure , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Islets of Langerhans/ultrastructure , Mice , Mice, Inbred C57BL , Microscopy, Confocal , Palmitic Acid/toxicity , Protein Kinase C/metabolism , Reactive Oxygen Species/metabolism , TelmisartanABSTRACT
Left atrial myxoma was diagnosed in a 42-year-old woman who had cutaneous and neurological manifestations without cardiac symptoms or signs. A two-dimensional echocardiogram revealed an orange-sized mobile mass in the left atrium. Magnetic resonance imaging showed multiple cerebral infarctions. Cardiac surgery for removal of the left atrial myxoma was successful and histopathology confirmed myxoma. Cutaneous and neurological manifestations were improved after the operation. Early surgical intervention may prevent the onset of severe neurological deficits in such patients.
Subject(s)
Erythema/etiology , Heart Neoplasms/complications , Memory Disorders/etiology , Myxoma/complications , Adult , Cerebral Infarction/diagnosis , Cerebral Infarction/etiology , Echocardiography , Female , Heart Atria , Heart Neoplasms/diagnosis , Humans , Magnetic Resonance Imaging , Myxoma/diagnosisABSTRACT
Tissue eosinophils have been previously implicated in allograft rejection and graft loss. The aim of this study was to evaluate the role of eosinophils in acute renal allograft rejection. Data from 71 patients with 114 renal biopsies with acute allograft rejection were compared with those from 26 controls. The median tissue eosinophil density (0.4-1.1 eosinophils per micron2 x 10(6)) and the median peripheral blood eosinophilia (1.5-3.0%) in all grades of acute interstitial rejection and in acute vascular rejection were higher than in controls (0.0 eosinophils per micron2 x 10(6), p < 0.0023, and 0.9%, p < 0.035). In all grades of rejection, 36-54% of biopsies had tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6), and 20-36% of patients had peripheral blood eosinophilia > or = 4%, compared with 0% and 4%, respectively, in controls (p < 0.000 and p = 0.0245). The sensitivity, specificity and overall accuracy of predicting acute rejection with tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6) is 41%, 100% and 52%, and for peripheral blood eosinophila > or = 4% is 23%, 96% and 40%, respectively. The median tissue eosinophil density in acute rejection with graft loss was 1.9 eosinophils per micron2 x 10(6) compared to 0.2 eosinophils per micron2 x 10(6) in acute rejection without graft loss (p = 0.014), and 67% of acute rejection with graft loss had tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6) compared with 28% of acute rejection without graft loss (p = 0.028).(ABSTRACT TRUNCATED AT 250 WORDS)
