ABSTRACT
DA-9801, a plant-based drug used for the treatment of diabetic neuropathy, is known to improve angiotensin II (Ang II)-induced vascular endothelial cell dysfunction. However, the underlying mechanism is not fully understood. We aimed to determine whether the protective effect of DA-9801 against Ang II-induced endothelial cell dysfunction was mediated via inhibition of endothelial cell inflammation and apoptosis. Ang II-induced oxidative stress was attenuated by pretreatment of human dermal microvascular endothelial cells (HDMECs) with DA-9801. This prevented the Ang II-induced upregulation of NAD(P)H oxidase (the NOX4 and p22phox subunits) and reactive oxygen species. Further, pretreatment of HDMECs with DA-9801 ameliorated Ang II-mediated nuclear factor kappa B activity via prevention of the upregulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. It also decreased the Ang II-stimulated increase in inducible nitric oxide synthase (NOS) and decreased endothelial NOS protein expression. DA-9801 decreased Ang II-induced upregulation of intercellular adhesion molecule 1, vascular adhesion molecule, and E-selectin in HDMECs. Moreover, TUNEL and annexin V-FITC fluorescence staining for apoptosis and the activities of caspases 9, 7, and 3 decreased in HDMECs pretreated with DA-9801, indicating that the drug enhanced anti-apoptotic pathways. Thus, DA-9801 modulated Ang II-induced endothelial cell dysfunction via inflammatory and apoptotic pathways.
Subject(s)
Angiotensin II/adverse effects , Apoptosis/drug effects , Endothelial Cells/pathology , Endothelial Cells/physiology , Inflammation/metabolism , Plant Preparations/pharmacology , Cells, Cultured , Dermis/cytology , Humans , Intercellular Adhesion Molecule-1/metabolism , NADPH Oxidases/metabolism , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis. We examined 93 patients with DTC over 12months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1year. The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12months, were -0.88, -1.3 and -0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine -2.1%, femoral neck -2.2%, and hip -2.1%; all P<0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P=0.041) and femoral neck (P=0.010). TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period.
Subject(s)
Bone and Bones/metabolism , Cell Differentiation/drug effects , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/metabolism , Thyrotropin/antagonists & inhibitors , Thyroxine/therapeutic use , Bone Density , Bone Resorption/complications , Bone Resorption/pathology , Bone and Bones/drug effects , Bone and Bones/physiopathology , Calcium/pharmacology , Female , Humans , Male , Middle Aged , Postmenopause/drug effects , Postoperative Period , Thyroid Neoplasms/physiopathology , Thyroid Neoplasms/surgery , Thyroxine/pharmacology , Vitamin D/pharmacologyABSTRACT
AIMS/INTRODUCTION: Little is known about the long-term effects of Roux-en-Y gastric bypass (RYGB) in severely obese Asian individuals. METHODS AND MATERIALS: A total of 33 severely obese patients with type 2 diabetes underwent RYGB. All patients were followed up for 2 years. Visceral and abdominal subcutaneous fat areas were assessed using computed tomography (CT) before, and 12 and 24 months after RYGB. The muscle attenuation (MA) of paraspinous muscles observed by CT were used as indices of intramuscular fat. RESULTS: The mean percentage weight loss was 22.2 ± 5.3% at 12 months, and 21.3 ± 5.1% at 24 months after surgery. Compared with the baseline values, the visceral fat area was 53.6 ± 17.1% lower 24 months after surgery, and the abdominal subcutaneous fat area was 32.7 ± 16.1% lower 24 months after surgery. The MA increased from 48.7 ± 10.0 at baseline to 52.2 ± 8.9 (P = 0.009) 12 months after surgery. The MA after the first 12 months maintained changes until 24 months. Triglycerides and free fatty acids were reduced after surgery, whereas the high-density lipoprotein cholesterol levels were increased significantly after surgery. At the last follow-up visit, 18 patients (55%) had diabetes remission. The percentage of iron and vitamin D deficiency was 30% and 52%, respectively. CONCLUSIONS: We found that patients subjected to RYGB had significant sustained reductions in visceral and intramuscular fat. There were durable improvements in the cardiometabolic abnormalities without any significant comorbidities. However, there were mild nutritional deficiencies in these patients despite daily supplementation with multivitamins and minerals.