ABSTRACT
Pemafibrate, a selective peroxisome proliferator-activated receptor (PPAR) α modulator, is a new drug that specifically modulates PPARα conformation and co-activator recruitment, thereby lowers plasma triglycerides with less off-target effects. Classical PPARα ligands such as fenofibrate suppress inflammatory cells including microglia. However, effects of pemafibrate on microglia have never been addressed. Here we show that pemafibrate, like other PPARα ligands, potently suppressed NF-κB phosphorylation and cytokine expression in microglial cells. PPARα knockdown significantly amplified LPS-induced cytokine expression. Pemafibrate-induced suppression of IL-6 expression was reversed by PPARα knockdown. However, suppression by fenofibrate was not reversed by PPARα knockdown but by Sirtuin 1 (SIRT1) knockdown. In conclusion, pemafibrate and fenofibrate similarly suppresses microglial activation but through distinct PPARα and SIRT1-dependet pathways.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Benzoxazoles/pharmacology , Butyrates/pharmacology , Microglia/drug effects , PPAR alpha/metabolism , Signal Transduction/drug effects , Sirtuin 1/metabolism , Animals , Cell Line , Inflammation/drug therapy , Inflammation/metabolism , Male , Mice , Mice, Inbred C57BL , Microglia/metabolismABSTRACT
We report of a case of Graves' ophthalmopathy presented solely with symptoms of the eyes with normal thyroid function tests and negative immunoreactive TSH receptor autoantibody. 40-year-old male was referred to our hospital due to 2-month history of ocular focusing deficit without any signs or symptoms of hyper- or hypothyroidism. Serum thyroid function tests and 99mTc uptake were both within the normal range. Anti-thyroid autoantibodies were all negative except for the cell-based assay for serum TSH receptor stimulating activity. Since orbital CT scan and MRI gave typical results compatible with Graves' ophthalmopathy, we treated the patients with corticosteroid pulse therapy and orbital radiation therapy, leading to a partial improvement of the symptoms. This case gives insights into the potential pathophysiologic mechanism underlying Graves' ophthalmopathy and casts light upon the difficulties of establishing the diagnosis in a euthyroid case with minimal positive results for anti-thyroid autoantibodies.
ABSTRACT
We herein describe a case of pulmonary tumor thrombotic microangiopathy (PTTM) with rapidly progressing colon cancer. A 61-year-old man who had been receiving treatment for type 2 diabetes mellitus for 3 years was hospitalized due to critical hypoxemia. Computed tomography, which had not shown any abnormalities 3 months previously, revealed a tumor in the ascending colon, multiple nodules in the liver, and the absence of any lung abnormalities. On day 3 of hospitalization, a sudden onset of severe dyspnea and tachycardia occurred, followed by death. Autopsy revealed microscopic metastatic tumor emboli in multiple pulmonary vessels with fibrin thrombus and intimal proliferation, which led to a diagnosis of PTTM.
Subject(s)
Colonic Neoplasms/complications , Colonic Neoplasms/pathology , Diabetes Mellitus, Type 2/complications , Lung Neoplasms/complications , Lung Neoplasms/secondary , Thrombotic Microangiopathies/complications , Autopsy , Humans , Hypoxia , Liver/pathology , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasms, Second Primary , Neoplastic Cells, Circulating/pathology , Thrombotic Microangiopathies/pathology , Tomography, X-Ray ComputedABSTRACT
Clinicians sometimes encounter difficulty in diagnosing hypoglycaemia. Here, we present a case report of a 53-year-old woman with recurrent nocturnal hypoglycaemia. A continuous glucose monitoring system (CGMS) revealed postprandial hyperglycaemia and subsequent hypoglycaemia, and an oral glucose tolerance test showed an impaired glycaemic and delayed hyperinsulinaemic pattern. On the basis of these clinical findings, we diagnosed her unexplained hypoglycaemia as reactive hypoglycaemia. CGMS showed a sharp contrast of diurnal variation in blood glucose levels including hypoglycaemia between before and after treatment with an alpha-glucosidase inhibitor, voglibose. Her hypoglycaemic attacks disappeared.