Nobuyuki Asanuma

PPARα and GR Differentially Down-Regulate the Expression of Nuclear Factor-κB-Responsive Genes in Vascular Endothelial Cells

The antiinflammatory action of glucocorticoids is mediated partly by the inhibition of the expression of several cytokines and adhesion molecules. Some activators for nuclear receptors other than the GR have also been shown to inhibit the expression of these inflammatory molecules, although their molecular mechanisms remain unidentified. We therefore examined the effects of the PPARα activator fenofibrate and the GR activator dexamethasone on TNFα-stimulated expression of IL-6 and vascular cell adhesion molecule-1 in vascular endothelial cells. Both fenofibrate and dexamethasone reduced TNFα-induced IL-6 production in human vascular endothelial cells, but only fenofibrate reduced TNFα-stimulated vascular cell adhesion molecule-1 expression in these cells. Transient transfection of bovine aortic endothelial cells with an IL-6 promoter construct or a vascular cell adhesion molecule-1 promoter construct revealed that fenofibrate inhibited TNFα-induced IL-6 promoter as well as vascular cell adhesion molecule-...

Menopause, but not age, is an independent risk factor for fasting plasma glucose levels in nondiabetic women.

Objective:Glucose metabolism is influenced by various genetic and environmental factors. In women the prevalence of abnormal glucose metabolism is known to increase around and after age 50. The aim of this study was to determine whether menopause augments fasting plasma glucose (FPG) levels in women. Design:Of 672 Japanese women who underwent health examinations, we studied 505 nondiabetic participants who had no history of hysterectomy and had never used estrogens or progestins. All participants were administered an oral glucose tolerance test, and their blood measurements and information about their menopause status were obtained. Results:Of these 505 women, 208 were premenopausal and 297 were postmenopausal. Age, body mass index, triglycerides level, total cholesterol level, low-density lipoprotein cholesterol level, blood pressure, and homeostasis model assessment insulin sensitivity index rose across quintiles of FPG levels, whereas high-density lipoprotein cholesterol level and homeostasis model assessment pancreatic &bgr;-cell function index did not. The number of premenopausal women declined and the number of postmenopausal women increased across quintiles of FPG levels. Univariate regression analysis demonstrated that age, body mass index, triglycerides level, low-density lipoprotein cholesterol level, and menopause status were associated with FPG level, whereas high-density lipoprotein cholesterol level was not. Stepwise multivariate regression analysis showed that the independent risk factors for elevated FPG levels were body mass index, menopause, and triglycerides level, whereas age and low-density lipoprotein cholesterol level did not contribute to FPG levels. Conclusions:Menopause, but not age, is directly involved in augmented FPG levels in nondiabetic women.

Masked early symptoms of pneumonia in patients with rheumatoid arthritis during tocilizumab treatment: a report of two cases

Although reports of serious infections in clinical trials for rheumatoid arthritis (RA) with tocilizumab, anti-interleukin6 (IL-6) receptor antibody, have been relatively few, there is still some concern about infections. We report here two cases of patients who developed severe pneumonia during tocilizumab treatment for RA. Both patients initially presented with only minimal clinical symptoms and modest elevations in serum C-reactive protein. Tocilizumab might suppress the early inflammatory symptoms of pneumonia.

Independent association between insulin‐like growth factor‐I and dehydroepiandrosterone sulphate in women in middle adulthood

Objective  The age‐related decrease in circulating dehydroepiandrosterone sulphate (DHEAS) and insulin‐like growth factor (IGF)‐I levels is suggested to be involved in various age‐related changes. As both hormones are regulated differently, by ACTH and GH, respectively, reasons for the almost parallel changes of their circulating levels during ageing remain unknown. The objectives of this study were to verify variables that influence serum IGF‐I as well as DHEAS levels in subjects in middle adulthood.

Reduced epinephrine reserve in response to insulin-induced hypoglycemia in patients with pituitary adenoma

OBJECTIVE Hypoglycemia induces rapid secretion of counterregulatory hormones such as catecholamine, glucagon, cortisol, and GH. Insulin-induced hypoglycemia is used for evaluating GH-IGF-I and ACTH-adrenal axes in patients with pituitary disorders. The aim of this study was to determine whether the response of catecholamine secretion to hypoglycemia is disrupted in patients with pituitary adenoma. METHODS The study population comprised 23 patients with pituitary adenoma (non-functioning adenoma or prolactinoma). An insulin tolerance test was performed and serum catecholamines as well as plasma GH and serum cortisol were measured. RESULTS The study patients showed diminished response of plasma epinephrine to insulin-induced hypoglycemia. With the cutoff level of peak epinephrine for defining severe impairment set at 400 pg/ml, more patients with secondary adrenal insufficiency showed severe impairment of the epinephrine response than did those without it. Peak epinephrine levels to insulin-induced hypoglycemia were significantly correlated with peak cortisol levels. In patients with secondary hypothyroidism, secondary hypogonadism, GH deficiency, or diabetes insipidus, the prevalence of severe impairment of the epinephrine response was similar to that in patients without these deficiencies. CONCLUSIONS Impaired epinephrine secretion in response to insulin-induced hypoglycemia was frequently observed in patients with pituitary adenoma. This disorder was especially severe in patients with secondary adrenal insufficiency.

Regeneration of tubular complex is promoted by a free space.

Objectives: Regeneration of the pancreas is initiated by the tubular complexes that consist of a cluster of epithelia surrounded by the mesenchymal cells. They have the potential to become pancreatic lobes, but their growth stops before the complete regeneration of the organ. To elucidate the possibility that we could promote the regeneration of the pancreas, the potential for growth or differentiation of tubular complex was analyzed. Methods: The intact lobes were growing around the silk knot after ligation of the pancreas in adult mice. To develop this reaction to a quantitative assay, tubular complexes were induced on the silk strings in the pancreas and were growing into a free space under the silicon cover. The proliferation and differentiation of new lobes with or without the space were analyzed. Results: The number of tubular complexes, which express PDX-1, was increased 5.4 times by the space effect. The proliferating cell nuclear antigen labeling index of acinar cells was 1.7 times stimulated, but that of tubular complex was not changed. The amputated pancreas recovered 49.5% of the resected part under the silicon cover; however, it remained the same weight without the cover. Conclusion: The proliferation and differentiation of tubular complex are promoted by a free space.

Painless thyroiditis occurring during post-menopausal period, following remission of Graves' disease

Painless thyroiditis (also called “silent thyroiditis”) is a clinical entity that belongs to the spectrum of autoimmune thyroiditis (1). Patients usually experience an initial thyrotoxic phase, followed by a hypothyroid state and returning to a euthyroid state. This disorder often develops in patients with positive tests for anti-thyroid antibodies during the post-partum period (2). Thyrotoxicosis observed in painless thyroiditis differs from that in Graves’ disease. In the former, thyroid hormones leak into the circulation as a result of thyroid destruction, whereas in the latter anti-TSH receptor antibodies stimulate production and secretion of thyroid hormones. The therapeutic approaches for both disorders are completely different and thus differential diagnosis is important in clinical practice. Here, we describe a patient developing painless thyroiditis during menopausal pe