[Endocrinological aspects of diabetes mellitus in the elderly].

Glucose-mediated energy production in central nervous system(CNS) reduces in the elderly. The reduction is also observed in young patients with diabetes mellitus(DM). Deviated endocrinological function is observed in both the elderly and young patients with DM.

Design, synthesis, and structure-activity relationship (SAR) of N-[7-(4-hydroxyphenoxy)-6-methylindan-4-yl]malonamic acids as thyroid hormone receptor β (TRβ) selective agonists.

Highly TRβ selective thyromimetics have several potential therapeutic applications. Based on the novel indane derivative KTA-439 with high receptor (TRβ) and organ (liver) selectivity, a series of thyroid hormone analogues were prepared, in which the isopropyl at the 3'-position was replaced with alkyl and aralkyl moieties of variable lengths and branches. Binding assays for these human TRs and reporter cell assays showed that 2-arylethyl derivatives had higher TRβ selectivity than KTA-439.

Discovery of novel indane derivatives as liver-selective thyroid hormone receptor β (TRβ) agonists for the treatment of dyslipidemia.

Thyromimetics that specifically target TRβ have been shown to reduce plasma cholesterol levels and avoid atherosclerosis through the promotion of reverse cholesterol transport in an animal model. We designed novel thyromimetics with high receptor (TRβ) and organ (liver) selectivity based on the structure of eprotirome (3) and molecular modeling. We found that indane derivatives are potent and dual-selective thyromimetics expected to avoid hypothyroidism in some tissues as well as heart toxicity.

American ginseng improves neurocognitive function in senescence-accelerated mice: possible role of the upregulated insulin and choline acetyltransferase gene expression.

Aim: To investigate the effects of American ginseng on neurocognitive function and glucose regulation in senescence-accelerated mice.

Methods: Male senescence-resistant inbred strains (SAMR1) and senescence-prone inbred strains (SAMP10) mice were divided into five groups and fed either a control diet or an American ginseng-supplemented diet (1% or 2% g/g) from 6 weeks to 10 months of age. Bodyweight, levels of fasting plasma glucose (FPG) and grading scores were monitored every month and neurocognitive functions were evaluated at 9 months of age with a KUROBOX apparatus using a stress-free positive cue task.

{mu}-Crystallin, new candidate protein in endotoxin-induced uveitis.

PURPOSE. micro-Crystallin (CRYM) is a major taxon-specific lens protein. The purpose of this study was to investigate the function of CRYM in eyes of mice with endotoxin-induced uveitis (EIU).

Five cases of severe hyponatremia in the elderly successfully treated with low doses of hydrocortisone.

Hyponatremia is commonly defined as a serum sodium concentration of 135 mEq/L or less, which is reported to occur in 0.97-2.48% of hospitalized patients.

Lymphocytic infundibuloneurohypophysitis: long-term follow-up of a case cured with glucocorticoid.

Objective: To report a case of infundibuloneurohypophysitis treated with steroid.

Clinical Presentation: A 65-year-old woman who was well until 4 weeks before admission and was not taking any medication presented with acute development of polydipsia and polyuria. Urinary volume was increased to 4,500 ml/day.

Leydig cell tumor and malignant lymphoma in a patient with nonclassical 21-hydroxylase deficiency.

A 46-year-old man was admitted in our hospital with hypoglycemia; his FPG was 43 mg/mL. Five years earlier, he underwent simultaneous surgeries for an adrenal adenoma, a benign Leydig cell tumor (LCT), and a malignant lymphoma. Based on the laboratory results, he was diagnosed as congenital adrenal hyperplasia (CAH) due to nonclassical 21-hydroxylase deficiency (21-OHD).

Acromegaly accompanied by Turner syndrome with 47,XXX/45,X/46,XX mosaicism.

A 33-year-old woman was hospitalized for examination of edematous laryngopharynx. She was acromegalic. A pituitary adenoma with elevated serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) was detected, indicating acromegaly caused by GH-secreting pituitary adenoma.

Spontaneous remission of diabetes insipidus due to CNS sarcoidosis.

Central nervous system (CNS) sarcoidosis is a crucial disease and has a poor prognosis. A 58-year-old woman had acute development of polydipsia and polyuria. Her pituitary MRI demonstrated a swelling of pituitary gland and hypophyseal stalk.

Atypical early onset of diabetes, deafness and lung cancer in a male patient with mitochondrial mutations in peripheral mononuclear cells.

As mitochondria play a major role in the conversion of dietary calories into usable energy, generating reactive oxygen species as a toxic byproduct, mitochondrial dysfunction plays a role in a wide range of age-related disorders and various forms of cancer. The present report concerns a heavy smoker who died of lung cancer at age 40. He also developed progressive diabetes and sensory hearing loss.

Biphasic function of focal adhesion kinase in endothelial tube formation induced by fibril-forming collagens.

Migration and tube formation of endothelial cells are important in angiogenesis and require a coordinated response to the extra-cellular matrix (ECM) and growth factor. Since focal adhesion kinase (FAK) integrates signals from both ECM and growth factor, we investigated its role in angiogenesis. Type I and II collagens are fibril-forming collagens and stimulate human umbilical vein endothelial cells (HUVECs) to form tube structure.

Do PPARgamma Ligands Suppress the Growth of Cholangiocarcinoma or the Cholangiohepatitis Induced by the Tumor?

Cholangiocarcinoma is a predominantly fatal cancer, which can be difficult to treat. It has been reported that the administration of pioglitazone temporarily improved not only diabetic control, but also bile duct carcinoma-induced cholangiohepatitis. Pioglitazone is considered to have both direct and indirect mechanisms of action on the tumor-related hepatitis.

Beneficial effects of pioglitazone on cholangiohepatitis induced by bile duct carcinoma.

Cholangiocarcinoma is a predominantly fatal cancer, which can be difficult to treat. We report a 73-year-old man who developed cholangiocarcinoma with cholangiohepatitis and diabetes. Administration of pioglitazone, peroxisome proliferator-activated receptor gamma (PPARgamma).

mu-crystallin, a NADPH-dependent T(3)-binding protein in cytosol.

Thyroid hormone action is initiated through nuclear thyroid hormone receptors (TRs). Before the discovery of these nuclear receptors, possible major binding sites for thyroid hormones were thought to be cytosolic owing to high thyroid hormone-binding activity in crude cytosolic fractions. Several cytosolic thyroid hormone-binding proteins have been identified, including reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent 3,5,3'-triiodo-L-thyronine (T(3))-binding protein, also known as mu-crystallin, which was initially cloned as the ortholog of bacterial ornithine cyclodeaminase.

The effect of long-term treatment with sulindac on the progression of diabetic retinopathy.

Objective: To evaluate the effects of long-term treatment with sulindac on the progression of diabetic retinopathy (DR).

Research Design And Methods: 40 Japanese patients with type 2 diabetes were enrolled in a randomized, single-blind controlled trial in which the effects of sulindac (200 mg/day, 100 mg twice a day; n = 16 patients) on the progression of DR were compared to controls (24 patients) for 3 years. All patients were comparable in their age, gender, duration of disease, body mass index, dipstick proteinuria, insulin therapy, glycemic control, and clinical stages of DR.

Adiponectin inversely correlates with high sensitive C-reactive protein and triglycerides, but not with insulin sensitivity, in apparently healthy Japanese men.

Adiponectin, an antiatherogenic peptide, has diverse biological actions on insulin sensitivity, inflammation and lipid metabolism. To explore physiological and pathophysiological significance of adiponectin in the Japanese general population, we systematically analyzed the relationship between adiponectin and high sensitive CRP (hsCRP), lipids, insulin sensitivity, and anthropometric parameters in 166 consecutive adult male health examinees. By univariate analysis, serum adiponectin was positively correlated with age and HDL-cholesterol, and inversely correlated with fasting plasma glucose, fasting insulin, homeostasis model assessment insulin-resistance, waist, body mass index, triglycerides and hsCRP.

Normal mortality in the elderly with diabetes under strict glycemic and blood pressure control: outcome of 6-year prospective study.

Mortality, macroangiopathic events and end-stage renal disease (ESRD) in the elderly under long-term, intensive multifactorial diabetes control were prospectively investigated. Three hundred and eighty-eight elderly patients (> or =65 years) with type 2 diabetes (the mean age 72.9 years, men/women ratio 176/212) were followed-up for 6 years with HbA1c 7.

Development, worsening, and improvement of diabetic microangiopathy in older people: six-year prospective study of patients under intensive diabetes control.

Objectives: To examine retinopathy and nephropathy in elderly patients with diabetes mellitus (DM) under intensive multifactorial DM control.

Design: Six-year interventional observation study.

Setting: Multicenter study including four hospitals.

Long-term follow-up of patients with multiple endocrine neoplasia type 1.

Whether early surgical treatment of non-functioning pancreas islet cell tumor (NFPT) provides a favorable quality of life and life expectancy in patients with multiple endocrine neoplasia type 1 (MEN1) remains controversial. We analyzed the long-term clinical courses and surgical outcomes of 14 Japanese patients with MEN1-associated NFPTs. NFPTs smaller than 20 mm in diameter did not show any apparent growth over a long monitoring period.