Cyclic ferrocenylnaphthalene diimide derivative as a new class of G-quadruplex DNA binding ligand.

To identify an effective ligand that binds to a G-quadruplex structure but not a double-stranded DNA (dsDNA), a set of biophysical and biochemical experiments were carried out using newly synthesized cyclic ferrocenylnaphthalene diimide (cFNDI, 1) or the non-cyclic derivative (2) with various structures of G-quadruplex DNAs and dsDNA. Compound 1 bound strongly to G-quadruplexes DNAs (106M-1 order) with diminished binding to dsDNA (104M-1 order) in 100mM AcOH-AcOK buffer (pH 5.5) containing 100mM KCl. Interestingly, 1 showed an approximately 50-fold higher selectivity to mixed hybrid-type telomeric G-quadruplex DNA (K=3.4×106M-1 and a 2:1 stoichiometry) than dsDNA (K=7.5×104M-1) did. Furthermore, 1 showed higher thermal stability to G-quadruplex DNAs than it did to dsDNA with a preference for c-kit and c-myc G-quadruplex DNAs over telomeric and thrombin binding aptamers. Additionally, 1 exhibited telomerase inhibitory activity with a half-maximal inhibitory concentration (IC50) of 0.4µM. Compound 2 showed a preference for G-quadruplex; however, the binding affinity magnitude and preference were improved in 1 because the former had a cyclic structure.

Add-on effect of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning hypertension and left ventricular hypertrophy in patients undergoing long-term amlodipine monotherapy.

High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy. The add-on effects of doxazosin at the maximum dose of 6 mg at bedtime on home blood pressure and left ventricular geometry for 1 year were investigated in 49 subjects (37 men and 12 women, aged 57.5+/-9.1 years) with morning hypertension who had been treated with amlodipine alone for more than 1 year. Doxazosin induced a significant decrease in morning blood pressure (145.6+/-5.6/91.5+/-5.4 to 132.4+/-3.7/83.6+/-5.6 mmHg, p

The Resection of Thyroid Cancer Was Associated with the Resolution of Hyporesponsiveness to an Erythropoiesis-stimulating Agent in a Hemodialysis Patient with Aceruloplasminemia.

We herein report the case of a hemodialysis patient whose response to an erythropoiesis-stimulating agent (ESA) improved following the resection of thyroid cancer. Her hemoglobin level remained below 7 g/dL, despite the use of ESA. During the search for the causes of her hyporesponsiveness to ESA, papillary thyroid cancer and aceruloplasminemia were found. The existence of other potential causes, such as iron deficiency, infectious disease, severe hyperparathyroidism and malnutrition were ruled out. Following the resection of the thyroid cancer tumor, her hemoglobin level increased to 10.2 g/dL over a period of 4 months. This is the first report to demonstrate the resolution of hyporesponsiveness to ESA following the resection of a malignant tumor.

Isolated adrenocorticotropic hormone deficiency presenting with hypercalcemia in a patient on long-term hemodialysis.

The authors report on a 44-year-old female hemodialysis (HD) patient who presented with hypercalcemia secondary to isolated adrenocorticotropic hormone (ACTH) deficiency. She had been suffering from nausea and abdominal pain caused by recurrent esophageal ulcer. Blood calcium (Ca) adjusted for serum albumin concentration was increased to 14.9 mg/dL (3.72 mmol/L) concurrently with fever and hypotension. Serum intact parathyroid hormone (PTH)-related peptide was not elevated, but serum intact PTH and 1,25-(OH)2 vitamin D3 were decreased to 31 pg/mL (ng/L) and 8.1 pg/mL (2.6 pmol/L), respectively. Endocrinologic examination found that plasma ACTH was reduced below 5.0 pg/mL (0.22 pmol/L). A single ACTH stimulation normally increased blood cortisol, whereas a single corticotropin-releasing hormone injection failed to increase plasma ACTH and cortisol. Pituitary magnetic resonance imaging disclosed no enlargement of pituitary gland. Circulating bone formation and absorption markers were not elevated. Blood Ca was normalized shortly after pamidronate disodium administration without glucocorticoid supplementation. This case suggested that secondary adrenal insufficiency caused by isolated ACTH deficiency could be an occult cause of severe hypercalcemia in HD subjects.

Severe hypoglycemia and hypokalemia in association with liver metastases of gastric cancer.

We report an 80-year-old man who presented with non-islet cell tumor hypoglycemia (NICTH) in association with hepatic recurrence of gastric cancer. His serum potassium was reduced from 3.9 to 3.1 mmol/l 5 weeks after gastrectomy, and he subsequently developed hypoglycemic coma. He was diagnosed as having NICTH because of the presence of serum big IGF-II and positive staining for IGF-II in gastric cancer cells obtained at surgery. A computed tomography showed multiple liver metastases. His hypoglycemia was refractory to steroid therapy. This case suggested that NICTH could develop in association with hepatic metastases of gastric cancer. Unexpected hypokalemia may be a manifestation of occult NICTH.

A case of anemia with schistocytosis, thrombocytopenia, and acute renal failure caused by adenomyosis.

A 51-year-old woman with adenomyosis was admitted because of anemia with schistocytosis, thrombocytopenia, and acute renal failure (ARF). Thrombotic microangiopathy (TMA) was considered. Plasma exchange and steroid therapies improved laboratory results. However, renal biopsy specimen revealed acute tubular necrosis (ATN), but not TMA, and thrombocytopenia, diagnosed it as disseminated intravascular coagulation (DIC) but not TMA. Few cases of DIC associated with benign tumors of the uterus and, especially, adenomyosis have been reported. In adenomyosis patients, ARF is usually caused by obstructive uropathy. However, the rare case suggests that hemolytic anemia, DIC, and ARF due to ATN can occur in adenomyosis patients.