Prostanoids in the Therapy of Glaucoma

Elevated intraocular pressure (IOP) is one of the most important risk factors for the development of glaucoma, which is a progressive optic neuropathy. Lowering IOP is currently the only therapeutic approach to the therapy of glaucoma. Since the use of pilocarpine eye drops for glaucoma treatment was reported in the late 1870s, academic researchers and pharmaceutical companies attempted to discover new drugs with more potent, prolonged, and safer IOP‐reducing effects. These persistent efforts finally paid off, and prostanoids with FP‐receptor agonist activity were found to be very potent IOP‐lowering agents. To date, three prostanoids (latanoprost, travoprost and bimatoprost) have been launched in many countries, and now a new FP‐receptor agonist, tafluprost, is entering clinical development. All of these prostanoids are superior to the β‐adrenoceptor antagonists in their IOP‐lowering efficacy, and no severe side effects have been reported in their long‐term clinical use. In addition, tafluprost may be expected to improve ocular blood flow. Hence, prostanoids currently occupy center stage among glaucoma medications. It cannot be denied that in terms of efficacy, safety, patient compliance, and medical economy prostanoids are currently the first‐line medicines among ocular antihypertensive drugs.     

Right and left ventricular volume characteristics in children with transposition of the great arteries after Mustard's procedure

With use of biplane cine-angiocardiograms, the measurements of right and left ventricular volume were determined in 11 children with transposition of the great arteries following Mustard's procedure. Right ventricular end-diastolic volume (RVEDV) ranged from 124 to 264 percent of the normal right ventricular volume with an average of 188 +/- 40 (SDM) percent, and left ventricular end-diastolic volume (LVEDV) ranged from 57 to 181 (122 +/- 43) percent of the normal (p less than 0.01, vs. RVEDV). Right ventricular ejection fraction (RVEF) ranged from 0.26 to 0.66 (0.42 +/- 0.11), and left ventricular ejection fraction (LVEF) ranged from 0.51 to 0.79 (0.66 +/- 0.09) (p less than 0.001, vs RVEF). Left ventriculography showed a deviation of the interventricular septum toward the left ventricle in patients with simple transposition of the great arteries not associated with left ventricular hypertension. The left to right ventricular systolic pressure ratio ranged from 0.22 to 1.02 (0.48 +/- 0.28), and the left to right ventricular end-diastolic volume ratio ranged from 0.43 to 1.00 (0.63 +/- 0.18). There was a high correlation between the left to right ventricular systolic pressure ratio and the left to right ventricular end-diastolic volume ration (r = 0.94, p less than 0.001). The left to right ventricular systolic pressure ratio also correlated well with the right ventricular ejection fraction (r = 0.90, p less than 0.001). Deviation of the interventricular septum was considered to result in a diminished ejection fraction of the right ventricle, in patients with simple transposition of the great arteries not associated with left ventricular hypertension, after Mustard's procedure.     

Vitamin K2 and bone quality

Effects of vitamin K(2) (menatetrenone) and alendronate on bone mineral content and bone mechanical property in rats fed a low-magnesium diet. Recent clinical studies have shown that the occurrence of new fractures does not always depend on bone mineral density. Therefore bone quality has become an important issue in osteoporosis research. No animal model for evaluating bone quality has been established. In this study, we found that the treatment of rats with a low-magnesium (Mg) diet reduced their bone strength without decreasing bone mineral content (BMC), so the low Mg diet model is considered to be a good model for examining bone quality. Using this model, we investigated the effects of vitamin K(2) (V.K(2)) and alendronate (ALN). V.K(2) increased maximum load and elastic modulus without influencing BMC. ALN increased maximum load with increasing BMC. By using Fourier transform infrared microscopic analysis, the low-Mg diet treatment increased the mineral/matrix ratio of bones, and V.K(2) suppressed the increase in this ratio. These findings suggest that the mineral/matrix ratio may be a factor involved in bone quality, and that V.K(2) may improve bone quality.     

Impact of Weekly Teriparatide on the Bone and Mineral Metabolism in Hemodialysis Patients With Relatively Low Serum Parathyroid Hormone: A Pilot Study

Adynamic bone disease in HD patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a downregulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating adynamic bone disease without a history of parathyroidectomy. Fifteen HD patients with low PTH were recruited in this prospective observational study. Of them, 10 received teriparatide for 12 months and five nontreated patients were enrolled as control. Primary outcomes were defined as the changes in bone mineral density and bone turnover markers. Bone mineral density at the lumbar spine increased by 3.7% and 2.5% at 6 and 12 months, respectively, and bone formation markers increased, while bone resorption markers did not change in the teriparatide group. At 12 months after teriparatide administration, endogenous PTH was secreted followed by the recovery of low bone turnover. 40% of patients in the teriparatide group dropped out due to adverse events and the most common adverse event was transient hypotension. This study suggests that weekly teriparatide for HD patients with low PTH in the absence of parathyroidectomy accelerates bone formation and bone turnover, leading to increased trabecular bone mass and secretion of endogenous PTH.     

Monosomy 13 in metaphase spreads is a predictor of poor long-term outcome after bortezomib plus dexamethasone treatment for relapsed/refractory multiple myeloma

We retrospectively investigated the prognostic impact of high-risk cytogenetic abnormalities (CAs) on the outcome of treatment with bortezomib plus dexamethasone (BD) in 43 relapsed/refractory (Rel/Ref) multiple myeloma patients. Fluorescence in situ hybridization (FISH) analysis identified del(13q) in 25 patients, t(4;14) in 14, t(14;16) in 4, 1q21 abnormality in 12 and del(17p) in 2, while G-banding also detected chromosome 13 monosomy (-13) in metaphase spreads from 7 patients. Eighteen of 25 patients with FISH-detected chromosome 13 abnormalities also exhibited other abnormalities. Median observation period was 510 days, and median overall survival (OS) and progression-free survival (PFS) were 912 days and 162 days, respectively. Detection of del(13q), t(4;14), t(14;16) or 1q21 abnormalities by FISH and co-occurrence of chromosome 13 abnormality with other abnormalities were not associated with poorer outcomes. In contrast, detection of -13 by G-banding in metaphase spreads showed significant association with shorter OS, although the overall response rate and PFS were not inferior to those for patients without -13 detected by G-banding. BD therapy may be a potent weapon for overcoming most classical high-risk CAs, while the detection of -13 in metaphase spreads may serve as a predictor of highly progressive disease, even when treated with BD.