Unforeseen Effect of Thyroxine Binding Globulin when Using the Microencapsulated Antibody Method to Determine Free Thyroxine (FT4): Misleading Results. Due to Circulating Unsaturated Thyroxine Binding Globulin

Peer Reviewe

Topical nipradilol: effects on optic nerve head circulation in humans and periocular distribution in monkeys,”

PURPOSE. To investigate the effects of topical nipradilol on blood velocity in the optic nerve head (ONH) in normal humans and the ocular and periocular distribution of topically instilled nipradilol in monkeys. METHODS. In normal humans, 0.25% nipradilol was instilled in one eye and vehicle in the other twice daily for 7 days, and blood velocity in the ONH was measured by the laser speckle method. In monkeys, after a single instillation of 1% [ 14 C]nipradilol in one eye, distribution of radioactivity was evaluated by whole-head autoradiography. RESULTS. Twice-daily 7-day instillation of nipradilol temporarily but significantly increased human ONH blood velocity, in the ipsilateral eye only (P ϭ 0.005), independent of a reduction in the intraocular pressure. In monkeys, equivalent nipradilol concentration in the periocular tissue around the optic nerve insertion was higher on the ipsilateral side than on the contralateral side (140 Ϯ 25 ng/g and 42 Ϯ 10 ng/g, P ϭ 0.022, n ϭ 5). Radioactivity was higher in the periocular tissue behind the equator than around the optic nerve insertion on the ipsilateral side (P ϭ 0.004), but not on the contralateral side. The equivalent nipradilol concentration in the ipsilateral posterior retina-choroid was 636 Ϯ 92 ng/g, which was significantly higher than that on the contralateral control side (521 Ϯ 92 ng/g, P Ͻ 0.001). CONCLUSIONS. The ipsilateral increase in ONH blood velocity induced by topical nipradilol in humans was attributed to drug that penetrated locally. Whole-head autoradiographic study suggests that topically instilled nipradilol can rapidly reach the posterior periocular tissue at pharmacologic concentrations. (Invest Ophthalmol Vis Sci. 2002;43:3243-3250) G laucoma is a disease that primarily damages the optic nerve head (ONH). One of the major risk factors in glaucoma is chronically elevated intraocular pressure (IOP). 1 However, reports of the relation between a subtype of glaucoma and low blood pressure, 2 migraine, 3 and optic disc hemorrhage 4 or findings on the favorable effect of a Ca 2ϩ channel blocker on the visual field 5-8 suggest that not only an increase in IOP but disorders of the systemic and/or local circulation are involved in the development of glaucomatous ONH damage. 9 -11 There are two ways for antiglaucoma agents to modify circulation in the ONH. One is to increase ocular perfusion pressure (OPP) while decreasing IOP. It is not known, however, whether a chronic increase in OPP in fact causes a chronic change in blood flow in the ONH. 12-14 The other way is to effect direct, drug-mediated vascular dilatation. Several in vitro studies are available on the vasodilatory effects of antiglaucoma agents. The ophthalmic artery branches into the central retinal artery, posterior ciliary arteries, and anterior ciliary arteries. Short posterior ciliary arteries, separate from the posterior ciliary artery, penetrate the eye wall around the insertion of the optic nerve and are essential in supplying blood to the ONH. Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino)propoxy-3-nitroxy-2H-1-benzopyran, molecular weight: 326.35) is a newly developed antiglaucoma ophthalmic agent that has nonselective ␤-receptor and selective ␣ 1 -receptor blocking properties 22,23 with a nitric oxide (NO) donative action. 24 Topical instillation of 0.25% nipradilol lowers IOP as effectively as 0.5% timolol with a less systemic ␤-blocking effect. 25 In this study, we examined whether topically instilled nipradilol also influences blood velocity in the ONH in eight normal humans as a pilot study. Because the result suggested that the effect was attributable to local penetration of the drug, we examined the ocular and periocular distribution pattern of nipradilol after topical instillation, by analysis of whole-head autoradiographs in monkeys. METHODS The study of human ONH blood velocity was approved by the Ethics Review Committee of the University of Tokyo School of Medicine and the tenets of the Declaration of Helsinki were observed. Before admission into the study, each subject signed a written consent form after the nature of the study had been fully explained and routine eye examinations had been performed. Animal experiments were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic Vision Research. Effects on ONH Circulation in Humans Eight young volunteers (20 -24 years of age) with no history of smoking, who had neither systemic nor ocular disease and only mild refractive errors, participated in the study. On the day on which measureFrom th

Evaluation of Glycerol-Treated Liquid Pooled Serum with Special Reference to Stabilizing Effect on Lactate Dehydrogenase

金沢大学医療技術短期大学部The addittion of ethylene glycol or glycerol to pooled human serum protects lactate dehydrogenase (LDH) activity during storage at-10°C or 4°C.At-20°Cethylene glycol caused a significant decreasein LDH activity during storage, the decrease depending on the proportion of added ethylene glycol.Reduced activity was accompanied by loss of the LDH3, LDH4 and LDH5 isoenzymes.ln contrast, glycerol addition to serum completely stabilizes LDH activity even at-20°C, and concomitant measurement of alkaline phosphatase, glucose and cholesterol showed no alteration in activity or concentrations.Glycerol treated pooled serum would thus seem valuable for quality control for clinical use

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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