The toxicity of beta-blocker, Befunolol HCl (BFE), to the retinal pigment epithelium was investigated electrophysiologically. Rabbit in vivo ERG b- and c-waves were recorded after intravitreal injections of 0.1 ml of 0.25, 1, 2, 4, 6 and 10% BFE solutions with osmolalities of 304, 340, 383, 432, 493 and 618 mOsm respectively. Phosphate solutions with osmotic pressure corresponding to the BFE solutions were injected as control. In eyes injected with 0.25% BFE, amplitude of either b- and c-waves were unchanged for 60 min, while in eyes injected with BFE with a higher concentration than 1%, the b-waves attenuated but the c-waves enhanced in proportion to the BFE concentrations. In the control group, the b-waves attenuated and the c-waves enhanced by the injection of the high osmotic phosphate solutions up to 500 mOsm, which corresponded to the osmotic pressure of 6% BFE, but attenuated by the phosphate solutions higher than 600 mOsm. Based on the above result, no acute toxicity of BFE to the retina was suggested in dose of its therapeutic use. The attenuation of b-waves by BFE was likely due to the influence of osmotic pressure since no significant difference in the b-waves amplitudes was found between BFE and equimolar phosphate solutions. However, high concentration of BFE itself was suggested to exhibit an effect to enhance the c-wave because a manifest difference was observed in the c-wave amplitudes between the group at higher BFE concentrations and the correspond control group.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Regional difference of capillary-to-fiber ratio in the heart of monocrotaline-treated rats.

This study was designed to investigate the capillary-to-fiber (CF) ratio, and regional differences in this ratio in the hearts of monocrotaline-induced pulmonary hypertensive rats (MCT rats) as compared with normal rats in an attempt to examine capillary proliferation relative to that of muscle cells responding to the pressure stress on right ventricle (RV). Ten Sprague-Dawley male rats (5 weeks old) were injected with 60 mg/Kg monocrotaline, while eight rats were injected with saline as a control. At the age of 8 weeks they were anesthetized and the heart was excised and immediately frozen. The capillaries were stained enzyme-histochemically by detecting alkaline phosphate and dipeptidylaminopeptidase IV. The main finding in this study was a decrease in the CF ratio of MCT rats in all regions of the heart except in the RV mid-layer and endocardium. The CF ratio in the RV-mid-layer was 1.21 +/- 0.11 (mean +/- SD) in MCT rats and 1.27 +/- 0.12 in control rats (no change), while in the mid-layer of the interventricular septum (IVS) it was 1.13 +/- 0.05 in MCT rats and 1.35 +/- 0.07 in control rats (p < 0.001), and in the left ventricular (LV) mid-layer it was 1.20 +/- 0.06 in MCT rats and 1.40 +/- 0.12 in control rats (p < 0.001). This result indicates that capillary proliferation in the IVS and LV was poor in MCT rats, while in RV capillary proliferation was maintained at the control level. In MCT rats, the CF ratio in the RV endocardium and epicardium was significantly higher than the ratio in the LV epicardium, while in control rats the CF ratio in the LV endo- and mid-cardium was significantly higher than in the RV endo- and epicardium. It was suggested that in the hearts of growing MCT rats capillary proliferation in RV compensated for the suppressed capillary proliferation in the whole heart.

Animals↗

PubMedDate not supplied

Propeller flap for reconstruction of the tubercle of the upper lip.

A technique is presented for the correction of the whistling deformity of the upper lip, which is commonly seen in patients with repaired bilateral cleft lip. Two opposing transposition flaps based on the central portion of the upper vermilion are used. The shape of these flaps resembles a two-bladed propeller, thus we call the technique the "propeller flap". Each of the blades is rotated 180 degrees and the resulting dog-ear helps to add volume to the upper lip tubercle. Some representative cases are presented.

Adolescent↗

PubMedDate not supplied

Correction of cryptotia using a subcutaneous pedicled flap.

Cryptotia is a relatively common deformity of the ear among orientals. Although many methods for correcting this deformity have been reported, there is no one perfect method. We have developed a method using a subcutaneous pedicle flap raised from the retroauricular region, where relative abundance of skin exists. We have treated 9 ears of 7 patients by the method reported herein. Results are satisfactory in all cases.

Child↗

PubMedDate not supplied

Simple line closure for macrostomia repair.

In repair of macrostomia, many authors have used a Z-plasty to prevent postoperative scar contracture. We found that the Z-plasty scar may be conspicuous when the patients open their mouths. Here we present a method of nearly straight line closure resulting in an inconspicuous scar even when the patients move their mouths.

Female↗

PubMedDate not supplied

Measurement of bisphenol A levels in human urine.

We report a new approach for assessing human exposure to bisphenol A (BPA) by measuring BPA in urine after enzymatic deglucuronidation. This method involves addition of (13)C(12)-labeled BPA, enzymatic deconjugation, solid-phase extraction, and derivatization with pentafluorobenzyl bromide. The product of the derivatization is separated by gas chromatography followed by mass spectrometric detection using negative chemical ionization and selected ion monitoring. Using this analysis method, urine samples fortified with both a constant level of labeled BPA and a range of unlabeled BPA levels (0.27-10.6 ng/ml) demonstrated constant percentage recovery. In addition, a range of urine sample volumes (0.25-10.0 ml) with constant amounts of added internal standard produced a linear response (r(2)=0.99). The method limit of detection was 0.12 ng/ml. This method was validated by duplicate analyses using gas chromatography coupled to a high-resolution mass spectrometer.

Benzhydryl Compounds↗

PubMedDate not supplied

Effect of hydrocortisone on the synthesis of 2,3-diphosphoglycerate in human erythrocytes.

Studies were carried out on the mechanism of action of glucocorticoids on erythrocyte glycolysis. Inosine increased the levels of 2,3-DPG, lactate, and ATP in red blood cell samples with very low glucose concentrations in which the glycolytic system was unable to utilize glucose. With inosine and hydrocortisone added to red blood cells, 2,3-DPG and lactate increased more than in red blood cells supplemented with inosine alone. There was no significant increase in the level of ATP when glucose and inosine were added compared to the addition of inosine only. There were no changes in the activity of enzymes such as PFK and PGK. From these findings, it is suggested that glucocorticoids increase the level of red blood cell 2,3-DPG, by activating the conversion of 1,3-DPG to 2,3-DPG during glycolysis, probably by stimulating 2,3-DPG mutase.

2,3-Diphosphoglycerate↗

PubMedDate not supplied

Protein kinase A activity and protein phosphorylation during the mouse sperm acrosomal reaction.

Using two-dimensional gel electrophoresis, changes in protein phosphorylation caused by cyclic nucleotide-dependent protein kinases were analyzed with or without exposure to a protein kinase inhibitor, H-8, during the mouse sperm acrosomal reaction. The acrosomal reaction, induced by the treatment of sperm with dibutyryl cyclic AMP or dibutyryl cyclic GMP, was inhibited by H-8. The activities of cyclic AMP-dependent protein kinase (PKA) and cyclic GMP-dependent protein kinase induced by the sperm extract were also inhibited by H-8. When endogenous PKA in sperm was activated by the addition of cyclic AMP, a 45-kDa protein spot identified by electrophoresis indicated the occurrence of phosphorylation in vivo. Furthermore, the enhanced phosphorylation of the 45-kDa protein spot was inhibited by H-8. These results suggest that the PKA-catalyzed phosphorylation of the 45-kDa protein may be involved in the regulation of the mouse sperm acrosomal reaction.

Acrosome Reaction↗

PubMedDate not supplied

Influence of progesterone and GABAA receptor on calcium mobilization during human sperm acrosome reaction.

At fertilization, mammalian sperm has to undergo morphological changes of acrosome, namely acrosome reaction (AR), during which a dramatic increase of cytosolic calcium in consequence of extracellular calcium influx induces acrosomal exocytosis. It has been reported that progesterone is capable of inducing mammalian sperm AR. Several authors insisted that the agent, which was so far understood to bind with intracellular receptor, might act as an agonist against cell surface r-aminobutyric acid with type A (GABAA) receptor. The mode of action is, however, still in controversy. To investigate whether progesterone-induced AR is mediated by GABAA receptor, the present study examined pharmacologically the actions of progesterone on the morphological changes of acrosome and calcium mobilization during human sperm AR. Progesterone (15 microM) stimulated AR and increased cytosolic calcium, and the AR rate was further promoted by the coexistence of GABA (15 microM). Then these phenomena were suppressed by an antagonist of GABAA receptor (bicuculline, 10 microM), a blocker of GABAA receptor-coupled chloride channel (picrotoxin, 200 microM) and an antagonist of receptor-operated calcium channel (Lantan, 250 microM), respectively. These results indicated that the complex work of GABAA receptor-chloride channel and receptor operated calcium channel might participate in progesterone-induced AR and the transient increase of cytosolic calcium.

Acrosome Reaction↗

PubMedDate not supplied

Synthesis and antiviral activities of 5-substituted 1-(2-deoxy-2-C-methylene-4-thio-beta-D-ertythro-pentofuranosyl)uracils.

Various 5-substituted 1-(2-deoxy-2-C-methylene-4-thio-beta-D-erythro-pentofuranosyl)uracils (4'-thioDMDUs) were synthesized from D-glucose via sila-Pummerer-type glycosylation. All of the beta-anomers of 5-substituted 4'-thioDMDU, except the 5-hydroxyethyl derivative, showed potent anti-HSV-1 activity (ED50 = 0.016-0.096 microgram/mL). 5-Ethyl- and 5-iodo-4'-thioDMDUs were also active against HSV-2 (ED50 = 0.17 and 0.86 microgram/mL, respectively). 5-Bromovinyl-4'-thioDMDU was particularly active against VZV (ED50 = 0.013 microgram/mL).

Antineoplastic Agents↗

PubMedDate not supplied

Synthetic studies on 2'-substituted-4'-thiocytidine derivatives as antineoplastic agents.

As potential antineoplastic agents, we have synthesized 4'-thioFAC and 4'-thiocytarazid by developing an alternative synthetic method. 4'-ThioFAC showed potent antineoplastic activities in vivo as well as in vitro.

Animals↗