Michio Tsuruoka

Mode of Interaction of Loop Diuretics with Human Serum Albumin and Characterization of Binding Site

AbstractPurpose. The purpose of this study was to investigate the binding mechanism of loop diuretics with HSA and to characterize the binding site on HSA.nMethods. Quantitative analysis of potential interaction between ligands bound to HSA was performed by equilibrium dialysis and data for binding of the two ligands to HSA were analyzed on the basis of a theoretical model of simultaneous binding of two ligands.nResults. The binding of loop diuretics is dependent upon the N-B transition, conformational change of albumin. Furthermore, from the results of binding of the drugs to modified HSA, the lysine residue seems to be involved in the binding of loop diuretics to HSA.nConclusions. Analysis using models describing independent, competitive, cooperative and anti-cooperative binding led to the conclusion that loop diuretics bind to site I, particularly to the warfarin region on HSA.

Three Cases of Delivery under Sodium Valproate—Placental Transfer, Milk Transfer and Probable Teratogenicity of Sodium Valproate—

Abstract: Here is a report of three cases of dellvery from women who have taken sodium valproate (VPA). One neonate was born with polydactylism, and we reviewed the congenital malformations in children of mothers who have taken VPA. In the other two cases, we also examined the levels of VPA in the cord serum and breast milk. The levels of VPA in the cord serum were 50 μg/ml at 12 hours after the last maternal dose and 75 μg/ml at 14 hours after the last maternal dose. The blood levels of VPA in the two mothers were 48–59 μg/ml and 55–85 μg/ml in their late pregnancy, respectively. The levels of VPA in the breast milk were 2.0–3.5 μg/ml and the ratio of VPA in the breast milk to blood was 2–3%. These results suggest the high rate of placental transfer and the low rate of milk transfer of VPA.

Interaction of benzothiadiazides with human serum albumin studied by dialysis and spectroscopic methods

The interaction of a series of benzothiadiazides with human serum albumin (HSA) was investigated by equilibrium dialysis (ED) and spectroscopic methods including circular dichroism (CD). The primary binding site of benzothiadiazides was designated site II, the diazepam site on the HSA molecule, as indicated by displacement experiments using different site-selective probes. Tyrosine and lysine amino acid residues were probably involved in the binding site of these compounds to HSA. Both electrostatic and hydrophobic interactions were found to play a role in the binding of these compounds to HSA. Among the compounds tested, chlorothiazide had the highest affinity (K1 = 5.5 × 104M−1, K2 = 5.8 × 103 M−1).The primary binding affinity of the compounds for HSA was of the order: chlorothiazide > cyclopenthiazide > polythiazide > ethiazide > trichlormethiazide = methyclothiazde > hydrochlorothiazide. Binding was insensitive to the N-B transition of HSA. The binding site is proposed to consist of a cationic site on the surface of the HSA molecule with a hydrophobic crevice to accommodate the aromatic ring of the compounds. Positions 3 and 7 of the benzothiadiazide molecule is thought to affect the binding affinity to HSA.

Situation of Antibiotic Use at Miyazaki Medical College Hospital

Recently, transfiguration of infections has been caused by remarkable increase in the amount of antibiotics. We investigated the amount of use and combination of antibiotics during June of 1981, 1982, 1983 and 1984 at our hospital. The results were as follows:1) The total amount of antibiotics use decreased annually. 2) The amount of penicillins, especially carbenicillin and sulbenicillin, decreased remarkably. 3) Of the total combinations, 2-drug combinations occupied 75%-85%. 4) Combination of cephalosporins, especially those of the third generation, and aminoglycosides occurred in the largest number.

Quantitative Evaluation of Adhesion of Syrups on Surface of Polyethylene Containers

Polyethylene bottles are used as containers for syrup or liquid medicines. Easiness of pouring syrup out of a bottle or measurement of syrup depends on viscosity of the syrup on the container surface and on wetting between the syrup and the container surface. We studied the rheological property of some syrups by measuring their viscosity with rheometer and by plotting the quantitative changes in abhesion. The results were as follows:1) Adhesion of syrups on the surface of polyethylene containers was less than that on glass containers. 2) Most commercial syrup products showed the property of non-Newtonian fluid, and the refractions in the plot Wt-2 against t were observed. 3) There was little difference of adhesion among several commercial syrup products in polyethylene containers.

Utilization of UV Spectrum in Identification of Tablets

Requests for tablet identification, one of the drug information services, compose as much as 32% of the total requests made to our drug information office. It is often difficult for hospital pharmacists to identify when no information is labelled on the tablet and on the package. In order to settle the difficulty, the contents of tablets were identified by the UV absorption technique, which proved more reliable than the conventional method. As the spectrophotometry is easy to operate and versatile to apply, the technique is one of the most practically useful methods of the tablet identification.