Masami Nemoto

Reactivity of Taurine with Aldehydes and Its Physiological Role.

The chemical reactions of the amino group of taurine with aldehydes were investigated. Glucose, acetaldehyde, and malondialdehyde were used as aldehydes. After taurine had reacted, the amounts of remaining taurine and aldehydes were measured, and the reactivity was evaluated. Amino acids such as glycine, alpha-alanine, and beta-alanine were compared because of their structural resemblance to each other. Taurine showed a high reactivity with each one of the aldehydes tested. It is known that protein is altered through reactions of the amino group with various aldehydes. Low density lipoprotein (LDL) was used as a model protein and the inhibiting effect of taurine against the modification of LDL by malondialdehyde was examined. It was shown that the inhibiting effects of taurine correlated with the reactivity of malondialdehyde with amino acids. Further, the taurine-glucose reaction product showed an antioxidative effect on the peroxidation of liposomes made of yolk phosphatidylcholine as a biomembrane model. The results suggest the possibility of an inhibiting effect of taurine against the modification of protein, as well as an antioxidative effect through the reactions of taurine with aldehydes in vivo.

Reactivity of taurine with aldehydes and its physiological role.

The chemical reactions of the amino group of taurine with aldehydes were investigated. Glucose, acetaldehyde, and malondialdehyde were used as aldehydes. After taurine had reacted, the amounts of remaining taurine and aldehydes were measured, and the reactivity was evaluated. Amino acids such as glycine, alpha-alanine, and beta-alanine were compared because of their structural resemblance to each other. Taurine showed a high reactivity with each one of the aldehydes tested. It is known that protein is altered through reactions of the amino group with various aldehydes. Low density lipoprotein (LDL) was used as a model protein and the inhibiting effect of taurine against the modification of LDL by malondialdehyde was examined. It was shown that the inhibiting effects of taurine correlated with the reactivity of malondialdehyde with amino acids. Further, the taurine-glucose reaction product showed an antioxidative effect on the peroxidation of liposomes made of yolk phosphatidylcholine as a biomembrane model. The results suggest the possibility of an inhibiting effect of taurine against the modification of protein, as well as an antioxidative effect through the reactions of taurine with aldehydes in vivo.

Comparative Study of Pharmacokinetic Parameters Between Clarithromycin and Erythromycin Stearate in Relation to Their Physicochemical Properties

Pharmacokinetic parameters for clarithromycin (CAM) and erythromycin stearate (EMS) were obtained from a model including decomposition in the gastrointestinal tract. To confirm the accuracy of the parameters, various physicochemical properties of both drugs were examined. The ratio of the in vivo dissolution rate, the in vivo decomposition rate and the absorption rate between CAM and EMS were well correlated to the ratio of the in vitro intrinsic dissolution rate, the decomposition rate in the acidic solution, and partition coefficient, respectively. One of the reasons for the excellent absorption of CAM compared with that of EMS was the higher stability in the acidic solution and the higher partition coefficient of CAM. These findings indicate that the ratio of the partition coefficient to the decomposition rate constant in acidic solution plays an important role in determining drug bioavailability for macrolide antibiotics.

THE REACTIVITY OF TAURINE WITH HYPOCHLOROUS ACID AND ITS APPLICATION FOR EYE DROPS

The ability of taurine to protect biomembranes attacked by HOCl was examined using canine erythrocytes which had been pre-treated with HOCl. Of the amino acids tested, taurine was the most effective in inhibiting attack by HOCl, followed by glycine, alpha-alanine and beta-alanine. During the incubation of HOCl-treated erythrocytes with taurine, an appreciable amount of monochlorotaurine (TauNHCl) was detected in the supernatant. This suggests that taurine may remove the oxidized chlorine from HOCl-treated erythrocytes, resulting in the production of TauNHCl. The effect of taurine on the removal of Cl+ moiety was examined using Sepharose gel with amino groups. Taurine removed Cl+ from HOCl-treated Sepharose gel. The yield of TauNHCl depended on the concentration of taurine. The effectiveness of taurine in preventing ocular surface damage caused by HOCl was investigated in albino rabbits. The activity of lactate dehydrogenase (LDH) released from ocular tissues into tears during eye irritation was used as an index of ocular surface damage. Taurine effectively protected ocular surface tissues from damage induced by HOCl, and arrested the progression of tissue damage that had already been initiated by HOCl. These finding suggest that taurine may be clinically useful in the treatment of ocular surface damage caused by oxidants such as HOCl.

Method of increasing the sensitivity of liquid chromatography-atmospheric pressure chemical ionization mass spectrometry using a semi-micro column

Abstract A method for increasing the signal intensity of liquid chromatography-atmospheric chemical ionization mass spectrometry (LC-APCI-MS) using a semi-micro column was studied. Prostaglandin E1 was used as a model compound. However, this method was not effective for detection with APCI-MS without an improved APCI interface, in which the diameter of the micro-pipe on the APCI interface was decreased from 0.1 to 0.05 mm. The signal intensity of APCI-MS detection using a semi-micro column with an improved APCI interface was five times that obtained with use of a conventional column.

Sensitivity improvement achieved by acetyl-derivatization in atmospheric pressure chemical ionization-mass spectrometry.

A method of increasing the detection response by acetyl-derivatization on atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) has been investigated. By acetylation on compounds having primary alcohol, primary amine and phenolate, it was found that the detection responses of their acetylated forms were increased by 2 to 5 fold over their intact forms. This suggests that acetyl-derivatization was an effective method of increasing response on APCI-MS for compounds having these groups. A possible reason is that acetylation caused increased proton affinity (PA). So, PA should be well considered when trying to increase the response on APCI-MS by derivatization. This acetyl-derivatization method seems promising for increasing the response on LC/APCI-MS.

Interaction between Polyethylene Films and Bromhexine HCl in Solid Dosage Forms. I. Effects of Moisture Contents in the Solid Dosage Forms on the Sorption of the Drug

The decrease of bromhexine HCl contents in granules and tablets was determined when the preparations were stored in polyethylene film package. Effects of temperature, contact area with film, excipients and moisture contents in the preparation on the remaining amount of bromhexin HCl were studied in order to investigate the interaction mechanism between bromhexine HCl and polyethylene film. It was observed that the decrease of bromhexine HCl was due to the sorption to the polyethylene film. The results indicated that the moisture contents of the dosage forms determined the rate of sorption predominantly, and that removal of adsorbed water from dosage forms was effective to prevent bromhexine HCl content decrease.