A fast method has been established for the precise measurement and quantification of the dynamics of hyperpolarized (HP) xenon-129 ((129)Xe) in the mouse brain. The key technique is based on repeatedly applying radio frequency (RF) pulses and measuring the decrease of HP (129)Xe magnetization after the brain Xe concentration has reached a steady state due to continuous HP (129)Xe ventilation. The signal decrease of the (129)Xe nuclear magnetic resonance (NMR) signal was well described by a simple theoretical model. The technique made it possible to rapidly evaluate the rate constant α, which is composed of cerebral blood flow (CBF), the partition coefficient of Xe between the tissue and blood (λ(i)), and the longitudinal relaxation time (T(1i)) of HP (129)Xe in the brain tissue, without any effect of depolarization by RF pulses and the dynamics in the lung. The technique enabled the precise determination of α as 0.103 ± 0.018  s(-1) (± SD, n = 5) on healthy mice. To investigate the potential of this method for detecting physiological changes in the brain of a kainic acid (KA) -induced mouse model of epilepsy, an attempt was made to follow the time course of α after KA injection. It was found that the α value changes characteristically with time, reflecting the change in the physiological state of the brain induced by KA injection. By measuring CBF using (1)H MRI and (129)Xe dynamics simultaneously and comparing these results, it was suggested that the reduction of T(1i), in addition to the increase of CBF due to KA-induced epilepsy, are possible causes of the change in (129)Xe dynamics. Thus, the present method would be useful to detect a pathophysiological state in the brain and provide a novel tool for future brain study.

Complement activation is important for removing foreign substances by the mononuclear phagocyte system in vivo. The interaction between liposomes and complement components is considered to affect the clearance of liposomes from the circulation. It has been previously demonstrated in our laboratory that multilamellar vesicles (MLV) with surfaces modified by cetylmannoside (Man) were eliminated from the circulation rapidly and showed an approximately 2-fold higher hepatic accumulation compared with control MLV (PC-MLV) (Yamashita et al., Int. J. Pharmaceut., 70, 225, 1991). In this study, we investigated the effect of Man-modification on complement system activation. As far as elimination from the blood is concerned, the initial values of blood liposome concentration were decreased and liposomes were removed from the circulation rapidly in accordance with the extent of the Man content into their membranes. The Man-modification also affected the organ distribution of injected liposomes and their stability in rat serum. Except for MLV containing 50 mol% Man, it was observed that the hepatic uptake of liposomes was enhanced according to the increasing Man content, whereas splenic uptake was decreased and the splenic clearance was comparable. The stability of liposomes in rat serum decreased with increasing Man content. Liposomal instability in rat serum was significantly reduced by preheating the serum at 56 degrees C for 30 min, the treatment with anti-C3 antiserum and with EDTA but not abolished in serum treated with EGTA/MgCl2. Thus, it is considered that the activation of the complement system through the alternative pathway is facilitated as a result of increasing the Man content in the liposomes.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

No abstract