No abstract

Dynamic deformation and recovery responses of red blood cells (RBCs) to a cyclically reversing shear flow generated in a 30-microm clearance, with the peak shear stress of 53, 108, 161, and 274 Pa at the frequency of 1, 2, 3, and 5 Hz, respectively, were studied. The RBCs' time-varying velocity varied after the glass plate velocity without any time lag, whereas the L/W change, where L and W were the major and minor axes of RBCs' ellipsoidal shape, exhibited a rapid increase and gradual decay during the deformation and recovery phase. The time of minimum L/W occurrence lagged behind the zero-velocity time of the glass plate (zero stress), and the delay time normalized to the one-cycle duration remained constant at 8.0%. The elongation of RBCs at zero stress time became larger with the reversing frequency. A simple mechanical model consisting of an elastic linear element during a rapid elongation period and a parallel combination of elements such as a spring and dashpot during the nonlinear recovery phase was suggested. The dynamic response behavior of RBCs under a cyclically reversing shear flow was different from the conventional shape change where a steplike force was applied to and completely released from the RBCs.

No abstract

No abstract

Liposome-entrapped streptomycin (SM) was compared with free SM for therapeutic efficacy against experimental salmonellosis in mice. All of the mice infected with the virulent strain of Salmonella enteritidis 116-54 died between days 5 and 7, and a dose of 20 mg of free SM per kg administered 24 h after the bacterial inoculation did not prolong the survival. In contrast, the same dose of SM entrapped in liposomes prolonged the survival for all mice to more than 15 days. The therapeutic activity paralleled the dose in the liposomes, and a dose as low as 1. Synthetic phospholipid bilayer vesicles, called liposomes, have attracted considerable interest as potent drug carriers (6). They are nontoxic and biodegradable and can protect the entrapped drugs from enzymatic attack or immune recognition until they reach the target cells. The toxicity of a drug itself can be reduced by this shielding in the liposomes. Upon intravenous injection, liposomes, especially multiplelayer vesicles, are removed rapidly by reticuloendothelial (RE) cells and at least partly localized in lysosomes, where they are slowly degraded (7,13,15). This behavior of liposomes has some advantages for the treatment of diseases caused by intracellular parasites (5).In this study, experimental salmonellosis in mice was adopted as a model system of bacterial infection by intracellular parasites, and the therapeutic effect of streptomycin (SM) entrapped in liposomes was investigated. The results clearly indicated that the administration of liposomeentrapped SM could prolong the survival far more than the injection of free SM. Various applications of this method of selective drug delivery to RE cells were discussed. MATERIALS AND METHODSMice. Male C57BL/6 mice were obtained from the Laboratory of Experimental Animals (Institute of Medical Science, University of Tokyo, Japan). The animals were maintained on laboratory chow and acidified chlorinated water and used when 2 to 4 months old.Lipids. Egg yolk phosphatidylcholine was prepared by chromatography on alumina and silicic acid. Dipalmitoylphosphatidic acid and cholesterol were purchased from Sigma Chemical Co., St. Louis, Mo. Preparation of liposomes containing SM. Liposomes were * Corresponding author. prepared from a lipid mixture of egg yolk phosphatidylcholine (5 p.mol), cholesterol (5 ,umol), and dipalmitoylphosphatidic acid (0.5 ,umol) (negatively charged). The dried lipid film, obtained on rotary evaporation and subsequent vacuum desiccation, was dispersed in 0.5 ml of an SM solution (streptomycin sulfate, Meiji Seika Co. Ltd., Tokyo, Japan) in saline at the following concentrations: 250 mg/ml for an injection of 20 mg/kg, 125 mg/ml for 10 mg/kg, 62.5 mg/ml for 5 mg/kg, 31.2 mg/ml for 2.5 mg/kg, and 15.6 mg/ml for 1.2 mg/kg. Unencapsulated SM was removed by centrifugation at 20,000 x g for 20 min at 4°C, and the final pellet was resuspended in 5 ml of saline. Under these experimental conditions the entrapment of SM in the liposomes was equivalent to about 2 to 4% of the original solution.Measu...