Once-daily linagliptin showed safety and tolerability over 1 year and provided effective add-on therapy leading to significant HbA1c reductions, similar to metformin, over 52 weeks in Japanese patients.
The contribution of mannose receptors on the cell surface of mouse peritoneal macrophages to the process of liposome-induced phagocytosis of immunoglobulin G-opsonized sheep red blood cells (SRBCs) through Fc gamma receptor has been investigated. Fc gamma receptor-mediated phagocytosis of opsonized SRBCs was activated by modified alpha 2-macroglobulin, which was produced in the incubation mixture of alpha 2-macroglobulin and liposome-treated splenic B cells. The phagocytosis was specifically inhibited by the addition of D-mannose, and the inhibition was dependent on the D-mannose concentration. The binding of modified alpha 2-macroglobulin to macrophages was also reduced by the addition of D-mannose. The activation effect of modified alpha 2-macroglobulin was not inhibited when in the presence of alpha 2-macroglobulin-trypsin and -methylamine complexes. In the presence of cycloheximide, activated phagocytosis was reduced to the control level. By Scatchard plot analysis of IgG binding studies, the number of Fc gamma receptors of a macrophage had been increased to 4.6-fold that of a control macrophage by treatment with modified alpha 2-macroglobulin. These findings suggest that macrophage mannose receptors are involved in activating the process of Fc gamma receptor-mediated phagocytosis of opsonized SRBCs induced by modified alpha 2-macroglobulin. Lectins may participate in a signal transduction in macrophage activation by liposomes.
Macrophage phagocytic activity has previously been shown to be increased by binding of modified α2‐macroglobulin (α2M) with mannose residues at termini of sugar chains to mannose receptors on macrophages, with a subsequent increase in the number of Fcγ receptors at the cell surface. In the present study, an examination was made of the association of protein tyrosine kinase with the increase in number of Fcγ receptors following binding of modified α2M to mannose receptors. The phagocytosis of IgG‐opsonized sheep red blood cells through the action of the Fcγ receptor by modified α2M was inhibited by mannose and herbimycin A and slightly so by genistein. The mannose receptor would thus appear to be associated with tyrosine kinase activity. By Western blotting, tyrosine phosphorylated proteins with molecular weights of 32 000, 34 000, 36 000, 65 000, 85 000 and 110 000 appeared or increased upon treating macrophages with modified α2M. The degree of tyrosine phosphorylated proteins was the same for control macrophages following incubation in the presence of mannose and herbimycin A. Genistein treatment affected only tyrosine phosphorylated proteins of 65 000 and 110 000. The binding of modified α2M to mannose receptors was demonstrated by the inducement of tyrosine kinase activation that was sensitive to herbimycin A, followed by an increase in Fcγ receptors and consequently greater phagocytosis.
Stress applied to rats is known to result in a quick decrease in blood fluidity. Although electrical acupuncture stimulation (ACU) attenuates stress responses, the influence of ACU on blood fluidity has not been well examined. In the present study, the effect of ACU on blood fluidity and platelet adhesion was examined using a Micro Channel Array Flow Analyzer and a laser scattering platelet aggregometer (PA-20), respectively. Male Wistar rats (7-8 weeks old) were used. ACU (1 Hz, 3-5 V), which causes slight muscle twitching, was applied to acupoints for 60 minutes/day once or on 2 consecutive days. Stimulated acupoints were as follows: ZuSanli (ST-36), Sanyinjiao (SP-6), Hegu (L-I4), Neiguan (P-6), and Shenshu (BL-23). ACU applied to ST-36, SP-6, and L-14 revealed significant increases in blood fluidity while platelet adhesion activity decreased. No significant changes were observed when ACU was applied to P-6 and BL-23. Results indicate that ACU affects blood fluidity depending on the acupoints. Blood fluidity changed with ACU within 1 day. In other words, the effect of acupuncture has an immediate effect. In addition, platelet aggregation decreased with ACU, suggesting that an increase in blood fluidity is associated with platelet aggregation ability.
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