romurtide and Body-Weight

MDP-Lys (N2-[(N-acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine), a macrophage activator, is a lipophilic derivative of muramyl dipeptide (MDP). Multilamellar liposome incorporated MDP-Lys was prepared using phosphatidylcholine and phosphatidylserine by conventional film method, and its inhibitory effect on lung metastasis was compared with MDP-Lys as a solution in hamster's osteosarcoma. The lung metastatic rates after transplantation of the tumor to a lower extremity, in which the extremity was amputated 3 weeks later, were 50% and 100% 3 and 7 weeks, respectively, after transplantation. The rates after amputation were reduced by the treatment with MDP-Lys proportionally to the logarithmic MDP-Lys dose, and the rates 7 weeks after transplantation were 55% and 60%, respectively, in the MDP-Lys solution (50 microg/day) and liposomal MDP-Lys (20 microg twice/week) groups. Fifty percent of hamsters treated with liposomal MDP-Lys survived for more than 6 months. Considering that hamsters had a lung metastasis rate of 50% before MDP-Lys treatment, liposomal MDP-Lys given at a dose of 20 microg twice/week was effective for inhibiting lung metastasis at a far lower dose of MDP-Lys than that given as a solution (40 microg vs. 350 microg per week). No significant side effect of liposomal MDP-Lys, as evaluated by the comparison of body weight changes among differently treated hamsters, was detected. This greater inhibitory effect of liposomal MDP-Lys can be considered to be due to the longer retention of the liposomal form in the lung.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Body Weight; Bone Neoplasms; Cricetinae; Liposomes; Lung Neoplasms; Male; Mesoderm; Neoplasm Transplantation; Osteosarcoma; Survival Analysis; Time Factors

We examined changes of blood cell counts and development of arthritis induced by daily subcutaneous injections of MDP-Lys(L18), an analogue of muramyl dipeptide (MDP), in rats. The numbers of neutrophils markedly increased in the peripheral blood 4 hr after the 1st, 7th, and 14th administrations of MDP-Lys(L18), but they recovered to the control levels within 24 hr. Monocyte and lymphocyte counts increased after the 7th and 14th administrations, respectively, although both decreased after the 1st dosing. Serum inflammatory markers, such as albumin, globulin, mucoprotein, sialic acid, and iron, showed marked changes after the 1st administration. Histopathologically, the synovial membrane of the tarsal joint showed a multilayer arrangement of synoviocytes with vesicular cytoplasms and infiltration of neutrophils from 6 hr after the 1st administration of the drug. The acute synovitis was gradually enhanced until 24 hr later. The synovitis was greatly decreased in degree after the 3rd administration, but increased again later. After the 7th and 14th administrations, mononuclear cells and lymphocytes, respectively, infiltrated the synovial membrane, in a manner corresponding to the hematological findings. However, exudative changes and neutrophilic infiltration were still observed after the 14th drug administration, and the synovitis was repaired after a 7-day recovery period.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Arthritis; Body Weight; Bone Marrow; Bone Marrow Cells; Female; Leukocyte Count; Male; Rats; Rats, Inbred Strains; Sex Factors; Synovial Membrane; Tarsal Joints; Time Factors

The reproductive toxicity of the anomeric mixture of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a new immunomodulator, was investigated in mice and rabbits after subcutaneous injection. Neither the male or female fertility nor the reproductive performance of the mice was affected by doses of up to 1 x 10(4) micrograms/kg. MDP-Lys(L18) elicited no evidence of teratogenicity when injected subcutaneous during the period of organogenesis to pregnant mice at doses of up to 3 x 10(4) micrograms/kg, or to pregnant rabbits at doses of up to 25 micrograms/kg. However, the female mice receiving 3 x 10(4) micrograms/kg showed induration and scabbing of the injection sites. Decrease of maternal body weight and food intake was seen in rabbits at doses of 5 and 25 micrograms/kg. Lacrimation, bloodshot eyes and swelling of eyelid were observed in does at a dose of 25 micrograms/kg. In perinatal and postnatal toxicity study in mice using doses of up to 2 x 10(4) micrograms/kg, a decrease in body weight of dams was seen at a dose of 2 x 10(4) micrograms/kg. Decrease in body weight of pups at birth was observed at a dose of 2 x 10(4) micrograms/kg.

Topics: Abnormalities, Drug-Induced; Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Body Weight; Female; Fertility; Male; Mice; Pregnancy; Pregnancy, Animal; Rabbits