romurtide and Bacterial-Infections

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Bacterial Infections; Cytokines; Drug Synergism; Hematopoiesis; Humans; Infections; Leukopenia; Mice; Mycoses; Neoplasms; Virus Diseases

N2-[(N-Acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a derivative of muramyl dipeptide, is known to have the activity to augment the number of white blood cells (WBC) via colony-stimulating factor. Muroctasin has been expected to be applied to leukopenia caused by anticancer chemotherapy. When WBC decreased to less than or equal to 3,000/mm3 after the 1st course of chemotherapy, 131 patients with lung cancer, who were previously classified by the combination regimens of chemotherapy, were enrolled in the study and randomized into 3 groups, 200 micrograms (H), 100 micrograms (L) and untreated control (C) groups. The patients were then subcutaneously treated once daily for 6 consecutive days. WBC and its differential count were measured on Days 4, 7 and 15 after commencement of the study. WBCs in H and L groups were recovered greater than in C group. In WBC differential count, the recovery of neutrophil was prominent in muroctasin treated groups. The portion of immature neutrophil in the bone marrow was also increased by muroctasin treatment. A restorative effect on WBC and neutrophil counts was also confirmed only in the second course of H group. On the other hand, fever and pain in the injected site as side effects were common in the H group and L group in both of courses. In this study, the usefulness of muroctasin in leukopenia was suggested when administered at dosages of 200 micrograms for 6 days.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Aged; Antineoplastic Agents; Bacterial Infections; Blood Cell Count; Bone Marrow; Female; Humans; Leukocyte Count; Leukopenia; Lung Neoplasms; Male; Middle Aged

Romurtide given orally enhanced the nonspecific resistance against microbial infections and hematopoiesis up to the levels achieved by subcutaneous (s.c.) injection of the compound in mice. Oral romurtide conferred protection and, in consequence, enhanced therapeutic efficacy of antibiotics against systemic infections in mice. The leukocytosis followed by the elevations of colony stimulating activity in serum and the colony forming unit of granulocyte-macrophage (c.f.u.-GM) in femoral bone marrow was observed as successive event in mice treated orally with romurtide. To obtain a comparable potency to s.c. injection of the compound at a dose of 0.1 mg per mouse, oral application required doses of 3 and 10 mg per mouse for stimulating the nonspecific resistance to infection and hematopoiesis, respectively.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Bacterial Infections; Disease Susceptibility; Dose-Response Relationship, Drug; Hematopoiesis; Male; Mice; Mice, Inbred Strains; Mycoses

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Bacterial Infections; Complement C3; Elapid Venoms; Male; Mice; Mice, Inbred Strains

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Bacterial Infections; Bacterial Proteins; Chemotaxis, Leukocyte; Glycoproteins; Male; Mice; Neutrophils

Stimulation of resistance to infection induced by the analogs of muramyl dipeptide (MDP) having substituted functions in the gamma-carboxyl group of D-isoglutamyl residue was examined in experimental Escherichia coli infections in mice. An MDP analog which is an efficient strengthener of resistance to infection, N alpha-MDP-N epsilon-stearoyllysine [MDP-Lys(L18)], was selected through the comparative assessment of a number of compounds in three categories: (i) gamma-alkylamides, (ii) gamma-esters, and (iii) N alpha-MDP-N epsilon-acyllysine derivatives. Furthermore, the antiinfectious activity of MDP-Lys(L18) was evaluated bacteriologically in comparison with that of MDP. The effect of MDP-Lys(L18) on the susceptibility of mice to infections with various species of microorganisms was studied. Protective activity was greatest against E. coli and staphylococcal infections, considerable against Pseudomonas and Candida infections, and least against Klebsiella infection. The effects of bacterial inoculum size and MDP treatment timing, dose, and route of administration on protective activity were studied. The efficacy of MDP-Lys(L18) in protection tests was demonstrated for all administration routes, even the oral. Its high potency was confirmed by the smaller influence of inoculum size and particularly small value of the minimum dosage required for inducing protective activity. A decrease in bacterial survival was observed in the blood and organs of mice treated with the analog and infected with E. coli. The following two useful effects were obtained: the synergistic effect of glycopeptide and chemotherapeutic agents and the stimulation of resistance to infection in animals immunocompromised by cyclophosphamide treatment.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Bacterial Infections; Candidiasis; Cefazolin; Cyclophosphamide; Drug Synergism; Escherichia coli; Escherichia coli Infections; Gentamicins; Immunity, Innate; Kidney; Liver; Male; Mice; Structure-Activity Relationship; Time Factors