ABSTRACT
Thymomodulin (Leucotrofina), an orally administrable thymic derivative endowed with interesting immunomodulating and myelomodulating properties, was tested for mutagenicity by means of the following in vitro and in vivo tests: mutagenesis on S. typhimurium with and without metabolic activation system (S-9), gene conversion on S. cerevisiae D 7 with and without metabolic activation, urinary assay in the mouse with and without metabolic activation, urinary assay in the mouse with S. cerevisiae D 7, host mediated assay in the mouse with S. cerevisiae and DNA repair test with and without metabolic activation. On the basis of the results obtained thymomodulin proved to be free of mutagenic activity.
Subject(s)
Mutagens , Thymus Extracts/toxicity , Animals , Biotransformation , DNA Repair , Humans , Male , Mice , Mutagenicity Tests , Rats , Rats, Inbred Strains , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Thymus Extracts/metabolism , Thymus Extracts/urineABSTRACT
Thymomodulin (Ellem Industria Farmaceutica spa, Milan, Italy) is a calf thymus acid lysate with immunomodulating activities. It is composed of several peptides with a molecular weight range of 1-10kD. Extensive studies in animal systems showed that Thymomodulin exhibited no, or very little toxicity even when used at high doses. Studies done in vitro and in vivo demonstrated that Thymomodulin is a biologically active compound which regulates the maturation of human and murine pre T lymphocytes, as well as modulate the functions of apparently mature human and animal B and T lymphocytes. It was observed that Thymomodulin can promote myelopoiesis as demonstrated by an increase of granulocyte-macrophage colonies in agar. Although additional studies to examine its target cell lineage are required, it appears that Thymomodulin exhibits specificity toward T cells. Therefore, enhancement of other cell lineage functions by Thymomodulin may be indirect, and mainly due to its effect on T cells. Of major importance is to note that Thymomodulin is prepared in a manner which allows it to maintain its biological activity when administered orally.
Subject(s)
Acquired Immunodeficiency Syndrome/therapy , Adjuvants, Immunologic , Hepatitis B/therapy , Thymus Extracts/therapeutic use , Thymus Gland/immunology , Aged , Amino Acids/analysis , Animals , Cattle , Clinical Trials as Topic , Double-Blind Method , Humans , Hypersensitivity , Mice , Mutagenicity Tests , Mutagens , Rats , Rats, Inbred Strains , Thymus Extracts/pharmacology , Thymus Extracts/toxicityABSTRACT
Thymostimulin (Tp-1 Serono) was tested toxicological in rats and monkeys during 6 weeks of repeated administration. Corresponding to the therapeutic use intended in man the substance was given to rats and monkeys intramuscularly in dosages of 10 or 100 mg/kg b.w. and due to technical reasons subcutaneously in a dosage of 1000 mg/kg b.w. No substance-related effects, either systemic or local, were observed in the monkeys. After treatment with the high dose level (1000 mg/kg b.w. s.c.) the rats exhibited inflammatory changes in the region of the injection sites.
Subject(s)
Thymus Extracts/toxicity , Animals , Female , Haplorhini , Male , Rats , Rats, Inbred StrainsABSTRACT
Detailed investigations on pharmacological properties of biologically active thymus extract were performed. Its acute and chronic toxicity was determined. Influence on the circulatory and the respiratory systems as well as on the parenchymatous and the smooth muscle organs, development of fetuses and reproductive functions were evaluated. Preparation TFX proved to be well tolerated and its acute action was manifested only at high doses injected intravenously. Its effect on the smooth muscle organs and its teratogenic activity were determined in the long-term experiments. It was assumed that it can be introduced in clinical use excluding women in the reproductive period.
Subject(s)
Thymus Extracts/pharmacology , Abnormalities, Drug-Induced/etiology , Animals , Blood/drug effects , Blood Pressure/drug effects , Cats , Cricetinae , Female , Hematopoietic System/drug effects , Lymphatic System/drug effects , Mice , Muscle, Smooth/drug effects , Pregnancy , Rabbits , Rats , Reproduction/drug effects , Respiration/drug effects , Thymus Extracts/toxicityABSTRACT
Treatment of adult AKR mice with tissue-specific mitotic inhibitor mol. wt. 1,000--20,000 extracted from the AKR thymus significantly delayed the onset of spontaneous thymus leukaemia, whereas extracts of other organs were without effect. A slight prolongation of survival time was found with spleen extract when administered to BALB/c mice infected with Rauscher virus, which causes leukaemia starting in the spleen. Thymus extracts of MW 100,000--300,000 caused myocardial degeneration in some leukaemic and nonleukaemic mice.
