thymosin and Body-Weight

Topics: Angiopoietin-1; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Mice; Mice, Transgenic; Nerve Fibers; Receptor, TIE-2; Sciatic Nerve; Signal Transduction; Thymosin

Thymosin-alpha1 (Talpha1) is indicated for the treatment of certain viral infections, including hepatitis B and C, and cancers, such as melanoma. In this paper, the fusion genes encoding human serum albumin (HSA) and Talpha1 with (rHSA-L-Talpha1) and without a linker peptide (rHSA-Talpha1) were constructed and overexpressed in P. pastoris. Through the process of ion interaction chromatography (Q-Sepharose F.F), hydrophobic interaction chromatography (Phenyl Sepharose HP) and affinity chromatography (Blue Sepharose F.F), the purity of fusion proteins was greater than 97%. In contrast to the reactivity of normal spleen cells to Con A, the data of in vitro murine spleen lymphocytes proliferation experiment suggested that spleen cells achieved a higher degree of T cell maturation after rHSA-L-Talpha1, rHSA-Talpha1 and Talpha1 treatments, respectively. Moreover, rHSA-L-Talpha1, rHSA-Talpha1 and Talpha1 can also antagonize dexamethasone-induced apoptosis of thymocyte sub-populations. In hydrocortisone-induced immunosuppression mice (in vivo experiments), after subcutaneous injections with two fusion proteins and Talpha1 for seven consecutive days, the net increment of body weight, the spleen index and the thymus index were significantly improved. Simultaneously, the increase in SOD level and the decrease in MDA level in plasma were observed. The pharmacokinetic data of rHSA-L-Talpha1 and rHSA-Talpha1 administered in rats showed an improved pharmacokinetic profile with a conspicuous prolonged half life. The analysis of bioactivity and pharmacokinetics suggested that fusion proteins rHSA-L-Talpha1 and rHSA-Talpha1 were new drug candidates.

Topics: Aldehydes; Animals; Apoptosis; Body Weight; Cell Proliferation; Cells, Cultured; Female; Humans; Immunization; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Pichia; Protein Engineering; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins; Serum Albumin; Superoxide Dismutase; T-Lymphocyte Subsets; T-Lymphocytes; Thymalfasin; Thymosin

Thymus lymphocyte subsets in uraemic rats were studied using monoclonal antibodies. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the weight of the thymus decreased in uraemic rats. As for lymphocyte subsets, the frequency of W3/25+OX8+ decreased and those of W3/25-OX8-, W3/25+OX8- and W3/25- OX8+ relatively increased in uraemic rats. All these changes were more significant in severely uraemic than in moderately uraemic rats. When thymosin fraction 5 (TF5) was administered to severely uraemic rats, the weight of the thymus increased and the lymphocytes subsets normalized. These results suggest that uraemia may cause a maturational impairment of thymus lymphocytes by the depression of thymic hormone secretion.

Topics: Animals; Antibodies, Monoclonal; Antigens, Differentiation; Body Weight; Lymphocyte Subsets; Male; Organ Size; Rats; Rats, Inbred Strains; Thymosin; Thymus Gland; Uremia

To evaluate the effects of a gonadotropin-releasing hormone agonist on non-reproductive systems, we administered [D-Leu6,Des-gly10]-GnRH ethylamide (leuprolide; 5 micrograms/day) for 21 days to female Sprague-Dawley rats. In Experiment 1, continuous infusion (Alzet minipumps sc) was compared to injection. Increased thymus and body weights and decreased estradiol and uterine weights were noted for both administration methods. Spleen weight increased only in rats treated by continuous infusion. Ovary, kidney and liver weights did not change. Only leuprolide-injected rats had elevated LH with decreased corticosterone and ACTH levels, possibly related to the injection process. Glucose, insulin, progesterone, FSH and corticosterone/ACTH were not different. In Experiment 2, intact and ovariectomized rats were implanted with minipumps delivering leuprolide or 0.9% NaCl. Body and thymus weights increased, whereas uterine weight and estradiol declined in both leuprolide-treated and ovariectomized rats. No synergism between leuprolide and ovariectomy was noted. Thymosin alpha 1, but not thymosin beta 4, increased in leuprolide-treated ovariectomized rats. Peripheral white blood cell count was elevated in leuprolide-treated intact rats and ovariectomized rats. In bone marrow, non-nucleated cell count declined in leuprolide-treated intact rats, contributing to the decreased total cell count in this group. Nucleated cell count was unaffected. Therefore, thymus weight gain was accompanied only in some cases by functional changes. Our results demonstrate that leuprolide affects non-reproductive systems, in a similar manner to ovariectomy. We suggest that such alterations may be due to the hypoestrogenic environment produced by leuprolide.

Topics: Adrenocorticotropic Hormone; Analysis of Variance; Animals; Body Weight; Corticosterone; Estradiol; Female; Gonadotropin-Releasing Hormone; Injections, Subcutaneous; Kidney; Leuprolide; Liver; Organ Size; Ovariectomy; Radioimmunoassay; Rats; Rats, Inbred Strains; Spleen; Thymosin; Thymus Gland; Uterus

There is a large body of evidence for the role of thymosin peptides in immunogenesis and immunity. In this paper we report on the influence of prothymosin alpha 1 (ProT-alpha 1), a hormone-like peptide derived from the calf thymus, on humoral and cellular immune reactions in the rat. Young adults received intraperitoneal injections of ProT-alpha 1 in the periods before and after immunization with cellular and soluble antigens. ProT-alpha-treatment produced a dose-dependent increase of both humoral and cell-mediated immune responses. The thymus weight increased but not that of spleen. Treatment of nonimmunized rats with this polypeptide significantly elevated the number of CD4+ and decreased the number of CD8+ cells in the peripheral blood. The results suggest a potent immunostimulatory activity of ProT-alpha 1 and imply direct action of this polypeptide on T lymphocytes.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Monoclonal; Antibody Formation; Arthus Reaction; Blood Cell Count; Body Weight; CD4 Antigens; CD8 Antigens; Erythrocytes; Hemolytic Plaque Technique; Hypersensitivity; Hypersensitivity, Delayed; Immunity, Cellular; Lymphocytes; Male; Organ Size; Protein Precursors; Rats; Rats, Inbred Strains; Sheep; Thymosin

In this study we evaluated the immunorestorative activity of prothymosin-alpha (ProT-alpha) in senescence. Aged rats were repeatedly injected with ProT-alpha after antigen challenge. Both humoral and cell-mediated immune reactions were tested. The results show that ProT-alpha exerted a marked immunopotentiating effect in aged rats. Moreover, ProT-alpha induced enhancement of PFC response, and skin hypersensitivity reactions were more pronounced in senescent rats than in young adult controls. ProT-alpha treatment increased thymus and spleen weights in aged rats, and induced qualitative and quantitative improvements of the cellular make-up of the thymus and thymus-dependent areas of the spleen. The results imply that "restoring" thymus endocrine function by exogenous administration of ProT-alpha may improve immune system homeostasis in senescence.

Topics: Aging; Animals; Antibody Formation; Body Weight; Female; Hemagglutination; Hemolytic Plaque Technique; Immunity, Cellular; Organ Size; Protein Precursors; Rats; Rats, Inbred Strains; Skin Tests; Thymosin

The present studies were performed to determine the effects of severe protein deficiency and subsequent injection of thymosin fraction 5 (TF5) on T and B cell functions. BALB/c mice, 4 weeks old, were fed a normal protein (21%), a low protein (4%) or a protein free (0%) diet and then injected with TF5 or buffer (PBS). A significant increase was observed in the PHA (phytohemagglutinin) and LPS (lipopolysaccharide) induced mitogenesis with increasing age of the well-nourished, PBS injected animals. The severely protein malnourished mice, PBS injected and the well nourished mice, injected with TF5 had smaller increases in both B and T cell mitogenesis with increasing age. TF5 injection of the malnourished mice increased PHA and LPS mitogenesis nearly to the levels of the well-nourished mice. The protein malnourished mice consistently had higher serum corticosteroid levels than controls. No changes in serum corticosteroids were observed with TF5 injection of controls, but there was a significant decrease in the corticosteroid levels of the severely malnourished with TF5 injection. Cytoxicity assays of T cell function, antibody dependent cellular cytoxicity and cytoxicity to mouse thymona tumor cells, in mice fed moderately protein deficient diets showed suppression compared to controls fed 20% protein. TF5 injection partially and temporarily increased these functions in the malnourished mice.

Topics: Animals; Antibody-Dependent Cell Cytotoxicity; Body Weight; Female; Immunosuppression Therapy; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Organ Size; Protein-Energy Malnutrition; T-Lymphocytes; Thymosin

Mixed bovine gangliosides have been reported to enhance neuronal regeneration and sprouting. The Wobbler mouse model of motor neuron disease was used to test the clinical effects of long-term ganglioside administration on the course of the disease. Mixed gangliosides were injected subcutaneously into a group of 5 Wobbler mice and compared to a control group of 5 Wobbler mice which received saline. Because of several reports implicating involvement of the immune system in ALS, a 3rd group of 5 Wobbler mice received thymosin. All mice were 4 weeks old at commencement of injections. The 3 groups were examined weekly and graded with respect to front leg power, ability to climb a vertical grating, and walking posture. After 4 months of treatment, no significant difference between either experimental group and the controls was found.

Topics: Animals; Body Weight; Drug Evaluation, Preclinical; Gangliosides; Mice; Mice, Neurologic Mutants; Motor Neurons; Nerve Regeneration; Neuromuscular Diseases; Thymosin

Adult male mice were treated with various doses of 6-hydroxydopamine in order to assess the effects of this drug upon thymic dependent immunity. A consistent decrease in primary antibody titers to sheep erythrocytes was observed following treatment with this drug. Serum levels of thymosin alpha 1 were increased by day three after 6-OHDA with a return to normal by day five. Thymocyte terminal deoxynucleotidyl transferase changes were biphasic with an initial decrease after 6-OHDA followed by an increase. Changes in mitogen responsiveness were observed but were not consistently reproducible. Involvement of both catecholamines and corticosteroids in bringing about these observed changes was discussed.

Topics: Adrenalectomy; Animals; Antibody Formation; Antibody-Producing Cells; Body Weight; DNA Nucleotidylexotransferase; Hemolytic Plaque Technique; Hydroxydopamines; Immunosuppressive Agents; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mitogens; Organ Size; Oxidopamine; Rats; Spleen; Thymalfasin; Thymosin; Thymus Gland

The authors studied the relationship between thymus and growth of long bones in rats in the pre-puberal stage. 150 rats of both sexes were divided in 3 groups: thymectomized, sham-thymectomized and controls. The animals were sacrificed 15 days after surgery, the femurs were collected and measured, in length and breadth. Thymectomized animals have a bone growth significantly lesser in length and breadth when compared to the sham-thymectomized animals. The latter ones also presented a lesser bone growth when compared to the controls. The average body weight was also significantly lesser in thymectomized rats than in controls, the same happening with the shamthymectomized rats. It is suggested that the thymus probably presents some kind of relation with the hypothalamus through a positive feed-back, simulating secretion of substances that would act on the adenohypophysis rising the secretion of growth hormone and the thymus playing a role in maintaining the serum levels of growth hormone and thyroxine necessary for the growth and development of bones.

Topics: Age Factors; Animals; Body Weight; Bone Development; Female; Femur; Growth Disorders; Hypothalamus; Male; Osteogenesis; Pituitary Gland, Anterior; Rats; Reference Values; Sex Factors; Stress, Physiological; Thymectomy; Thymosin; Thymus Gland; Thyroxine