Chrono- and Immunocorrection of Inflammatory Disorders of Internal Reproductive Organs in Women of Reproductive Age.

We compared the effectiveness of immunomodulators used in the treatment of patients with chronic salpingitis and oophoritis with or without changes in succinate dehydrogenase (SDH) activity in blood lymphocytes at incubation with the drug. Diurnal variations in individual reaction of SDH in blood lymphocytes to thymalin or ridostin were revealed. In the groups of women receiving ridostin or thymalin during the reaction of lymphocyte SDH to it, improvement of clinical laboratory and immunological parameters was observed in the majority of the patients and no effect was found in a lesser group of patients than in the groups treated with drugs during the absence of lymphocyte SDH reaction thereto. The timing of the presence of SDH reaction to drugs in the immunocompetent cells makes it possible to set the optimal daily regime of their application and to select a drug that would be most effective in each particular case.

[Age- and sex-related differences of neuroendocrine center reactions in the hypothalamus on preparation thymalin and alpha-tocopherol acetate].

In experiment the action of Thymalin, alpha-tocopherol and stress on the centers of hypothalamus related to the regulation of the gonadotropic function has been investigated and the age-specific features of such influence as well. The results of experiments indicate the presence of neuron's reaction of the rostra preoptical area and arcuate nucleus for experimental influences. As a stress exposure and alpha-tocopherol injection to the young animals a reduction of neuron's kernels of the arcuate nucleus was observed, a sexual distinction wasn't revealed in the process. The response age-specific feature for alpha-tocopherol injection of the nucleus neuron's rostra preoptical and arcuate area of the hypothalamus of white rats is a reduction in a degree of response. Thymalin reduces a threshold of sensitivity of the neuron's arcuate center to action of stress.

Humoral and cell-mediated immunopotentiation in vaccinated chicken layers by thymic hormones and zinc.

The humoral and cell-mediated immunities to a trivalent killed vaccine, administered subcutaneously to white leghorn-chicken layers at 29 and 31 weeks of age, and containing antigens of infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), and Newcastle disease virus (NDV), were quantitated in five vaccinated and one unvaccinated-control group. Four out of the five vaccinated groups were immunopotentiated by various combinations of zinc and thymic hormones administered intraperitoneally in a volume of 0.1 ml per bird at an interval of three days for a period of three weeks, starting at 29 weeks of age. At each time interval, each bird of the first group received thymulin (10 ng) and ZnCl2 (1 microM), while each bird of the second group received thymopoietin (25 ng) and ZnCl2 (1 microM); in the third group, each bird received thymulin (10 ng), thymopoietin (25 ng), and ZnCl2 (1 microM), while each bird of the fourth group received only ZnCl2 (1 microM). Birds of the fifth group were only vaccinated and the control birds in the sixth group were left without vaccination or other immunopotentiation. Among all combinations, the thymulin-ZnCl2 resulted in birds with the highest humoral immunopotentiation to IBV, IBDV, and NDV antigens with respective percent increase in the mean titer at 33 weeks of age, compared with initial titer at 29 weeks of age, equivalent to 199%, 671.7%, and 86.4%. The highest cell-mediated delayed hypersensitivity reaction, measured at 48 h following an intradermal administration of the trivalent vaccine in the wattles at 33 weeks of age, was obtained in chickens immunopotentiated by the thymulin-thymopoietin-ZnCl2 combination.

Functional roles of phenylalanine(7) of thymic humoral factor-gamma 2 in the impaired blastogenic response of uremic T-lymphocytes.

The peptide analogs of thymic humoral factor-gamma 2 (THF-gamma 2) in which phenylalanine residue at the 7th position are replaced by phenylglycine (Phg), homophenylalanine (Hph), and 1-naphthylalanine (1-Nal) were synthesized by a solid-phase method and the immunological significance of the aromatic amino acid of this position was comparatively investigated. The in vitro restoring effect of the synthetic peptides on the impaired phytohemagglutinin (PHA) response of T-lymphocytes from uremic patients was tested. The observed activities of these peptides were in order (1-Nal7) thymic humoral factor [THF]-gamma 2 > 4-Fluoro (Phe7) THF-gamma 2 > THF-gamma 2. However, the other two analogs, [Phg7] THF-gamma 2 and [Hph7] THF-gamma 2, had no restoring effect even at a higher concentration.

Evaluation of multiple parameters of HIV-1 replication cycle in testing of AIDS drugs in vitro.

Evaluation of the activities of antiretroviral agents and an immunoregulatory compound has been made using two models of HIV-1 infection and three measurements of virus expression. Acute infection of Jurkat cells or chronic/inducible infection in U1.1 cells was monitored at multiple time points after drug treatment. The 50% effective concentrations (EC50) of the HIV-1 inhibitors suramin, 3'-azido-3'-deoxythymidine (AZT), and 2',3'-dideoxycytidine, as measured by HIV-1 RNA hybridization in Jurkat cells two days after infection, were comparable to EC50 values obtained in parallel measurements of extracellular p24 levels and percent HIV-1 IF-positive cells. However, these measurements diverged: at seven days after infection the EC50 of AZT was greater than 10 microM when intracellular HIV-1 RNA was assayed, 0.2 microM by IF, and 0.03 microM by p24 assay. Human thymic humoral factor displayed no direct inductive activity in chronic HIV-1 infection in U1.1 cells, while phorbol ester and lymphocyte supernatants induced all parameters. These observations warrant care when interpreting results of only a single assay and suggest that definitive assay of HIV-1 infection requires measurements of multiple parameters of virus expression.

Neural responses to antigenic challenges and immunomodulatory factors.

In studies designed to examine the effects of the immune system, recordings of multi-unit electrical activity (MUA) in the central nervous system were made in the preoptic area/anterior hypothalamus (POA/AH) and paraventricular nucleus (PVN) of rats, following sheep red blood cell (SRBC) immunization. Peak increases in POA/AH MUA were observed on the fifth day following SRBC sensitization, the day on which serum antibodies were first detected. A significant increase in paraventricular nucleus (PVN) MUA was also observed on the sixth day. These changes in POA/AH and PVN MUA were found to be associated with increased plasma corticosterone levels on day 8. Induction of a second immune response to SRBC evoked a POA/AH MUA increase of extended duration but reduced amplitude, while administration of the immunosuppressive drug, cyclophosphamide, prevented both antibody generation and any increases in POA/AH MUA. These data suggest that activation of the immune system may provide signals, in the form of chemical messengers, which are able to alter neural activity in some regions of the brain that are important in neuroendocrine regulatory mechanisms. Accordingly, intracerebroventricular injections of thymic humoral factor or alpha-interferon decreased POA/AH MUA, increased EEG synchronization, and decreased plasma levels of corticosterone. Histamine and interleukin 1 did not alter POA/AH MUA but decreased EEG synchronization and increased plasma levels of corticosterone.

The effect of "facteur thymique serique" (FTS) on catecholamine and serotonin neurotransmission in discrete brain regions of mice.

The dose-related effect of Facteur Thymique Serique (FTS) on hypothalamic, mesencephalic and striatal neurotransmission were investigated after intracerebroventricular (icv) administration. FTS pretreatment with dose of 1 microgram (icv) increased the mesencephalic serotonin content, while failed to influence the hypothalamic and striatal serotonin levels. The nonapeptide in a dose of 0.1 microgram (icv) decreased the hypothalamic, while in a dose of 1 microgram the hypothalamic and also the mesencephalic dopamine content, but did not influence the striatal dopamine level. FTS in a dose of 1 microgram (icv) significantly decreased the hypothalamic noradrenaline level, but did not influence the noradrenaline content of the mesencephalon and striatum. These results suggest that FTS is able to modify central neurotransmission.

The effects of thymus-derived peptides on hypothalamic LRF and pituitary gonadotropin content in prepubertal congenitally athymic nude mice and their normal heterozygous littermates.

Congenitally athymic nude mice have recognized reproductive defects, accompanied by decreased pituitary gonadotropin and hypothalamic LRF concentrations at 3 weeks of age, compared to their normal heterozygous littermates. To determine if these hormonal changes are due to decreased secretion of thymic peptides, we measured pituitary concentrations of LH and FSH and hypothalamic LRF content at 21 days of age in 122 congenitally athymic nude (nu/nu) mice and in 190 heterozygous (nu/+) littermates administered daily injections of a crude thymic extract, semipurified thymosin fraction 5, or a synthetic thymic protein preparation. All animals receiving crude thymic protein extract, and some receiving either thymosin or synthetic thymic factor, had reduced levels of hypothalamic LRF. The changes in concentrations of gonadotropins were more variable. All mice receiving crude thymic extract (with reduced hypothalamic LRF content) appeared to have increased pituitary concentrations of LH, FSH, or both when compared to control animals, although statistical significance was not achieved in all groups. A similar but less marked trend toward increased pituitary gonadotropins was also noted in mice receiving thymic factor. These preliminary results suggest that thymus-derived peptides can affect hypothalamic-pituitary function and support our hypothesis that thymic hormones may play a role in programming the hypothalamic-pituitary axis in the prepubertal period in rodents.

Thymosin stimulates secretion of luteinizing hormone-releasing factor.

Partially purified thymosin fraction 5 and one of its synthetic peptide components, thymosin beta 4, but not thymosin alpha 1, stimulated secretion of luteinizing hormone--releasing factor from superfused medial basal hypothalami from random cycling female rats. In addition, luteinizing hormone was released from pituitary glands superfused in sequence with hypothalami. No release of luteinizing hormone in response to thymosin was observed from pituitaries superfused alone. These data provide the first evidence of a direct effect of the endocrine thymus on the hypothalamus and suggest a potentially important role for thymic peptides in reproductive function.