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Traumatic brain injury (TBI) is one of the leading causes of death worldwide. There are currently no effective treatments for TBI, and trauma survivors suffer from a variety of long-lasting health consequences. With nutritional support recently emerging as a vital step in improving TBI patients' outcomes, we sought to evaluate the potential therapeutic benefits of nutritional supplements derived from bovine thymus gland, which can deliver a variety of nutrients and bioactive molecules. In a rat model of controlled cortical impact (CCI), we determined that animals supplemented with a nuclear fraction of bovine thymus (TNF) display greatly improved performance on beam balance and spatial memory tests following CCI. Using RNA-Seq, we identified an array of signaling pathways that are modulated by TNF supplementation in rat hippocampus, including those involved in the process of autophagy. We further show that bovine thymus-derived extracts contain antigens found in neural tissues and that supplementation of rats with thymus extracts induces production of serum IgG antibodies against neuronal and glial antigens, which may explain the enhanced animal recovery following CCI through possible oral tolerance mechanism. Collectively, our data demonstrate, for the first time, the potency of a nutritional supplement containing nuclear fraction of bovine thymus in enhancing the functional recovery from TBI., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Recurrent infection with human alphaherpesvirus 1 (HHV-1) may be associated with immune exhaustion that impairs virus elimination. Thymic peptides enhance immune function and thus could overcome immune exhaustion. In this study, we investigated whether reactivation of herpes infections was associated with immune exhaustion. Moreover, we examined the impact of treatment with thymostimulin on the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on T and B lymphocytes in patients suffering from recurrent HHV-1 reactivation. We also assessed the effector function of peripheral blood mononuclear cells (PBMCs) after stimulation with thymic peptides. We enrolled 50 women with reactivated HHV-1 infections and healthy volunteers. We measured the expression of various activation and exhaustion markers on the surface of PBMCs using flow cytometry. In ex vivo experiments, we measured the secretion of inflammatory cytokines by PBMCs cultured with thymostimulin. Compared with controls, patients with reactivated HHV-1 infections had increased percentages of CD3+ co-expressing CD25, an activation marker ( p < 0.001). Moreover, these patients had increased percentages of CD4+ and CD8+ cells co-expressing the inhibitory markers PD-1 and PD-L1. In cultures of PBMCs from the patients, thymostimulin increased the secretion of interferon gamma ( p < 0.001) and interleukin (IL)-2 ( p = 0.023), but not IL-4 or IL-10.Two-month thymostimulin therapy resulted in no reactivation of HHV-1 infection during this period and the reduction of PD-1 and PD-L1 expression on the surface of T and B lymphocytes ( p < 0.001). In conclusion, reactivation of herpes infection is associated with immune exhaustion, which could be reversed by treatment with thymic peptides.

The goal of this work was the evaluation of the frequency of human CMV infection among the women, whose pregnancy ended in miscarriage, detection of active forms of infection and treatment before pregnancy. Virological and sero-immunological techniques were used. A total of 116 women who had miscarriages before the 28 week of pregnancy were submitted to the CMV test. 109 women (94.0%) demonstrated positive results. 49 women (42.2%) had active form of the cytomegalovirus infection. 13 women (26.5%) had the recurrent form and 36 patients (73.5%) had the persistent form of CMV infection (stage of productive replication). All the women with active CMVI were treated before the next pregnancy. Immunomodulatory therapy for the treatment was used.

Background: Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour cells and to resist infections due to immunosuppression induced by the disease and antineoplastic therapy., Objectives: To evaluate the effectiveness of pTE and sTP for the management of cancer., Search Strategy: We searched CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE, EMBASE, AMED, BIOETHICSLINE, BIOSIS, CATLINE, CISCOM, HEALTHSTAR, HTA, SOMED and LILACS (to February 2010)., Selection Criteria: Randomised trials of pTE or sTP in addition to chemotherapy or radiotherapy, or both, compared to the same regimen with placebo or no additional treatment in adult cancer patients., Data Collection and Analysis: Two authors independently extracted data from published trials. We derived odds ratios (OR) from overall survival (OS) and disease-free survival (DFS) rates, tumour response (TR) rates, and rates of adverse effects (AE) related to antineoplastic treatments. We used a random-effects model for meta-analysis., Main Results: We identified 26 trials (2736 patients). Twenty trials investigated pTE (thymostimulin or thymosin fraction 5) and six trials investigated sTP (thymopentin or thymosin α(1)). Twenty-one trials reported results for OS, six for DFS, 14 for TR, nine for AE and 10  for safety of pTE and sTP. Addition of pTE conferred no benefit on OS (RR 1.00, 95% CI 0.79 to 1.25); DFS (RR 0.97, 95% CI 0.82 to 1.16); or TR (RR 1.07, 95% CI 0.92 to 1.25). Heterogeneity was moderate to high for all these outcomes. For thymosin α(1) the pooled RR for OS was 1.21 (95% CI 0.94 to 1.56, P = 0.14), with low heterogeneity; and 3.37 (95% CI 0.66 to 17.30, P = 0.15) for DFS, with moderate heterogeneity. The pTE reduced the risk of severe infectious complications (RR 0.54, 95% CI 0.38 to 0.78, P = 0.0008; I² = 0%). The RR for severe neutropenia in patients treated with thymostimulin was 0.55 (95% CI 0.25 to 1.23,  P = 0.15). Tolerability of pTE and sTP was good. Most of the trials had at least a moderate risk of bias., Authors' Conclusions: Overall, we found neither evidence that the addition of pTE to antineoplastic treatment reduced the risk of death or disease progression nor that it improved the rate of tumour responses to antineoplastic treatment. For thymosin α(1), there was a trend for a reduced risk of dying and of improved DFS. There was preliminary evidence that pTE lowered the risk of severe infectious complications in patients undergoing chemotherapy or radiotherapy.

Background: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial., Methods: The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky >or=60%/Child-Pugh

The interference between thymus and pineal gland during their involution is considered in this review. The research data about influence of thymus peptides on pineal gland and pineal peptides on thymus is summarized. Analysis of these data showed that pineal peptides (epithalamin, epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (thymalin, thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

The aim of this study was to evaluate the efficacy of treatment of Lewis rats with calf thymus extract (TFX®) and its six-peptide fraction on the course of experimental allergic encephalomyelitis (EAE). Interferon- ß served as a reference drug. We found that intramuscular administration of the thymus extract fraction significantly reduced clinical, immunological, histological, and ultrastructural alterations inherent in the disease. We suggest that TFX® or TFX®-derived fractions have potential as therapeutics in treatment of neurodegenerative diseases such as multiple sclerosis.

The aim of the study was to determine the effect of thymus factor X (TFX-Jelfa) on the percentage of apoptotic and necrotic lymphocytes in the spleen, mesenteric lymph nodes, and muscle tissue of mice infected with 200 larvae of Trichinella spiralis. TFX was administered subcutaneously at a dose of 15mg/kg. On days 7, 14, 21, 28, 35, 42, and 60 after infection, apoptotic and necrotic cells were detected by flow cytometry after staining with the Annexin V-Fluos Staining Kit. TFX increased the percentage of apoptotic lymphocytes in the spleen, mesenteric lymph nodes, and muscle tissue of mice infected with T. spiralis. The effect of TFX on the percentage of necrotic lymphocytes was weaker and less clear. Parasite load was lower in infected mice treated with TFX than in the untreated control mice. The effect of TFX on the host immune response and the survival of parasite larvae was therefore probably affected by the extent of inflammatory infiltrates, and not by the percentage of lymphocytes undergoing apoptosis.

Background: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma., Methods: 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival., Results: Median survival was 11.5 months (95% CI 7.9-15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8-12). Grade 1 local reactions following injection were the only side effects., Conclusion: Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept., Trial Registration: Current Controlled Trials ISRCTN29319366.

The results of treatment of 161 patients with diffuse forms of peritonitis with, using of the immunostimulators are analyzed. The algorithm of staged complex immunocorrection for patients with acute pancreatitis, including aged patients, is worked out. The use of it improves the results of treatment and allows decrease the morbidity.

Background & Objectives: Though high dose chemo-therapy combined with autologous hematopoietic stem cell transplantation (AHSCT) has made great progress on the treatment of chemo-sensitive malignant tumors, the relapse rate remains high. Successful immune reconstitution after AHSCT may reduce recurrence; therefore this study was to explore the characteristics of immune reconstitution after AHSCT and assess its feasibility in clinical use., Methods: Twenty four cases after AHSCT were enrolled in our study. There were 19 Non-hodgkin Lymphoma (NHL), 3 Hodgkin Lymphoma (HD) and 2 rhabdomyosarcoma. Nineteen cases had achieved complete remission (CR) while 5 partial remission (PR) before AHSCT. All cases were administered Interleukin (IL)-2 and Interferon (IFN)-alpha after AHSCT. Some patients were given thymus factor and/or CIK infusion. Phenotypes of peripheral blood T, B, NK subsets and immunological profile of TH1/TH2 by intracellular staining of cytokines after PMA/ionomycin stimulation were evaluated., Results: 75% of the cases achieved CR while 4.17% were progression of disease (PD) and 16.67% were relapsed during the median follow-up time of 12 (2-60) months. The changes of immune parameters after AHSCT were as followed: (1) CD4+T cells (normal control 33.5+/-6.9%) started to decrease dramatically one month after AHSCT, which was 2.5-13% (median rate 5.6%)in the 2nd month; and then slowly increased to 10-20% in the 7th month, but did not return back to normal even after one year in all patients. In addition, reversed ratio of CD4/CD8 lasted for a long period of time. B cells also began to decrease 1 month after AHSCT, and recovered to normal in the 4th month. But B cells remained 0% in the 6th month and 1% in 12th month in patients treated by rituximab before receiving AHSCT. The ratio of NK cells was 10-20% (higher than normal controls) in the 2nd month, then returned to normal thereafter. (2) The cytokine secretion by T cell: there were 48.79% patients whose TH1 was lower than normal controls or at the lower limit of normal range. All the patients with normal TH1 were treated by IFN-alpha or CIK cell infusion. TH2 was much higher than normal level among 68.29% cases and this abnormality lasted at least for 1 year in some cases. TH2 at normal range was only observed in cases receiving IFN-alpha treatment. Furthermore, IFN-alpha could significantly decrease TH2 level. (3) Increasing tendency of CD4+CD25+/CD4+, CD4+CD69+/CD4+ ratio was observed in patients received additional thymus factor treatment compared to those did not., Conclusions: Administration of CIK cells, thymus factor, IL-2 and IFN-alpha after AHSCT could improve the immunologic function of patients, and TH1/TH2 ratio may virtually reflect the immune status of patients. However more information is required to make prognostic assessments of immune reconstruction and the long-term survival rate.

Introduction: In this study, the chemiluminescence (CL) of peripheral blood polymorphonuclear leukocytes (PMNLs) and the serum total antioxidative system (TAS) were assessed in patients with chronic C hepatitis (CCH) before and after 3 and 6 months of treatment with interferon (IFN)-alpha and thymus factor X (TFX)., Material/methods: The study included 26 patients with CCH aged between 25-63 years (mean: 42.67). Combined therapy with IFN-alpha 2a and a TFX preparation was applied. PMNL metabolic activity was assessed applying the whole-blood CL method. We measured CL response of neutrophils unstimulated and stimulated by opsonized zymosan, N-formyl-methionylleucyl-phenylalanine (N-fMLP), and phorbol-myristate-acetate (PMA) without and after priming with tumor necrosis factor alpha (10 ng/ml). The assessment of serum TAS was performed directly before the beginning of therapy with IFN-alpha and TFX and after 3 and 6 months of the treatment. A colorimetric method based on the reduction of the cationic radical ABTS*(+) (cation 2, 2'-azido-bis-[3-ethylobenzothiazolino-6-sulfonate]) in the presence of serum antioxidants was used., Results: As a result of the treatment with IFN-alpha and TFX, the formation of free oxygen radicals by resting (unprimed) neutrophils increased statistically significantly both without stimulation and following stimulation by fMLP and PMA. A statistically significant increase in the serum antioxidant capacity was observed, which suggests the induction of compensatory processes., Conclusions: Increased in vitro reactive oxygen species production by both stimulated and unstimulated peripheral blood neutrophils of patients with CCH was observed. Treatment with IFN-alpha and TFX resulted in a compensatory increase in serum antioxidative capacity.

Neonatal thymus graft and thymus calf extract (TME) in vivo treatment exert similar corrective actions on different mouse age-related alterations. The aim of the present paper is to investigate whether a vegetal extract, wheat sprout extract (WESPRE), could mimic the thymus action on recovering age-related alterations and if this extract can cure an age-associated pathology, the cataract in dogs. Present experiments were carried out by using WESPRE and TME in vivo in old mice to check their ability to recover the altered DNA synthesis in hepatocyte primary cultures. Old mice treated with WESPRE and TME showed a recovery of hepatocyte DNA synthesis levels when compared with the old untreated ones. The increase of DNA and protein contents observed in aged animals is reduced by WESPRE treatments to levels observed in young mice hepatocytes. We measured also WESPRE phosphorylation activity by endogenous kinase: it was from 10 to 40 times higher with respect to wheat seeds. Old dogs were orally treated for a month and the lens opacity analysed before and after the treatment. Results showed a reduction from 25 to 40% of lens opacity. The efficacy of wheat sprouts in the recovery of age-related alterations and in treating age-associated pathologies could be due to the contemporary presence of small regulatory acid peptides, a remarkable level of highly energetic phosphoric radicals and antioxidant molecules, peculiarities that may be, to some extent, related to the aging process regulation.

The target of the case study was to investigate the efficiency of an alternative combined therapy scheme of herpes simplex infections versus the routine therapy by acyclovir or famvir as applicable to HIV-infected patients. leukinferon was shown to induce the antoherpetic acyclovir efficiency. The use of the latter concurrently with cycloferon for the treatment of infections provoked by herpes simple virus-1 (HSV-1) and HSV-2 in HIV-infected patients prolongs the remission period in case of the above opportunistic infections. The leukinferon anti-herpetic efficiency is, obviously, related with the phagocytosis stimulation and with its positive influence exerted on hemopoiesis. The combined therapy can be stated to be most effective in HIV, clinical stages B1 and 2.

We studied the effect of combination treatment with T-activin and vitamin E on acute toxicity and antitumor activity of cyclophosphamide in mice. Combined administration of these preparations 1.37-fold increased the maximum permissible dose of cyclophosphamide without affecting its LD(50)and delayed mouse death from cyclophosphamide toxicity. Most mice died only 3 days after combination treatment with the test preparations and cyclophosphamide in doses of LD(16)-LD(84). The second peak of death from hematologic toxicity of cyclophosphamide was absent under these conditions. T-activin and vitamin E did not abolish the antitumor effect of cyclophosphamide on mice with subcutaneously implanted P-388 lympholeukemia. Tumor growth was suppressed by 100%.

Two hundred and ninety-six patients with diabetic retinopathy (DR) were examined: conservative therapy and laser coagulation of the retina were applied in 120 and 176 of them, respectively. The ecological situation in the residence region and its impact on the morbidity and immune status of DR patients were analyzed. The comfort degree of the environment and the level of anthropogenic contamination affect the morbidity and immunogram results. Immune-correctors, i.e. T-activin, sodium nucleinate and laser blood irradiation (LBI), were used within treatment schemes in DR. Laser coagulation of the retina is advisable to assign in combination with sodium nucleinate and LBI in the aftercare of patients concurrently with complex therapy; T-activin is used, within conservative therapy, to correct the unfavorable ecological impact exerted on patient's body.

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies worldwide. A variety of pharmacological strategies has been evaluated in the treatment of HCC: classical chemotherapy, tamoxifen, octreotide, thymostimulin, pravastatin, (131)I-lipiodol as well as transarterial chemoperfusion (TAC) and chemoembolisation (TACE). TACE monotherapy or TACE combined with pravastatin resulted in a survival benefit of selected HCC patients. New strategies such as immunotherapy, antiangiogenic agents or cyclooxygenase inhibitors are under clinical investigation and might play a role in future therapies for HCC. Efficient strategies for the primary prevention of HCC are available and promising concepts in the secondary prevention have been reported.

Unlabelled: Compartmentalisation of mucosal immune response seems to be the result mainly of the preferential migration of activated cells back to their inductive sites. The aim of this report was to demonstrate, in a model of secondary immunodeficiency in Wistar rats (severely protein deprived at weaning and refed with casein 20%; group R21), that the oral administration of Thymomodulin (group:R21TmB) has different effects on gut and BALT (Bronchus-associated lymphoid tissue). Tissue sections (5 mu) were studied by immunohistochemistry 1). The oral administration of Thymomodulin restores only in gut Lamina propria (LP) the IgA B and CD4 T cell populations to control levels. The CD8a and CD25 subpopulations do not vary in gut as they return to control levels when refed with 20% casein diet. All the populations mentioned above remained decreased even after receiving Thymomodulin by the oral route. However, the same behaviour was observed for the TCR delta T cells that were decreased and return to normal levels in both mucosae by the effect of the immunomodulator; 2) when studying the iIEL (intestinal intraepithelial lymphocytes) CD8 alpha, CD25 and TCR gamma delta T cells, that were increased in R21, return to control levels in R21TmB. In BALT intraepithelium CD8 alpha and CD25 T cells remained decreased, while only TCR gamma delta T cells (increased in R21) return to control values., Conclusions: 1) there exists a compartmentalisation between both mucosae, as T CD4+ and IgA B+ cells are restored by TmB only in gut; 2) only those iIEL involved in inflammation (CD8 alpha+/CD25+ and TCR gamma delta+/CD25+) are normalised by means of the Thymomodulin 3) however, in BALT,only TCR gamma delta+ T cells are restored 4) the oral administration of the present immunomodulator may be useful as a therapeutic agent, although the preferential survival in the tissue of initial stimulation is the major factor in the preferential distribution of activated cells.

The paper presents the outcomes of surgical treatment in 117 patients with complicated liver echinococciasis in the past 9 years. Hepatic function and immunity, their pre- and postoperative changes in the combined use of essentiale and T-activin were studied. It has been found that the functional status of the liver, its detoxifying function in particular, largely impairs and immunosuppression develops in patients with complicated liver echinococciasis. The postoperative combined use of essentiale and T-activin led to the normalization of hepatic function and immunity. The combined treatment reduced the incidence of postoperative complications from 34.83 to 17.2%, such as acute hepatic failure, suppuration of a wound and a residual cavity, isolated abdominal abscesses, pleurisy, and pneumonia.

Due to disorders of hormonal balance in the organism, a decrease in thymic endocrine function occurred in rats after thyroidectomy. After removing the thyroid gland, we observed 1,3-2,2-fold decrease in the level of thymic hormone thymulin in the blood serum. When thyroxin was applied at a suppressive dose, endocrine function of the thymus did not restore. Injections of thymostimulin (Tp1) or its combination with thyroxin to thyroidectomized animals restored the level of thymulin up to the level in the intact rats due to effects of either injected preparation or induction of substances possessing thymosine-like activity.

Progressive ascitic growth of a spontaneous transplantable T-cell lymphoma, designated as Dalton's lymphoma (DL), in a murine host has been shown to be associated with an involution of thymus accompanied by a massive depletion of the cortical region and an alteration in the distribution of thymocytes by a decrease of CD4+CD8+, CD4+CD8- and CD4-CD8+ phenotypes caused by an enhanced induction of apoptosis in thymocytes. Moreover, an inhibition of humoral and cell mediated immune responses involving non-specific as well as antigen-specific T cell proliferative and cytolytic abilities with a decrease in the production of interferon gamma (IFNg) by the T cells of DL bearing mice has been observed. Results of the present study show that the administration of total thymic extract (TE) in DL bearing mice results in an increased survival of the DL bearing mice alongwith a significant increase in the weight of thymus and the total number of thymocytes with a lesser number of percent apoptotic thymocytes as compared to that in untreated DL-bearing mice. It is also shown that TE administration has a positive immunomodulatory effect on T cell functions as T cells obtained from TE administered DL bearing mice show an increased IFNg, production and an improved antigen specific proliferative ability. Moreover, the study indicates that TE acts directly on T cells as in an in vitro assay TE antagonised DL growth-associated induction of thymocyte apoptosis. Taken together, the results support the immunomodulatory function of the adult thymus and utilization of thymus derived factors as a potential immunotherapeutic agent for reversing tumor growth-associated immunosuppression.

Clinical and instrumental-laboratory investigations have been conducted in 372 patients with chronic antral gastritis (CAG, n = 131), diffuse gastritis (DG, n = 108) and ulcer disease (UD, n = 135). Immunomodulators tactivin and levamisol were added to standard treatment of 75 CAG, 63 DG and 85 UD patients. Healing of the lesions was observed, on the average, on the treatment day 24.3 +/- 0.5 and 18.4 +/- 0.6 in the standard treatment and with the added immunomodulator, respectively. Adjuvant levamisol diminished the number of recurrences of chronic gastritis and UD.

Immune status and condition of regional lymphoid tissue were studied in 28 patients with various forms of acute pancreatitis untreated with immunomodulating therapy and in 12 patients receiving combined therapy including lymphotropic regional therapy with T-activin. Acute pancreatitis patients were found to have aquired immunodeficiency, secondary autoimmune syndrome and reaction of toxic immune complexes the severity of which decreased under the action of T-activin therapy.

Purpose: Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic radiotherapy?, Material and Methods: Fifty-six patients with an indication for adjuvant pelvic irradiation after curative surgery were double-blind randomized. All patients took 3 x 4 capsules study medication daily during radiotherapy. Twenty-eight patients in the enzyme group (EG) received capsules containing papain, trypsin and chymotrypsin, 28 in the placebo group (PG) received placebo capsules. All patients were irradiated with 5 x 1.8 Gy weekly to 50.4 Gy using four-field-box technique after CT-based planning. Primary objective was the grade of diarrhea, nausea, vomiting, fatigue and epitheliolysis during radiotherapy. Secondary objectives were the number of supportive medications and treatment interruptions due to acute toxicity., Results: None/mild diarrhea: 43% EG, 64% PG. Moderate/severe diarrhea: 57% EG, 36% PG (P = 0.11). Mean duration: 11 days in EG, 10 days in PG. None/mild nausea: 93% EG, 93% PG. Moderate/severe nausea: 7% EG, 7% PG. None/mild vomiting: 100% EG, 97% PG. None/mild fatigue: 82% EG, 93% PG. Moderate/severe fatigue: 18% EG, 7% PG (P = 0.23). None/mild epitheliolysis: 75% EG, 93% PG. Moderate/severe epitheliolysis: 25% EG, 7% PG (P = 0.16). Treatment interruption (mean days): 2.44 in EG, 1.46 in PG. Number of supportive medication: 29 in EG, 19 in PG., Conclusions: The prophylactic use of proteolytic enzymes does not reduce acute toxicities, treatment interruptions and number of supportive medication and therefore does not improve tolerance of adjuvant pelvic radiotherapy., (Copyright 2002 Elsevier Science Ireland Ltd.)

Regulating effect of thyroid hormones on functions of organs of the immune system has been demonstrated in the experiment. Deficiency of thyroid hormones affects thymulin synthesis and morphofunctional status of immunogenesis organs. Combination of thymostimulin and thyroxin in the thyroidectomized animals, as compared to their separate use, is pathogenetically the most adequate correcting therapy aiming normalization of structural and functional disorders in the thymus and spleen. Prolonged reaction of tissual basophils saturated with heparin, indicated hormonal activation of blood anticoagulative system, and complex of the above hormones can be used for prevention of thromboembolic complications.

Aim: To examine the functional status of the immune system in patients with lung and intrathoracic lymph nodes sarcoidosis and to evaluate the efficiency of immunomodulation alone and in its inclusion in combined treatment of the disease., Materials and Methods: 58 patients with the disease of varying severity were followed up. Comprehensive examination, involving clinical, immunological, X-ray, and physical studies, in patients treated with combined immunotherapy was performed. Initial examination revealed mixed immunodefficiency with impaired T- and phagocytic activity. According to the degree of immunological changes, the patients were given immunotherapy, including polyoxidonium, T-activin (or immunophan) injections, a complex of multivitamins and trace elements, and total adaptogens. After partial or complete normalization of an immunogram, all the patients received licopid (two-three 10-day courses, 10 mg/day)., Results: The optimal result (as long as 3-year remission) was achieved in the first time diagnosed sarcoidosis who have not taken glucocorticoidal hormones., Conclusion: The follow-up shows that addition of licopid is a compulsory component of immunotherapy in this disease; the efficiency of treatment is determined by its multimodality. The courses of therapy should be repeated when immunological indices deteriorated.

Immunofan and tactivin, employed as a means of immunological correction in the complex treatment of adenocarcinoma, decrease the onset frequency of radiation-induced complications and exhibit a pronounced immunocorrector effect. This was indicated by increasing level of lymphocytes (including CD3+, CD4+, CD8+, and CD19+), helper coefficient (CD4+/CD8+), and phagocyte activity of neutrophils, as well as by the tendency to normalization of the HCT-test results. Immunofan somewhat exceeds tactivin in the efficacy of endometrium adenocarcinoma treatment.

The immunomodulating and antimetastatic activity of clinically approved, low molecular weight, standardized thymic peptide (TP) preparations was evaluated in BALB/c-mice. Daily applications (subcutaneously, s.c.; intraperitoneally, i.p.; intramusculary, i.m.) of two commercially available TP preparations (7 consecutive days, 10, 50 and 100 micrograms per mouse and injection) up-regulated the thymus weight and thymocyte counts as well as peripheral blood leukocyte and lymphocyte counts in liver metastases-bearing mice. The immunomodulating activity of TP application was most pronounced and statistically significant for thymus weight and counts of thymocytes, leukocytes and lymphocytes after s.c. administration of both TP preparations and concentrations. I.p. and i.m. TP-injections were less effective at reaching statistical significance, however, for defined dosages and parameters, only. To evaluate the influence of TP on experimental liver metastases, RAW 117 lymphosarcoma cells were intravenously inoculated into BALB/c-mice. TP (10, 50, 100 micrograms/mouse) were s.c., i.p. and i.m. administered daily for 7 consecutive days starting 24 hours after tumor cell challenge. Liver colonization was investigated on day 14 after tumor cell inoculation and demonstrated a statistically significant (p < 0.05) reduction of experimental liver metastases for s.c. (both preparations and concentrations) as well as i.p. and i.m. (dose-dependent) TP-treated mice.

Results are presented of studies on local nonspecific defence in patients with protracted pneumonia in the bronchoalveolar lavage fluid (BALF) during the course of conventional therapy involving the use of T-activin and extractum Glycerrhiza glabra L. The course of conventional therapy has not been shown to be associated with a substantial normalization of cytosis in the BALF cell precipitate or augmentation of sIgA content of lysozyme. T-activin makes for a reduction in the content of mature neutrophilous granulocytes and for an increase in humoral factors of defence. Extractum Glycerrhiza glabra L. has been found to be superior to T-activin in diminishing neutrophilic granulocytes count, increase in the BALF content of macrophages, lysozyme, s IgA; it proved to be endowed with an antiphospholipase activity, which facts predetermine apperant efficacy of the drug with respect to the lung local defence system in those patients presenting with protracted pneumonia.

Persistent lymphopenia of various intensity has been noted in 45% of persons who had a history of infectIous mononucleosis. The group consisted od 500 patients, (236 males and 264 females). In all of them the diagnosis of mononucleosis had been based on the characteristic clinical signs and symptoms and changes in the blood picture and confirmed by the non-specific and/or specific serologic tests. In 33 persons (10 males and 18 females) the total number of lymphocytes varied from 884 to 992 per 1 cmm, the distribution being as follows: B lymphocytes--146 to 198, CD4--482 to 645 and CD8--245 to 364 per 1 cmm. 18 persons (18 males and 10 females) were given thymosine (TFX) subcutaneously for 30 days in the dose of 0.02 g daily, the remaining 15 (7 males and 8 females) received 3.0 g of isoprinosine per day for the same period. The total lymphocytes count and that of B, CD4 and CD8 was performed before and after the treatment and then followed once a month until 180 days since the treatment had been started. The TFX therapy was repeated after 8-12 months since the end of the first course in 3 patients and that with isoprinosine in 4. The strategy and the examination pattern were the same as before, control examinations being performed every 6 months and final analysis was done after 5 years of follow-up. Among the 33 patients who received immunomodulating treatment, normalisation of the lymphocytes count appeared in 24 (64%). Among the 12 persons with less pronounced lymphopenia, who did not received any treatment, spontaneous normalisation appeared in 5 (40%). It may be therefore assumed, that in persons with the history of infectious mononucleosis with persistent marked lymphopenia, thymosine and isoprinosine may be used in the therapy as additional immunomodulators.

The influence of the some immunomodulators (PHA-P, TFX and dexamethasone) on the process of apoptosis, occurring in the course of trichinellosis in mice, has been studied. It has been found that PHA-P activates this process in the jejunum mucosa and prolongs it in the muscular inflammatory infiltration, whereas TFX has no influence and dexamethasone distinctly decreases the level of the apoptotic cells. The number of the intestinal trichinae on the successive days of infection was similar in all groups of animals, however, the number of the muscular larvae in the groups receiving immunostimulators was much lower and in the group treated with dexamethasone--a little higher than that in control. As in mice receiving PHA-P and TFX, the cellular inflammatory infiltration in the muscles was larger than that in control, and in the group to which dexamethasone was administrated--smaller, the authors think that it was extensiveness of the infiltration and not the level of the apoptotic cells that influenced the number of the outliving larvae.

In the examination of 64 patients with chronic obstructive bronchitis, some specificities of functioning of decompensation mechanisms in the glutathione antiradical system were established as were changes in morphofunctional and receptor properties of erythrocytes in chronic obstructive bronchitis. The patients were shown to have derived benefit from a combined treatment involving the use of the enzymic drug preparation Wobe-Mugos E which was found to make for improvement of rheological properties of erythrocytes, their capability of depositing and transporting catecholamines.

A total of 44 patients with lung carcinoma underwent combined treatment involving systemic enzyme therapy with Wobe-Mugos E. In conducting radio- and polychemotherapy, the above enzyme therapy did not complicate the postoperative course, with the pyo-septic complications having gotten reduced, the origination of pneumofibroses prevented.

The systemic enzymotherapy using Wobe-Mugos E in the combined treatment of 32 patients with pulmonary cancer and of 21 patients with malignant thymoma was applied. After the chemotherapy and radiotherapy conduction the reduction of the postoperative septic-purulent complications, the pneumofibrosis occurrence prophylaxis was noted.

We report our initial clinical experience with local transrectal application of enzymatic treatment for chronic nonbacterial prostatitis and prostatodynia in 20 patients. Using a specially designed symptom score for evaluation of subjective treatment parameters, a statistically significant improvement of symptoms was found in the areas of pain, micturition, and recreational activities. No statistically significant differences were noted in laboratory values before and after treatment. Minimal local side effects were seen in only one patient. A favorable clinical response was noted in 75% of patients, whereas the remaining 25% showed only moderate improvement of symptoms. No patient experienced complete treatment failure.

Experimental series of 60 cotton rats and 150 white mice infected with echinococcus showed that 80-100% glycerin and 3% peroxide solution were effective scolicidal solutions for inactivation of the parasite. 344 patients have been operated on for hydatid disease with inactivation of the parasite by means of these scolicidal solutions. Glycerin during the surgical management of the hydatid cysts is effective and harmless in uncomplicated hydatid liver disease and any hydatid pulmonary cysts. Glycerin is contraindicated in complicated hydatid liver disease because of immunity disturbance. In complicated hydatid liver disease management of the hydatid cysts by 3% peroxide is effective and harmless. It is necessary to correct the hydatid liver disease patients' immunity in the preoperative and postoperative periods. Tactivin and antiechinococcus drug SK-1 are effective immunomodulators in hydatid liver disease.

All tested variables showed a tendency in favor for Wobe-Mugos E therapy as addition to standard therapy. Enzymes improve the quality of life by reducing cancer disease typical symptoms, they reduce side effects of chemo-/radiotherapy and they have a potential of prolonging life (preliminary data only).

Hemorheological indices were studied in 89 patients. In 61 patients the authors have revealed somewhat increased viscosity potential of blood and negligible changes in the aggregation activity of erythrocytes which is thought by the authors to be due to the saved compensatory potentialities of the organism. In 28 patients with the complicated course of the disease the rheological parameters of blood became worse because of the suppressed compensatory potentialities of organism. So, in addition to the adequate transfusion-infusion therapy the complex of treatment must include immunostimulating means (Levamisole, Prodigiozan, Tactivin etc.).

The protective effect of Wobe-Mugos appliance on the kidney function and biochemical state in polyuric stage of sublimate nephropathia at the moment of tubulointerstitial component formation was revealed in experiments on 40 white male rats. It appeared in the increase of hydrogenous ion excretion, titred acids, renal tissue fibrinolytic and proteolytic activity. The succinatdehydrogenase activation in renal cortex matter pointed out on the improvement of energy balance.

Streptosotocin was administered to 21 test animals and 19 control ones. Preventively, the former were given T-activin, the latter--saline. 73% of the test animals were free of hyperglycemia, insulinopenia, activation of lipid peroxidation, morphologic evidence of beta-cell damage. In control animals diabetes mellitus arose in 84% manifesting with marked hyperglycemia, insulinopenia, LPO activation, morphological signs of beta-cell damage, lymphocytic infiltration of the islets. From the results obtained it can be concluded that T-activin has a prominent protective effect against diabetes mellitus (chi-square = 6.34, p < 0.05) which can be explained by its antioxidant and immunotropic activity.