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Treatment of Toxocara canis infections in mice with liposome-incorporated benzimidazole carbamates and immunomodulator glucan.

Benzimidazole carbamates (mebendazole, albendazole and fenbendazole) are the most commonly used anthelmintic drugs for the treatment of larval toxocariasis (Toxocara canis) in paratenic hosts. However, the bioavailability of these drugs for tissues is very low due to their extremely low solubility, resulting in the administration of relatively high doses over a long period. To overcome this problem, neutral, negatively or positively charged and stabilized liposome drug carriers were examined in the chronic phase of T. canis infections in mice each orally inoculated with 1000 eggs. Moreover, liposomized albendazole and fenbendazole were co-administered with liposomized immunomodulator glucan. The highest efficacy of both drugs, evaluated 4 weeks after treatment, was recorded after their subcutaneous administration (ten doses of 25 mg kg(-1)) in stabilized liposomes and intramuscular co-administration of liposomized glucan (two doses of 5 mg kg(-1)). Fenbendazole was more effective in muscles (91.5%) whereas albendazole was more effective in the brain (92.2%). Liposomes with incorporated benzimidazole carbamate anthelmintics provide sustained drug-release reservoirs and can considerably enhance drug efficacy. Moreover, despite suppression by T. canis antigens, stimulation of the immune system by the immunomodulator glucan potentiates the effects of these antiparasitic drugs.

Adjuvants, Immunologic↗

Application-dependent immunomodulating and antimetastatic efficacy of thymic peptides in BALB/c-mice.

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.

Adjuvants, Immunologic↗

[Use of immunomodulators isolated from marine invertebrates for reducing the toxic effects of thermostable toxin and lipopolysaccharides from Yersinia pseudotuberculosis on a macroorganism].

The possibility to use immunomodulators isolated from marine invertebrates for the lowering of the toxic effects caused by Yersinia pseudotuberculosis thermoresistant toxin and lipopolysaccharide was investigated. Effects were evaluated by the animals survival rate in per cent and mice average lifetime after toxin lethal dose injection. It was shown that polypeptide gangleen when compared to timalin as well as glycanes mitilane and strombus had dose-dependent protective effect. These substances increased animals survival rate to 15-17 per cent and prolonged life period for about two times when compared to control group. These results demonstrates the possibility to use investigated immunomodulators is clinical practice at the treatment of the patients with pseudotuberculosis.

Adjuvants, Immunologic↗

Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado.

Viral diseases, including emerging and chronic viruses, are an increasing worldwide health concern. As a consequence, the discovery of new antiviral agents from plants has assumed more urgency than in the past. A number of native Amazonian medicines of plant origin are known to have antimicrobial and anti-inflammatory activity, although only a few have been studied for their antiviral properties and immunomodulating effects. Those most studied include: Sangre de Grado (drago) (Croton lechleri) in the Euphorbiaceae family and Una de Gato (Uncaria tomentosa) in the Rubiaceae family. This article reviews the chemical composition, pharmacological properties, state of current research, clinical use, and potential antiviral and immunomodulating activity of these and other plants from the Peruvian Amazon.

Antibody Formation↗

Mycobacterium phlei as an oral immunomodulator with Newcastle disease vaccine.

Experiments were conducted in chickens to understand the effects of oral immunomodulation. Heat inactivated M phlei, a commensal Mycobacterium and a non-specific immunomodulator, was administered orally prior to live Newcastle disease F (ND F) strain vaccination. In experimental birds it lead to an enhanced cell mediated Immune response (CMI) against the vaccine. There was a reduction in the Haemagglutination inhibiting (HI) antibodies. However, it did not affect the protection against a virulent challenge, as the protection percentage was more or less same in vaccinated birds irrespective of the M.phlei administration. M. phlei administration could not enhance the immune response to inactivated ND F vaccine administered orally. The results indicate that M. phlei favours a CMI response to orally administered live ND F vaccine. It may be of potential use in enhancing CMI against vaccines and a cheaper alternative to costlier recombinant cytokines.

Adjuvants, Immunologic↗

Effects of immunomodulators on acute Trypanosoma Cruzi infection in mice.

BACKGROUND: Patients who recover from acute trypanosomiasis may succumb to chronic Chagas' disease later in life due to age related immunosuppression, immune system disorders such as AIDS, or during periods of immunosuppressive therapy for organ transplantation. In this study, effects of immunomodulators with diverse properties were examined on the course of an acute and lethal Trypanosoma cruzi infection. MATERIAL/METHODS: ICR (Swiss) mice inoculated with Tulahuen (lethal) strain of T. cruzi were treated with 6 different immunomodulators and the course of infection was studied. RESULTS: Tacrolimus (FK-506) and dexamethasone increased parasitemia in mice when compared to infected untreated animals. Mycophenolate mofetil (RS-61443) and recombinant interleukin-15 (IL-15) treatment decreased the number of parasites but had no effect on animal survival. In contrast, compound L-685-818 (tacrolimus analog) and CD40 ligand (CD40L), provided protection against lethal infection. Mice that survived initial infection were all protected against reinfection. CONCLUSIONS: This study demonstrates the dangers of immunosuppression with tacrolimus and dexamethasone in T. cruzi infected subjects. While mycophenolate did not exacerbate the infection, our data suggest potential therapeutic applications for L-685-818 and CD40 ligand in trypanosomiasis.

Adjuvants, Immunologic↗

Influence of bacterial immunomodulators on the induction of specific IGG with patients during a peroral hyposensitization therapy.

Peroral administration of allergen during hyposensitization therapy with allergic patients is in comparison with an administration by injection of a wilder inductor of specific IgG antibodies. The peroral administration of bacterial immunomodulators increases IgG formation significantly. The described experiment examines the influence of bacterial immunomodulator Olimunostim on the level of specific antibodies during peroral hyposensitization therapy with allergic patients.

Adjuvants, Immunologic↗

[Preventive treatment of multiple sclerosis. Rules for treatment with immunomodulators].

INTRODUCTION AND METHOD: At present treatment of multiple sclerosis (EM) is a challenge for neurologists in general and specialists in EM in particular, who have the problem of digesting the avalanche of information they receive. Use of immuno modulators has shown that it is possible to change the natural course of the disease and improve life expectancy in EM. Both the number of exacerbations of EM and the overall improvement benefit from such treatment. Immunomodulators have an established place in the treatment of the remitting relapsing form, although its efficacy seems to become less when it is used at more advanced stages of EM and seems to have been ruled out for progressive primary forms. Immunomodulators may be useful during initial stages of the disorder in the first episodes before a definite diagnosis has been established, although it is obvious that markers for prognosis are still needed. MR and cerebrospinal fluid studies may be useful for this. CONCLUSION: Patient selection is essential to obtain good results. Although it is not fully established, it seems that early use of high doses improves long term control of the disease.

Adjuvants, Immunologic↗

[Ani immunomodulator Hepon inhibits hepatitis C virus replication in human cell cultures in vitro].

Antiviral activity of immunomodulator "Hepon" was evaluated in human cells culture infected with hepatitis C virus. "Hepon" presence protected human cells SW-13 from cytopathogenic effect of hepatitis C virus. Maximum antiviral effect was demonstrated by "Hepon" at concentration 1 mcg/mL. Control antiviral agent reaferon (interferon alfa-2a) was more potent as vitality protecting agent in the case of SW-13 human cells culture. "Hepon" activity is based on changes of cytokins and interferons spectrum so this immunomodulator is expected to be effective against different viruses including herpes virus and encephalocarditis virus.

Adjuvants, Immunologic↗

[Study on immunomodulating mechanism of the active fraction of liuwei dihuang decoction].

OBJECTIVE: To investigate the immunomodulating mechanism of 3A, an active fraction extracted from the ethanol-soluble portion of Liuwei Dihuang Decoction (LWDHD). METHODS: Influence of 3A on T-lymphocyte subsets, IgG production of B cells, interferon-gamma (IFN-gamma) mRNA expression in cyclophosphamide (Cy)-treated mice, tumor bearing mice and senescence accelerated mouse-prone/8 (SAMP8) were assessed in vivo and in vitro. RESULTS: Oral administration of 3A could elevate the decreased T-lymphocyte subsets in all model mice, it also could promote the IgG secretion of splenic cells in SAMP8 and increase IFN-gamma mRNA expression in Cy-treated mice. CONCLUSION: The immunomodulating effect of 3A is related with its effects in regulating ratio of T and B cells or in improving their functions.

Adjuvants, Immunologic↗

[Immunomodulation by herbal agents. A double-blind study in a medical university hospital involving a hepatitis B vaccine adjuvant model].

AIMS: Using the hepatitis B vaccination as a model, to investigate the extent to which the herbal immunomodulator, Esberitox N, supports seroconversion. METHOD: 346 medical students participated in the placebo-controlled, randomized double-blind study. They took 3 x 2 tablets of the test substances daily, beginning 3 days prior to the injection and ending two weeks after it. The target outcomes were seroconversion and the level of the anti-HBs titer. RESULTS: The data of 157 volunteers treated with the test substance, and 161 treated with placebo were analysed. After the first injection, the seroconversion rate was 22% in both test substance and placebo groups, and showed no advantage for the volunteers receiving the test substance. After the second injection, 89% of all members of each group revealed seroconversion. After the first injection, anti-HBs titers were appreciably higher in the test substance group (n = 34) than in the placebo group (n = 36; PWilcoxon = 0.003). The respective median values were 37.0 IU/L (95% CI: 18-68) and 15.5 IU/L (95% CI: 8-30). CONCLUSION: The immunomodulator tested has negligible influence on seroconversion, but does enhance the immune response of subjects experiencing seroconversion.

Adjuvants, Immunologic↗

[The state of immune system and effects of current therapy and immunomodulators].

To test the conception about a pathogenetic role of correlation between gastric comtamination with Helicobacter pylori (Hp) and immune system disorders in duodenal ulcer (DU), immune status and its response to current pharmacotherapy were studied in 84 patients in an acute recurrence phase. The patients were divided into 4 representative groups to receive monotherapy with omeprasol (group 1), combination denol + amoxicillin + tinidasol (group 2), quadrotherapy with drugs of group 1 and 2 (group 3), the above quadrotherapy plus immunomodulating drugs (imunofan + tactivin + oligovit) (group 4). In recurrent DU all the components of the immune system are affected especially cellular immunity. The response to the treatment was highest in group 1 and 4 (90% healing for 3 weeks), the worst in group 2 (68%). The complex of antibacterial drugs produces a moderate immunosuppressive action. The addition of immunomodulating drugs to the quadrotherapy promotes correction of secondary immunodeficiency and secondary Hp resistance to antibacterial drugs. This leads to a rise in eradication effect from 33-55 to 84% and a decrease in the number of early recurrences (during the first 6-12 months) from 42.1-33.6 to 12.5%.

Adjuvants, Immunologic↗

Evaluation of risk and benefit of oral immunomodulation using heat-killed enterococcus faecalis FK-23 preparation in healthy dogs.

The risk and benefit of oral immunomodulation using heat-killed Enterococcus faecalis FK-23 preparation (FK-23) were evaluated in healthy dogs. Dogs were administered perorally 100 mg/kg of FK23 daily for 3 months. FK-23 did not affect the findings of complete blood count, leukocyte differential count, blood chemistry, serum electrolyte, radiography, or physical conditions of the dogs tested. Increase in myeloid/erythroid ratio and granulocytic lineage was found in bone marrow of the FK-23 treated dogs. Neutrophil function assessed by zymosan-dependent chemiluminescence was activated by treatment of the drug. FK-23 also stimulated in vitro lymphocyte blast transformation of PHA, Con A, and LPS. FK-23 thus appears to be a useful immunomodulating drug to stimulate non-specific host immune responses without adverse side effects.

Journal Article↗

Effect of natural and synthetic immunomodulators on the synthesis of interferon by peritoneal cells of mice.

The effect of different natural and synthetic immunomodulators on the spontaneous interferon (IFN) synthesis by freshly isolated resident peritoneal cells of BALB/c, NZB and C3H mice was investigated. Actinomycetal glycolipids isolated from Curtobacterium betae, Faenia rectivirgula, Rothia dentocariosa and Saccharopolyspora hirsuta at the concentration 1-20 micrograms/ml were found to potentiate the IFN synthesis by the peritoneal cells of BALB/c mice. Similar results were obtained when dsRNA, LPS of Shigella sonnei and lipid A isolated from the LPS were used. The effect of potentiation of the physiological IFN production by the immunomodulators was observed also in the cells of C3H and NZB mice. In contrast, the inhibition of the IFN synthesis was observed when the peritoneal cells of BALB/c and NZB mice were treated with imuthiol at concentration 0.1-10 micrograms/ml. Thymomodulin (TFX-Polfa) at concentration of 1-100 micrograms/ml had no effect on the spontaneous IFN production.

Adjuvants, Immunologic↗

[Experience in the use of present day immunomodulators for prophylaxis of exacerbations of chronic adenoiditis and development of pharyngeal tonsil hypertrophy in poor health children].

Children having frequent acute respiratory infections and chronic adenoiditis were given immunomodulators (ridostin, IRS-19, polyoxidonium). As a result of such prophylaxis, respiratory infections and exacerbations of chronic adenoiditis occurred in poor-health children 2-2.5 times less frequently. Their local immunity and nonspecific resistance improved. Thus, modern immunomodulators can be used in poor-health children with chronic adenoiditis to prevent acute respiratory viral infection and development of pharyngeal tonsil hypertrophy as well as to treat them.

Adenoids↗

[Effectiveness of using immunomodulators in combined treatment of patients with chronic gastritis and ulcer disease].

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.

Adjuvants, Immunologic↗

[Correlation of immunomodulating effects induced by lysozyme and naphthoquinones in acute blood loss].

The role of erythrocytes in realization of interrelation of the immunomodulating effects of lysozyme and naphthoquinones in normal and under conditions of acute hemorrhage was studied. Interaction of lysozyme and menadione at the level of intact erythrocytes and their stroma resulted in formation of highly efficient immunomodulating factors. The effect of such factors under conditions of acute hemorrhage was mediated by cytokines of the spleen macrophagael cells.

Acute Disease↗

[The effect of the synthetic immunomodulator thymogen on radiation-induced carcinogenesis in rats].

Five month-old female rats were given a mixture of Sr-90 and Cs-137 in drinking water in the dose of 0.1 and 0.2 microCi/day per animal over 12 months. Some animals received 12 monthly courses of a synthetic immunomodulating dipeptide--thymogen in the dose of 5 micrograms/animal for 5 consecutive days. Radionuclide-treated rats showed higher occurrence of tumors on the whole and of breast adenocarcinoma, in particular. Thymogen was shown to inhibit Sr-90- and Cs-137-induced radiation carcinogenesis, namely, a decrease in the total tumor and cancer occurrence was observed. The animals receiving thymogen alone showed longer life span, slower rate of aging and lower overall tumor and cancer occurrence. In this study, the ability of a synthetic peptide immunomodulator--thymogen to inhibit spontaneous and radionuclide-induced carcinogenesis in female rats was first established.

Adjuvants, Immunologic↗