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1.
Acta Microbiol Immunol Hung ; 48(1): 107-13, 2001.
Article in English | MEDLINE | ID: mdl-11233694

ABSTRACT

Following intraperitoneally (i.p.) applied treatment with 12.5 mg/mouse prednisolonum (PRD) no bacterial translocation (BT) was observed in mice. The PRD treatment applied in combination with lymphotropic cytostatics as dianhydrogalactitol (30 mg/kg i.p.) or chlorpromazine (75 mg/kg i.p.) both causing BT, did not increase the mice's drug sensitivity to the used agents. According to our results, PRD can be suitable for combined application with other immunosuppressive agents as it can increase immunosuppression without increase of side-effects such as those induced by bacterial translocation.


Subject(s)
Bacterial Translocation/drug effects , Immunosuppressive Agents/pharmacology , Prednisolone/pharmacology , Animals , Chlorpromazine/pharmacology , Dianhydrogalactitol/pharmacology , Drug Interactions , Female , Immunity, Cellular/drug effects , Lymphocytic Choriomeningitis/immunology , Male , Mice
3.
Orv Hetil ; 142(43): 2377-80, 2001 Oct 28.
Article in Hungarian | MEDLINE | ID: mdl-11760455

ABSTRACT

The author provide evidence from several aspects that the normal microbial flora has a permanent and life-long immune modulating role in conventional organisms and a stimulating effect both on specific and non-specific defence. However, in case of artificial interventions (stress, drugs) affecting the organism, existence of the normal flora may have an adverse effect (endotoxin effect, bacterial translocation). The immunomodulants show a stimulating affect mainly in organisms with undeveloped immune system, and their effects are independent from the presence or absence of the microbial flora. With ageing, effect of immunomodulants can change and become indifferent or even suppressive. Dose-dependence of stimulating or suppressing effect of immunomodulants may be related to their non-immunological effects (endotoxin effect, bacterial translocation). Finally, on the basis of the results, the authors consider the germfree mouse suitable for examining the effect of a given agent in the practice, on one hand, and for observing the host organism's reactions, free from the influence of the normal microbial flora, on the other. Along with the known physiological and pathological events, the results draw also attention to as distant fields as drug sensitivity, drug interactions influencing drug sensitivity. The author put emphasis on importance of germfree environment during immunosuppressive treatments in humans and when making special examinations under experimental conditions.


Subject(s)
Aging/immunology , Bacterial Translocation/immunology , Endotoxins/adverse effects , Immunosuppressive Agents/adverse effects , Mice/immunology , Mice/microbiology , Stress, Psychological/complications , Animals , Dose-Response Relationship, Drug , Germ-Free Life , Immune Tolerance , Immunologic Factors/immunology
4.
Acta Pharm Hung ; 70(1): 11-4, 2000 Feb.
Article in Hungarian | MEDLINE | ID: mdl-10957809

ABSTRACT

Following intraperitoneally (i.p.) applied treatment with 12.5 mg/mouse prednisolonum (PR) no bacterial translocation (BT) was observed in mice. The PR treatment applied in combination with lymphotropic cytostatics as dianhydrogalactitol (30 mg/kg i.p.) or chlorpromazine (75 mg/kg i.p.) both causing BT, did not increase the mice's drug sensitivity to the used agents. According to our results, RP can be suitable for combined application with other immunosuppressive agents as it can increase immunosuppression without increase of side-effect such as those induced by bacterial translocation.


Subject(s)
Bacterial Translocation/drug effects , Chlorpromazine/pharmacology , Dianhydrogalactitol/pharmacology , Immunosuppressive Agents/pharmacology , Prednisone/pharmacology , Animals , Chlorpromazine/administration & dosage , Dianhydrogalactitol/administration & dosage , Drug Interactions , Immunosuppressive Agents/administration & dosage , Injections, Intraperitoneal , Mice , Prednisone/administration & dosage
5.
Acta Pharm Hung ; 69(2): 69-71, 1999 Apr.
Article in Hungarian | MEDLINE | ID: mdl-10389300

ABSTRACT

Following intraperitoneally applied treatment with 0.5 ml of ana partes diluted antilymphocyte serum (ALS) of immunosuppressive effect no bacterial translocation (BT) was observed in mice. The ALS treatment applied in combination with other immunosuppressive agents such as lymphotropic cytostatics as dianhydrogalactitol (30 mg/kg) or chlorpromazine (75 mg/kg) did not increase the mice drug sensitivity to used agents. According to our results, ALS can be suitable for combined application with other immunosuppressive agents as it can increase immunosuppression without side-effects such as those induced by bacterial translocation.


Subject(s)
Antilymphocyte Serum/pharmacology , Bacterial Translocation/drug effects , Immunosuppressive Agents/pharmacology , Animals , Chlorpromazine/pharmacology , Dianhydrogalactitol/pharmacology , Mice
6.
Acta Microbiol Immunol Hung ; 45(2): 257-61, 1998.
Article in English | MEDLINE | ID: mdl-9768294

ABSTRACT

Following intraperitoneally applied treatment with antilymphocyte serum (ALS) of immunosuppressive effect no bacterial translocation (BT) was observed in mice. The ALS treatment applied in combination with other immunosuppressive agents such as lymphotropic cytostatics as dianhydrogalactitol or chlorpromazine did not increase the mice's drug sensitivity to the used agents. According to our results, ALS can be suitable for combined application with other immunosuppressive agents as it can increase immunosuppression without side-effects such as those induced by bacterial translocation.


Subject(s)
Antilymphocyte Serum/pharmacology , Bacterial Translocation/drug effects , Immunosuppressive Agents/pharmacology , Animals , Chlorpromazine/pharmacology , Dianhydrogalactitol/pharmacology , Female , Liver/microbiology , Lymph Nodes/microbiology , Lymphocyte Count , Male , Mice , Spleen/microbiology
7.
Acta Microbiol Immunol Hung ; 45(3-4): 317-22, 1998.
Article in English | MEDLINE | ID: mdl-9873938

ABSTRACT

The working group on immunology under the leadership of Pál Földes began its activity with poliovirus studies during the severe epidemics of 1957. It was he who first in Hungary isolated poliovirus strain from patients [1]. His colleague was Ilona, Szeri who had gained her first experiences in virology at József Sinkovics's virus laboratory. Then Zsuzsanna Bános and Piroska Anderlik joined them and became permanent members of the working group on immunology. Since 1965 with the leadership of Ilona Szeri, they have been conducting basic researches into immunology for over three decades at the Institute, with a wide sphere of collaborators. Research has been intended to acquire more thorough and precise knowledge of the role in immunobiology of the thymus and lymphoid system and of pathogenesis of the wasting syndrome as well as of interactions of the microorganisms and the organism. The most significant results are going to be summed up in the following.


Subject(s)
Poliomyelitis/immunology , Research/trends , Wasting Syndrome/immunology , Allergy and Immunology , Humans , Hungary , Research/organization & administration , Schools, Medical/organization & administration , Universities/organization & administration
8.
Acta Microbiol Immunol Hung ; 45(3-4): 323-8, 1998.
Article in English | MEDLINE | ID: mdl-9873939

ABSTRACT

In our experiments we evidence from several aspects that the normal microbial flora has a permanent and life-long immune modulating role in conventional organisms and a stimulating effect both on specific and non-specific defense. However, in case of artificial interventions (stress, drugs) affecting the organism, existence of the normal flora may have an adverse effect on it (endotoxin effect, bacterial translocation). The immunomodulants show a stimulating effect mainly in organisms with undeveloped immune system, and their effects are independent from the presence or absence of the microbial flora. With ageing, effect of immunomodulants can change and become indifferent or even suppressive. Dose-dependence of stimulating or suppressing effect of immunomodulants may be related to their non-immunological effects (endotoxin effect, bacterial translocation). Finally, on the basis of our experiments, we consider the Gf mouse suitable for examining the effect of a given agent in the practice, on the one hand, and for observing the host organism's reactions, free from the influence of the normal microbial flora, on the other. Along with the known physiological and pathological events, our results draw also attention to as distant fields as drug sensitivity, drug interactions influencing drug sensitivity. The authors put emphasis on importance of germfree environment during immunosuppressive treatments in humans and when making special examinations under experimental conditions.


Subject(s)
Mice/immunology , Animals , Endotoxins , Immune Tolerance , Mice/microbiology
9.
Acta Microbiol Immunol Hung ; 45(3-4): 329-33, 1998.
Article in English | MEDLINE | ID: mdl-9873940

ABSTRACT

Certain viruses do not kill the cells they infect. The immunological response of the host in such situations may be involved in the development of pathologic changes and clinical illness. Pioneering work by Rowe has shown that death associated with acute LCMV infection in the mouse is resulted from the immune response. Many investigators using a variety of techniques including neonatal thymectomy, irradiation, or treatment of adult mice with antilymphoid drugs or antithymocyte sera have confirmed and extended Rowe's observations. The study of LCMV and the disease it causes in its natural murine host has provided the initial findings that open new fields in viral immunobiology, viral immunopathology, and cell-cell recognition.


Subject(s)
Lymphocytic Choriomeningitis/immunology , Acute-Phase Reaction , Animals , Disease Models, Animal , Immunity, Cellular , Lymphocytic Choriomeningitis/pathology , Lymphocytic Choriomeningitis/virology , Lymphocytic choriomeningitis virus/immunology , Mice
11.
Acta Pharm Hung ; 66(4): 165-9, 1996 Jul.
Article in Hungarian | MEDLINE | ID: mdl-9082837

ABSTRACT

The plasma fibronectin (pFN) concentration (cc)-determined by electro-immunodiffusion method-of untreated genetically or artificially athymic mice, or treated with TP-4 (thymus hormone sequence analog synthetic preparation) showed no significant difference from their euthymic or untreated controls. In contrast, the pFN cc in mice with different microbiological state showed significant alterations; the highest level occurred in conventional mice. The lower level in germfree mice was increased by bacterial monocontamination. The alternation from SPF into conventional state in athymic mice or treatment of athymic and euthymic mice with Bordetella pertussis vaccine also resulted in the increase of the pFN cc. Based on these and earlier results, it was assumed that the pFN cc is independent from the presence or absence of the thymus, but it depends on the actual microbiological state of the macroorganism.


Subject(s)
Adjuvants, Immunologic/pharmacology , Fibronectins/blood , Peptide Fragments/pharmacology , Pertussis Vaccine/immunology , Thymopoietins/pharmacology , Thymus Gland/physiology , Animals , Germ-Free Life , Mice , Mice, Inbred BALB C , Mice, Nude , Thymus Gland/immunology
12.
Acta Pharm Hung ; 65(5): 163-6, 1995 Sep.
Article in Hungarian | MEDLINE | ID: mdl-7484163

ABSTRACT

In acute toxicity experiments authors observed increased mortality on the first day following 75 mg/kg chlorpromazine (CPZ) treatment in mice pretreated with Bordetella pertussis vaccine (9 x 10(9) killed bacterium/mouse) compared to control animals treated with CPZ alone. Initially, the increased drug sensitivity observed after combined treatment was attributed to summation of the toxic effects. However, the cumulation of mortality did not cease on the following days; furthermore, an increase of bacterial translocation (translocation index of P-CPZ group: 4.5) was observed on days 6 and 7, i.e. when the lymphocytosis, splenic hypertrophy and shrinkage of thymus--changes consequent to the vaccination--were at their maximum levels. On the basis of all these and on literary data it is supposed that the early cumulation of deaths after combined treatment may be in connection with an interaction between the two agents and that the side-effects following vaccination of humans may be induced by undesirable pharmacological interactions.


Subject(s)
Chlorpromazine/toxicity , Pertussis Vaccine/toxicity , Whooping Cough/physiopathology , Animals , Bordetella pertussis/drug effects , Bordetella pertussis/physiology , Drug Interactions , Humans , Mice , Mice, Inbred Strains , Whooping Cough/pathology
13.
Acta Pharm Hung ; 65(1): 5-8, 1995 Jan.
Article in Hungarian | MEDLINE | ID: mdl-7725928

ABSTRACT

In acute toxicity experiments the changes in drug sensitivity and in the rate of bacterial translocation (BT) were investigated in mice treated with immunomodulatory drugs: dianhydrogalactitol (DAG) in doses 20 and 30 mg/kg, chlorpromazine (CPZ) in doses 60 and 75 mg/kg and Mannozym (M) in dose 40 mg/kg for zymosan content. The drugs were used separately or in combination. The sensitivity of mice to immunosuppressive DAG or CPZ was higher in the case of combined treatment, than that of separately treated ones. The rate of BT was also higher in combined treated mice. The pretreatment with M that has immunostimulatory effect, influenced neither the sensitivity of mice to DAG or CPZ, nor the normal very low rate of BT. The present results reinforced the authors' earlier observations, that the effects of immunosuppressive drugs could cumulate and cause more serious damage of the organism. The authors suggest that the increase in drug sensitivity to immunosuppressive agents is in connection with increased rate of BT and effect of endotoxin.


Subject(s)
Adjuvants, Immunologic/toxicity , Bacterial Physiological Phenomena , Chlorpromazine/toxicity , Dianhydrogalactitol/toxicity , Mannans/toxicity , Animals , Bacteria/drug effects , Drug Interactions , Immunosuppressive Agents/toxicity , Mice , Mice, Inbred Strains , Zymosan/analysis
14.
Acta Microbiol Immunol Hung ; 42(4): 395-401, 1995.
Article in English | MEDLINE | ID: mdl-8689092

ABSTRACT

In acute toxicity experiments the mortality of mice pretreated with Bordetella pertussis vaccine increased on the first day following chlorpromazine (CPZ) treatment, compared to control animals treated with CPZ alone. Initially, the increased drug sensitivity observed after combined treatment was attributed to summation of the toxic effects. However, the cumulation of mortality did not cease on the following days, furthermore, an increase of bacterial translocation was observed on days 6 and 7, i.e. when the lymphocytosis, splenic hypertrophy and shrinkage of thymus-changes consequent to the vaccination-were at their maximum levels. On the basis of all these and on literary data it is supposed that the early cumulation of deaths after combined treatment may be in connection with an interaction between the two agents and that the side-effects following vaccination of humans may be induced by undesirable pharmacological interactions.


Subject(s)
Chlorpromazine/toxicity , Immunosuppressive Agents/toxicity , Pertussis Vaccine/toxicity , Animals , Bacterial Physiological Phenomena , Female , Intestines/microbiology , Male , Mice , Movement , Vaccination
15.
Acta Microbiol Immunol Hung ; 42(3): 261-9, 1995.
Article in English | MEDLINE | ID: mdl-8548199

ABSTRACT

In acute toxicity experiments changes in drug sensitivity and in the rate of bacterial translocation (BT) were investigated in mice treated with immunomodulatory drugs: dianhydrogalactitol (DAG) in doses 20 and 30 mg/kg, chlorpromazine (CPZ) in doses 60 and 75 mg/kg and Mannozym (M) in dose equivalent to 40 mg per kg zymosan. The drugs were used separately or in combination. The sensitivity of mice to immunosuppressive DAG or CPZ was higher in the case of combined treatment than that of separately treated ones. The rate of BT was also higher in mice receiving combined treatment. Pretreatment with M exerting an immunostimulatory effect, influenced neither the sensitivity of mice to DAG or CPZ nor the very low normal rate of BT. The present results reinforced the authors' earlier observations that the effects of immunosuppressive drugs cumulated in and caused more serious damage of the organism. The increase in drug sensitivity to immunosuppressive agents may be connected with an increased rate of BT and effect of endotoxin.


Subject(s)
Bacteria/drug effects , Chlorpromazine/toxicity , Dianhydrogalactitol/toxicity , Immunosuppressive Agents/toxicity , Animals , Bacterial Physiological Phenomena , Female , Male , Mannans/pharmacology , Mice , Movement
16.
Acta Microbiol Hung ; 40(2): 159-64, 1993.
Article in English | MEDLINE | ID: mdl-8184670

ABSTRACT

The plasma fibronectin (pFN) concentration (cc) of untreated genetically or artificially athymic mice, or treated with TP-4 (thymus hormone sequence analog synthetic preparation) showed no significant difference from their euthymic or untreated controls. In contrast, the pFN cc in mice with different microbiological state showed significant alterations; the highest level occurred in conventional mice and the lower level in germfree mice was increased by bacterial monocontamination. The alternation from SPF into conventional state in nude mice also resulted in the increase of the pFN cc. Based on these and earlier results, it was assumed that the pFN cc is independent from the presence or absence of the thymus, but it depends on the actual microbiological state of the macroorganism.


Subject(s)
Fibronectins/blood , Thymus Gland/immunology , Animals , Female , Fibronectins/immunology , Germ-Free Life , Gram-Positive Bacterial Infections/immunology , Immunity, Innate , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Peptostreptococcus/immunology , Thymectomy , Thymus Gland/surgery
17.
Acta Pharm Hung ; 62(4): 167-71, 1992 Jul.
Article in Hungarian | MEDLINE | ID: mdl-1442095

ABSTRACT

Balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with TP-4 (a synthetic tetrapeptide, thymopoietin sequence analog, Pharmaceutical Product's Factory Gedeon Richter, Budapest, Hungary) or with Mannozym (0.1% zymosan suspension, Institute for Serobacterological Production and Research, HUMAN, Budapest, Hungary), and were infected intracerebrally with LCM virus. Both of the agents contributed to the development of fatal choriomeningitis, consequently they stimulated the cellular immune response in euthymic mice, but the athymic mice, either treated or not, survived the infection, consequently the agents had no effect on the course of LCM virus infection. The results showed that the cellular immune response stimulating effect by both agents was thymus-dependent. Using these agents immunostimulatory effect can be realized only in the presence of the thymus or the T-dependent lymphoid system, respectively.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Lymphocytic Choriomeningitis/immunology , Mannans/therapeutic use , Peptide Fragments/therapeutic use , Thymopoietins/therapeutic use , Animals , Mice , Mice, Inbred BALB C , Mice, Nude
18.
Acta Microbiol Hung ; 39(1): 13-9, 1992.
Article in English | MEDLINE | ID: mdl-1632194

ABSTRACT

Old mice with thymus involution were treated intraperitoneally with a live vaccine containing a mesogenic strain of attenuated Newcastle Disease Virus or with Mannozym (M, 1% zymosan suspension). One day after the treatments mice were infected with lymphocytic choriomeningitis virus (LCMV) intracerebrally. The fatal course of the consequent LCMV infection was stimulated by each of the pretreatments, indicating that the cellular immune response was stimulated. The results are compared with results of experiments carried out on suckling, young adult and old mice in similar experimental systems. The authors' previous publication suggesting that the direction and degree of the immunomodulant effect may be influenced by the actual age-dependent condition of the lymphoid system, have been confirmed.


Subject(s)
Adjuvants, Immunologic/pharmacology , Aging/immunology , Lymphocytic Choriomeningitis/drug therapy , Thymus Gland/pathology , Animals , Female , Lymphocytic Choriomeningitis/immunology , Lymphocytic Choriomeningitis/mortality , Male , Mannans/pharmacology , Mice , Mice, Inbred C3H , Newcastle disease virus/immunology , Vaccines, Attenuated/pharmacology
19.
Acta Microbiol Hung ; 39(1): 3-11, 1992.
Article in English | MEDLINE | ID: mdl-1632196

ABSTRACT

Adult germfree (Gf) mice with undeveloped immune system due to antigen deficient environment, conventional (Cv) mice with normal immune system and Cv suckling mice with undeveloped immune system due to age were treated intraperitoneally with Mannozym (M, 0.1% zymosan suspension) 4 days or 4 days and 1 day before the intracerebral inoculation with lymphocytic choriomeningitis virus (LCMV). One dose of M was equal to 40 mg/kg of zymosan. In suckling mice, both applied doses of M contributed the development of fatal lymphocytic choriomeningitis after infection with 100 LD50 dose of LCMV, thus M pretreatment increased the cellular immune response to LCMV infection. M pretreatments had no influence on the course of LCMV infection either in adult Gf or in Cv mice. Spleen hypertrophy was caused by applied doses of M both in adult (Gf and Cv) and Cv suckling mice, but modulating effect on the cellular immune response manifested simultaneously only in Cv sucklings.


Subject(s)
Aging/immunology , Immune System/immunology , Lymphocytic Choriomeningitis/immunology , Mannans/pharmacology , Animals , Animals, Suckling/immunology , Animals, Suckling/microbiology , Drug Administration Schedule , Female , Immune System/drug effects , Injections, Intraperitoneal , Lymphocytic Choriomeningitis/drug therapy , Lymphoid Tissue/immunology , Lymphoid Tissue/microbiology , Lymphoid Tissue/physiopathology , Male , Mannans/administration & dosage , Mice , Mice, Inbred C3H
20.
Acta Microbiol Hung ; 39(3-4): 235-9, 1992.
Article in English | MEDLINE | ID: mdl-1343936

ABSTRACT

Balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with TP-4 (a synthetic tetrapeptide, thymopoietin sequence analog) or with Mannozym (1% zymosan suspension), and were infected intracerebrally with LCM virus. Both of the agents contributed to the development of fatal choriomeningitis, consequently stimulated the cellular immune response in euthymic mice, but the athymic mice either treated or not, survived the infection, consequently the agents had no effect on the course of LCM virus infection. Both agents exerted a thymus-dependent cellular immune response stimulating effect. That is, an immunostimulatory effect can be realized only in the presence of the thymus or the T-dependent lymphoid system.


Subject(s)
Adjuvants, Immunologic/pharmacology , Lymphocytic Choriomeningitis/etiology , Mannans/pharmacology , Peptide Fragments/pharmacology , Thymopoietins/pharmacology , Animals , Female , Immunity, Cellular , Lymphocytic Choriomeningitis/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , T-Lymphocytes/immunology
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