The Experts below are selected from a list of 171 Experts worldwide ranked by ideXlab platform
Andrzej Myśliwski - One of the best experts on this subject based on the ideXlab platform.
-
analogues of Muramyl Dipeptide mdp and tuftsin limit infection and inflammation in murine model of sepsis
Vaccine, 2009Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Andrzej Myśliwski, Magdalena Szarynska, Maria Dąbrowskaszponar, Katarzyna Wiśniewska, Piotr TrzonkowskiAbstract:Abstract Pharmacological manipulation of the balance between pro- and anti-inflammatory mediators emerges as a key aspect of a successful treatment of sepsis. A murine model of septic shock was developed and chosen conjugates (1a, 1b, 8a, 8c) and analogs (T2) of Muramyl Dipeptide and tuftsin were tested in this model as prospective anti-bacterial drugs or adjuvants. The phagocytic activity of monocytes/macrophages was determined (flow cytometry, bacterial clearance from vital organs). To evaluate cytokines levels (TNFα, IFNγ, IL6, IL10) we used real-time PCR. The most promising immunomodulatory properties were displayed by the analogue T2 and two conjugates: 8a, 8c.
-
immunomodulatory properties of new conjugates of Muramyl Dipeptide and nor Muramyl Dipeptide with retro tuftsin arg pro lys thr ome
International Immunopharmacology, 2006Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Piotr Trzonkowski, Andrzej MyśliwskiAbstract:Abstract Six new conjugates of Muramyl Dipeptide and nor-Muramyl Dipeptide with retro-tuftsin were synthesised at Gdansk University of Technology. All compounds were investigated at Medical University of Gdansk. Their immunomodulatory properties were assessed using in vitro cultures of human subpopulations of white blood cells (peripheral blood mononuclear cells, peripheral blood lymphocytes, monocytes). We examined the viability of blood cells incubated with examined conjugates, as well as their ability to stimulate secretion of cytokines (TNFα—tumour necrosis factor α, IL6—interleukin 6) and cytotoxic activity of NK (Natural Killer) cells. Complementation in biological activity of Muramyl Dipeptide (MDP) and tuftsin in conjugates proved to be beneficial in the field of immunoadjuvanticity. Our investigations proved that new conjugates acquired features that native immunomodulators did not reveal separately. In examined compound, the part responsible for inducing cytotoxic activity of NK cells was the tuftsin part of the conjugates. MDP in conjugates was responsible for compound-induced synthesis of TNFα. The results of our study imply usefulness of the examine compounds (mainly A and B), as potential therapeutic agents.
-
Muroctasin, a Muramyl Dipeptide derivative
Postȩpy higieny i medycyny doświadczalnej, 1992Co-Authors: Danuta Sosnowska, Krystyna Dzierzbicka, Andrzej Myśliwski, Aleksander M. KolodziejczykAbstract:: This paper presents a review of studies on the metabolism, pharmacological and clinical properties of a new synthetic Muramyl Dipeptide derivative N2-/(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl/-N6-stearoyl-L-lysine(MD P- Lys(L18), muroctasin). Due to its effect on the number of peripheral blood leukocytes this compound is expected to be a useful drug for the treatment of leukopenia induced by cancer chemotherapy or radiation therapy.
Anna Wardowska - One of the best experts on this subject based on the ideXlab platform.
-
New conjugates of tuftsin and Muramyl Dipeptide as stimulators of human monocyte-derived dendritic cells.
Protein and Peptide Letters, 2013Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Agnieszka Menderska, Piotr TrzonkowskiAbstract:Muramyl Dipeptide (MDP) and tuftsin are known biologically active compound displaying a significant influence on various cell populations of innate immune response. MDP, as a fragment of bacterial cell wall, stimulates not only macrophages and monocytes, but also dendritic cells. In contrast, little is known about tuftsin influence on these cells. Therefore it seemed vital to access whether tuftsin or its derivatives conjugated with MDP could influence the activity of this subpopulation of antigen presenting cells (APC). Immature dendritic cells (iDCs) were derived from human monocytes through eight-day tissue culture supplemented with hrIL-4 and hrGM-CSF. On the day 9 DCs were stimulated with newly synthesized conjugates of tuftsin and Muramyl Dipeptide. The influence of the examined compounds on the activity and maturity of monocyte-derived DCs was estimated by flow cytometry analysis. The flow cytometry analysis revealed that tuftsin and some of its analogues do stimulate maturation and activity of DCs but to a lesser extend in comparison to MDP. The obtained results suggest further development of the experiments concerning the influence of MDP and tuftsin analogues on the activity of dendritic cells.
-
analogues of Muramyl Dipeptide mdp and tuftsin limit infection and inflammation in murine model of sepsis
Vaccine, 2009Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Andrzej Myśliwski, Magdalena Szarynska, Maria Dąbrowskaszponar, Katarzyna Wiśniewska, Piotr TrzonkowskiAbstract:Abstract Pharmacological manipulation of the balance between pro- and anti-inflammatory mediators emerges as a key aspect of a successful treatment of sepsis. A murine model of septic shock was developed and chosen conjugates (1a, 1b, 8a, 8c) and analogs (T2) of Muramyl Dipeptide and tuftsin were tested in this model as prospective anti-bacterial drugs or adjuvants. The phagocytic activity of monocytes/macrophages was determined (flow cytometry, bacterial clearance from vital organs). To evaluate cytokines levels (TNFα, IFNγ, IL6, IL10) we used real-time PCR. The most promising immunomodulatory properties were displayed by the analogue T2 and two conjugates: 8a, 8c.
-
immunomodulatory properties of new conjugates of Muramyl Dipeptide and nor Muramyl Dipeptide with retro tuftsin arg pro lys thr ome
International Immunopharmacology, 2006Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Piotr Trzonkowski, Andrzej MyśliwskiAbstract:Abstract Six new conjugates of Muramyl Dipeptide and nor-Muramyl Dipeptide with retro-tuftsin were synthesised at Gdansk University of Technology. All compounds were investigated at Medical University of Gdansk. Their immunomodulatory properties were assessed using in vitro cultures of human subpopulations of white blood cells (peripheral blood mononuclear cells, peripheral blood lymphocytes, monocytes). We examined the viability of blood cells incubated with examined conjugates, as well as their ability to stimulate secretion of cytokines (TNFα—tumour necrosis factor α, IL6—interleukin 6) and cytotoxic activity of NK (Natural Killer) cells. Complementation in biological activity of Muramyl Dipeptide (MDP) and tuftsin in conjugates proved to be beneficial in the field of immunoadjuvanticity. Our investigations proved that new conjugates acquired features that native immunomodulators did not reveal separately. In examined compound, the part responsible for inducing cytotoxic activity of NK cells was the tuftsin part of the conjugates. MDP in conjugates was responsible for compound-induced synthesis of TNFα. The results of our study imply usefulness of the examine compounds (mainly A and B), as potential therapeutic agents.
Piotr Trzonkowski - One of the best experts on this subject based on the ideXlab platform.
-
New conjugates of tuftsin and Muramyl Dipeptide as stimulators of human monocyte-derived dendritic cells.
Protein and Peptide Letters, 2013Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Agnieszka Menderska, Piotr TrzonkowskiAbstract:Muramyl Dipeptide (MDP) and tuftsin are known biologically active compound displaying a significant influence on various cell populations of innate immune response. MDP, as a fragment of bacterial cell wall, stimulates not only macrophages and monocytes, but also dendritic cells. In contrast, little is known about tuftsin influence on these cells. Therefore it seemed vital to access whether tuftsin or its derivatives conjugated with MDP could influence the activity of this subpopulation of antigen presenting cells (APC). Immature dendritic cells (iDCs) were derived from human monocytes through eight-day tissue culture supplemented with hrIL-4 and hrGM-CSF. On the day 9 DCs were stimulated with newly synthesized conjugates of tuftsin and Muramyl Dipeptide. The influence of the examined compounds on the activity and maturity of monocyte-derived DCs was estimated by flow cytometry analysis. The flow cytometry analysis revealed that tuftsin and some of its analogues do stimulate maturation and activity of DCs but to a lesser extend in comparison to MDP. The obtained results suggest further development of the experiments concerning the influence of MDP and tuftsin analogues on the activity of dendritic cells.
-
analogues of Muramyl Dipeptide mdp and tuftsin limit infection and inflammation in murine model of sepsis
Vaccine, 2009Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Andrzej Myśliwski, Magdalena Szarynska, Maria Dąbrowskaszponar, Katarzyna Wiśniewska, Piotr TrzonkowskiAbstract:Abstract Pharmacological manipulation of the balance between pro- and anti-inflammatory mediators emerges as a key aspect of a successful treatment of sepsis. A murine model of septic shock was developed and chosen conjugates (1a, 1b, 8a, 8c) and analogs (T2) of Muramyl Dipeptide and tuftsin were tested in this model as prospective anti-bacterial drugs or adjuvants. The phagocytic activity of monocytes/macrophages was determined (flow cytometry, bacterial clearance from vital organs). To evaluate cytokines levels (TNFα, IFNγ, IL6, IL10) we used real-time PCR. The most promising immunomodulatory properties were displayed by the analogue T2 and two conjugates: 8a, 8c.
-
immunomodulatory properties of new conjugates of Muramyl Dipeptide and nor Muramyl Dipeptide with retro tuftsin arg pro lys thr ome
International Immunopharmacology, 2006Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Piotr Trzonkowski, Andrzej MyśliwskiAbstract:Abstract Six new conjugates of Muramyl Dipeptide and nor-Muramyl Dipeptide with retro-tuftsin were synthesised at Gdansk University of Technology. All compounds were investigated at Medical University of Gdansk. Their immunomodulatory properties were assessed using in vitro cultures of human subpopulations of white blood cells (peripheral blood mononuclear cells, peripheral blood lymphocytes, monocytes). We examined the viability of blood cells incubated with examined conjugates, as well as their ability to stimulate secretion of cytokines (TNFα—tumour necrosis factor α, IL6—interleukin 6) and cytotoxic activity of NK (Natural Killer) cells. Complementation in biological activity of Muramyl Dipeptide (MDP) and tuftsin in conjugates proved to be beneficial in the field of immunoadjuvanticity. Our investigations proved that new conjugates acquired features that native immunomodulators did not reveal separately. In examined compound, the part responsible for inducing cytotoxic activity of NK cells was the tuftsin part of the conjugates. MDP in conjugates was responsible for compound-induced synthesis of TNFα. The results of our study imply usefulness of the examine compounds (mainly A and B), as potential therapeutic agents.
Krystyna Dzierzbicka - One of the best experts on this subject based on the ideXlab platform.
-
New conjugates of tuftsin and Muramyl Dipeptide as stimulators of human monocyte-derived dendritic cells.
Protein and Peptide Letters, 2013Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Agnieszka Menderska, Piotr TrzonkowskiAbstract:Muramyl Dipeptide (MDP) and tuftsin are known biologically active compound displaying a significant influence on various cell populations of innate immune response. MDP, as a fragment of bacterial cell wall, stimulates not only macrophages and monocytes, but also dendritic cells. In contrast, little is known about tuftsin influence on these cells. Therefore it seemed vital to access whether tuftsin or its derivatives conjugated with MDP could influence the activity of this subpopulation of antigen presenting cells (APC). Immature dendritic cells (iDCs) were derived from human monocytes through eight-day tissue culture supplemented with hrIL-4 and hrGM-CSF. On the day 9 DCs were stimulated with newly synthesized conjugates of tuftsin and Muramyl Dipeptide. The influence of the examined compounds on the activity and maturity of monocyte-derived DCs was estimated by flow cytometry analysis. The flow cytometry analysis revealed that tuftsin and some of its analogues do stimulate maturation and activity of DCs but to a lesser extend in comparison to MDP. The obtained results suggest further development of the experiments concerning the influence of MDP and tuftsin analogues on the activity of dendritic cells.
-
analogues of Muramyl Dipeptide mdp and tuftsin limit infection and inflammation in murine model of sepsis
Vaccine, 2009Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Andrzej Myśliwski, Magdalena Szarynska, Maria Dąbrowskaszponar, Katarzyna Wiśniewska, Piotr TrzonkowskiAbstract:Abstract Pharmacological manipulation of the balance between pro- and anti-inflammatory mediators emerges as a key aspect of a successful treatment of sepsis. A murine model of septic shock was developed and chosen conjugates (1a, 1b, 8a, 8c) and analogs (T2) of Muramyl Dipeptide and tuftsin were tested in this model as prospective anti-bacterial drugs or adjuvants. The phagocytic activity of monocytes/macrophages was determined (flow cytometry, bacterial clearance from vital organs). To evaluate cytokines levels (TNFα, IFNγ, IL6, IL10) we used real-time PCR. The most promising immunomodulatory properties were displayed by the analogue T2 and two conjugates: 8a, 8c.
-
immunomodulatory properties of new conjugates of Muramyl Dipeptide and nor Muramyl Dipeptide with retro tuftsin arg pro lys thr ome
International Immunopharmacology, 2006Co-Authors: Anna Wardowska, Krystyna Dzierzbicka, Piotr Trzonkowski, Andrzej MyśliwskiAbstract:Abstract Six new conjugates of Muramyl Dipeptide and nor-Muramyl Dipeptide with retro-tuftsin were synthesised at Gdansk University of Technology. All compounds were investigated at Medical University of Gdansk. Their immunomodulatory properties were assessed using in vitro cultures of human subpopulations of white blood cells (peripheral blood mononuclear cells, peripheral blood lymphocytes, monocytes). We examined the viability of blood cells incubated with examined conjugates, as well as their ability to stimulate secretion of cytokines (TNFα—tumour necrosis factor α, IL6—interleukin 6) and cytotoxic activity of NK (Natural Killer) cells. Complementation in biological activity of Muramyl Dipeptide (MDP) and tuftsin in conjugates proved to be beneficial in the field of immunoadjuvanticity. Our investigations proved that new conjugates acquired features that native immunomodulators did not reveal separately. In examined compound, the part responsible for inducing cytotoxic activity of NK cells was the tuftsin part of the conjugates. MDP in conjugates was responsible for compound-induced synthesis of TNFα. The results of our study imply usefulness of the examine compounds (mainly A and B), as potential therapeutic agents.
-
Muroctasin, a Muramyl Dipeptide derivative
Postȩpy higieny i medycyny doświadczalnej, 1992Co-Authors: Danuta Sosnowska, Krystyna Dzierzbicka, Andrzej Myśliwski, Aleksander M. KolodziejczykAbstract:: This paper presents a review of studies on the metabolism, pharmacological and clinical properties of a new synthetic Muramyl Dipeptide derivative N2-/(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl/-N6-stearoyl-L-lysine(MD P- Lys(L18), muroctasin). Due to its effect on the number of peripheral blood leukocytes this compound is expected to be a useful drug for the treatment of leukopenia induced by cancer chemotherapy or radiation therapy.
RJ Playford - One of the best experts on this subject based on the ideXlab platform.
-
detection of Muramyl Dipeptide sensing pathway defects in patients with crohn s disease
Inflammatory Bowel Diseases, 2006Co-Authors: David A Van Heel, Karen A Hunt, Katherine S King, S Ghosh, S M Gabe, Christopher G Mathew, A Forbes, RJ PlayfordAbstract:Crohn's disease is strongly associated with double mutations in NOD2/CARD15. Three common mutations (Arg702Trp, Gly908Arg, Leu1007fs) impair innate immune responses to bacterial Muramyl Dipeptide. Rare NOD2 variants occur, but it is difficult to both identify them and assess their functional effect. We assessed the true frequency of defective Muramyl Dipeptide sensing in Crohn's disease and developed a rapid diagnostic assay.
-
Detection of Muramyl Dipeptide-sensing pathway defects in patients with Crohn's disease
INFLAMM BOWEL DIS, 2006Co-Authors: RJ PlayfordAbstract:Background and Aims: Crohn's disease is strongly associated with double mutations in NOD2/CARD15. Three common mutations (Arg702Trp, Gly908Arg, Leu1007fs) impair innate immune responses to bacterial Muramyl Dipeptide. Rare NOD2 variants occur, but it is difficult to both identify them and assess their functional effect. We assessed the true frequency of defective Muramyl Dipeptide sensing in Crohn's disease and developed a rapid diagnostic assay.Materials and Methods: An ex vivo assay was established and validated based on Muramyl Dipeptide stimulation of peripheral blood mononuclear cell cytokine production. Muramyl Dipeptide-induced enhancement of interleukin (IL)-8 secretion and synergistic increase in lipopolysaccharide-induced IL-1 beta secretion were studied. Assay results were compared with NOD2 genotype status (3 common mutations and rare variants) in 91 individuals including a prospective cohort of 49 patients with Crohn's disease.Results: The assay was highly sensitive and specific for detection of profound defects in Muramyl Dipeptide sensing caused by double NOD2 mutations (IL-8 P = 0.0002; IL-1 beta P = 0.0002). Disease state, active inflammation, or concur-rent use of immunosuppressive medication did not influence results. Healthy NOD2 heterozygotes had modest impairment of Muramyl Dipeptide induced IL-8 secretion (P = 0.003). Only 1 of 7 patients with Crohn's disease with both a common mutation and a rare variant had a profound Muramyl Dipeptide-sensing defect.Conclusions: Profound defects in Muramyl Dipeptide sensing were found in 10% of patients with Crohn's disease. Defects were caused exclusively by inherited mutations in NOD2. The ex vivo assay has multiple potential applications as a clinical diagnostic tool to distinguish patients with Muramyl Dipeptide-sensing defects and for research investigation.
