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M Szczypka

Publications and source records attributed to M Szczypka.

At least 19 recordsLinked to original sources
PubMed2005

Effect of calf thymus extract and zinc supplementation on the cellular response of mice exposed to restraint stress.

The studies were carried out on Balb/c mice exposed to restraint stress twice for 12 h at 24 h intervals. Prior to stress exposure, the mice were treated with calf thymus extract (TFX - Jelfa) i.p. at a dose of 10 mg/kg, ten times at 24 h intervals. TFX was used per se or with zinc ions interaction, by adding zinc ions (as sulfate salt) to drinking water at a dose of 72 microg/mouse per day. The results obtained show that restraint stress dramatically decreased the total number of thymocytes and splenocytes which is also accompanied by decreasing weight ratio of the thymus and spleen. The decreasing number of thymic and spleen cells corresponded to a diminishing percentage of immature, double-positive CD4+CD8+ thymocytes, mature single-positive CD4+ thymic cells and CD4+, CD8+ and CD19+ splenocytes. Changes in the number of thymic cells affect their activity, which is expressed as a decreased proliferative response of thymocytes stimulated in vitro with concanavalin A (Con A) and phytohaemagglutinin (PHA). Besides, exposure to the restraint stress decreased interleukin-1 (IL-1) production by murine intraperitoneal macrophages stimulated in vitro with lipopolisacharide (LPS) from E. coli. Previous treatment with TFX counteracted restraint stress-induced immunosuppression, which is expressed as partial normalisation of the total number of thymic and spleen cells, accelerated regeneration of these two lymphatic organs, shortned suppressive action of restraint stress on the percentage of immature CD4+CD8+ thymocytes and CD4+ splenocytes and in total normalisation of the CD4+ thymocytes and CD8+ splenocytes. TFX administered prior to restraint stress not only counteracted the suppresive effects of stress on the proliferative activity of thymic cells stimulated in vitro with Con A and PHA, but also augmented the proliferative response of these cells to two mitogens. The immunorestorative effect of TFX was augmented by zinc supplementation.

Animals↗
PubMed2003

Comparative effects of fluoroquinolones on subsets of T lymphocytes in normothermic and hyperthermic mice.

The subsets of T lymphocytes in thymus, spleen and mesenteric lymph nodes were investigated in normothermic and hyperthermic mice treated with fluoroquinolones administered orally six times at 24 h intervals at doses of 15 or 75 mg/kg (flumequine, norfloxacin and ciprofloxacin) and 5 or 25 mg/kg (enrofloxacin). It has been found that fluoroquinolones can modulate CD3+, CD4+ and CD8+ marker expression on thymocytes, splenocytes and lymphocytes of mesenteric lymph nodes. Flumequine (15 mg/kg) decreased the percentage of immature CD4+CD8+ thymic cells and increased the percentage of mature CD4+ and CD8+. When the dose of flumequine was increased to 75 mg/kg a reduction in the maturation of thymocytes was observed. Administration of flumequine, norfloxacin and ciprofloxacin, irrespective of doses applied, increased the percentages of CD3+ splenocytes of CD4+ spleen cells. Exposure to enrofloxacin decreased the percentage of T helper-inducer cells. Flumequine and ciprofloxacin augmented the percentage of CD3+ mesenteric lymph node cells and increased the percentage of CD8+ cells. In contrast, norfloxacin and enrofloxacin decreased the percentage of CD3+ mesenteric lymph node cells and the percentage of CD4+ cells. Lipopolysaccharide (LPS) from E. coli (25 micro g/mouse) increased the percentage of single-positive CD4+ thymocytes, but did not affect the percentage of CD3+, CD4+ and CD8+ splenocytes and mesenteric lymph node cells. Flumequine and ciprofloxacin administered to mice pior to LPS potentiated its stimulant effect on the maturation of thymic cells ( increased percentage of mature CD4+ and CD8+ thymocytes). Pre-treatment with norfloxacin or enrofloxacin either reduced or did not modify the stimulant effect of LPS on maturation of thymic cells. Flumequine, norfloxacin, enrofloxacin and ciprofloxacin administered prior to LPS decreased the percentage of CD8+ splenocytes and increased the percentage of CD4+ spleen cells. Norfloxacin and ciprofloxacin at a dose of 75 mg/kg reduced the percentage of CD8+ mesenteric lymph node cells in hyperthermic mice. Pretreatment with norfloxacin at a dose of 15 mg/kg augmented the percentage of mesenteric lymph node cells. It was concluded that the modulating effects of fluoroquinolones depends on the chemial structure of drugs, dose administered as well as immunologic status.

Animals↗
PubMed2002

Effects of thymomimetic drugs and zinc supplementation on the cellular immune response in hydrocortisone-suppressed mice.

The studies were carried out on Balb/c mice (5-6 weeks of age) exposed to immunosuppression by a single intraperitoneal dose (125 mg/kg) of hydrocortisone. Prior to hydrocortisone injection the mice were treated with diethyldithiocarbamate (DTC) intra-peritoneally at a dose of 20 mg/kg, five times at 48 h intervals or calf thymus extract (TFX) at a dose of 10 mg/kg, 10 times at 24 h intervals. The two drugs were used per se or in zinc ions interactions, by adding zinc ions (as sulphate salt) to drinking water at a dose of 72 microg/mouse per day. The results obtained in the study show that hydrocortisone injection drastically decreases the number of thymocytes and splenocytes, which is also accompanied by a decreasing weight ratio of the thymus and spleen. The decreasing number of thymic and spleen cells corresponds to a decreasing percentage of CD4+, CD8+ and CD19+ splenocytes and double positive CD4+CD8+ thymocytes. Changes in the number of thymic cells affect their activity, which is expressed in a decreased proliferative response of thymocytes stimulated in vitro with concanavalin A (Con A) and phytohaemagglutinin (PHA). It has also been found that a single hydrocortisone dose decreases interleukin (IL)-1 production by murine intraperitoneal macrophages stimulated in vitro with lipopolysaccharide (LPS) from Escherichia coli. TFX or DTC counteract hydrocortisone-induced immunosuppression, which is expressed in partial normalization of the total number of thymic and spleen cells, accelerated regeneration of the two lymphatic organs, shorter suppressive action of hydrocortisone on the percentage of CD4+, CD8+ splenocytes and double positive (CD4+CD8+) and CD4+ thymocytes. Furthermore, total counteraction against the suppressive action of hydrocortisone to proliferative activity of thymocytes stimulated in vitro with Con A and PHA was observed. TFX administered prior to hydrocortisone injection partially prevented the suppressive action of the drug on IL-1 production by intraperitoneal macrophages, but such an effect was not observed with DTC. The immunorestorative effect of TFX and DTC was augmented by zinc supplementation. The results obtained in the study show that neither TFX nor DTC administration per se and in interaction with zinc supplementation were able to change the suppressive effect of hydrocortisone on the percentage of B splenocytes (CD19+ cells).

Administration, Oral↗
PubMed2002

Modulation of murine macrophages and T lymphocytes by lysozyme dimer.

The effects of lysozyme dimer (2 and 20 microg/kg) administered i.p. once and four times to mice on the phagocytic and killing ability of peritoneal macrophages, interleukin-1 (IL-1) production by murine macrophages stimulated in vitro with lipopolisaccharide of E. coli and expression of thymocyte, splenocyte and mesenteric lymphonode cell CD3+, CD4+ and CD8+ markers were studied. It was found that lysozyme dimer administered once or four times at doses of 2 microg/kg and 20 microg/kg augments the phagocytic and killing activity of peritoneal macrophages. The strongest stimulating effect was noted after four injections of lysozyme dimer at a dose of 20 microg/kg. Moreover, lysozyme dimer is able to modulate the production of IL-1 by murine macrophages stimulated in vitro with LPS. Exposure to four doses of lysozyme dimer (20 microg/kg) enhances the synthesis and release of IL-1, but this drug administered once (2 microg/kg and 20 microg/kg) or four times (2 microg/kg) decreases IL-1 production by peritoneal macrophages. It was also found that administration of lysozyme dimer at a dose of 20 microg/kg, irrespective of the number of doses applied, increases the percentage of CD4+ thymocytes and splenocytes. Moreover, exposure to four doses of lysozyme dimer (2 and 20 microg/kg) increases the percentage of CD4+ and CD8+ mesenteric lymphonode cells.

Animals↗
PubMed2002

Modulatory effects of calf thymus extract on the subset of T lymphocytes in Trichinella spiralis-infected mice.

The immunotropic properties of calf thymus extract (TFX-Jelfa) is connected with the mimic action of the thymus to modulate the differentiation, maturation and function of prothymocytes and mature thymus dependent (T) cells. The studies were carried out on CFW male mice aged 3 months. The animals were infected per os with 200 larvae of Trichinella spiralis. TFX-Jelfa was administered i.p. at a dose of 10 mg/kg seven times at 24 hour intervals prior to infection. The percentage of CD4+ and CD8+ in suspension of splenocytes and mesenteric lymphonode cells by flow cytometry using monoclonal antibodies coupled with fluorescein isothiocyanate (FITC) or phycoerythrin (PE) were determined. At the same time, cryostat preparations, made from jejunum and muscle samples, were examined by the direct immunofluorescence method using FITC-labeled antibody to mouse CD4+ and CD8+. It has been found that infection with T. spiralis in mice decreases the percentage of CD8+ splenocytes, while the percentage of CD8+ mesenteric lymphonode cells does not change. However, in infected mice the percentage of CD4+ spleen cells and mesenteric lymphonode cells is increased. It has been also found that during the course of infection an increase in the number of CD8+ and CD4+ cells in the basal lamina propria of the intestines was observed. In infected mice, CD4+ lymphocytes were visible in the inflammatory infiltrates of the muscle tissue on the 14th day, whereas CD8+ lymphocytes were first observed a week later. Pretreatment with TFX does not change the inhibitory effect of infection on the percentage of CD8+ splenocytes, but potentiates the percentage of CD4+ spleen cells and mesenteric lymphonode cells increased by infection. Furthermore, administration of TFX prior to infection also potentiates the stimulatory effect of T. spiralis on the number of CD8+ and CD4+ in the basal lamina propria of the jejunum, and on the number of CD8+ cells in the inflammatory infiltrates of the muscle tissue.

Animals↗
PubMed1997

Antioxidant defence of red blood cells and plasma in stored human blood.

Blood collected routinely from donors, and preserved with CPDA-1 anticoagulant (citrate, phosphate, dextrose, adenine), was investigated. The concentration of reduced glutathione, and glutathione peroxidase, glutathione S-transferase, glutathione reductase, superoxide dismutase, and catalase activities in erythrocytes, as well as the total radical-trapping antioxidant parameter in plasma were determined on days 1, 3, 7, 12, 16, 20 and 25 of storage. At the end of the study, a 30% decrease in the reduced glutathione concentration (P < 0.001) and decreases in glutathione S-transferase (over 20%, P < 0.001), glutathione reductase (over 8%, P < 0.01) and superoxide dismutase (over 10%, P < 0.001) activities in erythrocytes, together with up to a 30% diminution of total antioxidant activity in plasma (P < 0.001) were noted. Thus, during blood storage, glutathione-dependent antioxidant systems in erythrocytes and antioxidant defence in plasma are depleted. From the present study, a twelve-day period can be considered a safe storage limit. The sequence of events occurring in stored blood, leading to peroxidative injury in erythrocytes, is discussed.

Adult↗
PubMed1997

A new pathway for vacuolar cadmium sequestration in Saccharomyces cerevisiae: YCF1-catalyzed transport of bis(glutathionato)cadmium.

The yeast cadmium factor (YCF1) gene encodes an MgATP-energized glutathione S-conjugate transporter responsible for the vacuolar sequestration of organic compounds after their S-conjugation with glutathione. However, while YCF1 was originally isolated according to its ability to confer resistance to cadmium salts, neither its mode of interaction with Cd2+ nor the relationship between this process and organic glutathione-conjugate transport are known. Here we show through direct comparisons between vacuolar membrane vesicles purified from Saccharomyces cerevisiae strain DTY167, harboring a deletion of the YCF1 gene, and the isogenic wild-type strain DTY165 that YCF1 mediates the MgATP-energized vacuolar accumulation of Cd-glutathione complexes. The substrate requirements, kinetics and Cd2+/glutathione stoichiometry of cadmium uptake and the molecular weight of the transport-active complex demonstrate that YCF1 selectively catalyzes the transport of bis(glutathionato)cadmium (Cd x +GS2). On the basis of these results--the Cd2+ hypersensitivity of DTY167, versus DTY165, cells, the inducibility of YCF1-mediated transport, and the rapidity and spontaneity of Cd-GS2 formation--this new pathway is concluded to contribute substantially to Cd2+ detoxification.

ATP-Binding Cassette Transporters↗
PubMed1996

The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate pump.

The yeast cadmium factor gene (YCF1) from Saccharomyces cerevisiae, which was isolated according to its ability to confer cadmium resistance, encodes a 1,515 amino acid ATP-binding cassette (ABC) protein with extensive sequence homology to the human multidrug resistance-associated protein (MRP1) (Szczypka, M., Wemmie, J. A., Moye-Rowley, W. S., and Thiele, D. J. (1994) J. Biol. Chem. 269, 22853-22857). Direct comparisons between S. cerevisiae strain DTY167, harboring a deletion of the YCF1 gene, and the isogenic wild type strain, DTY165, demonstrate that YCF1 is required for increased resistance to the toxic effects of the exogenous glutathione S-conjugate precursor, 1-chloro-2,4-di-nitrobenzene, as well as cadmium. Whereas membrane vesicles isolated from DTY165 cells contain two major pathways for transport of the model compound S-(2,4-dinitrophenyl)glutathione (DNP-GS), an MgATP-dependent, uncoupler-insensitive pathway and an electrically driven pathway, the corresponding membrane fraction from DTY167 cells is more than 90% impaired for MgATP-dependent, uncoupler-insensitive DNP-GS transport. Of the two DNP-GS transport pathways identified, only the MgATP-dependent, uncoupler-insensive pathway is subject to inhibition by glutathione disulfide, vanadate, verapamil, and vinblastine. The capacity for MgATP-dependent, uncoupler-insensitive conjugate transport in vitro strictly copurifies with the acuolar membrane fraction. Intact DTY165 cells, but not DTY167 cells, mediate vacuolar accumulation of the quorescent glutathione-conjugate, monochlorobimane-GS. Introduction of plasmid borne, epitope-tagged gene encoding functional YCF1 into DTY167 cells alleviates the 1-chloro-2,4-dinitrobenzene-hypersensitive phenotype concomitant with restoration of the capacity of vacuolar membrane vesicles isolated from these cells for MgATP-dependent, uncoupler-insensitive DNP-GS transport. On the basis of these findings, the YCF1 gene of S. cerevisiae is inferred to encode an MgATP-energized, uncoupler-insensitive vacuolar glutathione S-conjugate transporter. The energy requirements, kinetics, substrate specificity, and inhibitor profile of YCF1-mediated transport demonstrate that the vacuolar glutathione conjugate pump of yeast bears a strong mechanistic resemblance to the MRP1-encoded transporter of mammalian cells and the cognate, but as yet molecularly undefined, function of plant cells.

ATP-Binding Cassette Transporters↗
PubMed1996

Antioxidant and glutathione-associated enzymes in Wilms' tumour after chemotherapy.

The present study demonstrates the activities of antioxidant and glutathione-associated enzymes and the level of glutathione in Wilms' tumour (nephroblastoma) samples after chemotherapy (mainly actinomycin D and vincristine). We observed higher activity of superoxide dismutase in Wilms' tumour compared to adjacent morphologically unchanged kidney. On the other hand, in this tumour lower activities of catalase and the glutathione-associated enzymes glutathione synthetase, gamma-glutamyl transpeptidase, glutathione reductase and total glutathione S-transferases (GST) were found. Using isoelectric focusing we separated different forms of GST in tested tissues and revealed lower activities of the basic enzymes in Wilms' tumour, which may be responsible for the decrease of total GST activity. Moreover, we found the acidic isoenzymes to be the predominant class of GST in nephroblastoma. In Wilms' tumours with unfavourable histology a high activity of these isoenzymes together with a high level of GSH were observed. We suggest that these parameters may participate in the known phenomenon of anticancer drug resistance of tumours with unfavourable histology.

Antioxidants↗
PubMed1996

[Galactosemia: a problem still unsolved].

Classical galactosemia is an inherited metabolic disease that results from galactose-1-phosphate uridyltransferase deficiency. Untreated galactosemia has various manifestations, including central nervous system damage, hepatic failure, cataract. Galactose-restricted dietary treatment, the only therapy used in galactosemia, brings considerable improvement, especially in the neonatal period. However, in the most galactosemic patients this treatment does not prevent development of late-onset complications; mental retardation, ovarian failure and neurologic disturbances. This article presents a review of contemporary hypotheses on possible factors influencing the outcome in galactosemia, especially in regard to late-onset complications.

Galactosemias↗
PubMed1995

Glutathione S-transferase isoenzymes and glutathione in renal cell carcinoma and kidney tissue.

Many studies have established the role of the glutathione S-transferases (GSTs) and glutathione (GSH) in the neoplastic process and the drug resistance of tumor. Using isoelectric focusing we separated different forms of GSTs in 28 renal cell carcinomas (RCCs) and in morphologically unchanged adjacent kidney. In addition we determined in RCCs and adjacent kidney the level of GSH and the activities of enzymes participating in synthesis and uptake of this thiol compound. We found higher activity of acidic GSTs and higher level of GSH in RCCs versus kidney. Therefore we suggest that both parameters may play the significant role in the well known phenomenon of intrinsic cytostatic drug resistance of RCC. We also observed the elevation of GSH synthetase activity in tumor tissues in comparison to the kidneys. It may indicate that GSH synthetase, catalysing the final step in GSH synthesis, may participate in the elevation of GSH concentration in RCCs. In this work we also compared the tested parameters in RCCs in relation to the size and local extent of primary tumor (T). We found significantly lower activity of gamma-glutamyl transpeptidase (GGT) as well as GSH synthetase in the group of T3 and T4 tumors than in T2 tumors. However, no substantial differences in GSH concentrations were observed between these distinguished groups.

Adult↗
PubMed1995

[Genotoxic properties of 5-nitrofuran compounds].

5-nitrofurans are a large group of nitro-compounds and worldwide as human and veterinary drugs, food additives or preservatives. However, many adverse effects of these compounds and among mutagenic as well as carcinogenic activities create doubts about safety of their use. Present paper deals with various mechanisms of genotoxic action of 5-nitrofurans. Main metabolic pathways leading to the formation of their active metabolites are discussed.

Bacteria↗
PubMed1995

[Blood antioxidant defense in children with malignant disease. I. Plasma antioxidant activity and level of ceruloplasmin and transferrin].

In this study we examined selected elements of the antioxidant defence system in the plasma of children with the most common solid tumors (nephroblastoma, neuroblastoma, rhabdomyosarcoma, osteosarcoma). We observed a significant increase of plasma antioxidant activity (AOA) in the majority of the examined children. This factor changed during clinical treatment, i.e. induction of chemotherapy, surgery and/or radiotherapy and during maintenance chemotherapy. We conclude that the elevated plasma antioxidant activity in children with malignancy may be due to the higher concentration of ceruloplasmin in affected children than in their healthy counterparts.

Adolescent↗
PubMed1990

Studies on the effect of ascorbic acid and selenium on the genotoxicity of nitrofurans: nitrofurazone and furazolidone.

The genotoxic properties of nitrofurazone and furazolidone were studied using the Ames test and SOS-chromotest. Both compounds were found to act as strong mutagens on the TA97 and TA102 strains of S. typhimurium and to induce the SOS-repair system in the PQ37 strain of E. coli. A good concordance was found between the mutagenic activity and the ability to induce the SOS system. Ascorbic acid and sodium selenite only very slightly lowered the genotoxic effect of the 2 nitrofurans studied both in the Ames test and in the SOS-chromotest.

Antioxidants↗
PubMed1990

Red blood cells and serum antioxidant defense systems of galactosaemic children.

Many reports have pointed out that oxidative damage and disturbances in antioxidant defense systems of the lenses may play an important role in the development of cataract. In the present study the activities of glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, catalase and the level of glutathione and lipid peroxides were measured in red blood cells of galactosaemic children with cataract and without cataract. Furthermore the serum antioxidant activity and the level of uric acid. ceruloplasmin and transferrin in serum were estimated. It was found that in red blood cells of galactosaemic children with cataract the activity of glutathione reductase was slightly lower than in a control age-matched group of children and in galactosaemic children without cataract. The increase of serum antioxidant activity in both groups of galactosaemic children was also observed. Probably it could be due to the increase of the level of ceruloplasmin. Except glutathione reductase activity no other differences were found in the investigated components of the antioxidant defense systems of red blood cells and serum between galactosaemic children with cataract and those without cataract. Therefore it seems that red blood cells and serum metabolism are no good reflections of disturbances in antioxidant defense mechanisms which may be involved in the cataract development in galactosaemic children.

Antioxidants↗
PubMed1989

Urine mutagenicity of petroleum plant workers.

The mutagenicity of urinary extracts from workers employed in a petroleum plant was analyzed by means of the plate test using S. typhimurium strains TA98 and TA100. Mean urinary mutagenic activities in TA98 were 2-14 times higher in the petroleum plant workers than in the control group. In TA100 these differences were even bigger, the mutagenicity in petroleum plant workers' urine being 3-42 times higher than in the control group. These results suggest that the environmental exposure of people to mutagenic substances is markedly increased in a petrochemical plant.

Environmental Exposure↗