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ABSTRACT: Many biochemical processes are closely related to ion exchange, adsorption, and catalysis. Zeolites reversibly bind small molecules such as oxygen or nitric oxide; they possess size and shape selectivity, the possibility of metalloenzyme mimicry, and immunomodulatory activity. These properties make them interesting for pharmaceutical industry and medicine.
The experiments were performed on mice. Different biochemical and molecular methods were used.
Micronized zeolite (MZ) administered by gastric intubation to mice injected with melanoma cells significantly reduced the number of melanoma metastases. In mice fed MZ for 28 days, concentration of lipid-bound sialic acid (LSA) in serum increased, but lipid peroxidation in liver decreased. The lymphocytes from lymph nodes of these mice provoked a significantly higher alogeneic graft-versus-host (GVH) reaction than cells of control mice. After i.p. application of MZ, the number of peritoneal macrophages, as well as their production of superoxide anion, increased. However, NO generation was totally abolished. At the same time, translocation of p65 (NFkappaB subunit) to the nucleus of splenic cells was observed.
Here we report antimetastatic and immunostimulatory effect of MZ and we propose a possible mechanism of its action.
Journal of Cancer Research and Clinical Oncology 02/2002; 128(1):37-44. · 2.56 Impact Factor
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ABSTRACT: Zeolites are natural or synthetic crystalline alumosilicates with ion exchanging properties. Supplied in fodder, they promote biomass production and animal health. Our aim was to assess the effects of the natural zeolite, clinoptilolite, on hematopoiesis, serum electrolytes and essential biochemical indicators of kidney and liver function in mice. Two preparations differing in particle size were tested: a powderized form obtained by countercurrent mechanical treatment of the clinoptilolite (MTCp) and normally ground clinoptilolite (NGCp). Young adult mice were supplied with food containing 12.5, 25 or 50% clinoptilolite powder. Control animals received the same food ration without the clinoptilolite. After 10, 20, 30 and 40 days, six animals from each group were exsanguinated to obtain blood for hematological and serum for biochemical measurements as well as to collect femoral bone marrow for determination of hematopoietic activity. Clinoptilolite ingestion was well tolerated, as judged by comparable body masses of treated and control animals. A 20% increase of the potassium level was detected in mice receiving the zeolite-rich diet, without other changes in serum chemistry. Erythrocyte, hemoglobin and platelet levels in peripheral blood were not materially affected. NGCp caused leukocytosis, with concomitant decline of the GM-CFU content in the bone marrow, which was attributed to intestinal irritation by rough zeolite particles. The mechanically treated clinoptilolite preparation caused similar, albeit less pronounced, changes. In a limited experiment, mice having transplanted mammary carcinoma in the terminal stage showed increased potassium and decreased sodium and chloride levels, severe anemia and leukocytosis, decreased bone marrow cellularity and diminished content of hematopoietic progenitor cells in the marrow. The clinoptilolite preparations ameliorated the sodium and chloride decline, whereas the effects on hematopoiesis were erratic.
Food and Chemical Toxicology 08/2001; 39(7):717-27. · 3.00 Impact Factor
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ABSTRACT: Stress by overcrowding lasting 2 weeks or more depressed the Arthus reaction in rats, and repeated immobilization for 4 days depressed the plaque-forming cell (PFC) response in Jerne's assay. The concentrations of neurotransmitters in the brain showed 2 peaks during the overcrowding: at the beginning of the stress (day 2) there was a sharp rise of 5-hydroxy-indoleacetic acid (5-HIAA), a metabolite of serotonin, and in the second week (day 10) there was another rise of 5-HIAA, together with serotonin and noradrenaline. Plasma corticosterone showed an initial drop, followed by increase that also culminated on day 10 of the stress, indicating adaptation. Other stressful procedures (daily immobilizations, repeated injections of picrotoxin) alos changed the levels of neurotransmitter substances and glucocorticoid hormones. A conspicuous feature noted in all models was coincidence of increased 5-HIAA (indicating increased metabolism of serotonin) with either increase of fall of the corticosterone level in plasma. This seems to be related to the state of immunosuppression. Studies on the effects of stress on immunity in parallel with neuroendocrine responses, may give insight into possible neuroendocrine control of immune phenomena.
Biomedecine [?] Pharmacotherapy 02/1982; 36(1):23-8. · 2.00 Impact Factor
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ABSTRACT: The aim of this study was to investigate antitumour activity of cisplatin, dacarbasine, cyclophosphamide and a new compound from the nitrosourea group--acetamido-CNU ((2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)-urea)--applied with or without local hyperthermia (43.5 degrees C/60 min). The tumour model for the investigation of antitumour activity was a mouse melanoma B16 transplanted into the footpad. Dacarbasine, cyclophosphamide and acetamido-CNU applied as a single treatment had statistically significant antitumour activity, while cisplatin applied as a single agent had no effect. Local hyperthermia alone had statistically significant antitumour activity. The best therapeutic effect (synergistic) was obtained when combined treatment (cytotoxins plus local hyperthermia) was used. Synergistic therapeutic results were achieved even when cisplatin and hyperthermia were combined, although cisplatin was ineffective when given as a single agent. Therapeutic results achieved with acetamido-CNU (newly synthesized compound) applied alone were similar to the therapeutic results achieved with dacarbasine or cyclophosphamide. In combined therapy (acetamido-CNU + HT), achieved therapeutic results were significantly better (p < 0.05) than results achieved by combining cisplatin and hyperthermia or dacarbasine and hyperthermia.
International Journal of Hyperthermia 18(1):62-71. · 1.92 Impact Factor
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ABSTRACT: The purpose of this study was to investigate antitumor activity of novel fluoro-substituted 6-amino-2-phenylbenzothiazole hydrochloride salts in vitro and in vivo. A novel series of hydrochloride or dihydrochloride salts of the novel 2-(fluoro-substituted phenyl)-6-aminobenzothiazoles (5-7) have been prepared in multistep synthesis starting from 3- or 4-fluorobenzaldehydes and 2-amino-5-nitrothiophenol and evaluated for their antiproliferative activity against human cervical (HeLa), breast (MCF-7), colon (CaCO-2), and laryngeal (Hep-2) carcinomas and against fibroblast cell lines (WI-38). Also, antitumor activity of these compounds was evaluated in vitro and in vivo against murine melanoma (B16-F10), fibrosarcoma (FsaR), and squamous cell carcinoma (SCCVII). The tested compounds were found to exert good cytotoxic activity in vitro. The cytotoxic effect was selective, cell specific, and dose dependent, between 33 microM for MCF-7 and 110 microM for WI-38. Benzothiazoles reduced de novo protein and DNA synthesis up to 75%. All examined benzothiazoles had significant antitumor activity in vivo against melanoma B16-F10, fibrosarcoma, and squamous cell carcinoma. The best therapeutic results were achieved when therapy started 7 days after tumor cell implantation and when benzothiazoles were given repeatedly five times every 2 days, i.e., on day 7, 9, 11, 13, and 15 after transplantation of tumor cells.
Methods and Findings in Experimental and Clinical Pharmacology 28(6):347-54. · 0.93 Impact Factor