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Biomedical subjects

I Láng

Publications and source records attributed to I Láng.

At least 19 recordsLinked to original sources

[Biologic detection methods in the comparison of circulating tumor cells and micrometastases].

Early studies could not prove any diagnostic or prognostic value of the presence of tumor cells in the circulation. Recent knowledge in the field of molecular and cellular pathology provided better understanding of mechanisms of metastasis formation therefore advanced detection of circulating cancer cells has been suggested as a supplementary method of staging metastatic cancer. Beside the widely used immunocytochemical methods the reverse transcriptase-polymerase chain reaction (RT-PCR) is now the most relevant technique in studying micrometastases of solid tumors. Magnetic activated cell sorting (MACS) is a recently developed method for the enrichment of different cells from suspensions by magnetic labelling of their surface antigens. RT-PCR seems to be the most sensitive to detect circulating cancer cells or micrometastases, but it is possible by MACS to purify cells for further immunological, biochemical or genetic analysis. The aim of this review is to give a brief summary of recently used methods and to discuss the clinical relevance of the attainable results.

Biomarkers, Tumor

Preoperative work up and therapeutic schedule for patients with duplex tumors.

Authors analyze the cases of duplex and multiplex tumors among the more than two thousand operated upon patients a year at the Surgical Department of Uzsoki Hospital, Budapest, Hungary. The study enrolls a two years period evaluating the medical history of our patients in hope of a more sophisticated and effective diagnostic and therapeutic regimen. Our experience gained by analyzing data of our patients with synchron tumors shows that the patient's life expectancy is much better if performing a radical multivisceral tumor extirpation at the same sitting even if keeping in mind the higher perioperative risk. In accordance to the above mentioned concept we would like to stress the utmost importance of the interdisciplinary cooperation.

Cooperative Behavior

[Treatment of methimazole-induced agranulocytosis with granulocyte-macrophage colony stimulating factor].

The authors treated a patient with methimazol (Metothyrin)-induced agranulocytosis with human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). On day seven, after combined antibiotics, corticosteroid and at a dose of 270 ug daily subcutaneous GM-CSF therapy the septic state of the patients rapidly cured and the leucocytes reached the peripheric blood. No side effects were found. The publication of this case history might help to determine the place of human GM-CSF-s therapy in the treatment of agranulocytosis of different origin.

Administration, Cutaneous

Effect of the natural bioflavonoid antioxidant silymarin on superoxide dismutase (SOD) activity and expression in vitro.

The in vitro effects of the bioflavonoid antioxidant silymarin on the expression and activity of superoxide dismutase (SOD) enzyme was studied in erythrocytes and lymphocytes from patients with chronic alcoholic liver disease. In vitro incubation with the agent in a concentration corresponding to the usual therapeutic dosage markedly increased the SOD expression of lymphocytes as measured by flow-cytofluorimetry following staining with monoclonal anti-Cu/Zn-SOD antibody and FITC-conjugated anti-mouse Ig, as well as erythrocyte and lymphocyte SOD activities. The data indirectly suggest that antioxidant activity might be one of the important factors in the hepatoprotective action of this bioflavonoid.

Adult

The oxygen-centered radicals scavenging activity of sulfasalazine and its metabolites. A direct protection of the bowel.

Oxygen-centered radicals, such as superoxide (O2-) and hydroxyl radicals (.OH) generated by phagocytes have been suggested to be involved in the pathogenesis of chronic inflammations of the bowel, such as Crohn's disease and colitis ulcerosa. Recently, sulfasalazine (SASP) and its metabolites have been reported to exert their effects as a direct scavenger of oxygen-centered radicals in the bowel. To scavenge oxygen-centered radicals in vivo, however, SASP and its metabolites have to react with O2- and/or .OH in vitro very rapidly, furthermore they have to reach an appropriate (possible millimolar) concentration range at the site of inflammation. To test this possibility, we investigated the direct O2- and .OH scavenging activity of SASP and its metabolites using the specific electron paramagnetic resonance/spin trapping method, and we compared the 50% inhibition rates of SASP and its metabolites with their known concentrations in the bowel and in the human plasma. It was found that SASP and its metabolites, such as 5-amino-salicylic acid (5-ASA), and acetyl-5-amino-salicylic acid (AC-5-ASA), but not sulfapyridine (SP) and acetyl-sulfapyridine (Ac-SP) have a direct O2- and .OH scavenging activity in vitro systems. Among the compounds, SASP and 5-ASA can reach a concentration which is appropriate to scavenge oxygen-centered radicals in the bowel but not in the human plasma. It was concluded that the in vivo antiinflammatory effects of SASP and its metabolites are, at least partly, due to the direct oxygen-centered scavenging activity of these drugs.

Free Radical Scavengers

[The role of oxidative stress, caused by amiodarone, in the side effects of the drug].

It was supposed that free radicals are produced during the metabolism of amiodarone and involved in the mechanism of the drug's side effects. In vitro and in vivo experiments were performed in rats to check this hypothesis. We verified that amiodarone generated free radicals in vitro by chemiluminometric method. The light emission induced by amiodarone was inhibited by dihydroquinoline type antioxidants CH 402 and MTDQ--DA in a dose dependent manner. The malondialdehyde content, --one of the end products of lipid peroxidation--was increased by in vivo amiodarone administration in the serum and liver homogenate of rats. Amiodarone treatment increased significantly the NADPH and Fe3+ induced lipid peroxidation in rat liver microsomal fractions. The protective effect of antioxidants, MTDQ--DA and silibinin were ambiguous in these in vivo "short term" experiments.

Amiodarone

Effect of the bioflavonoid silymarin on the in vitro activity and expression of superoxide dismutase (SOD) enzyme.

Superoxide dismutase activity and expression of the erythrocytes and lymphocytes of patients suffering from chronic alcoholic liver disease and those of healthy controls were investigated after in vitro incubation with silymarin. It was concluded that silymarin treatment in a concentration achievable by in vivo treatment (10 micrograms/ml) significantly increased the SOD activity of both the erythrocytes and lymphocytes of patients with liver disease, whereas the SOD expression of the lymphocytes enhanced to a considerable extent. These results indirectly indicate that the scavenger silymarin is able to increase the antioxidant protection of the cells by ameliorating the deleterious effects of free radical reactions.

Adult

[Immunomodulator effect of silymarin therapy in chronic alcoholic liver diseases].

The effects of the hepatoprotective, antioxidant drug silymarin (Legalon) on some cellular immune parameters of patients with histologically proven chronic alcoholic liver disease were studied in a six month double blind study. The lectin induced proliferative activity of the lymphocytes got enhanced, the originally low T cell percentage and the originally high CD8+ cell percentage have been normalized, the antibody-dependent and natural cytotoxicity of the lymphocytes decreased during silymarin therapy. All these changes were significant, while in the placebo group no significant changes occurred, except for a moderate elevation of the T cell percentage. Thus, the immunomodulatory activity of silymarin might be involved in the hepatoprotective action of the drug and improves the depressed immunoreactivity of the patients.

Adjuvants, Immunologic

[Effect of silimarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double blind protocol)].

A double blind study. Antioxidant and antiperoxidative effects of the free radical scavenger agent silymarin (Legalon) were investigated in patients with chronic alcoholic liver disease in a double blind clinical trial. Six month treatment (at a daily dose of 420 mg) with silymarin significantly enhanced the originally low superoxide dismutase activity of erythrocytes and lymphocytes and also restored the diminished superoxide dismutase expression on lymphocytes as measured by flow-cytofluorimetry. In addition, silymarin therapy markedly increased the serum level of ree--SH groups and the activity of glutathione peroxidase. In contrast, a considerable fall in serum malondialdehyde concentration was detected in patients having received silymarin. However, in case of placebo-treated patients the above mentioned parameters of antioxidant defense system and lipid peroxidation failed to change significantly. These data indirectly suggest that antioxidant, antiperoxidative effects might be important factors in the mechanism of hepatoprotective action of silymarin.

Double-Blind Method

Hepatoprotective and immunological effects of antioxidant drugs.

The hepatoprotective and immunomodulatory effects of silymarin and amino-imidazole-carboxamide-phosphate were studied in 40 patients with alcoholic cirrhosis of the liver in a one-month double-blind clinical trial. Treatment with either of the drugs normalized the elevated levels of aspartate aminotransferase, alanine aminotransferase and serum bilirubin, markedly reduced the high level of gamma-glutamyl transferase, increased lectin-induced lymphoblast transformation, decreased the percentage of OKT8+ cells and suppressed lymphocytotoxicity. None of these changes occurred in the placebo-treated group. Thus, the hepatoprotective effects of silymarin and amino-imidazole-carboxamide-phosphate in alcoholic cirrhosis can partly be attributed to the immunomodulatory activity of the drugs.

Adult

Immunomodulatory and hepatoprotective effects of in vivo treatment with free radical scavengers.

The hepatoprotective and immunomodulatory effects of silymarin and amino-imidazol-carboxamid-phosphate were studied in 60 patients with compensated alcoholic cirrhosis of the liver in a one month double blind clinical trial. Treatment with both drugs normalized the elevated levels of aspartate aminotransferase, alanine aminotransferase and serum bilirubin, markedly reduced the high level of gamma-glutamyl transferase, increased lectin-induced lymphoblasttransformation, decreased the percentage of CD8+ cells and suppressed lymphocytotoxicity. None of these changes occurred in the placebo-treated group. Thus the hepato-protective effects of silymarin and amino-imidazol-carboxamid-phosphate are accompanied by changes in parameters of cellular immunoreactivity of the treated patients.

Adjuvants, Immunologic

Effect of in vitro Aica-P treatment on certain cellular immune functions.

The effect of the hepatoprotective agent and protein synthesis stimulator 4-amino-5-imidazole-carboxamide-phosphate on the resynthesis of the "E" receptors of T lymphocytes and on certain immunological functions was investigated in vitro. Aica-P treatment enhanced the resynthesis of the "E" receptors after trypsin digestion and inhibited the blastic transformation of the lymphocytes. The results corroborate the observations that Aica-P is able to enhance protein synthesis and to exert immunomodulatory activity.

Adult

Effects of two bioflavonoids on certain cellular immune reactions in vitro.

Oxidative and autoaggressive immune processes are supposed to be involved in the pathogenesis of certain chronic liver diseases. In this study the effects of two naturally occurring antioxidant flavonoids, (+)cyanidanol-3 and silymarin, were determined on T and active T cell percentages, antigen-dependent (ADCC), lectin-dependent (LDCC) and natural (NK) cell mediated cytotoxicity and on lectin induced blast transformation of lymphocytes from healthy subjects and patients with chronic alcoholic liver disease in vitro. We observed no effects on T and active T cell percentages and on ADCC activity. Both drugs decreased LDCC activities of patients and lectin-induced lymphoblast transformation of controls and patients, (+)cyanidanol slightly and silymarin significantly decreased NK activities of controls and patients. These suppressive effects could partly be explained by the free radical scavenger and lipoxigenase inhibitor activity of the drugs and support the promising role of bioflavonoids in the treatment of chronic liver diseases.

Adult

In vitro effect of 4-amino-5-imidazole-carboxamide-phosphate (AICA-P) on the enzyme activity and expression of superoxide dismutase.

Antioxidant effects of a newly developed hepatoprotective agent 4-amino-5-imidazole-carboxamide-phosphate (Aica-P) were studied in an in vitro test system using isolated peripheral blood cells from patients with chronic alcoholic liver disease and from healthy controls. In vitro incubation with the drug in a concentration corresponding to the usual therapeutic dosage enhanced the superoxide dismutase (SOD) activity of erythrocytes and lymphocytes and also increased the superoxide dismutase expression on lymphocytes. These results indirectly suggest that antioxidant capacity may be one of the important factors in the mechanisms of hepatoprotective action of the imidazole derivate Aica-P.

Adult

In vivo effect of free radical scavenger hepatoprotective agents on superoxide dismutase (SOD) activity in patients.

The in vivo effects of two hepatoprotective antioxidants (silymarin, and 4-amino-5-imidazole-carboxamide-phosphate) on the expression and activity of superoxide dismutase (SOD) enzyme were studied in erythrocytes from patients with alcoholic cirrhosis. In vivo treatment with any of the drugs markedly increased the SOD expression of lymphocytes as measured by flow-cytofluorimetry following staining with monoclonal anti-Cu, Zn-SOD-antibody and FITC-conjugated anti-mouse Ig, as well as erythrocyte and lymphocyte SOD activities. The data indirectly suggest that antioxidant activity might be one of the important factors in the hepatoprotective action of these agents.

Adult

[Liver-protective action of silymarin therapy in chronic alcoholic liver diseases].

The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin-aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients.

Chronic Disease

Depressed monocyte production of interleukin-1 and tumor necrosis factor-alpha in patients with alcoholic liver cirrhosis.

Interleukin-1 and tumor necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes were studied in patients with chronic alcoholic liver disease. Monocytes from cirrhotic patients were shown to have a significant reduction in IL-1 and TNF-a activity, compared with that from age- and sex-matched healthy controls. These findings indicate further immunoregulatory disturbances concerning alcoholic liver cirrhosis.

Adult