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Biological and toxicological properties of leukemia inhibitory factor (LIF)
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42
of Abstmcts - EUROTOX ‘94
at 39 C. refracteric to treatment, simetrical deep tendon reflexes, bothsided pathological reflexes, no meninde?l symptoms. CT revealed internal and external hydrocephalus,no evidences of oedema. Blood analysis: leucocytosis up to 40 0001mm3 with prevalence of lymphocytes (up to 60%). Administered treatment with corticosteroids (1 mg&/24 h). B group vitamins, diuretic and general supportive treatment. Eye contact with patient disappeared few days later and contractures with spasticity added to clinical piciure. Patient died on 43rd day of treatment. Finding of autopsy: hydrocephalus.destruction of white substance. Key WL
carbon monoxide; encephalopathy
Biological and Toxicological Properties of Leukemia lnhbltory Fector (LIF) M. Kammirller. Drug Safety- Toxico~oogSSlNDOZ Pharma Ltd. CU-4002 Base4 Switzerland LIE a 55 to 60 kDa glycoprotein (approximately 75% homology between human and murine protein), has been shown to possess a remarkable spectrum of biological actions in vitro. The acronym LIF therefore also stands for ‘Lots of Interesting Functions’. LIF is produced by a variety of cells. It inhibits embryonic stem-cell differentiation, induces monocyte differentiation and myoblast proliferation, stimulates megakatyocyte maturation, induces acutephase proteins in hepatocytes [l]. induces cholinergicdifferentiation of mature sympathetic neurons and has effects on lipid and bone metabolism. LIF shares some of its activities with other cytokines, notably interleukin-6 (lL-6). oncostatin M and ciliary neurotrophic factor (CNTF). Recent data suggest that shared receptor components with signal-transducingactivityprovide a basis for common biological activities for these cytokines [2]. The actions of LIF appear not to be species-specific as known for some other cytokines. Adverse effects of murine recombinant LIF in mice have been described 13).Effects of recombinant human LIF in rats and mice will be discussed. [ 1) Mayer R Geissler K. Ward M. Metcalf D. Blood. 61,3226 (1993). [2] Gearing Dl? Adv. Immunol. 53.31 (1993). )3] Metcalf D. Nicola NA, Gearing DF! Blood, 76.50 (1990).
Chronic Oral Musk Xylene Specifically Induces Cytcxhrome P450 lA2 in Long Evans Rats M. Keller, U. Bijlsterli l, R. Eichenberger, U. Borer. H. Sedlacek*, W. Meier *, W. Lichtensteiger, M. Schlumpf. inst. of Phannacoloa Universityof ZQrich,Zfirigh; ’ Inst. of Toxicolosv.UniK of Ztirich, Schwenenbach; 2 Zirrich Cantonal Laboratow Z0rich The synthetic fragrance musk xylene. a lipophilicand highly resistant compound, is widely used in parfumes. detergents, soaps and lotions. It bioaccumulates in fish and has been detected recently also in human fat and milk. Fat concentrations and liver enzyme induction (CYP lA2.7-ethoxyresufin-0-dealkylase (EAOD)) were analyzed in Long Evans rats chronicallyfed for 7 or 12 weeks with food pellets containing various amounts of the pollutant (1 @kg. 0.1 g/kg, 0.01 glkg and 0.001 g/kg). EROD was determined in microsomal preparations of liver homogenates by spectrofluorimetry and musk xylene concentrations in fat was analyzed by gas chromatography with ECD detection. EROD activity was increased 2 to 3 fold in animals fed on 0.1 g/kg musk xylene and approximately 7 fold after exposure to a diet containing 1 g/kg. Enzyme activity and fat concentrations tended to be higher in fema!e vs. male rats.
Cadmium Interaction with l-Ascorbic Acid In Rats Ewa Kleszczewska.Department of Ana&ticaland Inorganic Chemist& Universityof Warsaw in Biatystok,Janina MoniuszkoJakoniuk InterfacultyDepanment of ToxicologyMedical Academy in Eia&tok. The aim of this paper was to estimate the levels of L-ascorbicacid concentrations in rats that were treated with cadmium (as cadmium chloride. 5 ppm. 50 ppm) and to provide an explanation on how cadmium interacts with H$~sc. Investigations were carried out on Wistar rats. Selected tissues and blaod plasma were analyzed. Determination of L-ascorbic acid concentrates were performed by flow-injection analysis methods using a spectrophotometric detector. We found a decrease of L-ascorbic acid level in serum and in tissues of rats intoxicated with cadmium at a dosage of 5 ppm. The most significant decrease was observed in liver (from 13.5 mg/fOO g to 9.0 mg/lOO g). We have examined the concentration levels of cadmium chloride, L-ascorbic acid and complex Cd (II) with HzAsc by the same spectrophotometric methods. We have found that the decrease of L-ascorbic acid levels depend on cadmium intoxication (50 ppm). which may suggest competitive binding of cadmium (central atom) by L-ascorbicacid (ligand) into a tight complex (LK = 6).
42
of Abstmcts - EUROTOX ‘94
at 39 C. refracteric to treatment, simetrical deep tendon reflexes, bothsided pathological reflexes, no meninde?l symptoms. CT revealed internal and external hydrocephalus,no evidences of oedema. Blood analysis: leucocytosis up to 40 0001mm3 with prevalence of lymphocytes (up to 60%). Administered treatment with corticosteroids (1 mg&/24 h). B group vitamins, diuretic and general supportive treatment. Eye contact with patient disappeared few days later and contractures with spasticity added to clinical piciure. Patient died on 43rd day of treatment. Finding of autopsy: hydrocephalus.destruction of white substance. Key WL
carbon monoxide; encephalopathy
Biological and Toxicological Properties of Leukemia lnhbltory Fector (LIF) M. Kammirller. Drug Safety- Toxico~oogSSlNDOZ Pharma Ltd. CU-4002 Base4 Switzerland LIE a 55 to 60 kDa glycoprotein (approximately 75% homology between human and murine protein), has been shown to possess a remarkable spectrum of biological actions in vitro. The acronym LIF therefore also stands for ‘Lots of Interesting Functions’. LIF is produced by a variety of cells. It inhibits embryonic stem-cell differentiation, induces monocyte differentiation and myoblast proliferation, stimulates megakatyocyte maturation, induces acutephase proteins in hepatocytes [l]. induces cholinergicdifferentiation of mature sympathetic neurons and has effects on lipid and bone metabolism. LIF shares some of its activities with other cytokines, notably interleukin-6 (lL-6). oncostatin M and ciliary neurotrophic factor (CNTF). Recent data suggest that shared receptor components with signal-transducingactivityprovide a basis for common biological activities for these cytokines [2]. The actions of LIF appear not to be species-specific as known for some other cytokines. Adverse effects of murine recombinant LIF in mice have been described 13).Effects of recombinant human LIF in rats and mice will be discussed. [ 1) Mayer R Geissler K. Ward M. Metcalf D. Blood. 61,3226 (1993). [2] Gearing Dl? Adv. Immunol. 53.31 (1993). )3] Metcalf D. Nicola NA, Gearing DF! Blood, 76.50 (1990).
Chronic Oral Musk Xylene Specifically Induces Cytcxhrome P450 lA2 in Long Evans Rats M. Keller, U. Bijlsterli l, R. Eichenberger, U. Borer. H. Sedlacek*, W. Meier *, W. Lichtensteiger, M. Schlumpf. inst. of Phannacoloa Universityof ZQrich,Zfirigh; ’ Inst. of Toxicolosv.UniK of Ztirich, Schwenenbach; 2 Zirrich Cantonal Laboratow Z0rich The synthetic fragrance musk xylene. a lipophilicand highly resistant compound, is widely used in parfumes. detergents, soaps and lotions. It bioaccumulates in fish and has been detected recently also in human fat and milk. Fat concentrations and liver enzyme induction (CYP lA2.7-ethoxyresufin-0-dealkylase (EAOD)) were analyzed in Long Evans rats chronicallyfed for 7 or 12 weeks with food pellets containing various amounts of the pollutant (1 @kg. 0.1 g/kg, 0.01 glkg and 0.001 g/kg). EROD was determined in microsomal preparations of liver homogenates by spectrofluorimetry and musk xylene concentrations in fat was analyzed by gas chromatography with ECD detection. EROD activity was increased 2 to 3 fold in animals fed on 0.1 g/kg musk xylene and approximately 7 fold after exposure to a diet containing 1 g/kg. Enzyme activity and fat concentrations tended to be higher in fema!e vs. male rats.
Cadmium Interaction with l-Ascorbic Acid In Rats Ewa Kleszczewska.Department of Ana&ticaland Inorganic Chemist& Universityof Warsaw in Biatystok,Janina MoniuszkoJakoniuk InterfacultyDepanment of ToxicologyMedical Academy in Eia&tok. The aim of this paper was to estimate the levels of L-ascorbicacid concentrations in rats that were treated with cadmium (as cadmium chloride. 5 ppm. 50 ppm) and to provide an explanation on how cadmium interacts with H$~sc. Investigations were carried out on Wistar rats. Selected tissues and blaod plasma were analyzed. Determination of L-ascorbic acid concentrates were performed by flow-injection analysis methods using a spectrophotometric detector. We found a decrease of L-ascorbic acid level in serum and in tissues of rats intoxicated with cadmium at a dosage of 5 ppm. The most significant decrease was observed in liver (from 13.5 mg/fOO g to 9.0 mg/lOO g). We have examined the concentration levels of cadmium chloride, L-ascorbic acid and complex Cd (II) with HzAsc by the same spectrophotometric methods. We have found that the decrease of L-ascorbic acid levels depend on cadmium intoxication (50 ppm). which may suggest competitive binding of cadmium (central atom) by L-ascorbicacid (ligand) into a tight complex (LK = 6).