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  1. AU="Franzén, Anna"
  2. AU=Klonoff David C
  3. AU="DeCobelli, Francesco"
  4. AU="Zhang, KaiDong"

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  1. Article ; Online: The association of copeptin with metabolic risk markers is modified by region of origin.

    Franzén, Anna / Pikkemaat, Miriam / Melander, Olle / Bennet, Louise / Enhörning, Sofia

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 19651

    Abstract: Iraqi born immigrants in Sweden have higher prevalence of metabolic diseases compared to native Swedes. Copeptin, a marker for vasopressin, is associated with increased risk of metabolic disease. In this cross-sectional population study based on the ... ...

    Abstract Iraqi born immigrants in Sweden have higher prevalence of metabolic diseases compared to native Swedes. Copeptin, a marker for vasopressin, is associated with increased risk of metabolic disease. In this cross-sectional population study based on the MEDIM cohort we investigated differences in copeptin levels between Iraqi and Swedish born individuals and if the association between copeptin and cardiometabolic risk markers differed by region of origin. We included 1109 Iraqi and 613 Swedish born participants (58% men, mean age 47 years). The Swedish participants had a higher concentration of copeptin compared to the Iraqi born group after age and sex adjustment (p < 0.001). This difference existed only among male individuals with the highest copeptin concentrations, i.e. belonging to copeptin quartile 4 (median (25th; 75th percentile) 20.07 (15.27;33.28) pmol/L for the Swedish born versus 15.57 (13.91;19.00) pmol/L for the Iraqi born, p < 0.001). We found a significant interaction between copeptin (continuous ln-transformed) and being born in Iraq regarding the association with plasma triglycerides (P
    MeSH term(s) Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Glycopeptides ; Sweden/epidemiology ; Metabolic Diseases
    Chemical Substances copeptins ; Glycopeptides
    Language English
    Publishing date 2023-11-10
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-46908-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Toxicant-induced ER-stress and caspase activation in the olfactory mucosa.

    Franzén, Anna / Brittebo, Eva B

    Archives of toxicology

    2005  Volume 79, Issue 10, Page(s) 561–570

    Abstract: The potent olfactory toxicant 2,6-dichlorophenyl methylsulphone (2,6-diClPh-MeSO(2)) induces rapid cell death and long-term metaplastic changes in the olfactory regions of rodents. The damage is related to a tissue-specific and extensive cytochrome P450 ( ...

    Abstract The potent olfactory toxicant 2,6-dichlorophenyl methylsulphone (2,6-diClPh-MeSO(2)) induces rapid cell death and long-term metaplastic changes in the olfactory regions of rodents. The damage is related to a tissue-specific and extensive cytochrome P450 (CYP)-mediated metabolic activation of the compound to reactive intermediates. The aim of the present study was to examine the early, cell-specific changes leading to cell death in the olfactory mucosa of mice exposed to 2,6-diClPh-MeSO(2). We have examined the expression of the ER-specific stress protein GRP78, the presence of secretory glycoproteins, and the cellular activation of the initiator caspase 12 and the downstream effector caspase 3. 2,6-DiClPh-MeSO(2) induced rapid and cell-specific expression of GRP78, and activation of caspases 12 and 3 in the Bowman's glands. No similar early onset changes in the neuroepithelium were observed. Based on these results, we propose that extensive lesions are initiated in the Bowman's glands and that the metabolic activation of 2,6-diClPh-MeSO(2) elicits ER-stress response and subsequent apoptotic signaling at this site. Since most of the Bowman's glands had oncotic morphology, the results suggest that the terminal phase of apoptosis was blocked and that these glands finally succumb to other routes of cell death.
    MeSH term(s) Animals ; Apoptosis ; Benzene Derivatives/administration & dosage ; Benzene Derivatives/toxicity ; Caspase 12 ; Caspase 3 ; Caspases/metabolism ; Chlorobenzenes/administration & dosage ; Chlorobenzenes/toxicity ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/enzymology ; Enzyme Activation/drug effects ; Female ; Glycoproteins/metabolism ; Heat-Shock Proteins/metabolism ; Immunohistochemistry ; Mice ; Molecular Chaperones/metabolism ; Necrosis ; Neuroepithelial Cells/drug effects ; Neuroepithelial Cells/metabolism ; Neuroepithelial Cells/pathology ; Olfactory Mucosa/drug effects ; Olfactory Mucosa/enzymology ; Olfactory Mucosa/pathology ; Sulfones ; Time Factors
    Chemical Substances 2,6-dichlorophenyl methylsulfone ; Benzene Derivatives ; Chlorobenzenes ; Glycoproteins ; Heat-Shock Proteins ; Molecular Chaperones ; Sulfones ; molecular chaperone GRP78 ; Casp12 protein, mouse (EC 3.4.22.-) ; Casp3 protein, mouse (EC 3.4.22.-) ; Caspase 12 (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2005-10
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 124992-7
    ISSN 1432-0738 ; 0340-5761
    ISSN (online) 1432-0738
    ISSN 0340-5761
    DOI 10.1007/s00204-005-0670-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uf I Zs.90: Show issues Location:
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  3. Article: Isomer-specific bioactivation and toxicity of dichlorophenyl methylsulphone in rat olfactory mucosa.

    Franzén, Anna / Carlsson, Carina / Brandt, Ingvar / Brittebo, Eva B

    Toxicologic pathology

    2003  Volume 31, Issue 4, Page(s) 364–372

    Abstract: This study aimed to explain the isomer- and site-specific toxic effects of dichlorophenyl methylsulphone in the olfactory mucosa of rats. A single ip dose of the 2,6-chlorinated isomer (16 or 65 mg/kg) induced necrosis preferentially in the Bowman's ... ...

    Abstract This study aimed to explain the isomer- and site-specific toxic effects of dichlorophenyl methylsulphone in the olfactory mucosa of rats. A single ip dose of the 2,6-chlorinated isomer (16 or 65 mg/kg) induced necrosis preferentially in the Bowman's glands and neuroepithelium in the dorsomedial part of the olfactory region. Only minor damage occurred at this site in rats dosed with the 2,5-chlorinated isomer (65 mg/kg). A strong concentration- and time-dependent covalent binding of the (14)C-labeled 2,6-isomer to rat olfactory microsomes was demonstrated. In contrast, no significant covalent binding of the (14)C-labeled 2,5-isomer was observed. The cytochrome P450 (CYP) inhibitors metyrapone, tranylcypromine and acetonitrile inhibited covalent binding of the 2,6-isomer to olfactory microsomes. Glutathione (GSH) appeared to play a protective role as a scavenger of a reactive intermediate whereas methyl-GSH did not alter covalent binding to olfactory microsomes. As determined by microautoradiography, binding of the 2,6-chlorinated isomer in the olfactory mucosa was confined to the Bowman's glands. Both isomers showed a low binding to liver microsomes and caused no liver injury. We suggest that a CYP2A-catalyzed activation of the 2,6-chlorinated dichlorophenyl methylsulphone to a reactive intermediate and adduct formation in the Bowman's glands will initiate a site-specific toxicity of this isomer in the olfactory mucosa.
    MeSH term(s) Animals ; Aryl Hydrocarbon Hydroxylases/drug effects ; Autoradiography ; Biotransformation/drug effects ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Female ; Glutathione/pharmacology ; Isomerism ; Microsomes/drug effects ; Microsomes/metabolism ; Necrosis ; Olfactory Mucosa/drug effects ; Olfactory Mucosa/pathology ; Polychlorinated Biphenyls/chemistry ; Polychlorinated Biphenyls/metabolism ; Polychlorinated Biphenyls/toxicity ; Rats ; Rats, Sprague-Dawley ; Steroid Hydroxylases/drug effects ; Time Factors
    Chemical Substances Enzyme Inhibitors ; Polychlorinated Biphenyls (DFC2HB4I0K) ; Steroid Hydroxylases (EC 1.14.-) ; Aryl Hydrocarbon Hydroxylases (EC 1.14.14.1) ; steroid hormone 7-alpha-hydroxylase (EC 1.14.14.1) ; Glutathione (GAN16C9B8O)
    Language English
    Publishing date 2003-07
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 841009-4
    ISSN 0192-6233
    ISSN 0192-6233
    DOI 10.1080/01926230390201075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1975: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 473: Show issues

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  4. Article: CYP2A5-mediated activation and early ultrastructural changes in the olfactory mucosa: studies on 2,6-dichlorophenyl methylsulfone.

    Franzén, Anna / Carlsson, Carina / Hermansson, Veronica / Lang, Matti / Brittebo, Eva B

    Drug metabolism and disposition: the biological fate of chemicals

    2006  Volume 34, Issue 1, Page(s) 61–68

    Abstract: 2,6-Dichlorophenyl methylsulfone (2,6-diClPh-MeSO2) is a potent olfactory toxicant reported to induce endoplasmic reticulum (ER) stress, caspase activation, and extensive cell death in mice. The aim of the present study was to examine cytochrome P450 ( ... ...

    Abstract 2,6-Dichlorophenyl methylsulfone (2,6-diClPh-MeSO2) is a potent olfactory toxicant reported to induce endoplasmic reticulum (ER) stress, caspase activation, and extensive cell death in mice. The aim of the present study was to examine cytochrome P450 (P450)-dependent bioactivation, nonprotein sulfhydryl (NP-SH) levels, and early ultrastructural changes in mouse olfactory mucosa following an i.p. injection of 2,6-diClPh-MeSO2 (32 mg/kg). A high covalent binding of 2,6-diClPh-14C-MeSO2 in olfactory mucosa S9 fraction was observed, and the CYP2A5/CYP2G1 substrates coumarin and dichlobenil significantly decreased the binding, whereas the CYP2E1 substrate chlorzoxazone had no effects. An increased bioactivation was detected in liver microsomes of mice pretreated with pyrazole, known to induce CYP2A4, 2A5, 2E1, and 2J, and addition of chlorzoxazone reduced this binding. 2,6-DiClPh-14C-MeSO2 showed a marked covalent binding to microsomes of recombinant yeast cells expressing mouse CYP2A5 or human CYP2A6 compared with wild type. One and 4 h after a single injection of 2,6-diClPh-MeSO2, the NP-SH levels in the olfactory mucosa were significantly reduced compared with control, whereas there was no change in the liver. Ultrastructural studies revealed that ER, mitochondria, and secretory granules in nonneuronal cells were early targets 1 h after injection. We propose that lesions induced by 2,6-diClPh-MeSO2 in the mouse olfactory mucosa were initiated by a P450-mediated bioactivation in the Bowman's glands and depletion of NP-SH levels, leading to disruption of ion homeostasis, organelle swelling, and cell death. The high expression of CYP2A5 in the olfactory mucosa is suggested to play a key role for the tissue-specific toxicity induced by 2,6-diClPh-MeSO2.
    MeSH term(s) Animals ; Aryl Hydrocarbon Hydroxylases/antagonists & inhibitors ; Aryl Hydrocarbon Hydroxylases/metabolism ; Benzene Derivatives/antagonists & inhibitors ; Benzene Derivatives/metabolism ; Benzene Derivatives/toxicity ; Chlorzoxazone/pharmacology ; Coumarins/pharmacology ; Cytochrome P-450 CYP2A6 ; Cytochrome P450 Family 2 ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/ultrastructure ; Female ; Injections, Intraperitoneal ; Liver/chemistry ; Liver/drug effects ; Liver/metabolism ; Metyrapone/pharmacology ; Mice ; Microscopy, Electron, Transmission ; Microsomes, Liver/drug effects ; Microsomes, Liver/metabolism ; Mixed Function Oxygenases/antagonists & inhibitors ; Mixed Function Oxygenases/metabolism ; Nitriles/pharmacology ; Olfactory Mucosa/drug effects ; Olfactory Mucosa/metabolism ; Olfactory Mucosa/ultrastructure ; Pyrazoles/pharmacology ; Sulfhydryl Compounds/metabolism ; Sulfones/administration & dosage ; Sulfones/antagonists & inhibitors ; Sulfones/metabolism ; Sulfones/toxicity
    Chemical Substances 2,6-dichlorophenyl methylsulfone ; Benzene Derivatives ; Coumarins ; Nitriles ; Pyrazoles ; Sulfhydryl Compounds ; Sulfones ; pyrazole (3QD5KJZ7ZJ) ; coumarin (A4VZ22K1WT) ; Mixed Function Oxygenases (EC 1.-) ; Aryl Hydrocarbon Hydroxylases (EC 1.14.14.1) ; CYP2A6 protein, human (EC 1.14.14.1) ; Cyp2a5 protein, mouse (EC 1.14.14.1) ; Cytochrome P-450 CYP2A6 (EC 1.14.14.1) ; Cytochrome P450 Family 2 (EC 1.14.14.1) ; Chlorzoxazone (H0DE420U8G) ; dichlobanil (N42NR4196R) ; Metyrapone (ZS9KD92H6V)
    Language English
    Publishing date 2006-01
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.105.006221
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1014: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  5. Article: Cell-specific expression of CYP2A5 in the mouse respiratory tract: effects of olfactory toxicants.

    Piras, Elena / Franzén, Anna / Fernández, Estíbaliz L / Bergström, Ulrika / Raffalli-Mathieu, Françoise / Lang, Matti / Brittebo, Eva B

    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society

    2003  Volume 51, Issue 11, Page(s) 1545–1555

    Abstract: We performed a detailed analysis of mouse cytochrome P450 2A5 (CYP2A5) expression by in situ hybridization (ISH) and immunohistochemistry (IHC) in the respiratory tissues of mice. The CYP2A5 mRNA and the corresponding protein co-localized at most sites ... ...

    Abstract We performed a detailed analysis of mouse cytochrome P450 2A5 (CYP2A5) expression by in situ hybridization (ISH) and immunohistochemistry (IHC) in the respiratory tissues of mice. The CYP2A5 mRNA and the corresponding protein co-localized at most sites and were predominantly detected in the olfactory region, with an expression in sustentacular cells, Bowman's gland, and duct cells. In the respiratory and transitional epithelium there was no or only weak expression. The nasolacrimal duct and the excretory ducts of nasal and salivary glands displayed expression, whereas no expression occurred in the acini. There was decreasing expression along the epithelial linings of the trachea and lower respiratory tract, whereas no expression occurred in the alveoli. The hepatic CYP2A5 inducers pyrazole and phenobarbital neither changed the CYP2A5 expression pattern nor damaged the olfactory mucosa. In contrast, the olfactory toxicants dichlobenil and methimazole induced characteristic changes. The damaged Bowman's glands displayed no expression, whereas the damaged epithelium expressed the enzyme. The CYP2A5 expression pattern is in accordance with previously reported localization of protein and DNA adducts and the toxicity of some CYP2A5 substrates. This suggests that CYP2A5 is an important determinant for the susceptibility of the nasal and respiratory epithelia to protoxicants and procarcinogens.
    MeSH term(s) Animals ; Aryl Hydrocarbon Hydroxylases/biosynthesis ; Cytochrome P-450 CYP2A6 ; Cytochrome P450 Family 2 ; Environmental Pollutants/toxicity ; Enzyme Induction ; Female ; Immunohistochemistry ; In Situ Hybridization ; Male ; Methimazole/toxicity ; Mice ; Mice, Inbred DBA ; Mixed Function Oxygenases/biosynthesis ; Nasolacrimal Duct/cytology ; Nasolacrimal Duct/drug effects ; Nasolacrimal Duct/metabolism ; Nitriles/toxicity ; Olfactory Mucosa/cytology ; Olfactory Mucosa/drug effects ; Olfactory Mucosa/metabolism ; Phenobarbital/toxicity ; Pyrazoles/toxicity ; Respiratory System/cytology ; Respiratory System/drug effects ; Respiratory System/metabolism ; Salivary Glands/cytology ; Salivary Glands/drug effects ; Salivary Glands/metabolism
    Chemical Substances Environmental Pollutants ; Nitriles ; Pyrazoles ; pyrazole (3QD5KJZ7ZJ) ; Methimazole (554Z48XN5E) ; Mixed Function Oxygenases (EC 1.-) ; Aryl Hydrocarbon Hydroxylases (EC 1.14.14.1) ; Cyp2a5 protein, mouse (EC 1.14.14.1) ; Cytochrome P-450 CYP2A6 (EC 1.14.14.1) ; Cytochrome P450 Family 2 (EC 1.14.14.1) ; dichlobanil (N42NR4196R) ; Phenobarbital (YQE403BP4D)
    Language English
    Publishing date 2003-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218208-7
    ISSN 1551-5044 ; 0022-1554
    ISSN (online) 1551-5044
    ISSN 0022-1554
    DOI 10.1177/002215540305101114
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.321: Show issues Location:
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