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Article: Cellulite disséquante du cuir chevelu: étude rétrospective de 7 cas confirmant l'efficacité de l'isotrétinoïne per os.

Koudoukpo, C / Abdennader, S / Cavelier-Balloy, B / Gasnier, C / Yédomon, H

Annales de dermatologie et de venereologie

2014 Volume 141, Issue 8-9, Page(s) 500–506

Abstract: Background: Dissecting cellulitis of the scalp (DCS) is a rare and long-standing disease and its aetiopathogenesis remains unclear. Various therapeutic alternatives exist. We attempted to assess the efficacy of oral isotretinoin in a series of patients.! ...

Title translation	Dissecting cellulitis of the scalp: a retrospective study of 7 cases confirming the efficacy of oral isotretinoin.
Abstract	Background: Dissecting cellulitis of the scalp (DCS) is a rare and long-standing disease and its aetiopathogenesis remains unclear. Various therapeutic alternatives exist. We attempted to assess the efficacy of oral isotretinoin in a series of patients. Patients and methods: Seven cases of DCS followed and treated by one of the authors at the Sabouraud Centre in the Saint-Louis Hospital between 2007 and 2013 were retrospectively studied and the efficacy of oral isotretinoin was evaluated. Results: The seven patients included were males aged between 22 and 39 years, with alopecic nodules on the occiput (two cases) or the top of the vertex (five cases). Most patients were given oral isotretinoin at a dosage of 0.75mg/kg/day for at least nine months. The outcome was satisfactory with complete healing of the lesions and good regrowth in all cases. Follow-up after recovery lasted between 16 and 42 months. Conclusion: Based on published studies and the results of the present study, oral isotretinoin at a dose of 0.75mg/kg/day may be proposed as first-line treatment for DCS.
MeSH term(s)	Administration, Oral ; Adult ; Cellulitis/drug therapy ; Dermatologic Agents/administration & dosage ; Humans ; Isotretinoin/administration & dosage ; Male ; Retrospective Studies ; Scalp Dermatoses/drug therapy ; Young Adult
Chemical Substances	Dermatologic Agents ; Isotretinoin (EH28UP18IF)
Language	French
Publishing date	2014-08
Publishing country	France
Document type	English Abstract ; Evaluation Studies ; Journal Article
ZDB-ID	391805-1
ISSN	2214-5451 ; 0151-9638
ISSN (online)	2214-5451
ISSN	0151-9638
DOI	10.1016/j.annder.2014.06.007
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Article: Time- and dose-dependent effects of roundup on human embryonic and placental cells.

Benachour, N / Sipahutar, H / Moslemi, S / Gasnier, C / Travert, C / Séralini, G E

Archives of environmental contamination and toxicology

2007 Volume 53, Issue 1, Page(s) 126–133

Abstract: Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental- ... ...

Abstract	Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.
MeSH term(s)	Animals ; Aromatase/metabolism ; Aromatase Inhibitors/toxicity ; Cell Line ; Cell Line, Tumor ; Cell Survival/drug effects ; Glycine/analogs & derivatives ; Glycine/toxicity ; Horses ; Humans ; Kidney/embryology ; Kidney/enzymology ; Male ; Microsomes/enzymology ; Oxidoreductases/metabolism ; Placenta/enzymology ; Testis/enzymology ; Time Factors ; Glyphosate
Chemical Substances	Aromatase Inhibitors ; Oxidoreductases (EC 1.-) ; Aromatase (EC 1.14.14.1) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2007-05-04
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185986-9
ISSN	1432-0703 ; 0090-4341
ISSN (online)	1432-0703
ISSN	0090-4341
DOI	10.1007/s00244-006-0154-8
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Article ; Online: Cost-effectiveness evaluation of pre-counseling telephone interviews before face-to-face genetic counseling in cancer genetics.

Collet, Gaëlle / Parodi, Nathalie / Cassinari, Kevin / Neviere, Zoe / Cohen, Fanny / Gasnier, Céline / Brahimi, Afane / Lecoquierre, François / Thery, Jean-Christophe / Tennevet, Isabelle / Lacaze, Elodie / Berthet, Pascaline / Frebourg, Thierry

Familial cancer

2017 Volume 17, Issue 3, Page(s) 451–457

Abstract: One of the main challenges in cancer genetics is responding to the exponential demand for genetic counseling, especially in patients with breast and/or ovarian cancer. To address this demand, we have set up a new procedure, based on pre-genetic ... ...

Abstract	One of the main challenges in cancer genetics is responding to the exponential demand for genetic counseling, especially in patients with breast and/or ovarian cancer. To address this demand, we have set up a new procedure, based on pre-genetic counseling telephone interviews (PTI) followed by routing of patients: D1, a PTI is scheduled within 14 days; D7-D14, genetic counselors perform a 20 min PTI in order to establish a pre-genetic counseling file, by collecting personal and family medical history via a structured questionnaire and; D10-17, routing: pre-genetic counseling appointment files are analyzed by a cancer geneticist with 3 possible conclusions: (a) priority face-to-face genetic counseling (FTFGC) appointment with a cancer geneticist, if the genetic test results have an immediate therapeutic impact; (b) non-priority FTFGC with a genetic counselor, or (c) no FTFGC required or substitution by a more appropriate index case. In the context of breast and/or ovarian cancer, 1012 patients received PTIs, 39.1% of which did not lead to FTFGC. The mean delay for non-priority FTFGC was maintained at 18 weeks and priority FTFGC appointments were guaranteed within 8 weeks. The required resources for 1012 patients was estimated at 0.12 FTE secretaries, 0.62 FTE genetic counselors and 0.08 FTE cancer geneticists and the procedure was shown to be cost-effective. This new procedure allows the suppression of up to 1/3 of appointments, guarantees priority for appointments with therapeutic impact and optimizes the interaction and breakdown of tasks between genetic counselors and cancer geneticists.
MeSH term(s)	Breast Neoplasms/genetics ; Cost-Benefit Analysis ; Female ; Genetic Counseling/economics ; Genetic Counseling/methods ; Genetic Predisposition to Disease ; Humans ; Interviews as Topic/methods ; Ovarian Neoplasms/genetics ; Telephone
Language	English
Publishing date	2017-10-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1502496-9
ISSN	1573-7292 ; 1389-9600
ISSN (online)	1573-7292
ISSN	1389-9600
DOI	10.1007/s10689-017-0049-z
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Zs.A 6099: Show issues

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Article ; Online: Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines.

Gasnier, Céline / Dumont, Coralie / Benachour, Nora / Clair, Emilie / Chagnon, Marie-Christine / Séralini, Gilles-Eric

Toxicology

2009 Volume 262, Issue 3, Page(s) 184–191

Abstract: Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, ...

Abstract	Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, modified to tolerate high levels of these compounds in their cells. Up to 400 ppm of their residues are accepted in some feed. We exposed human liver HepG2 cells, a well-known model to study xenobiotic toxicity, to four different formulations and to glyphosate, which is usually tested alone in chronic in vivo regulatory studies. We measured cytotoxicity with three assays (Alamar Blue, MTT, ToxiLight), plus genotoxicity (comet assay), anti-estrogenic (on ERalpha, ERbeta) and anti-androgenic effects (on AR) using gene reporter tests. We also checked androgen to estrogen conversion by aromatase activity and mRNA. All parameters were disrupted at sub-agricultural doses with all formulations within 24h. These effects were more dependent on the formulation than on the glyphosate concentration. First, we observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor in MDA-MB453-kb2 cells for the most active formulation (R400), then from 2 ppm the transcriptional activities on both estrogen receptors were also inhibited on HepG2. Aromatase transcription and activity were disrupted from 10 ppm. Cytotoxic effects started at 10 ppm with Alamar Blue assay (the most sensitive), and DNA damages at 5 ppm. A real cell impact of glyphosate-based herbicides residues in food, feed or in the environment has thus to be considered, and their classifications as carcinogens/mutagens/reprotoxics is discussed.
MeSH term(s)	Adolescent ; Aromatase/drug effects ; Aromatase/genetics ; Aromatase/metabolism ; Cell Line, Tumor ; Comet Assay ; DNA Damage/drug effects ; Dose-Response Relationship, Drug ; Endocrine Disruptors/administration & dosage ; Endocrine Disruptors/toxicity ; Estrogen Receptor alpha/drug effects ; Estrogen Receptor alpha/metabolism ; Estrogen Receptor beta/drug effects ; Estrogen Receptor beta/metabolism ; Genes, Reporter/drug effects ; Glycine/administration & dosage ; Glycine/analogs & derivatives ; Glycine/toxicity ; Herbicides/administration & dosage ; Herbicides/toxicity ; Humans ; Male ; Pesticide Residues/toxicity ; RNA, Messenger/metabolism ; Receptors, Androgen/drug effects ; Receptors, Androgen/metabolism ; Toxicity Tests/methods ; Transcription, Genetic/drug effects ; Glyphosate
Chemical Substances	Endocrine Disruptors ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Herbicides ; Pesticide Residues ; RNA, Messenger ; Receptors, Androgen ; Aromatase (EC 1.14.14.1) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2009-06-17
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2009.06.006
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Article: Time- and Dose-Dependent Effects of Roundup on Human Embryonic and Placental Cells

Benachour, N / Sipahutar, H / Moslemi, S / Gasnier, C / Travert, C / Séralini, G. E

Archives of environmental contamination and toxicology. 2007 July, v. 53, no. 1

2007

Abstract: Roundup® is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce®) on human embryonic 293 and ... ...

Abstract	Roundup® is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce®) on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD₅₀) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 μM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.
Keywords	acidity ; active ingredients ; adjuvants ; fetal development ; glyphosate ; human reproduction ; humans ; kidneys ; lethal dose ; placenta ; pollutants ; synergism ; testes ; toxicity testing ; transgenic plants ; unspecific monooxygenase
Language	English
Dates of publication	2007-07
Size	p. 126-133.
Publisher	Springer-Verlag
Publishing place	New York
Document type	Article
ZDB-ID	185986-9
ISSN	1432-0703 ; 0090-4341
ISSN (online)	1432-0703
ISSN	0090-4341
DOI	10.1007/s00244-006-0154-8
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Article ; Online: Defined plant extracts can protect human cells against combined xenobiotic effects.

Gasnier, Céline / Laurant, Claire / Decroix-Laporte, Cécile / Mesnage, Robin / Clair, Emilie / Travert, Carine / Séralini, Gilles-Eric

Journal of occupational medicine and toxicology (London, England)

2011 Volume 6, Issue 1, Page(s) 3

Abstract: Background: Pollutants representative of common environmental contaminants induce intracellular toxicity in human cells, which is generally amplified in combinations. We wanted to test the common pathways of intoxication and detoxification in human ... ...

Abstract	Background: Pollutants representative of common environmental contaminants induce intracellular toxicity in human cells, which is generally amplified in combinations. We wanted to test the common pathways of intoxication and detoxification in human embryonic and liver cell lines. We used various pollutants such as Roundup residues, Bisphenol-A and Atrazine, and five precise medicinal plant extracts called Circ1, Dig1, Dig2, Sp1, and Uro1 in order to understand whether specific molecular actions took place or not. Methods: Kidney and liver are major detoxification organs. We have studied embryonic kidney and hepatic human cell lines E293 and HepG2. The intoxication was induced on the one hand by a formulation of one of the most common herbicides worldwide, Roundup 450 GT+ (glyphosate and specific adjuvants), and on the other hand by a mixture of Bisphenol-A and Atrazine, all found in surface waters, feed and food. The prevention and curative effects of plant extracts were also measured on mitochondrial succinate dehydrogenase activity, on the entry of radiolabelled glyphosate (in Roundup) in cells, and on cytochromes P450 1A2 and 3A4 as well as glutathione-S-transferase. Results: Clear toxicities of pollutants were observed on both cell lines at very low sub-agricultural dilutions. The prevention of such phenomena took place within 48 h with the plant extracts tested, with success rates ranging between 25-34% for the E293 intoxicated by Roundup, and surprisingly up to 71% for the HepG2. By contrast, after intoxication, no plant extract was capable of restoring E293 viability within 48 h, however, two medicinal plant combinations did restore the Bisphenol-A/Atrazine intoxicated HepG2 up to 24-28%. The analysis of underlying mechanisms revealed that plant extracts were not capable of preventing radiolabelled glyphosate from entering cells; however Dig2 did restore the CYP1A2 activity disrupted by Roundup, and had only a mild preventive effect on the CYP3A4, and no effect on the glutathione S-transferase. Conclusions: Environmental pollutants have intracellular effects that can be prevented, or cured in part, by precise medicinal plant extracts in two human cell lines. This appears to be mediated at least in part by the cytochromes P450 modulation.
Language	English
Publishing date	2011-01-20
Publishing country	England
Document type	Journal Article
ISSN	1745-6673
ISSN (online)	1745-6673
DOI	10.1186/1745-6673-6-3
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Article ; Online: Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines.

Gasnier, Céline / Benachour, Nora / Clair, Emilie / Travert, Carine / Langlois, Frédéric / Laurant, Claire / Decroix-Laporte, Cécile / Séralini, Gilles-Eric

Journal of occupational medicine and toxicology (London, England)

2010 Volume 5, Page(s) 29

Abstract: Background: Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface ... ...

Abstract	Background: Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts called Dig1. Methods: The cytotoxicity pathways of four formulations of glyphosate-based herbicides were studied using human hepatic cell lines HepG2 and Hep3B, known models to study xenobiotic effects. We monitored mitochondrial succinate dehydrogenase activity and caspases 3/7 for cell mortality and protection by Dig1, as well as cytochromes P450 1A1, 1A2, 3A4 and 2C9 and glutathione-S-transferase to approach the mechanism of actions. Results: All the four Roundup formulations provoke liver cell death, with adjuvants having stronger effects than glyphosate alone. Hep3B are 3-5 times more sensitive over 48 h. Caspases 3/7 are greatly activated in HepG2 by Roundup at non-cytotoxic levels, and some apoptosis induction by Roundup is possible together with necrosis. CYP3A4 is specifically enhanced by Roundup at doses 400 times less than used in agriculture (2%). CYP1A2 is increased to a lesser extent together with glutathione-S-transferase (GST) down-regulation. Dig 1, non cytotoxic and not inducing caspases by itself, is able to prevent Roundup-induced cell death in a time-dependant manner with an important efficiency of up to 89%, within 48 h. In addition, we evidenced that it prevents Caspases 3/7 activation and CYP3A4 enhancement, and not GST reduction, but in turn it slightly inhibited CYP2C9 when added before Roundup. Conclusion: Roundup is able to provoke intracellular disruption in hepatic cell lines at different levels, but a mixture of medicinal plant extracts Dig1 can protect to some extent human cell lines against this pollutants. All this system constitutes a tool for studying liver intoxication and detoxification.
Language	English
Publishing date	2010-10-27
Publishing country	England
Document type	Journal Article
ISSN	1745-6673
ISSN (online)	1745-6673
DOI	10.1186/1745-6673-5-29
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Article ; Online: The antimicrobial peptides derived from chromogranin/secretogranin family, new actors of innate immunity.

Shooshtarizadeh, Peiman / Zhang, Dan / Chich, Jean-François / Gasnier, Claire / Schneider, Francis / Haïkel, Youssef / Aunis, Dominique / Metz-Boutigue, Marie-Hélène

Regulatory peptides

2010 Volume 165, Issue 1, Page(s) 102–110

Abstract: Chromogranins/secretogranins are members of the granin family present in secretory vesicles of nervous, endocrine and immune cells. In chromaffin cells, activation of nicotinic cholinergic receptors induces the release, with catecholamines, of bioactive ... ...

Abstract	Chromogranins/secretogranins are members of the granin family present in secretory vesicles of nervous, endocrine and immune cells. In chromaffin cells, activation of nicotinic cholinergic receptors induces the release, with catecholamines, of bioactive peptides resulting from a natural processing. During the past decade, our laboratory has characterized new antimicrobial chromogranin-derived peptides in the secretions of stimulated bovine chromaffin cells. They act at the micromolar range against bacteria, fungi, yeasts, and are non-toxic for the mammalian cells. They are recovered in several biological fluids involved in defence mechanisms (human serum, neutrophil secretions and saliva). These new antimicrobial peptides demonstrate the major role of the adrenal medulla in innate immunity. In this review we focus on the antimicrobial peptides derived from human and bovine chromogranin A (CGA), chromogranin B (CGB) and secretogranin II (SGII) emphasizing their direct action against pathogens and their effects on immune cells.
MeSH term(s)	Animals ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Cattle ; Chromogranins/chemistry ; Chromogranins/pharmacology ; Humans ; Immunity, Innate/drug effects ; Peptides/chemistry ; Peptides/pharmacology
Chemical Substances	Anti-Infective Agents ; Chromogranins ; Peptides
Language	English
Publishing date	2010-11-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	225685-x
ISSN	1873-1686 ; 0167-0115
ISSN (online)	1873-1686
ISSN	0167-0115
DOI	10.1016/j.regpep.2009.11.014
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Article: Characterization and location of post-translational modifications on chromogranin B from bovine adrenal medullary chromaffin granules.

Gasnier, Claire / Lugardon, Karine / Ruh, Olivier / Strub, Jean-Marc / Aunis, Dominique / Metz-Boutigue, Marie-Hélène

Proteomics

2004 Volume 4, Issue 6, Page(s) 1789–1801

Abstract: Bovine chromoganin B (CGB)/secretogranin I, an acidic protein with a sequence of 626 residues and an isoelectric point of 5.2 is a major member of the chromogranin/secretogranin (CG/Sg) family. The difference between the theoretical molecular mass (76 ... ...

Abstract	Bovine chromoganin B (CGB)/secretogranin I, an acidic protein with a sequence of 626 residues and an isoelectric point of 5.2 is a major member of the chromogranin/secretogranin (CG/Sg) family. The difference between the theoretical molecular mass (76 kDa) and the value estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis results from post-translational modifications (glycosylation, phosphorylation and sulfation) and from the abundance of acidic residues (D 4.6%, and E 16.5%). Although the sequence of CGB is known, the structural analyses of the post-translational modifications have so far not been carried out. In the present study, using a combination of proteomic techniques including two-dimensional gel electrophoresis, Western blot, high-performance liquid chromatography purification, enzymatic digestion, sequencing, carbohydrate analysis, matrix-assisted laser desorption/ionization-time of flight and liquid chromatography mass spectrometry analysis, we have located 18 post-translational modifications on bovine CGB, isolated from adrenal medulla chromaffin granules. Furthermore, we have identified at the molecular level the presence of a mutation M/V on position 577 of natural CGB. All together these data reflect the complex structure of this protein marker of the neuroendocrine system.
MeSH term(s)	Adrenal Medulla/chemistry ; Amino Acid Sequence ; Amino Acids, Acidic ; Animals ; Cattle ; Chromaffin Granules/chemistry ; Chromogranins/chemistry ; Chromogranins/genetics ; Chromogranins/isolation & purification ; Chromogranins/metabolism ; Molecular Sequence Data ; Molecular Weight ; Mutation ; Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Proteome ; Proteomics/methods ; Sequence Analysis, Protein ; Sequence Homology, Amino Acid
Chemical Substances	Amino Acids, Acidic ; Chromogranins ; Proteome
Language	English
Publishing date	2004-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2032093-0
ISSN	1615-9861 ; 1615-9853
ISSN (online)	1615-9861
ISSN	1615-9853
DOI	10.1002/pmic.200300693
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Zs.A 5386: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Enhanced membrane disruption and antibiotic action against pathogenic bacteria by designed histidine-rich peptides at acidic pH.

Mason, A James / Gasnier, Claire / Kichler, Antoine / Prévost, Gilles / Aunis, Dominique / Metz-Boutigue, Marie-Hélène / Bechinger, Burkhard

Antimicrobial agents and chemotherapy

2006 Volume 50, Issue 10, Page(s) 3305–3311

Abstract: The histidine-rich amphipathic cationic peptide LAH4 has antibiotic and DNA delivery capabilities. Here, we explore the interaction of peptides from this family with model membranes as monitored by solid-state (2)H nuclear magnetic resonance and their ... ...

Abstract	The histidine-rich amphipathic cationic peptide LAH4 has antibiotic and DNA delivery capabilities. Here, we explore the interaction of peptides from this family with model membranes as monitored by solid-state (2)H nuclear magnetic resonance and their antibiotic activities against a range of bacteria. At neutral pH, the membrane disruption is weak, but at acidic pH, the peptides strongly disturb the anionic lipid component of bacterial membranes and cause bacterial lysis. The peptides are effective antibiotics at both pH 7.2 and pH 5.5, although the antibacterial activity is strongly affected by the change in pH. At neutral pH, the LAH peptides were active against both methicillin-resistant and -sensitive Staphylococcus aureus strains but ineffective against Pseudomonas aeruginosa. In contrast, the LAH peptides were highly active against P. aeruginosa in an acidic environment, as is found in the epithelial-lining fluid of cystic fibrosis patients. Our results show that modest antibiotic activity of histidine-rich peptides can be dramatically enhanced by inducing membrane disruption, in this case by lowering the pH, and that histidine-rich peptides have potential as future antibiotic agents.
MeSH term(s)	Amino Acid Sequence ; Animals ; Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Antimicrobial Cationic Peptides/chemistry ; Antimicrobial Cationic Peptides/pharmacology ; Bacterial Infections/microbiology ; Cell Membrane/drug effects ; Gram-Negative Bacteria/drug effects ; Gram-Positive Bacteria/drug effects ; Humans ; Hydrogen-Ion Concentration ; Magainins ; Magnetic Resonance Spectroscopy ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Peptides/chemical synthesis ; Peptides/chemistry ; Peptides/pharmacology ; Xenopus ; Xenopus Proteins/chemistry ; Xenopus Proteins/pharmacology
Chemical Substances	Anti-Bacterial Agents ; Antimicrobial Cationic Peptides ; LAH(4) protein, synthetic ; Magainins ; Peptides ; Xenopus Proteins ; magainin 2 peptide, Xenopus (108433-95-0)
Language	English
Publishing date	2006-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.00490-06
Database	MEDical Literature Analysis and Retrieval System OnLINE

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