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Article ; Online: Involvement of pro-inflammatory mediators and cell cycle disruption in neuronal cells induced by gliotoxin and ochratoxin A after individual and combined exposure.

Penalva-Olcina, Raquel / Juan, Cristina / Fernández-Franzón, Mónica / Juan-García, Ana

2024 Volume 393, Page(s) 24–32

Abstract: Mycotoxins such as gliotoxin (GTX) and ochratoxin A (OTA) are secondary metabolites of Aspergillus and Penicillum found in food and feed. Both mycotoxins have shown to exert a detrimental effect on neuronal activity. The following study was carried out ... ...

Abstract	Mycotoxins such as gliotoxin (GTX) and ochratoxin A (OTA) are secondary metabolites of Aspergillus and Penicillum found in food and feed. Both mycotoxins have shown to exert a detrimental effect on neuronal activity. The following study was carried out to elucidate the mechanisms by which GTX and OTA exert their toxicity. Non-differentiated SH-SY5Y neuronal-like cells were treated with GTX, OTA and their combinations to assess their cytotoxic effect using the MTT assay during 24, 48 and 72 h of exposure. Based on the results of the cytotoxic assays, cell cycle proliferation and immunological mediators were measured by determining the production of IL-6 and TNF-α using flow cytometry and ELISA, respectively. The IC
MeSH term(s)	Humans ; Gliotoxin/toxicity ; Tumor Necrosis Factor-alpha/pharmacology ; Interleukin-6 ; Neuroblastoma ; Ochratoxins/toxicity ; Mycotoxins/toxicity ; Cell Cycle
Chemical Substances	ochratoxin A (1779SX6LUY) ; Gliotoxin (67-99-2) ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Ochratoxins ; Mycotoxins
Language	English
Publishing date	2024-01-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2024.01.009
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Article ; Online: Thinking inside the box: intracellular roles for complement system proteins come into focus.

O'Brien, Rebecca M / Lynam-Lennon, Niamh / Olcina, Monica M

British journal of cancer

2023 Volume 128, Issue 2, Page(s) 165–167

Abstract: Over the last decade, perspectives on the complement system in the context of cancer have shifted, with complement proteins now implicated in many of the hallmarks of cancer. Systemically, the generation of complement anaphylatoxin C5a, the most potent ... ...

Abstract	Over the last decade, perspectives on the complement system in the context of cancer have shifted, with complement proteins now implicated in many of the hallmarks of cancer. Systemically, the generation of complement anaphylatoxin C5a, the most potent inflammatory mediator of the cascade, occurs following convertase-mediated cleavage of complement component C5. In a recent manuscript, Ding et al., propose that in colorectal cancer cells, C5 cleavage can occur intracellularly and in a convertase-independent manner, identifying cathepsin D as an enzyme capable of cleaving C5 into C5a [1]. Intracellular C5a is functional and promotes β-catenin stabilisation via the assembly of a KCTD5/cullin3/Roc-1 complex. Importantly, the blockade of C5aR1 prevents tumorigenesis. This study adds to a growing body of evidence indicating that complement proteins, previously thought to primarily have extracellular or membrane-bound functions, also have important intracellular roles.
MeSH term(s)	Humans ; Complement System Proteins/metabolism ; Complement C5/metabolism ; Complement C5a/metabolism ; Potassium Channels
Chemical Substances	Complement System Proteins (9007-36-7) ; Complement C5 ; Complement C5a (80295-54-1) ; KCTD5 protein, human ; Potassium Channels
Language	English
Publishing date	2023-01-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-022-02116-7
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Article ; Online: Cell cycle and enzymatic activity alterations induced by ROS production in human neuroblastoma cells SH-SY5Y exposed to Fumonisin B1, Ochratoxin A and their combination.

Penalva-Olcina, Raquel / Juan, Cristina / Fernández-Franzón, Mónica / Juan-García, Ana

Toxicology in vitro : an international journal published in association with BIBRA

2023 Volume 93, Page(s) 105670

Abstract: The presence of mycotoxins such as Fumonisin B1(FB1) and Ochratoxin A (OTA) in food and feed has become a threat to human and animal health since they can produce several afflictions. Different mechanisms of action by which they exercise their cytotoxic ... ...

Abstract	The presence of mycotoxins such as Fumonisin B1(FB1) and Ochratoxin A (OTA) in food and feed has become a threat to human and animal health since they can produce several afflictions. Different mechanisms of action by which they exercise their cytotoxic activity have been attributed to them, including the production of reactive oxygen species (ROS). For this reason, a measurement of the production of ROS species, and an evaluation of the intrinsic cell enzymatic antioxidant activity, including glutathione peroxidase (GPx), glutathione transferase (GTS), and catalase (CAT) together with a cytotoxicity and cell cycle assay have been performed in undifferentiated SH-SY5Y cells exposed to FB1, OTA and [FB1 + OTA] after 24 h and 48 h. FB1 and OTA. Monitoring of intracellular ROS production was carried out by the H
MeSH term(s)	Animals ; Humans ; Reactive Oxygen Species/metabolism ; Neuroblastoma ; Fumonisins/toxicity ; Mycotoxins/toxicity ; Antioxidants ; Cell Division ; Cell Cycle
Chemical Substances	ochratoxin A (1779SX6LUY) ; fumonisin B1 (3ZZM97XZ32) ; Reactive Oxygen Species ; Fumonisins ; Mycotoxins ; Antioxidants
Language	English
Publishing date	2023-08-24
Publishing country	England
Document type	Journal Article
ZDB-ID	639064-x
ISSN	1879-3177 ; 0887-2333
ISSN (online)	1879-3177
ISSN	0887-2333
DOI	10.1016/j.tiv.2023.105670
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Article ; Online: The importance of hypoxia in radiotherapy for the immune response, metastatic potential and FLASH-RT.

Moon, Eui Jung / Petersson, Kristoffer / Olcina, Monica M

International journal of radiation biology

2021 Volume 98, Issue 3, Page(s) 439–451

Abstract: Purpose: Hypoxia (low oxygen) is a common feature of solid tumors that has been intensely studied for more than six decades. Here we review the importance of hypoxia to radiotherapy with a particular focus on the contribution of hypoxia to immune ... ...

Abstract	Purpose: Hypoxia (low oxygen) is a common feature of solid tumors that has been intensely studied for more than six decades. Here we review the importance of hypoxia to radiotherapy with a particular focus on the contribution of hypoxia to immune responses, metastatic potential and FLASH radiotherapy, active areas of research by leading women in the field. Conclusion: Although hypoxia-driven metastasis and immunosuppression can negatively impact clinical outcome, understanding these processes can also provide tumor-specific vulnerabilities that may be therapeutically exploited. The different oxygen tensions present in tumors and normal tissues may underpin the beneficial FLASH sparing effect seen in normal tissue and represents a perfect example of advances in the field that can leverage tumor hypoxia to improve future radiotherapy treatments.
MeSH term(s)	Female ; Humans ; Hypoxia/radiotherapy ; Immunity ; Neoplasms/radiotherapy ; Oxygen ; Radiation Oncology ; Radiotherapy ; Radiotherapy Dosage
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2021-11-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3065-x
ISSN	1362-3095 ; 0020-7616 ; 0955-3002
ISSN (online)	1362-3095
ISSN	0020-7616 ; 0955-3002
DOI	10.1080/09553002.2021.1988178
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Article: Effectiveness of beetroot extract in SH-SY5Y neuronal cell protection against Fumonisin B1, Ochratoxin A and its combination

Penalva-Olcina, Raquel / Juan, Cristina / Fernández-Franzón, Mónica / Juan-García, Ana

Food and chemical toxicology. 2022 July, v. 165

2022

Abstract: Fumonisin B1 (FB1) and ochratoxin A (OTA) are fungal metabolites of worldwide concern because of their effect on human and animal health, as both have been classified by IARC as possible carcinogens (Group 2B). Beetroot is a source of dietary fiber, ... ...

Abstract	Fumonisin B1 (FB1) and ochratoxin A (OTA) are fungal metabolites of worldwide concern because of their effect on human and animal health, as both have been classified by IARC as possible carcinogens (Group 2B). Beetroot is a source of dietary fiber, folic acid, and vitamin C, and some studies have demonstrated their antioxidant activity. Therefore, this work presents the cytoprotective effect of beetroot extract (BRE) on a neuroblastoma cell line (SH-SY5Y cells) exposed to FB1, OTA, and its combination. Cytotoxicity was studied by the MTT ([3–4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, for 24 h and 48 h. Simultaneous treatment and pre-treatment strategies were tested with 1:512–1:2 and 1:0 dilutions of BRE, with a concentration range from 0.4 to 100 μM of FB1 and from 0.19 to 50 μM of OTA. IC₅₀ values of 5.8 μM and 9.1 μM at 24 h and 48 h, respectively were obtained for OTA while no cytotoxic effect was detected at the concentrations tested for FB1. Cytoprotection with increased viability was obtained when the simultaneous BRE + OTA strategy was performed. Finally, better protection was observed in the pretreatment strategy in which cells were exposed 24 h previously to BRE, compared to that shown in the simultaneous assay.
Keywords	antioxidant activity ; ascorbic acid ; beets ; cell lines ; cytotoxicity ; dietary fiber ; folic acid ; fumonisin B1 ; fungi ; metabolites ; neurons ; ochratoxin A ; viability
Language	English
Dates of publication	2022-07
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2022.113164
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Effectiveness of beetroot extract in SH-SY5Y neuronal cell protection against Fumonisin B1, Ochratoxin A and its combination.

Penalva-Olcina, Raquel / Juan, Cristina / Fernández-Franzón, Mónica / Juan-García, Ana

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2022 Volume 165, Page(s) 113164

Abstract	Fumonisin B1 (FB1) and ochratoxin A (OTA) are fungal metabolites of worldwide concern because of their effect on human and animal health, as both have been classified by IARC as possible carcinogens (Group 2B). Beetroot is a source of dietary fiber, folic acid, and vitamin C, and some studies have demonstrated their antioxidant activity. Therefore, this work presents the cytoprotective effect of beetroot extract (BRE) on a neuroblastoma cell line (SH-SY5Y cells) exposed to FB1, OTA, and its combination. Cytotoxicity was studied by the MTT ([3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, for 24 h and 48 h. Simultaneous treatment and pre-treatment strategies were tested with 1:512-1:2 and 1:0 dilutions of BRE, with a concentration range from 0.4 to 100 μM of FB1 and from 0.19 to 50 μM of OTA. IC
MeSH term(s)	Animals ; Cytoprotection ; Fumonisins/toxicity ; Humans ; Neuroblastoma ; Ochratoxins ; Plant Extracts/pharmacology
Chemical Substances	Fumonisins ; Ochratoxins ; Plant Extracts ; ochratoxin A (1779SX6LUY) ; fumonisin B1 (3ZZM97XZ32)
Language	English
Publishing date	2022-05-20
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2022.113164
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Article: The effects of radiation therapy on the macrophage response in cancer.

Beach, Callum / MacLean, David / Majorova, Dominika / Arnold, James N / Olcina, Monica M

Frontiers in oncology

2022 Volume 12, Page(s) 1020606

Abstract: The efficacy of radiotherapy, a mainstay of cancer treatment, is strongly influenced by both cellular and non-cellular features of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are a heterogeneous population within the TME and ... ...

Abstract	The efficacy of radiotherapy, a mainstay of cancer treatment, is strongly influenced by both cellular and non-cellular features of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are a heterogeneous population within the TME and their prevalence significantly correlates with patient prognosis in a range of cancers. Macrophages display intrinsic radio-resistance and radiotherapy can influence TAM recruitment and phenotype. However, whether radiotherapy alone can effectively "reprogram" TAMs to display anti-tumor phenotypes appears conflicting. Here, we discuss the effect of radiation on macrophage recruitment and plasticity in cancer, while emphasizing the role of specific TME components which may compromise the tumor response to radiation and influence macrophage function. In particular, this review will focus on soluble factors (cytokines, chemokines and components of the complement system) as well as physical changes to the TME. Since the macrophage response has the potential to influence radiotherapy outcomes this population may represent a drug target for improving treatment. An enhanced understanding of components of the TME impacting radiation-induced TAM recruitment and function may help consider the scope for future therapeutic avenues to target this plastic and pervasive population.
Language	English
Publishing date	2022-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.1020606
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Article ; Online: Reducing radiation-induced gastrointestinal toxicity - the role of the PHD/HIF axis.

Olcina, Monica M / Giaccia, Amato J

The Journal of clinical investigation

2016 Volume 126, Issue 10, Page(s) 3708–3715

Abstract: Radiotherapy is an effective treatment strategy for cancer, but a significant proportion of patients experience radiation-induced toxicity due to damage to normal tissue in the irradiation field. The use of chemical or biological approaches aimed at ... ...

Abstract	Radiotherapy is an effective treatment strategy for cancer, but a significant proportion of patients experience radiation-induced toxicity due to damage to normal tissue in the irradiation field. The use of chemical or biological approaches aimed at reducing or preventing normal tissue toxicity induced by radiotherapy is a long-held goal. Hypoxia-inducible factors (HIFs) regulate the production of factors that may protect several cellular compartments affected by radiation-induced toxicity. Pharmacological inhibitors of prolyl hydroxylase domain-containing enzymes (PHDs), which result in stabilization of HIFs, have recently been proposed as a new class of radioprotectors. In this review, radiation-induced toxicity in the gastrointestinal (GI) tract and the main cellular compartments studied in this context will be discussed. The effects of PHD inhibition on GI radioprotection will be described in detail.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Gastrointestinal Tract/metabolism ; Gastrointestinal Tract/pathology ; Gastrointestinal Tract/radiation effects ; Humans ; Neoplasms/radiotherapy ; Prolyl Hydroxylases/metabolism ; Prolyl-Hydroxylase Inhibitors/pharmacology ; Prolyl-Hydroxylase Inhibitors/therapeutic use ; Protein Stability ; Radiation Injuries/metabolism ; Radiation Injuries/prevention & control ; Radiation-Protective Agents/pharmacology ; Radiation-Protective Agents/therapeutic use ; Signal Transduction
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Prolyl-Hydroxylase Inhibitors ; Radiation-Protective Agents ; Prolyl Hydroxylases (EC 1.14.11.-)
Language	English
Publishing date	2016-08-22
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI84432
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Ua VI Zs.184: Show issues

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Article ; Online: WIP1 and senescence: oxygen matters.

Olcina, Monica M / Hammond, Ester M

Cell cycle (Georgetown, Tex.)

2014 Volume 13, Issue 7, Page(s) 1062

MeSH term(s)	Aging, Premature/metabolism ; Animals ; DNA Damage/physiology ; DNA Replication/physiology ; Oxygen/metabolism ; Phosphoprotein Phosphatases/metabolism ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Tumor Suppressor Protein p53 ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Oxygen (S88TT14065)
Language	English
Publishing date	2014-02-28
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.4161/cc.28385
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Article ; Online: Replication catastrophe induced by cyclic hypoxia leads to increased APOBEC3B activity.

Bader, Samuel B / Ma, Tiffany S / Simpson, Charlotte J / Liang, Jiachen / Maezono, Sakura Eri B / Olcina, Monica M / Buffa, Francesca M / Hammond, Ester M

Nucleic acids research

2021 Volume 49, Issue 13, Page(s) 7492–7506

Abstract: Tumor heterogeneity includes variable and fluctuating oxygen concentrations, which result in the accumulation of hypoxic regions in most solid tumors. Tumor hypoxia leads to increased therapy resistance and has been linked to genomic instability. Here, ... ...

Abstract	Tumor heterogeneity includes variable and fluctuating oxygen concentrations, which result in the accumulation of hypoxic regions in most solid tumors. Tumor hypoxia leads to increased therapy resistance and has been linked to genomic instability. Here, we tested the hypothesis that exposure to levels of hypoxia that cause replication stress could increase APOBEC activity and the accumulation of APOBEC-mediated mutations. APOBEC-dependent mutational signatures have been well-characterized, although the physiological conditions which underpin them have not been described. We demonstrate that fluctuating/cyclic hypoxic conditions which lead to replication catastrophe induce the expression and activity of APOBEC3B. In contrast, stable/chronic hypoxic conditions which induce replication stress in the absence of DNA damage are not sufficient to induce APOBEC3B. Most importantly, the number of APOBEC-mediated mutations in patient tumors correlated with a hypoxia signature. Together, our data support the conclusion that hypoxia-induced replication catastrophe drives genomic instability in tumors, specifically through increasing the activity of APOBEC3B.
MeSH term(s)	APOBEC Deaminases/metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Cytidine Deaminase/metabolism ; DNA Replication ; Deamination ; Humans ; Hydroxyurea/toxicity ; Minor Histocompatibility Antigens/metabolism ; Neoplasms/enzymology ; Stress, Physiological/genetics
Chemical Substances	Minor Histocompatibility Antigens ; APOBEC Deaminases (EC 3.5.4.5) ; APOBEC3B protein, human (EC 3.5.4.5) ; Cytidine Deaminase (EC 3.5.4.5) ; Hydroxyurea (X6Q56QN5QC)
Language	English
Publishing date	2021-06-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkab551
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