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Article ; Online: Editorial overview: New and revitalized old targets in metabolic disease.

Hansen, Jacob B / Novak, Ivana

2024 Volume 75, Page(s) 102434

MeSH term(s)	Humans ; Metabolic Diseases/drug therapy
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Editorial
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2024.102434
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Article ; Online: A brief overview of BNIP3L/NIX receptor-mediated mitophagy.

Marinković, Mija / Novak, Ivana

FEBS open bio

2021 Volume 11, Issue 12, Page(s) 3230–3236

Abstract: Mitophagy is a form of autophagy specialized to selectively remove mitochondria. Although the PINK1/Parkin pathway is the best described mitophagy of damaged mitochondria, receptor/mediated mitophagy seems to have a pivotal role in cellular development ... ...

Abstract	Mitophagy is a form of autophagy specialized to selectively remove mitochondria. Although the PINK1/Parkin pathway is the best described mitophagy of damaged mitochondria, receptor/mediated mitophagy seems to have a pivotal role in cellular development and specialization. The most studied mitophagy receptor BCL2/adenovirus E1B 19-kDa-interacting protein 3-like (BNIP3L/NIX) is shown to be important for the programmed removal of healthy mitochondria during terminal differentiation of erythrocytes, but its role has been proven in various cell types. Despite recent advances in our understanding of its regulation by phosphorylation and dimerization, there remain numerous questions on how BNIP3L/NIX tightly balances between cellular life and death decisions. This brief review intends to summarize ongoing dilemmas related to BNIP3L/NIX.
MeSH term(s)	Apoptosis Regulatory Proteins/metabolism ; Autophagy/physiology ; Cell Differentiation ; Humans ; Membrane Proteins/metabolism ; Membrane Proteins/physiology ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism ; Mitophagy/physiology ; Phosphorylation ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins/physiology ; Tumor Suppressor Proteins/metabolism ; Tumor Suppressor Proteins/physiology ; Ubiquitin-Protein Ligases
Chemical Substances	Apoptosis Regulatory Proteins ; BNIP3L protein, human ; Membrane Proteins ; Mitochondrial Proteins ; Proto-Oncogene Proteins ; Tumor Suppressor Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27)
Language	English
Publishing date	2021-10-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13307
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Article: A brief overview of BNIP3L/NIX receptor‐mediated mitophagy

Marinković, Mija / Novak, Ivana

FEBS Open Bio. 2021 Dec., v. 11, no. 12

2021

Abstract	Mitophagy is a form of autophagy specialized to selectively remove mitochondria. Although the PINK1/Parkin pathway is the best described mitophagy of damaged mitochondria, receptor/mediated mitophagy seems to have a pivotal role in cellular development and specialization. The most studied mitophagy receptor BCL2/adenovirus E1B 19‐kDa‐interacting protein 3‐like (BNIP3L/NIX) is shown to be important for the programmed removal of healthy mitochondria during terminal differentiation of erythrocytes, but its role has been proven in various cell types. Despite recent advances in our understanding of its regulation by phosphorylation and dimerization, there remain numerous questions on how BNIP3L/NIX tightly balances between cellular life and death decisions. This brief review intends to summarize ongoing dilemmas related to BNIP3L/NIX.
Keywords	death ; dimerization ; erythrocytes ; mitochondria ; mitophagy ; phosphorylation
Language	English
Dates of publication	2021-12
Size	p. 3230-3236.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2651702-4
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13307
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Article ; Online: Imaging of extracellular and intracellular ATP in pancreatic beta cells reveals correlation between glucose metabolism and purinergic signalling.

Ghiasi, Seyed M / Christensen, Nynne M / Pedersen, Per A / Skovhøj, Emil Z / Novak, Ivana

Cellular signalling

2024 Volume 117, Page(s) 111109

Abstract: Adenosine triphosphate (ATP) is a universal energy molecule and yet cells release it and extracellular ATP is an important signalling molecule between cells. Monitoring of ATP levels outside of cells is important for our understanding of physiological ... ...

Abstract	Adenosine triphosphate (ATP) is a universal energy molecule and yet cells release it and extracellular ATP is an important signalling molecule between cells. Monitoring of ATP levels outside of cells is important for our understanding of physiological and pathophysiological processes in cells/tissues. Here, we focus on pancreatic beta cells (INS-1E) and test the hypothesis that there is an association between intra- and extracellular ATP levels which depends on glucose provision. We imaged real-time changes in extracellular ATP in pancreatic beta cells using two sensors tethered to extracellular aspects of the plasma membrane (eATeam3.10, iATPSnFR1.0). Increase in glucose induced fast micromolar ATP release to the cell surface, depending on glucose concentrations. Chronic pre-treatment with glucose increased the basal ATP signal. In addition, we co-expressed intracellular ATP sensors (ATeam1.30, PercevalHR) in the same cultures and showed that glucose induced fast increases in extracellular and intracellular ATP. Glucose and extracellular ATP stimulated glucose transport monitored by the glucose sensor (FLII12Pglu-700uDelta6). In conclusion, we propose that in beta cells there is a dynamic relation between intra- and extracellular ATP that depends on glucose transport and metabolism and these processes may be tuned by purinergic signalling. Future development of ATP sensors for imaging may aid development of novel approaches to target extracellular ATP in, for example, type 2 diabetes mellitus therapy.
MeSH term(s)	Humans ; Insulin-Secreting Cells/metabolism ; Adenosine Triphosphate/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Signal Transduction ; Glucose/metabolism
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2024-02-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2024.111109
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Article ; Online: COVID-19 in kidney transplant recipients; a DALMATIAN single-center experience.

Dogas, Tina / Brkovic, Tonci / Novak, Ivana / Radic, Josipa

Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy

2022

Abstract: Introduction: We aimed to explore COVID-19 severity, complications, and outcome predictors in the Dalmatian population of kidney transplant recipients (KTRs).: Methods: KTRs confirmed with acute COVID-19 infection until May 2021 were included and ... ...

Abstract	Introduction: We aimed to explore COVID-19 severity, complications, and outcome predictors in the Dalmatian population of kidney transplant recipients (KTRs). Methods: KTRs confirmed with acute COVID-19 infection until May 2021 were included and followed up for 6 months. Results: Out of 50 KTRs average aged 63 years, 36 (72%) were men. Nine (18%) KTRs had no pulmonary infiltration, and twenty-nine (58%) did not require oxygen supplementation. Bilateral pulmonary infiltrates had 29 (58%) while high-flow nasal cannula or mechanical ventilation required 8 (16%) KTRs. The mortality rate was 16%. Acute kidney injury developed in 18 (36%), and acute renal replacement therapy required 2 (4%) KTRs. Nine (18%) KTRs were subsequently rehospitalized. Chronic COVID-19 syndrome reported 23 (58%) KTRs. Conclusions: D-dimers were found to be the key prognostic factor of clinical complications, emphasizing the importance of underlying thrombotic microangiopathy. Optimal immunosuppressant adjusting in KTRs with acute COVID-19 infection remains to be clarified.
Language	English
Publishing date	2022-06-09
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2119809-3
ISSN	1744-9987 ; 1091-6660 ; 1744-9979
ISSN (online)	1744-9987
ISSN	1091-6660 ; 1744-9979
DOI	10.1111/1744-9987.13894
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Zs.A 5208: Show issues

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Article ; Online: Role of the P2X7 receptor in the pathogenesis of type 2 diabetes and its microvascular complications.

Solini, Anna / Novak, Ivana

Current opinion in pharmacology

2019 Volume 47, Page(s) 75–81

Abstract: P2X7 receptors can be found in many tissues and organs, where they mediate several biological functions. This review summarizes the current knowledge about the role of this receptor in the pathogenesis of type 2 diabetes, in which the key clinical ... ...

Abstract	P2X7 receptors can be found in many tissues and organs, where they mediate several biological functions. This review summarizes the current knowledge about the role of this receptor in the pathogenesis of type 2 diabetes, in which the key clinical features are impaired insulin secretion and sensitivity, hyperglycemia, coexistence of other cardiovascular risk factors such as dyslipidemia and hypertension, and subclinical inflammation. The receptor modulates crucial pathways in the pancreatic islets (where it can either exert a trophic or detrimental action on β cells), and in the liver, in the adipose tissue and in the skeletal muscle, which are main sites of insulin resistance. P2X7 receptors also modulate a series of inflammatory responses that participate in the development of the microvascular complications of the disease. Potent and selective P2X7R blockers are available to be tested in Phase I/II clinical studies for the treatment of several chronic diseases, and it might be worthwhile to consider inclusion of patients with type 2 diabetes and its complications.
MeSH term(s)	Animals ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Diabetic Nephropathies/metabolism ; Diabetic Neuropathies/metabolism ; Diabetic Retinopathy/metabolism ; Humans ; Microvessels/metabolism ; Receptors, Purinergic P2X7/metabolism
Chemical Substances	Receptors, Purinergic P2X7
Language	English
Publishing date	2019-04-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2019.02.009
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Zs.A 5608: Show issues

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Article ; Online: Associations of Serum Calprotectin, Arterial Stiffness and Long COVID Symptoms in Dalmatian Kidney Transplant Recipients.

Đogaš, Tina / Novak, Ivana / Babić, Marija / Vučković, Marijana / Tandara, Leida / Radić, Josipa

Viruses

2023 Volume 15, Issue 8

Abstract: We aimed to explore long COVID symptoms, serum calprotectin levels, and the parameters of arterial stiffness in Dalmatian kidney transplant recipients (KTRs) and their possible associations. A cross-sectional, single-center case-control study on 98 KTRs ... ...

Abstract	We aimed to explore long COVID symptoms, serum calprotectin levels, and the parameters of arterial stiffness in Dalmatian kidney transplant recipients (KTRs) and their possible associations. A cross-sectional, single-center case-control study on 98 KTRs who had recovered from COVID-19 was performed. Long COVID symptoms were explored via standardized questionnaires assessing quality of life, and serum calprotectin was also measured. Out of 98 KTRs with a mean age of 62 years, 63 (64.3%) were men. Medical history, clinical and laboratory parameters, and arterial stiffness measurements were obtained for each study participant. Difficulties with mobility were present in 44.3% of the KTRs, while difficulties with self-care were present in 6.2%, difficulties with usual activities were demonstrated by 35.1%, pain in the extremities was present in 52.5%, and anxiety and depression were present in 26.8%. Our results showed significant differences regarding serum calprotectin levels in clinical manifestations of acute COVID-19 and follow-up laboratory parameters. The most significant positive predictors of the serum calprotectin value in the KTRs were respiratory insufficiency, acute kidney failure, the prescription of antihypertensives, leukocyte and neutrophil counts, the neutrophil/lymphocyte ratio and lactate dehydrogenase levels. Negative predictors were the time since COVID-19, high-density lipoprotein levels, kidney function parameters, and the lymphocyte count. To conclude, serum calprotectin has emerged as a possible promising biomarker for subclinical allograft rejection; however, further studies are needed to better understand this subject.
MeSH term(s)	Male ; Humans ; Middle Aged ; Female ; Post-Acute COVID-19 Syndrome ; COVID-19/diagnosis ; Case-Control Studies ; Cross-Sectional Studies ; Kidney Transplantation/adverse effects ; Quality of Life ; Vascular Stiffness ; Leukocyte L1 Antigen Complex
Chemical Substances	Leukocyte L1 Antigen Complex
Language	English
Publishing date	2023-08-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15081776
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Article ; Online: Mitophagy: a complex mechanism of mitochondrial removal.

Novak, Ivana

Antioxidants & redox signaling

2012 Volume 17, Issue 5, Page(s) 794–802

Abstract: Significance: Mitochondrial dynamics and turnover are crucial for cellular homeostasis and differentiation. The removal of damaged mitochondria that could contribute to cellular dysfunction or death is achieved through the process of mitochondrial ... ...

Abstract	Significance: Mitochondrial dynamics and turnover are crucial for cellular homeostasis and differentiation. The removal of damaged mitochondria that could contribute to cellular dysfunction or death is achieved through the process of mitochondrial autophagy, i.e., mitophagy. Moreover, mitophagy is responsible for removal of mitochondria during terminal differentiation of red blood cells and T cells. Recent advances: Recent work is elucidating how mitochondria are recognized for selective mitophagy either by PINK1 and Parkin or mitophagic receptors Nix and Bnip3 and their accompanying modulators. PINK1/Parkin-mediated mitophagy reveals their role of cargo recognition through polyubiquitination of mitochondrial proteins, while Nix functions as a regulated mitophagy receptor. These recognized modes of capture by the autophagy machinery operate at different efficiencies, from partial to complete elimination of mitochondria. Critical issues: It is critical to understand that the distinct regulatory mechanisms involve not only autophagy machinery, but also proteins associated with mitochondrial fusion and fission and therefore, regulation of mitochondrial morphology. The end result is either finely tuned quality control of damaged mitochondria, or mitochondrial clearance during development- induced mitophagy. Future directions: In this article, known mechanisms and future directions for deciphering the challenge of mitophagy regulation will be discussed.
MeSH term(s)	Cell Differentiation ; Homeostasis ; Humans ; Mitochondria/physiology ; Phagocytosis
Language	English
Publishing date	2012-09-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2011.4407
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Zs.A 5488: Show issues

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Article ; Online: P2X receptor-ion channels in the inflammatory response in adipose tissue and pancreas-potential triggers in onset of type 2 diabetes?

Novak, Ivana / Solini, Anna

Current opinion in immunology

2018 Volume 52, Page(s) 1–7

Abstract: Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP ... ...

Abstract	Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP impairs the function of two key players: β-cell and adipose tissue. In the former, P2Y and possibly some P2X receptors-ion channels regulate insulin secretion, but it is still debated whether excessive ATP can via P2X receptors impair β-cell function directly or whether cell damage is due to an excessive systemic release of cytokines. In human adipocytes, the P2X7 receptor promotes the release of inflammatory cytokines, at least in part via inflammasome activation, likely contributing to systemic insulin resistance. This receptor-inflammasome system is also strongly activated in macrophages infiltrating both pancreas and adipose tissue, mediating a deleterious cross-talk that perpetuates the damage.
MeSH term(s)	Adipocytes/metabolism ; Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Animals ; Diabetes Mellitus, Type 2/etiology ; Diabetes Mellitus, Type 2/metabolism ; Humans ; Inflammation/metabolism ; Insulin-Secreting Cells/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Pancreas/metabolism ; Pancreas/pathology ; Receptors, Purinergic P2X/metabolism
Chemical Substances	Receptors, Purinergic P2X
Language	English
Publishing date	2018-03-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2018.02.002
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Zs.A 2773: 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 ; Online: Purinergic Signaling in Pancreas-From Physiology to Therapeutic Strategies in Pancreatic Cancer.

Novak, Ivana / Yu, Haoran / Magni, Lara / Deshar, Ganga

International journal of molecular sciences

2020 Volume 21, Issue 22

Abstract: The purinergic signaling has an important role in regulating pancreatic exocrine secretion. The exocrine pancreas is also a site of one of the most serious cancer forms, the pancreatic ductal adenocarcinoma (PDAC). Here, we explore how the network of ... ...

Abstract	The purinergic signaling has an important role in regulating pancreatic exocrine secretion. The exocrine pancreas is also a site of one of the most serious cancer forms, the pancreatic ductal adenocarcinoma (PDAC). Here, we explore how the network of purinergic and adenosine receptors, as well as ecto-nucleotidases regulate normal pancreatic cells and various cells within the pancreatic tumor microenvironment. In particular, we focus on the P2X7 receptor, P2Y
MeSH term(s)	5'-Nucleotidase/genetics ; 5'-Nucleotidase/immunology ; Animals ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents, Immunological/therapeutic use ; Apyrase/genetics ; Apyrase/immunology ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/immunology ; Carcinoma, Pancreatic Ductal/pathology ; Clinical Trials as Topic ; GPI-Linked Proteins/genetics ; GPI-Linked Proteins/immunology ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/immunology ; Humans ; Immunotherapy/methods ; Pancreas/drug effects ; Pancreas/immunology ; Pancreas/pathology ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/pathology ; Pancreatic Stellate Cells/drug effects ; Pancreatic Stellate Cells/immunology ; Pancreatic Stellate Cells/pathology ; Receptors, Adenosine A2/genetics ; Receptors, Adenosine A2/immunology ; Receptors, Purinergic P2X7/genetics ; Receptors, Purinergic P2X7/immunology ; Receptors, Purinergic P2Y12/genetics ; Receptors, Purinergic P2Y12/immunology ; Receptors, Purinergic P2Y2/genetics ; Receptors, Purinergic P2Y2/immunology ; Signal Transduction/genetics ; Signal Transduction/immunology ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents, Immunological ; GPI-Linked Proteins ; P2RX7 protein, human ; P2RY12 protein, human ; Receptors, Adenosine A2 ; Receptors, Purinergic P2X7 ; Receptors, Purinergic P2Y12 ; Receptors, Purinergic P2Y2 ; 5'-Nucleotidase (EC 3.1.3.5) ; NT5E protein, human (EC 3.1.3.5) ; Apyrase (EC 3.6.1.5) ; ENTPD1 protein, human (EC 3.6.1.5)
Language	English
Publishing date	2020-11-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21228781
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