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Article: Atherosclerosis: lessons from LXR and the intestine

Bonamassa, Barbara / Moschetta, Antonio

Trends in endocrinology & metabolism. 2013 Mar., v. 24, no. 3

2013

Abstract: Modulation of the cholesterol-sensing liver X receptors (LXRs) and their downstream targets has emerged as promising therapeutic avenues in atherosclerosis. The intestine is important for its unique capabilities to act as a gatekeeper for cholesterol ... ...

Abstract	Modulation of the cholesterol-sensing liver X receptors (LXRs) and their downstream targets has emerged as promising therapeutic avenues in atherosclerosis. The intestine is important for its unique capabilities to act as a gatekeeper for cholesterol absorption and to participate in the process of cholesterol elimination in the feces and reverse cholesterol transport (RCT). Pharmacological and genetic intestine-specific LXR activation have been shown to protect against atherosclerosis. In this review we discuss the LXR-targeted molecular players in the enterocytes as well as the intestine-driven pathways contributing to cholesterol homeostasis with therapeutic potential as targets in the prevention and treatment of atherosclerosis..
Keywords	absorption ; atherosclerosis ; cholesterol ; enterocytes ; feces ; homeostasis ; liver ; receptors
Language	English
Dates of publication	2013-03
Size	p. 120-128.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2012.10.004
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 2999: Show issues

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Article ; Online: Atherosclerosis: lessons from LXR and the intestine.

Bonamassa, Barbara / Moschetta, Antonio

Trends in endocrinology and metabolism: TEM

2012 Volume 24, Issue 3, Page(s) 120–128

Abstract	Modulation of the cholesterol-sensing liver X receptors (LXRs) and their downstream targets has emerged as promising therapeutic avenues in atherosclerosis. The intestine is important for its unique capabilities to act as a gatekeeper for cholesterol absorption and to participate in the process of cholesterol elimination in the feces and reverse cholesterol transport (RCT). Pharmacological and genetic intestine-specific LXR activation have been shown to protect against atherosclerosis. In this review we discuss the LXR-targeted molecular players in the enterocytes as well as the intestine-driven pathways contributing to cholesterol homeostasis with therapeutic potential as targets in the prevention and treatment of atherosclerosis..
MeSH term(s)	ATP Binding Cassette Transporter 1/physiology ; ATP Binding Cassette Transporter, Subfamily G, Member 5 ; ATP Binding Cassette Transporter, Subfamily G, Member 8 ; ATP-Binding Cassette Transporters/genetics ; Animals ; Atherosclerosis/drug therapy ; Atherosclerosis/prevention & control ; Cholesterol/metabolism ; Homeostasis ; Humans ; Hypercholesterolemia/drug therapy ; Intestinal Absorption/physiology ; Intestinal Mucosa/metabolism ; Lipoproteins/genetics ; Liver X Receptors ; Membrane Proteins/genetics ; Membrane Proteins/physiology ; Membrane Transport Proteins ; Orphan Nuclear Receptors/physiology ; Sterol O-Acyltransferase/physiology ; Sterol O-Acyltransferase 2
Chemical Substances	ABCG5 protein, human ; ABCG8 protein, human ; ATP Binding Cassette Transporter 1 ; ATP Binding Cassette Transporter, Subfamily G, Member 5 ; ATP Binding Cassette Transporter, Subfamily G, Member 8 ; ATP-Binding Cassette Transporters ; Lipoproteins ; Liver X Receptors ; Membrane Proteins ; Membrane Transport Proteins ; NPC1L1 protein, human ; Orphan Nuclear Receptors ; Cholesterol (97C5T2UQ7J) ; Sterol O-Acyltransferase (EC 2.3.1.26)
Language	English
Publishing date	2012-11-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2012.10.004
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Zs.A 2999: Show issues

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Article ; Online: The Admission of Older Patients with COVID-19 in the General Wards

Tibullo, Loredana / Bonamassa, Barbara / De Blasio, Attilio / Verrillo, Daniela / Vargas, Nicola

Covid-19 Airway Management and Ventilation Strategy for Critically Ill Older Patients ; page 189-193 ; ISBN 9783030556204 9783030556211

2020

Keywords	covid19
Publisher	Springer International Publishing
Publishing country	us
Document type	Article ; Online
DOI	10.1007/978-3-030-55621-1_21
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The roles of hepatitis B virus-encoded X protein in virus replication and the pathogenesis of chronic liver disease.

Feitelson, Mark A / Bonamassa, Barbara / Arzumanyan, Alla

Expert opinion on therapeutic targets

2014 Volume 18, Issue 3, Page(s) 293–306

Abstract: Introduction: Hepatitis B virus (HBV) is a major cause of chronic liver disease (CLD) and hepatocellular carcinoma (HCC) worldwide. More than 350 million people are at risk for HCC, and with few treatment options available, therapeutic approaches to ... ...

Abstract	Introduction: Hepatitis B virus (HBV) is a major cause of chronic liver disease (CLD) and hepatocellular carcinoma (HCC) worldwide. More than 350 million people are at risk for HCC, and with few treatment options available, therapeutic approaches to targets other than the virus polymerase will be needed. This review suggests that the HBV-encoded X protein, HBx, would be an outstanding target because it contributes to the biology and pathogenesis of HBV in three fundamental ways. Areas covered: First, HBx is a trans-activating protein that stimulates virus gene expression and replication, thereby promoting the development and persistence of the carrier state. Second, HBx partially blocks the development of immune responses that would otherwise clear the virus, and protects infected hepatocytes from immune-mediated destruction. Thus, HBx contributes to the development of CLD without virus clearance. Third, HBx alters patterns of host gene expression that make possible the emergence of HCC. The selected literature cited is from the National Library of Medicine (Pubmed and Medline). Expert opinion: Understanding the mechanisms, whereby HBx supports virus replication and promotes pathogenesis, suggests that HBx will be an important therapeutic target against both virus replication and CLD aimed at the chemoprevention of HCC.
MeSH term(s)	Animals ; Gene Expression ; Hepatitis B virus/physiology ; Humans ; Liver Diseases/immunology ; Liver Diseases/metabolism ; Trans-Activators/physiology ; Virus Replication
Chemical Substances	Trans-Activators ; hepatitis B virus X protein
Language	English
Publishing date	2014-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1517/14728222.2014.867947
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Zs.A 5244: Show issues

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Article ; Online: Nonviral gene transfer as a tool for studying transcription regulation of xenobiotic metabolizing enzymes.

Bonamassa, Barbara / Liu, Dexi

Advanced drug delivery reviews

2010 Volume 62, Issue 13, Page(s) 1250–1256

Abstract: Numerous xenobiotic metabolizing enzymes are regulated by nuclear receptors at transcriptional level. The challenge we currently face is to understand how a given nuclear receptor interacts with its xenobiotics, migrates into nucleus, binds to the ... ...

Abstract	Numerous xenobiotic metabolizing enzymes are regulated by nuclear receptors at transcriptional level. The challenge we currently face is to understand how a given nuclear receptor interacts with its xenobiotics, migrates into nucleus, binds to the xenobiotic response element of a target gene, and regulates transcription. Toward this end, new methods have been developed to introduce the nuclear receptor gene into appropriate cells and study its activity in activating reporter gene expression under the control of a promoter containing xenobiotic response elements. The goal of this review is to critically examine the gene transfer methods currently available. We concentrate on the gene transfer mechanism, advantages and limitations of each method when employed for nuclear receptor-mediated gene regulation studies. It is our hope that the information provided highlights the importance of gene transfer in studying the mechanisms by which our body eliminates the potentially harmful substances and maintains the homeostasis.
MeSH term(s)	Animals ; Gene Expression Regulation ; Gene Transfer Techniques ; Humans ; Inactivation, Metabolic ; Rats ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Response Elements ; Xenobiotics/metabolism
Chemical Substances	Receptors, Cytoplasmic and Nuclear ; Xenobiotics
Language	English
Publishing date	2010-08-14
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2010.08.005
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Zs.A 2241: Show issues

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Article: Harmful effects behind the daily supplementation of a fixed vegetarian blend in the rat model

Bonamassa, Barbara / Andrea Sapone / Andrea Vornoli / Donatella Canistro / Fabio Vivarelli / Moreno Paolini / Vincenzo Longo

Food and chemical toxicology. 2016 Nov., v. 97

2016

Abstract: Fruit and vegetables (FV) have long been considered a panacea against major chronic diseases, including cancer. However, there is no convincing epidemiological, clinical or experimental evidence supporting FV chemopreventive ability. A daily mono- ... ...

Abstract	Fruit and vegetables (FV) have long been considered a panacea against major chronic diseases, including cancer. However, there is no convincing epidemiological, clinical or experimental evidence supporting FV chemopreventive ability. A daily mono-supplementation of lyophilized onion, tomato, peach, black grape or lettuce was compared with the daily combined administration of the same FV (5 a day-like diet). Ten days post-treatment, the phase-I/II xenobiotic metabolizing and antioxidant enzyme activities, protein and mRNA levels were investigated. As a marker of oxidative stress, the level of hydroperoxides was measured in rat serum samples. Here we show that a blend of FV orally administered to rats not only potentially manipulates metabolism but also disrupts systemic oxidative homeostasis. A daily combination of the five servings remarkably down-regulates the catalytic activity, protein and mRNA levels of a cohort of hepatic metabolizing enzymes, suggesting a possible depressed clearance upon exposure to ubiquitous carcinogens. Strikingly, we observed an impairment of antioxidant enzymes with a boost in systemic hydroperoxide levels. Our study identifies new potential factors of cancer risk connected with the persistent consumption of fixed servings of FV, suggesting that dietary guidance should rely on a “daily diversification” of FV.
Keywords	animal models ; blood serum ; carcinogens ; catalytic activity ; chemoprevention ; chronic diseases ; dietary recommendations ; enzyme activity ; enzymes ; freeze drying ; fruits ; grapes ; homeostasis ; hydroperoxides ; lettuce ; messenger RNA ; metabolism ; neoplasms ; onions ; oral administration ; oxidative stress ; peaches ; rats ; risk ; tomatoes ; toxicology ; vegetarian diet ; xenobiotics
Language	English
Dates of publication	2016-11
Size	p. 367-374.
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.2016.09.033
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Glucocorticoid receptor-mediated transcriptional regulation of N-acetyltransferase 1 gene through distal promoter.

Bonamassa, Barbara / Ma, Yongjie / Liu, Dexi

The AAPS journal

2012 Volume 14, Issue 3, Page(s) 581–590

Abstract: Human arylamine N-acetyltransferase 1, (HUMAN)NAT1, is a phase II xenobiotic-metabolizing enzyme that plays an important role in drug and carcinogen biotransformation and cancer development. Its gene expression has been shown to be regulated by ... ...

Abstract	Human arylamine N-acetyltransferase 1, (HUMAN)NAT1, is a phase II xenobiotic-metabolizing enzyme that plays an important role in drug and carcinogen biotransformation and cancer development. Its gene expression has been shown to be regulated by environmental factors. The purpose of the current study is to determine the involvement of nuclear receptors in transcriptional regulation of (HUMAN)NAT1 gene. We show that among the nuclear receptors examined, including the glucocorticoid receptor, retinoid acid receptor-related orphan receptor alpha, constitutive androstane receptor, pregnane X receptor, aryl hydrocarbon receptor, and retinoic acid receptor, the glucocorticoid receptor plays a dominant role in regulating (HUMAN)NAT1 gene expression through distal promoter (P3). The involvement of the glucocorticoid receptor in transcription regulation of (HUMAN)NAT1 gene expression was demonstrated by dexamethasone treatment, reporter assay using plasmid-containing 3 kbp of 5'-end region of promoter 3, and treatment of anti-glucocorticoid RU486 in primary culture of human hepatocytes and transfected HepG2 cells. In addition, translation inhibition did not affect dexamethasone-induced gene expression through P3, suggesting that dexamethasone effect is directly mediated by glucocorticoid receptor activation. Furthermore, deletion analysis revealed the presence of multiple responsive elements within the 3 kbp fragment of P3. Transfection assays in mice using hydrodynamics-based procedure and reporter gene assay in a mouse cell line revealed that glucocorticoid-induced NAT gene expression is species dependent. Dexamethasone treatment of transfected mice and mouse cell line decreased (MOUSE)Nat2 gene expression, (HUMAN)NAT1 homologue. These results suggest that glucocorticoids serve as a modulator for (HUMAN)NAT1 gene expression via the P3-containing 5'-flanking region.
MeSH term(s)	Animals ; Arylamine N-Acetyltransferase/genetics ; Base Sequence ; Cell Line ; DNA Primers ; Gene Expression Regulation/physiology ; Humans ; Isoenzymes/genetics ; Male ; Mice ; Promoter Regions, Genetic ; Real-Time Polymerase Chain Reaction ; Receptors, Glucocorticoid/physiology ; Transcription, Genetic/physiology
Chemical Substances	DNA Primers ; Isoenzymes ; Receptors, Glucocorticoid ; Arylamine N-Acetyltransferase (EC 2.3.1.5) ; N-acetyltransferase 1 (EC 2.3.1.5)
Language	English
Publishing date	2012-05-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1550-7416
ISSN (online)	1550-7416
DOI	10.1208/s12248-012-9370-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Harmful effects behind the daily supplementation of a fixed vegetarian blend in the rat model.

Bonamassa, Barbara / Canistro, Donatella / Sapone, Andrea / Vivarelli, Fabio / Vornoli, Andrea / Longo, Vincenzo / Paolini, Moreno

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

2016 Volume 97, Page(s) 367–374

Abstract	Fruit and vegetables (FV) have long been considered a panacea against major chronic diseases, including cancer. However, there is no convincing epidemiological, clinical or experimental evidence supporting FV chemopreventive ability. A daily mono-supplementation of lyophilized onion, tomato, peach, black grape or lettuce was compared with the daily combined administration of the same FV (5 a day-like diet). Ten days post-treatment, the phase-I/II xenobiotic metabolizing and antioxidant enzyme activities, protein and mRNA levels were investigated. As a marker of oxidative stress, the level of hydroperoxides was measured in rat serum samples. Here we show that a blend of FV orally administered to rats not only potentially manipulates metabolism but also disrupts systemic oxidative homeostasis. A daily combination of the five servings remarkably down-regulates the catalytic activity, protein and mRNA levels of a cohort of hepatic metabolizing enzymes, suggesting a possible depressed clearance upon exposure to ubiquitous carcinogens. Strikingly, we observed an impairment of antioxidant enzymes with a boost in systemic hydroperoxide levels. Our study identifies new potential factors of cancer risk connected with the persistent consumption of fixed servings of FV, suggesting that dietary guidance should rely on a "daily diversification" of FV.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Dietary Supplements/adverse effects ; Feeding Behavior ; Fruit/adverse effects ; Fruit/chemistry ; Hydrogen Peroxide/metabolism ; Male ; Oxidation-Reduction ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; Vegetables/adverse effects ; Vegetables/chemistry
Chemical Substances	Antioxidants ; Hydrogen Peroxide (BBX060AN9V)
Language	English
Publishing date	2016-11
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.2016.09.033
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Article: Hydrodynamic Gene Delivery and Its Applications in Pharmaceutical Research

Bonamassa, Barbara / Hai, Li / Liu, Dexi

Pharmaceutical research. 2011 Apr., v. 28, no. 4

2011

Abstract: Hydrodynamic delivery has emerged as the simplest and most effective method for intracellular delivery of membrane-impermeable substances in rodents. The system employs a physical force generated by a rapid injection of large volume of solution into a ... ...

Abstract	Hydrodynamic delivery has emerged as the simplest and most effective method for intracellular delivery of membrane-impermeable substances in rodents. The system employs a physical force generated by a rapid injection of large volume of solution into a blood vessel to enhance the permeability of endothelium and the plasma membrane of the parenchyma cells to allow delivery of substance into cells. The procedure was initially established for gene delivery in mice, and its applications have been extended to the delivery of proteins, oligo nucleotides, genomic DNA and RNA sequences, and small molecules. The focus of this review is on applications of hydrodynamic delivery in pharmaceutical research. Examples are provided to highlight the use of hydrodynamic delivery for study of transcriptional regulation of CYP enzymes, for establishment of animal model for viral infections, and for gene drug discovery and gene function analysis.
Keywords	gene therapy
Language	English
Dates of publication	2011-04
Size	p. 694-701.
Publisher	Springer US
Publishing place	Boston
Document type	Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-010-0338-9
Database	NAL-Catalogue (AGRICOLA)

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Article: Hepatitis C virus and host cell nuclear transport machinery: a clandestine affair.

Bonamassa, Barbara / Ciccarese, Francesco / Antonio, Veronica Di / Contarini, Andrea / Palù, Giorgio / Alvisi, Gualtiero

Frontiers in microbiology

2015 Volume 6, Page(s) 619

Abstract: There is growing evidence that factors encoded by cytoplasmic replicating viruses functionally interact with components of the nucleocytoplasmic transport apparatus. They do so either to access the cell nucleus, thus affecting genes expression, or to ... ...

Abstract	There is growing evidence that factors encoded by cytoplasmic replicating viruses functionally interact with components of the nucleocytoplasmic transport apparatus. They do so either to access the cell nucleus, thus affecting genes expression, or to interfere with nuclear transport functionality, hindering host immune response. Recent studies revealed that the hepatitis C virus (HCV) makes no exception, interacting with the host cell nuclear transport machinery at two different levels. On the one hand, small amounts of both core and NS5A localize within the host cell nucleus during productive infection, modulating gene expression and signaling functions to promote persistent infection. On the other hand, HCV infection causes a profound redistribution of certain nucleoproteins to the close proximity of endoplasmic reticulum membrane-derived viral replication factories, where viral RNA amplification occurs. These nucleoporins are believed to form nuclear pore complex-like structures, as suggested by their ability to recruit nuclear localization sequence-bearing proteins. Thus, both processes are linked to virus-induced persistence and pathogenesis, representing possible targets for the development of novel anti-HCV therapeutics.
Keywords	covid19
Language	English
Publishing date	2015-06-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2015.00619
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