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Article ; Online: The evolution of

Kolanko, Emanuel / Cargnoni, Anna / Papait, Andrea / Silini, Antonietta Rosa / Czekaj, Piotr / Parolini, Ornella

European respiratory review : an official journal of the European Respiratory Society

2024 Volume 33, Issue 171

Abstract: Lung fibrosis is a complex process, with unknown underlying mechanisms, involving various triggers, diseases and stimuli. Different cell types (epithelial cells, endothelial cells, fibroblasts and macrophages) interact dynamically through multiple ... ...

Abstract	Lung fibrosis is a complex process, with unknown underlying mechanisms, involving various triggers, diseases and stimuli. Different cell types (epithelial cells, endothelial cells, fibroblasts and macrophages) interact dynamically through multiple signalling pathways, including biochemical/molecular and mechanical signals, such as stiffness, affecting cell function and differentiation. Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing interstitial lung disease (fILD), characterised by a notably high mortality. Unfortunately, effective treatments for advanced fILD, and especially IPF and non-IPF progressive fibrosing phenotype ILD, are still lacking. The development of pharmacological therapies faces challenges due to limited knowledge of fibrosis pathogenesis and the absence of pre-clinical models accurately representing the complex features of the disease. To address these challenges, new model systems have been developed to enhance the translatability of preclinical drug testing and bridge the gap to human clinical trials. The use of two- and three-dimensional
MeSH term(s)	Humans ; Endothelial Cells/pathology ; Disease Progression ; Lung Diseases, Interstitial ; Idiopathic Pulmonary Fibrosis/pathology ; Drug Discovery
Language	English
Publishing date	2024-01-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1077620-5
ISSN	1600-0617 ; 0905-9180
ISSN (online)	1600-0617
ISSN	0905-9180
DOI	10.1183/16000617.0127-2023
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Article ; Online: Nano-Immunomodulation: A New Strategy for Skeletal Muscle Diseases and Aging?

Millozzi, Francesco / Papait, Andrea / Bouché, Marina / Parolini, Ornella / Palacios, Daniela

International journal of molecular sciences

2023 Volume 24, Issue 2

Abstract: The skeletal muscle has a very remarkable ability to regenerate upon injury under physiological conditions; however, this regenerative capacity is strongly diminished in physio-pathological conditions, such as those present in diseased or aged muscles. ... ...

Abstract	The skeletal muscle has a very remarkable ability to regenerate upon injury under physiological conditions; however, this regenerative capacity is strongly diminished in physio-pathological conditions, such as those present in diseased or aged muscles. Many muscular dystrophies (MDs) are characterized by aberrant inflammation due to the deregulation of both the lymphoid and myeloid cell populations and the production of pro-inflammatory cytokines. Pathological inflammation is also observed in old muscles due to a systemic change in the immune system, known as "inflammaging". Immunomodulation represents, therefore, a promising therapeutic opportunity for different skeletal muscle conditions. However, the use of immunomodulatory drugs in the clinics presents several caveats, including their low stability in vivo, the need for high doses to obtain therapeutically relevant effects, and the presence of strong side effects. Within this context, the emerging field of nanomedicine provides the powerful tools needed to control the immune response. Nano-scale materials are currently being explored as biocarriers to release immunomodulatory agents in the damaged tissues, allowing therapeutic doses with limited off-target effects. In addition, the intrinsic immunomodulatory properties of some nanomaterials offer further opportunities for intervention that still need to be systematically explored. Here we exhaustively review the state-of-the-art regarding the use of nano-sized materials to modulate the aberrant immune response that characterizes some physio-pathological muscle conditions, such as MDs or sarcopenia (the age-dependent loss of muscle mass). Based on our learnings from cancer and immune tolerance induction, we also discuss further opportunities, challenges, and limitations of the emerging field of nano-immunomodulation.
MeSH term(s)	Humans ; Aged ; Aging ; Muscle, Skeletal/pathology ; Sarcopenia/pathology ; Inflammation/pathology ; Immunity
Language	English
Publishing date	2023-01-07
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/ijms24021175
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Article ; Online: Amniotic MSC affect CD8 naive polarization toward SLEC/MPEC subsets by down-modulating IL-12Rβ1 and IL-2Rα signaling pathways.

Papait, Andrea / Vertua, Elsa / Signoroni, Patrizia Bonassi / Cargnoni, Anna / Magatti, Marta / Stefani, Francesca Romana / Romoli, Jacopo / Silini, Antonietta Rosa / Parolini, Ornella

iScience

2023 Volume 26, Issue 12, Page(s) 108483

Abstract: Mesenchymal stromal cells (MSCs) are known for their immunomodulatory activity. Here, we report that MSCs isolated from the amniotic membrane of human term placenta (hAMSCs) impact CD8 T cell fate through a multifaceted mechanism. We observed that hAMSCs ...

Abstract	Mesenchymal stromal cells (MSCs) are known for their immunomodulatory activity. Here, we report that MSCs isolated from the amniotic membrane of human term placenta (hAMSCs) impact CD8 T cell fate through a multifaceted mechanism. We observed that hAMSCs are able to impact the metabolism of naive CD8 lymphocytes by downregulating the phosphorylation of mTOR and AKT, thus blocking cell differentiation. This effect is due to the ability of hAMSCs to reduce the expression of two receptors, IL-12Rβ1 and IL-2RA, resulting in reduced phosphorylation of STAT4 and STAT5. In addition, hAMSCs reduce the expression of two transcriptional factors, Tbet and Eomes, directly involved in early effector cell commitment. Our results unravel an unknown feature of MSCs, offering alternative mechanistic insights into the effects of MSCs for the treatment of diseases characterized by an altered activation of memory subsets, such as autoimmune diseases and graft versus host disease.
Language	English
Publishing date	2023-11-17
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108483
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Article ; Online: Disclosing the molecular profile of the human amniotic mesenchymal stromal cell secretome by filter-aided sample preparation proteomic characterization.

Muntiu, Alexandra / Papait, Andrea / Vincenzoni, Federica / Vitali, Alberto / Lattanzi, Wanda / Romele, Pietro / Cargnoni, Anna / Silini, Antonietta / Parolini, Ornella / Desiderio, Claudia

Stem cell research & therapy

2023 Volume 14, Issue 1, Page(s) 339

Abstract: Background: The secretome of mesenchymal stromal cells isolated from the amniotic membrane (hAMSCs) has been extensively studied for its in vitro immunomodulatory activity as well as for the treatment of several preclinical models of immune-related ... ...

Abstract	Background: The secretome of mesenchymal stromal cells isolated from the amniotic membrane (hAMSCs) has been extensively studied for its in vitro immunomodulatory activity as well as for the treatment of several preclinical models of immune-related disorders. The bioactive molecules within the hAMSCs secretome are capable of modulating the immune response and thus contribute to stimulating regenerative processes. At present, only a few studies have attempted to define the composition of the secretome, and several approaches, including multi-omics, are underway in an attempt to precisely define its composition and possibly identify key factors responsible for the therapeutic effect. Methods: In this study, we characterized the protein composition of the hAMSCs secretome by a filter-aided sample preparation (FASP) digestion and liquid chromatography-high resolution mass spectrometry (LC-MS) approach. Data were processed for gene ontology classification and functional protein interaction analysis by bioinformatics tools. Results: Proteomic analysis of the hAMSCs secretome resulted in the identification of 1521 total proteins, including 662 unique elements. A number of 157 elements, corresponding to 23.7%, were found as repeatedly characterizing the hAMSCs secretome, and those that resulted as significantly over-represented were involved in immunomodulation, hemostasis, development and remodeling of the extracellular matrix molecular pathways. Conclusions: Overall, our characterization enriches the landscape of hAMSCs with new information that could enable a better understanding of the mechanisms of action underlying the therapeutic efficacy of the hAMSCs secretome while also providing a basis for its therapeutic translation.
MeSH term(s)	Humans ; Amnion/metabolism ; Proteomics/methods ; Secretome ; Mesenchymal Stem Cells/metabolism ; Mass Spectrometry
Language	English
Publishing date	2023-11-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-023-03557-4
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Article ; Online: Stable Housekeeping Genes in Bone Marrow, Adipose Tissue, and Amniotic Membrane-Derived Mesenchymal Stromal Cells for Orthopedic Regenerative Medicine Approaches.

Ragni, Enrico / Piccolo, Simona / Papait, Andrea / De Luca, Paola / Taiana, Michela / Grieco, Giulio / Silini, Antonietta Rosa / Parolini, Ornella / de Girolamo, Laura

International journal of molecular sciences

2024 Volume 25, Issue 3

Abstract: The therapeutic effect of mesenchymal stromal cells (MSCs) has been described for a variety of disorders, including those affecting musculoskeletal tissues. In this context, the literature reports several data about the regenerative effectiveness of MSCs ...

Abstract	The therapeutic effect of mesenchymal stromal cells (MSCs) has been described for a variety of disorders, including those affecting musculoskeletal tissues. In this context, the literature reports several data about the regenerative effectiveness of MSCs derived from bone marrow, adipose tissue, and an amniotic membrane (BMSCs, ASCs, and hAMSCs, respectively), either when expanded or when acting as clinical-grade biologic pillars of products used at the point of care. To date, there is no evidence about the superiority of one source over the others from a clinical perspective. Therefore, a reliable characterization of the tissue-specific MSC types is mandatory to identify the most effective treatment, especially when tailored to the target disease. Because molecular characterization is a crucial parameter for cell definition, the need for reliable normalizers as housekeeping genes (HKGs) is essential. In this report, the stability levels of five commonly used HKGs (
MeSH term(s)	Genes, Essential ; Bone Marrow ; Cell Differentiation/genetics ; Regenerative Medicine ; Amnion ; Adipose Tissue/metabolism ; Mesenchymal Stem Cells/metabolism ; Bone Marrow Cells/metabolism ; Cells, Cultured
Language	English
Publishing date	2024-01-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25031461
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Article ; Online: Muscle fibrosis as a prognostic biomarker in facioscapulohumeral muscular dystrophy: a retrospective cohort study.

Ragozzino, Elvira / Bortolani, Sara / Di Pietro, Lorena / Papait, Andrea / Parolini, Ornella / Monforte, Mauro / Tasca, Giorgio / Ricci, Enzo

Acta neuropathologica communications

2023 Volume 11, Issue 1, Page(s) 165

Abstract: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant epigenetic disorder with highly variable muscle involvement and disease progression. Ongoing clinical trials, aimed at counteracting muscle degeneration and disease progression in ... ...

Abstract	Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant epigenetic disorder with highly variable muscle involvement and disease progression. Ongoing clinical trials, aimed at counteracting muscle degeneration and disease progression in FSHD patients, increase the need for reliable biomarkers. Muscle magnetic resonance imaging (MRI) studies showed that the appearance of STIR-positive (STIR+) lesions in FSHD muscles represents an initial stage of muscle damage, preceding irreversible adipose changes. Our study aimed to investigate fibrosis, a parameter of muscle degeneration undetectable by MRI, in relation to disease activity and progression of FSHD muscles. We histologically evaluated collagen in FSHD1 patients' (STIR+ n = 27, STIR- n = 28) and healthy volunteers' (n = 12) muscles by picrosirius red staining. All patients (n = 55) performed muscle MRI before biopsy, 45 patients also after 1 year and 36 patients also after 2 years. Fat content (T1 signal) and oedema/inflammation (STIR signal) were evaluated at baseline and at 1- and 2-year MRI follow-up. STIR+ muscles showed significantly higher collagen compared to both STIR- (p = 0.001) and healthy muscles (p < 0.0001). STIR- muscles showed a higher collagen content compared to healthy muscles (p = 0.0194). FSHD muscles with a worsening in fatty infiltration during 1- (P = 0.007) and 2-year (P < 0.0001) MRI follow-up showed a collagen content of 3.6- and 3.7-fold higher compared to FSHD muscles with no sign of progression. Moreover, the fibrosis was significantly higher in STIR+ muscles who showed a worsening in fatty infiltration in a timeframe of 2 years compared to both STIR- (P = 0.0006) and STIR+ muscles with no sign of progression (P = 0.02). Fibrosis is a sign of muscle degeneration undetectable at MRI never deeply investigated in FSHD patients. Our data show that 23/27 of STIR+ and 12/28 STIR- muscles have a higher amount of collagen deposition compared to healthy muscles. Fibrosis is higher in FSHD muscles with a worsening in fatty infiltration thus suggesting that its evaluation with innovative non-invasive techniques could be a candidate prognostic biomarker for FSHD, to be used to stratify patients and to evaluate the efficacy of therapeutic treatments.
MeSH term(s)	Humans ; Muscular Dystrophy, Facioscapulohumeral/diagnosis ; Muscular Dystrophy, Facioscapulohumeral/pathology ; Muscle, Skeletal/pathology ; Prognosis ; Retrospective Studies ; Biomarkers ; Magnetic Resonance Imaging/methods ; Disease Progression ; Collagen
Chemical Substances	Biomarkers ; Collagen (9007-34-5)
Language	English
Publishing date	2023-10-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-023-01660-4
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Article: Fight the Cancer, Hit the CAF!

Papait, Andrea / Romoli, Jacopo / Stefani, Francesca Romana / Chiodelli, Paola / Montresor, Maria Cristina / Agoni, Lorenzo / Silini, Antonietta Rosa / Parolini, Ornella

Cancers

2022 Volume 14, Issue 15

Abstract: The tumor microenvironment (TME) is comprised of different cellular components, such as immune and stromal cells, which co-operate in unison to promote tumor progression and metastasis. In the last decade, there has been an increasing focus on one ... ...

Abstract	The tumor microenvironment (TME) is comprised of different cellular components, such as immune and stromal cells, which co-operate in unison to promote tumor progression and metastasis. In the last decade, there has been an increasing focus on one specific component of the TME, the stromal component, often referred to as Cancer-Associated Fibroblasts (CAF). CAF modulate the immune response and alter the composition of the extracellular matrix with a decisive impact on the response to immunotherapies and conventional chemotherapy. The most recent publications based on single-cell analysis have underlined CAF heterogeneity and the unique plasticity that strongly impact the TME. In this review, we focus not only on the characterization of CAF based on the most recent findings, but also on their impact on the immune system. We also discuss clinical trials and preclinical studies where targeting CAF revealed controversial results. Therefore, future efforts should focus on understanding the functional properties of individual subtypes of CAF, taking into consideration the peculiarities of each pathological context.
Language	English
Publishing date	2022-07-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14153570
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Article ; Online: Slow and steady wins the race: Fractionated near-infrared treatment empowered by graphene-enhanced 3D scaffolds for precision oncology.

Perini, Giordano / Palmieri, Valentina / Papait, Andrea / Augello, Alberto / Fioretti, Daniela / Iurescia, Sandra / Rinaldi, Monica / Vertua, Elsa / Silini, Antonietta / Torelli, Riccardo / Carlino, Angela / Musarra, Teresa / Sanguinetti, Maurizio / Parolini, Ornella / De Spirito, Marco / Papi, Massimiliano

Materials today. Bio

2024 Volume 25, Page(s) 100986

Abstract: Surgically addressing tumors poses a challenge, requiring a tailored, multidisciplinary approach for each patient based on the unique aspects of their case. Innovative therapeutic regimens combined to reliable reconstructive methods can contribute to an ... ...

Abstract	Surgically addressing tumors poses a challenge, requiring a tailored, multidisciplinary approach for each patient based on the unique aspects of their case. Innovative therapeutic regimens combined to reliable reconstructive methods can contribute to an extended patient's life expectancy. This study presents a detailed comparative investigation of near-infrared therapy protocols, examining the impact of non-fractionated and fractionated irradiation regimens on cancer treatment. The therapy is based on the implantation of graphene oxide/poly(lactic-co-glycolic acid) three-dimensional printed scaffolds, exploring their versatile applications in oncology by the examination of pro-inflammatory cytokine secretion, immune response, and in vitro and in vivo tumor therapy. The investigation into cell death patterns (apoptosis vs necrosis) underlines the pivotal role of protocol selection underscores the critical influence of treatment duration on cell fate, establishing a crucial parameter in therapeutic decision-making. In vivo experiments corroborated the profound impact of protocol selection on tumor response. The fractionated regimen emerged as the standout performer, achieving a substantial reduction in tumor size over time, surpassing the efficacy of the non-fractionated approach. Additionally, the fractionated regimen exhibited efficacy also in targeting tumors in proximity but not in direct contact to the scaffolds. Our results address a critical gap in current research, highlighting the absence of a standardized protocol for optimizing the outcome of photodynamic therapy. The findings underscore the importance of personalized treatment strategies in achieving optimal therapeutic efficacy for precision cancer therapy.
Language	English
Publishing date	2024-02-09
Publishing country	England
Document type	Journal Article
ISSN	2590-0064
ISSN (online)	2590-0064
DOI	10.1016/j.mtbio.2024.100986
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Article ; Online: Disclosing the molecular profile of the human amniotic mesenchymal stromal cell secretome by filter-aided sample preparation proteomic characterization

Alexandra Muntiu / Andrea Papait / Federica Vincenzoni / Alberto Vitali / Wanda Lattanzi / Pietro Romele / Anna Cargnoni / Antonietta Silini / Ornella Parolini / Claudia Desiderio

Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-

2023 Volume 32

Abstract: Abstract Background The secretome of mesenchymal stromal cells isolated from the amniotic membrane (hAMSCs) has been extensively studied for its in vitro immunomodulatory activity as well as for the treatment of several preclinical models of immune- ... ...

Abstract	Abstract Background The secretome of mesenchymal stromal cells isolated from the amniotic membrane (hAMSCs) has been extensively studied for its in vitro immunomodulatory activity as well as for the treatment of several preclinical models of immune-related disorders. The bioactive molecules within the hAMSCs secretome are capable of modulating the immune response and thus contribute to stimulating regenerative processes. At present, only a few studies have attempted to define the composition of the secretome, and several approaches, including multi-omics, are underway in an attempt to precisely define its composition and possibly identify key factors responsible for the therapeutic effect. Methods In this study, we characterized the protein composition of the hAMSCs secretome by a filter-aided sample preparation (FASP) digestion and liquid chromatography-high resolution mass spectrometry (LC–MS) approach. Data were processed for gene ontology classification and functional protein interaction analysis by bioinformatics tools. Results Proteomic analysis of the hAMSCs secretome resulted in the identification of 1521 total proteins, including 662 unique elements. A number of 157 elements, corresponding to 23.7%, were found as repeatedly characterizing the hAMSCs secretome, and those that resulted as significantly over-represented were involved in immunomodulation, hemostasis, development and remodeling of the extracellular matrix molecular pathways. Conclusions Overall, our characterization enriches the landscape of hAMSCs with new information that could enable a better understanding of the mechanisms of action underlying the therapeutic efficacy of the hAMSCs secretome while also providing a basis for its therapeutic translation.
Keywords	Proteomics ; Secretome ; Human amniotic mesenchymal stromal cells ; Filter-aided sample preparation ; Immunomodulation ; Regenerative medicine ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Shaping the Future of Perinatal Cells: Lessons From the Past and Interpretations of the Present.

Silini, Antonietta R / Masserdotti, Alice / Papait, Andrea / Parolini, Ornella

Frontiers in bioengineering and biotechnology

2019 Volume 7, Page(s) 75

Abstract: Since their discovery and characterization, mesenchymal stromal cells (MSC) have been a topic of great interest in regenerative medicine. Over the last 10 years, detailed studies investigated the properties of MSC from perinatal tissues and have ... ...

Abstract	Since their discovery and characterization, mesenchymal stromal cells (MSC) have been a topic of great interest in regenerative medicine. Over the last 10 years, detailed studies investigated the properties of MSC from perinatal tissues and have indicated that these cells may represent important tools for restoring tissue damage or promoting regeneration and repair of the tissue microenvironment. At first, perinatal tissue-derived MSC drew attention due to their potential differentiation capacities suggested by their early embryological origin. It is nowadays accepted that perinatal tissue-derived MSC are promising for a wide range of regenerative medicine applications because of their unique immune modulatory properties, rather than their differentiation ability. As a matter of fact, the activation and function of various cells of the innate and adaptive immune systems are suppressed and modulated by MSC from different perinatal tissues, such as human term placenta. However, the mechanisms by which they act on immune cells to facilitate tissue repair during pathological processes remain to be thoroughly elucidated to develop safe and efficient therapeutic approaches. In addition to immune modulatory ability, several other peculiar characteristics of placenta MSC, less explored and/or more debated, are being investigated. These include an understanding of the anti-microbial properties and the role of placental MSC in tumor progression. Moreover, a thorough investigation on preparation methods, bioactive factors, mechanisms of action of the cell secretome, and the development of potency assays to predict clinical efficacy of placenta MSC and their products, are necessary to provide a solid basis for their clinical application.
Language	English
Publishing date	2019-04-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2019.00075
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