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Article: A narrative review on tofacitinib: The properties, function, and usefulness to treat coronavirus disease 2019.

Hashemian, Seyed Mohammad Reza / Farhadi, Tayebeh

International journal of critical illness and injury science

2023 Volume 13, Issue 4, Page(s) 192–198

Abstract: In coronavirus disease 2019 (COVID-19), the formation of cytokine storm may have a role in worsening of the disease. By attaching the cytokines like interleukin-6 to the cytokine receptors on a cell surface, Janus kinase (JAK)-signal transducers and ... ...

Abstract	In coronavirus disease 2019 (COVID-19), the formation of cytokine storm may have a role in worsening of the disease. By attaching the cytokines like interleukin-6 to the cytokine receptors on a cell surface, Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway will be activated in the cytoplasm lead to hyperinflammatory conditions and acute respiratory distress syndrome. Inhibition of JAK/STAT pathway may be useful to prevent the formation of cytokine storm. Tofacitinib is a pan inhibitor of JAKs. In this review, the main characteristics of tofacitinib and its usefulness against COVID-19 pneumonia were reviewed. Tofacitinib may be a hopeful therapeutic candidate against COVID-19 respiratory injury since it inhibits a range of inflammatory pathways. Hence, the agent may be considered a potential therapeutic against the post-COVID-19 respiratory damage. Compared to other JAK inhibitors (JAKi), the administration of tofacitinib in COVID-19 patients may be safer and more effective. Other JAKi such as baricitinib are related to severe adverse events such as thrombotic events compared to more common side effects of tofacitinib.
Language	English
Publishing date	2023-12-26
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2638865-0
ISSN	2231-5004 ; 2229-5151
ISSN (online)	2231-5004
ISSN	2229-5151
DOI	10.4103/ijciis.ijciis_27_23
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Article ; Online: Mini review ATF4 and GRP78 as novel molecular targets in ER-Stress modulation for critical COVID-19 patients.

Shahriari-Felordi, Mahtab / Alikhani, Hani Keshavarz / Hashemian, Seyed-Mohammad Reza / Hassan, Moustapha / Vosough, Massoud

Molecular biology reports

2022 Volume 49, Issue 2, Page(s) 1545–1549

Abstract: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in more than 4.4 million deaths worldwide as of August 24, 2021. Viral infections such as SARS-CoV2 are associated with ... ...

Abstract	Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in more than 4.4 million deaths worldwide as of August 24, 2021. Viral infections such as SARS-CoV2 are associated with endoplasmic reticulum (ER) stress and also increased the level of reactive oxygen species. Activating transcription factor 4 (ATF4) is preferentially translated under integrated stress conditions and controls the genes involved in protein homeostasis, amino acid transport and metabolism, and also protection from oxidative stress. The GRP78, regulated either directly or indirectly by ATF4, is an essential chaperone in the ER and overexpressed and appears on the surface of almost all cells during stress and function as a SARS-CoV2 receptor. In this mini-review article, we briefly discuss the effects of SARS-CoV2 infection on the ER stress, and then the stress modulator functions of ATF4 and GRP78 as novel therapeutic targets were highlighted. Finally, the effects of GRP78 inhibitory components as potential factors for targeted therapies for COVID-19 critical cases were discussed.
MeSH term(s)	Activating Transcription Factor 4/metabolism ; COVID-19/metabolism ; Endoplasmic Reticulum Chaperone BiP/metabolism ; Endoplasmic Reticulum Stress/physiology ; Humans ; SARS-CoV-2/pathogenicity
Chemical Substances	ATF4 protein, human ; Endoplasmic Reticulum Chaperone BiP ; HSPA5 protein, human ; Activating Transcription Factor 4 (145891-90-3)
Language	English
Publishing date	2022-01-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-07071-9
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Article: Mini review ATF4 and GRP78 as novel molecular targets in ER-Stress modulation for critical COVID-19 patients

Shahriari-Felordi, Mahtab / Alikhani, Hani Keshavarz / Hashemian, Seyed-Mohammad Reza / Hassan, Moustapha / Vosough, Massoud

Molecular biology reports. 2022 Feb., v. 49, no. 2

2022

Abstract	Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in more than 4.4 million deaths worldwide as of August 24, 2021. Viral infections such as SARS-CoV2 are associated with endoplasmic reticulum (ER) stress and also increased the level of reactive oxygen species. Activating transcription factor 4 (ATF4) is preferentially translated under integrated stress conditions and controls the genes involved in protein homeostasis, amino acid transport and metabolism, and also protection from oxidative stress. The GRP78, regulated either directly or indirectly by ATF4, is an essential chaperone in the ER and overexpressed and appears on the surface of almost all cells during stress and function as a SARS-CoV2 receptor. In this mini-review article, we briefly discuss the effects of SARS-CoV2 infection on the ER stress, and then the stress modulator functions of ATF4 and GRP78 as novel therapeutic targets were highlighted. Finally, the effects of GRP78 inhibitory components as potential factors for targeted therapies for COVID-19 critical cases were discussed.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; amino acids ; endoplasmic reticulum ; homeostasis ; metabolism ; molecular biology ; oxidative stress ; reactive oxygen species ; therapeutics ; transcription factors
Language	English
Dates of publication	2022-02
Size	p. 1545-1549.
Publishing place	Springer Netherlands
Document type	Article
Note	Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-07071-9
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Article ; Online: A computational approach to design a multiepitope vaccine against H5N1 virus.

Dashti, Fatemeh / Raisi, Arash / Pourali, Ghazaleh / Razavi, Zahra Sadat / Ravaei, Fatemeh / Sadri Nahand, Javid / Kourkinejad-Gharaei, Fatemeh / Mirazimi, Seyed Mohammad Ali / Zamani, Javad / Tarrahimofrad, Hossein / Hashemian, Seyed Mohammad Reza / Mirzaei, Hamed

Virology journal

2024 Volume 21, Issue 1, Page(s) 67

Abstract: Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely ... ...

Abstract	Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human β-defensin-3 (HβD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.
MeSH term(s)	Animals ; Humans ; Influenza A Virus, H5N1 Subtype/genetics ; Epitopes, T-Lymphocyte/genetics ; Toll-Like Receptor 7 ; Toll-Like Receptor 8 ; Epitopes, B-Lymphocyte ; Vaccines ; Computational Biology/methods ; Molecular Docking Simulation ; Vaccines, Subunit/genetics
Chemical Substances	Epitopes, T-Lymphocyte ; Toll-Like Receptor 7 ; Toll-Like Receptor 8 ; Epitopes, B-Lymphocyte ; Vaccines ; Vaccines, Subunit
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2160640-7
ISSN	1743-422X ; 1743-422X
ISSN (online)	1743-422X
ISSN	1743-422X
DOI	10.1186/s12985-024-02337-7
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Article ; Online: End-of-life guidelines

Seyed Mohammad Reza Hashemian / James Miller

Biomedical and Biotechnology Research Journal, Vol 4, Iss 5, Pp 104-

Iran confronts COVID-19

2020 Volume 105

Keywords	Biotechnology ; TP248.13-248.65 ; covid19
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
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Article: Fosfomycin: the characteristics, activity, and use in critical care.

Hashemian, Seyed Mohammad Reza / Farhadi, Zinat / Farhadi, Tayebeh

Therapeutics and clinical risk management

2019 Volume 15, Page(s) 525–530

Abstract: Fosfomycin ( ... ...

Abstract	Fosfomycin (C
Language	English
Publishing date	2019-03-27
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2186560-7
ISSN	1178-203X ; 1176-6336
ISSN (online)	1178-203X
ISSN	1176-6336
DOI	10.2147/TCRM.S199119
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Article ; Online: Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial.

Stem cell research & therapy

2023 Volume 14, Issue 1, Page(s) 169

Abstract: Background and aims: The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as ... ...

Abstract	Background and aims: The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients. Materials and methods: COVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 10 Results: A total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14-1.11; P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005-1.26; P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041). Conclusion: MSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events. Trial registration IRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020, http://www.irct.ir/trial/47073 .
MeSH term(s)	Humans ; COVID-19/therapy ; Pandemics ; Treatment Outcome ; Respiratory Distress Syndrome/therapy ; Extracellular Vesicles ; Mesenchymal Stem Cells ; Mesenchymal Stem Cell Transplantation
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-023-03402-8
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Article ; Online: RdRp inhibitors and COVID-19: Is molnupiravir a good option?

Hashemian, Seyed Mohammad Reza / Pourhanifeh, Mohammad Hossein / Hamblin, Michael R / Shahrzad, Mohammad Karim / Mirzaei, Hamed

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2021 Volume 146, Page(s) 112517

Abstract: Rapid changes in the viral genome allow viruses to evade threats posed by the host immune response or antiviral drugs, and can lead to viral persistence in the host cells. RNA-dependent RNA polymerase (RdRp) is an essential enzyme in RNA viruses, which ... ...

Abstract	Rapid changes in the viral genome allow viruses to evade threats posed by the host immune response or antiviral drugs, and can lead to viral persistence in the host cells. RNA-dependent RNA polymerase (RdRp) is an essential enzyme in RNA viruses, which is involved in RNA synthesis through the formation of phosphodiester bonds. Therefore, in RNA viral infections such as SARS-CoV-2, RdRp could be a crucial therapeutic target. The present review discusses the promising application of RdRp inhibitors, previously approved or currently being tested in human clinical trials, in the treatment of RNA virus infections. Nucleoside inhibitors (NIs) bind to the active site of RdRp, while nonnucleoside inhibitors (NNIs) bind to allosteric sites. Given the absence of highly effective drugs for the treatment of COVID-19, the discovery of an efficient treatment for this pandemic is an urgent concern for researchers around the world. We review the evidence for molnupiravir (MK-4482, EIDD-2801), an antiviral drug originally designed for Alphavirus infections, as a potential preventive and therapeutic agent for the management of COVID-19. At the beginning of this pandemic, molnupiravir was in preclinical development for seasonal influenza. When COVID-19 spread dramatically, the timeline for development was accelerated to focus on the treatment of this pandemic. Real time consultation with regulators took place to expedite this program. We summarize the therapeutic potential of RdRp inhibitors, and highlight molnupiravir as a new small molecule drug for COVID-19 treatment.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/enzymology ; Clinical Trials as Topic/methods ; Cytidine/analogs & derivatives ; Cytidine/pharmacology ; Cytidine/therapeutic use ; Humans ; Hydroxylamines/pharmacology ; Hydroxylamines/therapeutic use ; RNA-Dependent RNA Polymerase/antagonists & inhibitors ; RNA-Dependent RNA Polymerase/metabolism ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Hydroxylamines ; Cytidine (5CSZ8459RP) ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; molnupiravir (YA84KI1VEW)
Language	English
Publishing date	2021-12-09
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2021.112517
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Article: Cytokines and microRNAs in SARS-CoV-2: What do we know?

Rarani, Fahimeh Zamani / Rashidi, Bahman / Jafari Najaf Abadi, Mohammad Hassan / Hamblin, Michael R / Reza Hashemian, Seyed Mohammad / Mirzaei, Hamed

Molecular therapy. Nucleic acids

2022 Volume 29, Page(s) 219–242

Abstract: The coronavirus disease 2019 (COVID-19) pandemic constitutes a global health emergency. Currently, there are no completely effective therapeutic medications for the management of this outbreak. The cytokine storm is a hyperinflammatory medical condition ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic constitutes a global health emergency. Currently, there are no completely effective therapeutic medications for the management of this outbreak. The cytokine storm is a hyperinflammatory medical condition due to excessive and uncontrolled release of pro-inflammatory cytokines in patients suffering from severe COVID-19, leading to the development of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS) and even mortality. Understanding the pathophysiology of COVID-19 can be helpful for the treatment of patients. Evidence suggests that the levels of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1 and IL-6 are dramatically different between mild and severe patients, so they may be important contributors to the cytokine storm. Several serum markers can be predictors for the cytokine storm. This review discusses the cytokines involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, focusing on interferons (IFNs) and ILs, and whether they can be used in COVID-19 treatment. Moreover, we highlight several microRNAs that are involved in these cytokines and their role in the cytokine storm caused by COVID-19.
Language	English
Publishing date	2022-06-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2022.06.017
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Article ; Online: Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS

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

a randomized controlled trial

2023 Volume 12

Abstract: Abstract Background and aims The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, ... ...

Abstract	Abstract Background and aims The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients. Materials and methods COVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 106 cells) or one dose of MSCs (100 × 106 cells) followed by one dose of MSC-derived extracellular vesicles (EVs). Patients were assessed for safety and efficacy by evaluating clinical symptoms, laboratory parameters, and inflammatory markers at baseline and 48 h after the second intervention. Results A total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14–1.11; P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005–1.26; P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041). Conclusion MSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events. Trial registration IRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020, http://www.irct.ir/trial/47073 .
Keywords	COVID-19 ; SARS-CoV-2 ; Acute respiratory distress syndrome ; Cytokine release syndrome ; Mesenchymal stromal cells ; Cell therapy ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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