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Article ; Online: The Renin-Angiotensin-Aldosterone System and Coronavirus Disease 2019.

Coto, Eliecer / Avanzas, Pablo / Gómez, Juan

European cardiology

2021 Volume 16, Page(s) e07

Abstract: The renin-aldosterone-angiotensin system (RAAS) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) ...

Abstract	The renin-aldosterone-angiotensin system (RAAS) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2 and the host's expression of this membrane-bound protein could affect susceptibility to infection. The RAAS is an important regulator of cardiovascular physiology and ACE2 has an essential role. People with hypertension and other traits have shown to have an imbalance in ACE/ACE2 levels and reduced levels of ACE2 could enhance the risk of adverse outcome in patients with COVID-19. It has been hypothesised that the RAAS may mediate the interplay between cardiovascular disease and COVID-19 severity. Evidence shows that antihypertensive drugs that target the RAAS have no significant effect on the risk of infection and disease outcome. Variations in RAAS genes have been associated with the risk of developing hypertension and cardiovascular disease and could partly explain the heterogenous response to SARS-CoV-2 infection. This article explores the interplay between the RAAS and COVID-19, with emphasis on the possible relationship between genetic variations and disease severity.
Language	English
Publishing date	2021-03-09
Publishing country	England
Document type	Journal Article ; Review
ISSN	1758-3764
ISSN (online)	1758-3764
DOI	10.15420/ecr.2020.30
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Article ; Online: Immunoglobulin genes and severity of COVID-19.

Vázquez-Coto, Daniel / Kimball, Christine / Albaiceta, Guillermo M / Amado-Rodríguez, Laura / García-Clemente, Marta / Gómez, Juan / Coto, Eliecer / Pandey, Janardan P

Immunogenetics

2024

Abstract: There is tremendous interindividual and interracial variability in the outcome of SARS-CoV-2 infection, suggesting the involvement of host genetic factors. Here, we investigated whether IgG allotypes GM (γ marker) 3 and GM 17, genetic markers of IgG1, ... ...

Abstract	There is tremendous interindividual and interracial variability in the outcome of SARS-CoV-2 infection, suggesting the involvement of host genetic factors. Here, we investigated whether IgG allotypes GM (γ marker) 3 and GM 17, genetic markers of IgG1, contributed to the severity of COVID-19. IgG1 plays a pivotal role in response against SARS-CoV-2 infection. We also investigated whether these GM alleles synergistically/epistatically with IGHG3 and FCGR2A alleles-which have been previously implicated in COVID-19-modulated the extent of COVID-19 severity. The study population consisted of 316 COVID-19 patients who needed treatment in the intensive care unit of Hospital Universitario Central de Asturias. All individuals were genotyped for GM 3/17, IGHG3 hinge length, and FCGR2A rs1801274 A/G polymorphisms. Among the 316 critical patients, there were 86 deaths. The risk of death among critical patients was significantly higher in subjects with GM 17 (IgG1) and short hinge length (IgG3). GM 17-carriers were at almost three-fold higher risk of death than non-carriers (p < 0.001; OR = 2.86, CI 1.58-5.16). Subjects with short hinge length of IgG3 had a two-fold higher risk of death than those with medium hinge length (p = 0.01; OR = 2.16, CI 1.19-3.90). GM 3/3 and IGHG3 (MM) genotypes were less frequent among death vs. survivors (9% vs 36%, p < 0.001) and associated with protective effect (OR = 0.18, 95% CI = 0.08-0.39). This is the first report implicating IgG1 allotypes in COVID-19-spurred death. It needs to be replicated in an independent study population.
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	186560-2
ISSN	1432-1211 ; 0093-7711
ISSN (online)	1432-1211
ISSN	0093-7711
DOI	10.1007/s00251-024-01341-z
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Article ; Online: Genetic Variants of the NF-κB Pathway: Unraveling the Genetic Architecture of Psoriatic Disease.

Queiro, Rubén / Coto, Pablo / González-Lara, Leire / Coto, Eliecer

International journal of molecular sciences

2021 Volume 22, Issue 23

Abstract: Psoriasis is a multifactorial genetic disease for which the genetic factors explain about 70% of disease susceptibility. Up to 30-40% of psoriasis patients develop psoriatic arthritis (PsA). However, PsA can be considered as a "disease within a disease", ...

Abstract	Psoriasis is a multifactorial genetic disease for which the genetic factors explain about 70% of disease susceptibility. Up to 30-40% of psoriasis patients develop psoriatic arthritis (PsA). However, PsA can be considered as a "disease within a disease", since in most cases psoriasis is already present when joint complaints begin. This has made studies that attempt to unravel the genetic basis for both components of psoriatic disease enormously difficult. Psoriatic disease is also accompanied by a high burden of comorbid conditions, mainly of the cardiometabolic type. It is currently unclear whether these comorbidities and psoriatic disease have a shared genetic basis or not. The nuclear factor of kappa light chain enhancer of activated B cells (NF-κB) is a transcription factor that regulates a plethora of genes in response to infection, inflammation, and a wide variety of stimuli on several cell types. This mini-review is focused on recent findings that highlight the importance of this pathway both in the susceptibility and in the determinism of some features of psoriatic disease. We also briefly review the importance of genetic variants of this pathway as biomarkers of pharmacological response. All the above may help to better understand the etiopathogenesis of this complex entity.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Arthritis, Psoriatic/genetics ; Arthritis, Psoriatic/pathology ; B-Lymphocytes/immunology ; CARD Signaling Adaptor Proteins/genetics ; Comorbidity ; Genetic Predisposition to Disease/genetics ; Guanylate Cyclase/genetics ; Humans ; Membrane Proteins/genetics ; NF-KappaB Inhibitor alpha/genetics ; NF-kappa B/genetics ; NF-kappa B/metabolism ; NF-kappa B p50 Subunit/genetics ; Receptors, Tumor Necrosis Factor, Type II/genetics ; Transcription Factor RelA/genetics ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; CARD Signaling Adaptor Proteins ; Membrane Proteins ; NF-kappa B ; NF-kappa B p50 Subunit ; NFKB1 protein, human ; NFKBIA protein, human ; NFKBIZ protein, human ; RELA protein, human ; Receptors, Tumor Necrosis Factor, Type II ; TNF protein, human ; TNFRSF1B protein, human ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha ; NF-KappaB Inhibitor alpha (139874-52-5) ; CARD14 protein, human (EC 4.6.1.-) ; Guanylate Cyclase (EC 4.6.1.2)
Language	English
Publishing date	2021-11-30
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/ijms222313004
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Article ; Online: The

Coto-Segura, Pablo / Vázquez-Coto, Daniel / Velázquez-Cuervo, Lucinda / García-Lago, Claudia / Coto, Eliecer / Queiro, Rubén

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: The melanoma differentiation-associated protein 5 (MDA5; encoded by ... ...

Abstract	The melanoma differentiation-associated protein 5 (MDA5; encoded by the
MeSH term(s)	Humans ; Interferon-Induced Helicase, IFIH1/genetics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Arthritis, Psoriatic/genetics ; Psoriasis/genetics ; Vincristine
Chemical Substances	Interferon-Induced Helicase, IFIH1 (EC 3.6.4.13) ; Vincristine (5J49Q6B70F) ; IFIH1 protein, human (EC 3.6.1.-)
Language	English
Publishing date	2023-09-30
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/ijms241914803
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Article: Influence of the HLA-Cw6 Allele and

Queiro, Rubén / Braña, Ignacio / Pardo, Estefanía / Loredo, Marta / Burger, Stefanie / González Del Pozo, Pablo / Alvarez, Paula / Fernández-Bretón, Eva / Coto, Pablo / Coto, Eliecer

Journal of clinical medicine

2024 Volume 13, Issue 3

Abstract: Background: Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check ... ...

Abstract	Background: Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check this finding in our setting. Methods: A cross-sectional observational study (n: 572 psoriasis patients, 30% with PsA) was conducted. Different study variables were collected in detail, as well as classic cardiometabolic risk factors. The distribution of the HLA-Cw6 allele and the Results: The study cohort included 309 men and 263 women, with a mean age of 46.7 years (SD 14.5) and a mean disease duration of 19.4 years (SD 14.8). We confirmed the known association between HLA-Cw6 and type I psoriasis (familial, severe, and early onset). Psoriasis severity (OR: 2.14), female sex (OR: 1.63), and the Conclusions: The influence of HLA-Cw6 on the cardiometabolic risk profile of psoriatic patients seems to be explained by other factors (age, sex, duration of the disease or arthritis) and not by this biomarker itself.
Language	English
Publishing date	2024-02-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13030845
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Article ; Online: NFKB1 variants were associated with the risk of Parkinson´s disease in male.

Perez-Oliveira, Sergio / Vazquez-Coto, Daniel / Pardo, Sara / Blázquez-Estrada, Marta / Menéndez-González, Manuel / Siso, Pablo / Suárez, Esther / García-Fernández, Ciara / Fages, Beatriz de la Casa / Coto, Eliecer / Álvarez, Victoria

Journal of neural transmission (Vienna, Austria : 1996)

2024

Abstract: The NF-κB pathway is involved in the pathogenesis of neurological disorders that have inflammation as a hallmark, including Parkinson's disease (PD). Our objective was to determine whether common functional variants in the NFKB1, NFKBIA and NFKBIZ genes ... ...

Abstract	The NF-κB pathway is involved in the pathogenesis of neurological disorders that have inflammation as a hallmark, including Parkinson's disease (PD). Our objective was to determine whether common functional variants in the NFKB1, NFKBIA and NFKBIZ genes were associated with the risk of PD. A total of 532 Spanish PD cases (61% male; 38% early-onset, ≤ 55 years) and 300 population controls (50% ≤55 years) were genotyped for the NFKB1 rs28362491 and rs7667496, NFKBIA rs696, and NFKBIZ rs1398608 polymorphisms. We compared allele and genotype frequencies between early and late-onset, male and female, and patient's vs. controls. We found that the two NFKB1 alleles were significantly associated with PD in our population (p = 0.01; total patients vs. controls), without difference between Early and Late onset patients. The frequencies of the NFKB1 variants significantly differ between male and female patients. Compared to controls, male patients showed a significantly higher frequency of rs28362491 II (p = 0.02, OR = 1.52, 95%CI = 1.10-2.08) and rs28362491 C (p = 0.003, OR = 1.62, 95%CI = 1.18-2.22). The two NFKB1 variants were in strong linkage disequilibrium and the I-C haplotype was significantly associated with the risk of PD among male (p = 0.002). In conclusion, common variants in the NF-kB genes were associated with the risk of developing PD in our population, with significant differences between male and female. These results encourage further studies to determine the involvement of the NF-kB components in the pathogenesis of Parkinson´s disease.
Language	English
Publishing date	2024-02-28
Publishing country	Austria
Document type	Journal Article
ZDB-ID	184163-4
ISSN	1435-1463 ; 0300-9564
ISSN (online)	1435-1463
ISSN	0300-9564
DOI	10.1007/s00702-024-02759-1
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Article ; Online: Lack of association between SNPsrs8176719 (O blood group) and COVID-19: Data from Spanish age matched patients and controls.

Coto, Eliecer / Albaiceta, Guillermo M / Clemente, Marta G / Gómez, Juan

Transfusion

2020 Volume 61, Issue 2, Page(s) 654–656

MeSH term(s)	ABO Blood-Group System ; COVID-19 ; Humans ; Retrospective Studies ; SARS-CoV-2
Chemical Substances	ABO Blood-Group System
Language	English
Publishing date	2020-12-01
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.16206
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Article ; Online: Hereditary angioedema caused by a novel intronic variant of SERPING1.

López-Martínez, Rocío / Martínez-Borra, Jesús / Fernández-González, Porfirio / Coto, Eliecer / Toyos-González, Paula

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology

2021 Volume 33, Issue 1, Page(s) e13681

MeSH term(s)	Angioedemas, Hereditary/diagnosis ; Angioedemas, Hereditary/genetics ; Complement C1 Inactivator Proteins/genetics ; Complement C1 Inhibitor Protein/genetics ; Humans ; Mutation ; Pedigree
Chemical Substances	Complement C1 Inactivator Proteins ; Complement C1 Inhibitor Protein ; SERPING1 protein, human
Language	English
Publishing date	2021-12-31
Publishing country	England
Document type	Letter
ZDB-ID	1057059-7
ISSN	1399-3038 ; 0905-6157 ; 0906-5784
ISSN (online)	1399-3038
ISSN	0905-6157 ; 0906-5784
DOI	10.1111/pai.13681
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Article ; Online: DNA genotyping of the ABO gene showed a significant association of the A-group (A1/A2 variants) with severe COVID-19.

Gómez, Juan / Albaiceta, Guillermo M / García-Clemente, Marta / García-Gala, José M / Coto, Eliecer

European journal of internal medicine

2021 Volume 88, Page(s) 129–132

Language	English
Publishing date	2021-02-25
Publishing country	Netherlands
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2021.02.016
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Article ; Online: Common mitochondrial haplogroups as modifiers of the onset-age for critical COVID-19.

Vázquez-Coto, Daniel / Albaiceta, Guillermo M / Amado-Rodríguez, Laura / Clemente, Marta G / Cuesta-Llavona, Elías / Gómez, Juan / Coto, Eliecer

Mitochondrion

2022 Volume 67, Page(s) 1–5

Abstract: As a key regulator of innate immunity, mitochondrial function is essential to maintain antiviral activities. Common mitochondrial DNA variants (haplogroups) have been associated with different physiological capacities and the nrisk of developing several ... ...

Abstract	As a key regulator of innate immunity, mitochondrial function is essential to maintain antiviral activities. Common mitochondrial DNA variants (haplogroups) have been associated with different physiological capacities and the nrisk of developing several diseases. Haplogroup H was associated with increased survival among sepsis patients, and lower risk of progression toward AIDS in HIV infected and lower manifestation of severe manifestation of herpex virus disease. We studied 316 Spanish with critical COVID-19, and found that the 7028C (haplogroup H) was protective among patients with early-onset disease (≤65 vs > 65 years, p = 0.01), while the ancestral 16223T was a risk factor for early-onset critical COVID-19 (OR = 3.36, 95 %CI = 1.49-7.54). Our work suggested that common mitochondrial variants may serve as predictors of COVID-19 severity. Additional studies to confirm this effect from other populations are of special interest.
MeSH term(s)	Humans ; Haplotypes ; COVID-19/genetics ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; Risk Factors
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2022-09-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2022.09.001
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