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Article ; Online: The p,p'-DDE disturbs the M1 function without affecting the M2 phenotype nor unstimulated bone marrow-derived macrophages from BALB/c mice.

Cortés-Montoya, Vanessa / Ortiz-Robles, Christian D / Rivera-Maya, Omar B / Palacios-Valladares, José R / Ramirez-Gutierrez, Erick F / Calderón-Aranda, Emma S

Toxicology

2023 Volume 493, Page(s) 153554

Abstract: ... persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved ... has been evaluated scanty. Herein, we evaluated the impact of p,p'-DDE at environmentally relevant ... or with IL-4 +IL-13 to M2. Thus we study whether the p,p'-DDE induces M0 to a specific phenotype or ...

Abstract	DDT, a persistent organic pollutant, remains affecting human health worldwide. DDT and its most persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved in protecting against pathogens Such metabolite decreases the capability to limit intracellular growth of Mycobacterium microti and yeast. However, the effect on unstimulated (M0) and anti-inflammatory macrophages (M2) has been evaluated scanty. Herein, we evaluated the impact of p,p'-DDE at environmentally relevant concentrations (0.125, 1.25, 2.5, and 5 µg/mL) on bone marrow-derived macrophages stimulated with IFNγ+LPS to M1 or with IL-4 +IL-13 to M2. Thus we study whether the p,p'-DDE induces M0 to a specific phenotype or modulates activation of the macrophage phenotypes and explains, at least partly, the reported effects of p,p'-DDE on the M1 function. The p,p'-DDE did not affect the cell viability of M0 or the macrophage phenotypes. In M1, the p,p'-DDE decreased NO•- production and IL-1β secretion, but increasing cellular ROS and mitochondrial O
MeSH term(s)	Animals ; Humans ; Mice ; Arginase/genetics ; Arginase/metabolism ; Arginase/pharmacology ; DDT/metabolism ; DDT/pharmacology ; Dichlorodiphenyl Dichloroethylene/toxicity ; Dichlorodiphenyl Dichloroethylene/metabolism ; Macrophages/drug effects ; Macrophages/metabolism ; Mice, Inbred BALB C ; Phenotype ; Reactive Oxygen Species/metabolism ; Tumor Necrosis Factor-alpha/genetics
Chemical Substances	Arginase (EC 3.5.3.1) ; DDT (CIW5S16655) ; Dichlorodiphenyl Dichloroethylene (4M7FS82U08) ; Reactive Oxygen Species ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2023-05-24
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2023.153554
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Article ; Online: The p,p’-DDE disturbs the M1 function without affecting the M2 phenotype nor unstimulated bone marrow-derived macrophages from BALB/c mice

Cortés-Montoya, Vanessa / Ortiz-Robles, Christian D. / Rivera-Maya, Omar B. / Palacios-Valladares, José R. / Ramirez-Gutierrez, Erick F. / Calderón-Aranda, Emma S.

Toxicology. 20232023 July 24, May 24, v. 493 p.153554-

2023

Abstract: ... persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved ... has been evaluated scanty. Herein, we evaluated the impact of p,p’-DDE at environmentally relevant ... or with IL-4 +IL-13 to M2. Thus we study whether the p,p’-DDE induces M0 to a specific phenotype or ...

Abstract	DDT, a persistent organic pollutant, remains affecting human health worldwide. DDT and its most persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved in protecting against pathogens Such metabolite decreases the capability to limit intracellular growth of Mycobacterium microti and yeast. However, the effect on unstimulated (M0) and anti-inflammatory macrophages (M2) has been evaluated scanty. Herein, we evaluated the impact of p,p’-DDE at environmentally relevant concentrations (0.125, 1.25, 2.5, and 5 µg/mL) on bone marrow-derived macrophages stimulated with IFNγ+LPS to M1 or with IL-4 +IL-13 to M2. Thus we study whether the p,p’-DDE induces M0 to a specific phenotype or modulates activation of the macrophage phenotypes and explains, at least partly, the reported effects of p,p’-DDE on the M1 function. The p,p’-DDE did not affect the cell viability of M0 or the macrophage phenotypes. In M1, the p,p’-DDE decreased NO•- production and IL-1β secretion, but increasing cellular ROS and mitochondrial O₂•-, but did not alter iNOS, TNF-α, MHCII, and CD86 protein expression nor affect M2 markers arginase activity, TGF-β1, and CD206; p,p'-DDE, did not affect marker expression in M0 or M2, supporting that its effects on M1 parameters are not dependent on M0 nor M2 modulation. The decreasing of NO•- production by the p,p’-DDE without altering iNOS levels, Arginase activity, or TNF-α, but increasing cellular ROS and mitochondrial O₂ suggests that p,p’-DDE interferes with the iNOS function but not with its transcription. The p,p’-DDE decreasing of IL-1β secretion, without any effect on TNF-α, suggest that an alteration of specific targets involved in IL-1β secretion may be affected and related to ROS induction. The p,p’-DDE effect on iNOS function and the IL-1β secretion process, as the NLRP3 activation, deserves further study.
Keywords	DDE (pesticide) ; Mycobacterium microti ; arginase ; cell viability ; human health ; immune response ; interleukin-4 ; macrophages ; metabolites ; mitochondria ; persistent organic pollutants ; phenotype ; protein synthesis ; secretion ; toxicology ; yeasts ; p ; p’-DDE ; M1 phenotype ; M2 phenotype ; Nitric oxide ; INOS ; IL-1β
Language	English
Dates of publication	2023-0524
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2023.153554
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Article ; Online: Association of the POT1 Germline Missense Variant p.I78T With Familial Melanoma.

Wong, Kim / Robles-Espinoza, Carla Daniela / Rodriguez, David / Rudat, Saskia S / Puig, Susana / Potrony, Miriam / Wong, Chi C / Hewinson, James / Aguilera, Paula / Puig-Butille, Joan Anton / Bressac-de Paillerets, Brigitte / Zattara, Hélène / van der Weyden, Louise / Fletcher, Christopher D M / Brenn, Thomas / Arends, Mark J / Quesada, Víctor / Newton-Bishop, Julia A / Lopez-Otin, Carlos /

Bishop, D Timothy / Harms, Paul W / Johnson, Timothy M / Durham, Alison B / Lombard, David B / Adams, David J

JAMA dermatology

2019 Volume 155, Issue 5, Page(s) 604–609

Abstract: ... germline POT1 variant (p.I78T, c.233T>C, chromosome 7, g.124870933A>G, GRCh38) that was subsequently found ... Identification of the POT1 p.I78T variant; (2) evaluation of the clinical features and characteristics ... Results: The POT1 p.I78T variant was found in 3 melanoma pedigrees, all of persons who self-reported ...

Abstract	Importance: The protection of telomeres 1 protein (POT1) is a critical component of the shelterin complex, a multiple-protein machine that regulates telomere length and protects telomere ends. Germline variants in POT1 have been linked to familial melanoma, and somatic mutations are associated with a range of cancers including cutaneous T-cell lymphoma (CTCL). Objective: To characterize pathogenic variation in POT1 in families with melanoma to inform clinical management. Design, setting, and participants: In this case study and pedigree evaluation, analysis of the pedigree of 1 patient with melanoma revealed a novel germline POT1 variant (p.I78T, c.233T>C, chromosome 7, g.124870933A>G, GRCh38) that was subsequently found in 2 other pedigrees obtained from the GenoMEL Consortium. Main outcomes and measures: (1) Identification of the POT1 p.I78T variant; (2) evaluation of the clinical features and characteristics of patients with this variant; (3) analysis of 3 pedigrees; (4) genomewide single-nucleotide polymorphism genotyping of germline DNA; and (5) a somatic genetic analysis of available nevi and 1 melanoma lesion. Results: The POT1 p.I78T variant was found in 3 melanoma pedigrees, all of persons who self-reported as being of Jewish descent, and was shown to disrupt POT1-telomere binding. A UV mutation signature was associated with nevus and melanoma formation in POT1 variant carriers, and somatic mutations in driver genes such as BRAF, NRAS, and KIT were associated with lesion development in these patients. Conclusions and relevance: POT1 p.I78T is a newly identified, likely pathogenic, variant meriting screening for in families with melanoma after more common predisposition genes such as CDKN2A have been excluded. It could also be included as part of gene panel testing.
MeSH term(s)	Adult ; Aged ; Germ-Line Mutation ; Humans ; Jews ; Male ; Melanoma/ethnology ; Melanoma/genetics ; Middle Aged ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Shelterin Complex ; Skin Neoplasms/ethnology ; Skin Neoplasms/genetics ; Telomere-Binding Proteins/genetics ; Melanoma, Cutaneous Malignant
Chemical Substances	POT1 protein, human ; Shelterin Complex ; Telomere-Binding Proteins
Language	English
Publishing date	2019-01-11
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701761-8
ISSN	2168-6084 ; 2168-6068
ISSN (online)	2168-6084
ISSN	2168-6068
DOI	10.1001/jamadermatol.2018.3662
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Article ; Online: Community structure and diversity of five groups of zooplankton in the Perdido region of the Gulf of Mexico using DNA metabarcoding [Correction: Mar. 2023, 57(1), p. 241

Gasca-Pineda, Jaime / Galindo-Sánchez, Clara E. / Martinez-Mercado, Miguel A. / Jiménez-Rosenberg, Sylvia P. A. / Hereu, Clara María / Nakamura, Yasuhide / Herzka, Sharon Z. / Compaire, Jesus C. / Gomez-Reyes, Ricardo / Robles-Flores, Javier / Saavedra-Flores, Anaid / Arteaga, Maria Clara

Aquat Ecol. 2023 Mar., v. 57, no. 1, p. 149-164

2023 , Page(s) 149–164

Abstract: The evaluation of biodiversity is a primary concern for natural sciences and society, including marine ecosystems. Zooplankton plays a crucial role in marine ecosystems, transferring energy between trophic levels and participating in carbon and nutrient ... ...

Abstract	The evaluation of biodiversity is a primary concern for natural sciences and society, including marine ecosystems. Zooplankton plays a crucial role in marine ecosystems, transferring energy between trophic levels and participating in carbon and nutrient cycling. Zooplankton communities respond to changes in environmental conditions in complex ways and are highly susceptible to anthropogenic impacts, including climate change. However, the study of their diversity relative to environmental conditions has been hindered by their extremely high taxonomic diversity, which requires a high level of specialization for the morphological identification of specific taxa. We used metabarcoding to evaluate the relationship between zooplankton diversity and oceanic conditions along two transects in the Perdido region of the northwestern Gulf of Mexico during the summer and fall of 2016. This area has active oil production and ongoing exploratory wells. We focused on five zooplankton groups: Mollusca, Calanoida, Non-Calanoid copepods, Decapoda, and Amphipoda. We found that the studied groups had different levels of diversity that varied among sampling stations and seasons, and the taxonomic composition had larger differences among stations than between seasons. We found that environmental variables may have influenced the presence of zooplanktonic groups; however, we conclude that it is not possible to generalize deterministic factors that influence zooplankton diversity and that both the spatial and temporal scales are needed to take into account to determine the factors that shape such diversity.
Keywords	Amphipoda ; Calanoida ; DNA barcoding ; Decapoda ; Mollusca ; carbon ; climate change ; community structure ; energy ; oils ; species diversity ; summer ; taxonomy ; zooplankton ; Gulf of Mexico
Language	English
Dates of publication	2023-03
Size	p. 149-164
Publishing place	Springer Netherlands
Document type	Article ; Online
ZDB-ID	1411979-1
ISSN	1573-5125 ; 1386-2588
ISSN (online)	1573-5125
ISSN	1386-2588
DOI	10.1007/s10452-022-10002-w
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Article ; Online: P-33 EVALUATION OF CIRCULATING METABOLOME IN THE SEARCH OF POTENTIAL DRUG-INDUCED LIVER INJURY BIOMARKERS

Daniel E. Di Zeo-Sánchez / Inmaculada Medina-Cáliz / Judith Sanabria-Cabrera / Miren Garcia-Cortes / Aida Ortega-Alonso / Alejandro Cueto-Sanchez / Rocio San Juan-Jimenez / Andrés Gonzalez-Jimenez / Ismael Álvares-Álvarez / Hao Niu / Cristina Alonso / Guruprasad P Aithal / Raul J. Andrade / M. Isabel Lucena / Mercedes Robles-Diaz

Annals of Hepatology, Vol 24, Iss , Pp 100397- (2021)

2021

Abstract: ... whereas the glycerophospholipids MEPE and MAPC were decreased (p<0.05) when DILI was compared to control (visits 1&2). More ... glutamic acid and lysine were significantly increased in DILI patients as compared to controls (p<0,05) but did ... not differ between ALI and controls (p>0,05). Conclusion: Most metabolomic differences are found ...

Abstract	Introduction: Idiosyncratic drug-induced liver injury (DILI) is a complex hepatic condition whose diagnosis is challenging due to lack of specific biomarkers. Objectives: We aimed to evaluate serum metabolomic differences between patients with DILI and with other causes of liver injury in search for specific DILI biomarkers. Methods: Metabolomic profiles of serum samples from 26 Spanish DILI patients, 34 with non-DILI acute liver injury (ALI) and 48 healthy controls, were analyzed using UHPLC-MS. To assess changes in disease progression, DILI and ALI patients were followed-up from detection (visit 1), one week (visit 2) and >30 days (visit 3). Data were analyzed using Shapiro-Wilk, Student's t and Wilcoxon tests. Results: Several amino acids, fatty acids (FAs), LPI and bile acids were increased, whereas the glycerophospholipids MEPE and MAPC were decreased (p<0.05) when DILI was compared to control (visits 1&2). More metabolites were altered when ALI was compared to controls, with higher levels of FAs and lower levels of MEPE and MEPC. Both DILI and ALI showed fewer differences at visit 3 compared to controls, although several FAs remained increased. The differences found were more limited when ALI vs DILI were compared. However, at visit 1 ALI showed a significant higher increase in the bile acids and 31 FAs than DILI patients, but with lower levels of MEPE, tryptophan and alanine. Remarkably, the amino acids Phe-Phe, taurine, glutamic acid and lysine were significantly increased in DILI patients as compared to controls (p<0,05) but did not differ between ALI and controls (p>0,05). Conclusion: Most metabolomic differences are found at times closer to DILI recognition (visits 1&2), although abnormal values of FAs remain during recovery. Some FAs species and the amino acids taurine, Phe-Phe glutamic acid, lysine, tryptophan and alanine seem promising DILI biomarker candidates that should be further explored. Funding: CIBERehd, ISCiii-FEDER PI18/00901, PI19/00883.
Keywords	Specialties of internal medicine ; RC581-951
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: A novel genetic variant in the NM_000169.2 region of the GLA gene (p.Gly163*) responsible for Fabry disease.

Robles-Mezcua, Ainhoa / Morcillo-Hidalgo, Luis / Martín-Velázquez, Mónica / León-Fradejas, Miriam / García-Pinilla, José Manuel

Revista espanola de cardiologia (English ed.)

2021 Volume 74, Issue 8, Page(s) 712–714

MeSH term(s)	Fabry Disease/genetics ; Humans ; Mutation ; Pedigree ; alpha-Galactosidase/genetics
Chemical Substances	alpha-Galactosidase (EC 3.2.1.22)
Language	Spanish
Publishing date	2021-02-13
Publishing country	Spain
Document type	Case Reports
ZDB-ID	2592481-3
ISSN	1885-5857 ; 1885-5857
ISSN (online)	1885-5857
ISSN	1885-5857
DOI	10.1016/j.rec.2021.01.004
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Article ; Online: Translational insights into mechanisms underlying residual venous obstruction and the role of factor XI, P-selectin and GPVI in recurrent venous thromboembolism.

Iding, A F J / Kremers, B M M / Nagy, M / Pallares Robles, A / Ten Cate, H / Spronk, H M H / Ten Cate-Hoek, A J

Thrombosis research

2022 Volume 221, Page(s) 58–64

Abstract: ... Patients with RVO (102/306, 33 %) had higher rates of PTS (24 vs. 12 %, p = 0.008), but similar rates ... of recurrence (16 vs. 15 %, p = 0.91) and arterial events (7 vs. 4 %, p = 0.26). RVO was associated ...

Abstract	Background: Residual venous obstruction (RVO) after deep vein thrombosis (DVT) is considered a risk factor of recurrent venous thromboembolism (VTE), arterial events and post-thrombotic syndrome (PTS). We hypothesized thrombo-inflammatory markers might be associated with RVO and clinical outcomes. Materials and methods: In a DVT cohort with routine RVO-assessment and 5-year follow-up, patients were invited for blood withdrawal after stopping anticoagulants. Thrombin generation potential, coagulation enzyme:inhibitor complexes, soluble platelet markers and clinical markers were measured in platelet-poor plasma. Associations were represented as odds ratio (OR) or hazard ratio (HR) per standard deviation. Results: Patients with RVO (102/306, 33 %) had higher rates of PTS (24 vs. 12 %, p = 0.008), but similar rates of recurrence (16 vs. 15 %, p = 0.91) and arterial events (7 vs. 4 %, p = 0.26). RVO was associated with thrombin peak height (OR 1.40 [1.04-1.88]), endogenous thrombin potential (ETP, OR 1.35 [1.02-1.79]), and CRP (OR 1.74 [1.10-2.75]). Recurrent VTE was associated with ETP (HR 1.36 [1.03-1.81]), FXIa:C Conclusions: Our findings indicate RVO was associated with thrombo-inflammation, but this did not predict clinical outcomes in this setting. Importantly, we found recurrent VTE was associated with ongoing coagulation and platelet activation in patients well beyond the acute phase of DVT. Furthermore, sGPVI indicated an increased risk of arterial events, highlighting the role of platelets in arterial thrombosis following DVT.
Language	English
Publishing date	2022-11-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2022.11.023
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Article ; Online: The Novel Variant NP_00454563.2 (p.Glu259Glyfs*77) in Gene PKP2 Associated with Arrhythmogenic Cardiomyopathy in 8 Families from Malaga, Spain

Robles-Mezcua, Ainhoa / Ruíz-Salas, Amalio / Medina-Palomo, Carmen / Robles-Mezcua, María / Díaz-Expósito, Arancha / Ortega-Jiménez, María Victoria / Gimeno-Blanes, Juan Ramón / Jiménez-Navarro, Manuel F. / García-Pinilla, José Manuel

Genes (Basel). 2023 July 19, v. 14, no. 7

2023

Abstract: ... p.(Glu259Glyfs*77) variant in the PKP2 gene. The genetic testing employed next-generation sequencing ...

Abstract	Introduction and objectives: Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. Methods: A descriptive observational study that included eight initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p.(Glu259Glyfs*77) variant in the PKP2 gene. The genetic testing employed next-generation sequencing for the index cases and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. Results: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years and a median follow-up of 39 [24–59] months. Worthy of note are the high incidences of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9%, respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (four patients, 16.7%) and biventricular (four patients, 16.7%); we found no statistical differences in any of the variables analysed. Conclusions: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in eight families of our geographical area in Malaga (Andalusia, Spain), suggesting a founder effect in this area and describe the clinical and risk characteristics.
Keywords	cardiomyopathy ; death ; founder effect ; genes ; heart failure ; myocardium ; observational studies ; penetrance ; phenotype ; risk ; Spain
Language	English
Dates of publication	2023-0719
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14071468
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Article: Natural history of the late-onset phenotype of Fabry disease due to the p.F113L mutation.

Azevedo, Olga / Gago, Miguel F / Miltenberger-Miltenyi, Gabriel / Robles, Ana Raquel / Costa, Maria Antónia / Pereira, Olga / Vide, Ana Teresa / Castelo Branco, Gonçalo / Simões, Sónia / Guimarães, Maria José / Salgado, Ana / Sousa, Nuno / Cunha, Damião

Molecular genetics and metabolism reports

2020 Volume 22, Page(s) 100565

Abstract: Background: The common : Methods: 203 consecutive adult Fabry patients with p.F113L mutation ...

Abstract	Background: The common Methods: 203 consecutive adult Fabry patients with p.F113L mutation (79 males; mean age 46 ± 18 years), from this region, were submitted at baseline to a predefined diagnostic protocol. The occurrence of FD manifestations was analyzed in each decade of age in both genders. Results: In males, left ventricular hypertrophy (40.2%) and late gadolinium enhancement (21.4%) arose over 30 years; heart failure (HF) (21.9%), ventricular tachycardia (8.9%) and conduction disorders over 40 years; and bifascicular (13.1%) and complete atrioventricular blocks (5.9%) beyond 50 years of age. Cardiac manifestations occurred more commonly and 1-2 decades earlier in males; their frequency increased with age. Septum and posterior wall thickness, LV mass, QRS interval duration and pro-BNP levels increased with age in both genders. Mean survival free from HF (64 ± 1 vs. 76 ± 2 years) and pacemaker (71 ± 2 vs. 86 ± 1 years) was higher in females ( Conclusion: This study improves the knowledge on natural history of late-onset variants of FD, carrying major impact on clinical decisions and guidelines.
Language	English
Publishing date	2020-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2821908-9
ISSN	2214-4269
ISSN	2214-4269
DOI	10.1016/j.ymgmr.2020.100565
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Article ; Online: Correlation between urinary KIM-1 and kidney protein expression of p-ERK following damage in rats exposed to gentamicin or lead acetate.

Ruiz-Ramirez, Carolina / Antaño-Martinez, Alejandro R / Robles, Juvencio / Gallegos-Corona, Marco A / Gallegos-Reyes, Marco A / Avila, Eva E / Martinez-Alfaro, Minerva

Journal of biochemical and molecular toxicology

2021 Volume 35, Issue 10, Page(s) e22875

Abstract: ... the association between the kidney overexpression pattern of cytoplasmic phosphorylated-ERK (p-ERK) protein and ... overexpression of cytoplasmic p-ERK protein correlated with increased urinary KIM-1 levels ... that KIM-1 and p-ERK share a common mechanism in kidney injury mediated by both toxic substances ...

Abstract	Kidney injury molecule-1 (KIM-1) is a membrane receptor upregulated in the proximal tubule cells following various types of kidney injuries. Notably, studies have suggested a correlation between KIM-1 expression and extracellular signal-regulated kinase (ERK) activation. In this study, we aimed to investigate the association between the kidney overexpression pattern of cytoplasmic phosphorylated-ERK (p-ERK) protein and increased urinary KIM-1 levels in rats exposed to gentamicin or lead acetate, both at the end of toxic exposure and after a 4-week recovery period. Although other proteins were evaluated, only kidney overexpression of cytoplasmic p-ERK protein correlated with increased urinary KIM-1 levels. For both toxic substances, the increased urinary KIM-1 levels corresponded with kidney inflammation. Our results suggest that KIM-1 and p-ERK share a common mechanism in kidney injury mediated by both toxic substances that induce proximal tubule damage.
MeSH term(s)	Acute Kidney Injury/chemically induced ; Acute Kidney Injury/urine ; Animals ; Calcium Channels/metabolism ; Cation Transport Proteins/metabolism ; Cell Adhesion Molecules/urine ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cytoplasm/metabolism ; Disease Models, Animal ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gentamicins/toxicity ; Histones/metabolism ; Kidney Tubules, Proximal/injuries ; Kidney Tubules, Proximal/metabolism ; Male ; Organometallic Compounds/toxicity ; Phosphorylation ; Rats ; Rats, Wistar ; Signal Transduction/drug effects ; TRPV Cation Channels/metabolism
Chemical Substances	Calcium Channels ; Cation Transport Proteins ; Cdkn1a protein, rat ; Cell Adhesion Molecules ; Cyclin-Dependent Kinase Inhibitor p21 ; Gentamicins ; Havcr1protein, rat ; Histones ; Organometallic Compounds ; TRPV Cation Channels ; TRPV5 protein, rat ; solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2 ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; lead acetate (RX077P88RY)
Language	English
Publishing date	2021-08-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1410020-4
ISSN	1099-0461 ; 1095-6670
ISSN (online)	1099-0461
ISSN	1095-6670
DOI	10.1002/jbt.22875
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