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Article ; Online: Tezepelumab: una nueva opción para el tratamiento del asma grave.

Maldonado-Ríos, Valente Armando / Ardila-Herrera, Juan Camilo / Galicia-Sánchez, Luz María / Celis-Preciado, Carlos Andrés

Revista medica del Instituto Mexicano del Seguro Social

2023 Volume 61, Issue 6, Page(s) 841–848

Abstract: In Latin America, asthma is a public health problem with a significant impact on both patients and health systems. The greater understanding of the pathophysiology and the recognition of the central role that inflammation has in the severity of asthma ... ...

Title translation	Tezepelumab: a new option for the treatment of severe asthma.
Abstract	In Latin America, asthma is a public health problem with a significant impact on both patients and health systems. The greater understanding of the pathophysiology and the recognition of the central role that inflammation has in the severity of asthma has favored the development of monoclonal antibodies that have IL-5, IL-4, IL-13 and IgE as therapeutic targets. Although these therapeutic alternatives promote better control of the disease, not all patients respond favorably to these treatments. Therefore, it is of particular interest to explore monoclonal antibodies such as Tezepelumab, directed against thymic stromal lymphopoietin (TSLP), an alarmin (epithelial cytokine) that participates in the initiation and perpetuation of inflammation in Asthma. Therefore, in this review, we will show the clinical efficacy of tezepelumab in reducing the annual rate of exacerbations, improving lung function, and reducing bronchial hyperreactivity, regardless of the patient's baseline biomarker levels. Therefore, this new molecule is a highly effective therapeutic option for patients with severe asthma.
MeSH term(s)	Humans ; Asthma/drug therapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; Cytokines/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Inflammation
Chemical Substances	tezepelumab (RJ1IW3B4QX) ; Antibodies, Monoclonal, Humanized ; Cytokines ; Antibodies, Monoclonal
Language	Spanish
Publishing date	2023-11-06
Publishing country	Mexico
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	732133-8
ISSN	2448-5667 ; 0443-5117 ; 0484-7849
ISSN (online)	2448-5667
ISSN	0443-5117 ; 0484-7849
DOI	10.5281/zenodo.10064422
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Article ; Online: Repositioning of pentoxifylline as an immunomodulator and regulator of the renin-angiotensin system in the treatment of COVID-19.

Maldonado, Valente / Loza-Mejía, Marco A / Chávez-Alderete, Jaime

Medical hypotheses

2020 Volume 144, Page(s) 109988

Abstract: Pentoxifylline (PTX) is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines to ultimately influence the renin- ... ...

Abstract	Pentoxifylline (PTX) is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines to ultimately influence the renin-angiotensin system (RAS) in vitro by inhibiting angiotensin 1 receptor (AT1R) expression. The rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19 by helping reduce the production of the inflammatory cytokines without deleterious effects on the immune system to delay viral clearance. Moreover, PTX can restore the balance of the immune response, reduce damage to the endothelium and alveolar epithelial cells, improve circulation, and prevent microvascular thrombosis. There is further evidence that PTX can improve ventilatory parameters. Therefore, we propose repositioning PTX in the treatment of COVID-19. The main advantage of repositioning PTX is that it is an affordable drug that is already available worldwide with an established safety profile, further offering the possibility of immediately analysing the result of its use and associated success rates. Another advantage is that PTX selectively reduces the concentration of TNF-α mRNA in cells, which, in the case of an acute infectious state such as COVID-19, would seem to offer a more strategic approach.
MeSH term(s)	Alveolar Epithelial Cells/drug effects ; Angiotensin II/physiology ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/physiopathology ; Complement Activation/drug effects ; Cytokines/biosynthesis ; Cytokines/genetics ; Disease Models, Animal ; Drug Repositioning ; Endothelial Cells/drug effects ; Gene Expression Regulation/drug effects ; Humans ; Immunologic Factors/pharmacology ; Immunologic Factors/therapeutic use ; Inflammation ; Lymphocyte Subsets/drug effects ; Microcirculation/drug effects ; Oxidative Stress ; Pandemics ; Pentoxifylline/pharmacology ; Pentoxifylline/therapeutic use ; Rats ; Receptors, Virus/metabolism ; Renin-Angiotensin System/drug effects ; Renin-Angiotensin System/physiology ; SARS-CoV-2/physiology ; Signal Transduction/drug effects ; Venous Thromboembolism/etiology ; Venous Thromboembolism/prevention & control ; COVID-19 Drug Treatment
Chemical Substances	Cytokines ; Immunologic Factors ; Receptors, Virus ; Angiotensin II (11128-99-7) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Pentoxifylline (SD6QCT3TSU)
Keywords	covid19
Language	English
Publishing date	2020-06-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.109988
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Article ; Online: Repositioning of pentoxifylline as an immunomodulator and regulator of the renin-angiotensin system in the treatment of COVID-19

Maldonado, Valente / Loza-Mejía, Marco A. / Chávez-Alderete, Jaime

Medical Hypotheses

2020 Volume 144, Page(s) 109988

Keywords	General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.109988
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Could biological tissue preservation methods change chemical elements proportion measured by energy dispersive X-ray spectroscopy?

Ladeira, Luiz Carlos Maia / Dos Santos, Eliziária Cardoso / Valente, Gilmar Edilberto / da Silva, Janaina / Santos, Talita Amorim / Dos Santos Costa Maldonado, Izabel Regina

Biological trace element research

2019 Volume 196, Issue 1, Page(s) 168–172

Abstract: Energy dispersive X-ray spectroscopy (EDS) is a powerful technical tool used in the biomedical field to investigate the proportion of chemical elements of interest in research, such as heavy metal bioaccumulation and the enzymatic cofactors and ... ...

Abstract	Energy dispersive X-ray spectroscopy (EDS) is a powerful technical tool used in the biomedical field to investigate the proportion of chemical elements of interest in research, such as heavy metal bioaccumulation and the enzymatic cofactors and nanoparticle therapy in various pathologies. However, the correct evaluation of the proportion of the elements is subject to some factors, including the method of sample preservation. In this study, we seek to investigate the effect of biological tissue preservation methods on the proportion of chemical elements obtained by the EDS methodology. For such, we used EDS to measure the proportion of chemical elements with biomedical interest in preserved livers, using three common methods for preserving biological tissues: (a) freezing, (b) paraformaldehyde fixative solution, and (c) Karnovsky solution. We found an increased level of sodium and reduced contents of potassium and copper in samples fixed in fixative solutions, when compared to frozen samples (p < 0.05). Our data indicate that preservation methods can change the proportion of chemical elements in biological samples, when measured by EDS. Frozen preservation should be preferred to retain the actual chemical content of samples and allow a correct assessment of the proportion of their elements.
MeSH term(s)	Animals ; Liver/chemistry ; Male ; Metals, Alkali/analysis ; Metals, Alkaline Earth/analysis ; Metals, Heavy/analysis ; Mice ; Spectrometry, X-Ray Emission ; Tissue Preservation
Chemical Substances	Metals, Alkali ; Metals, Alkaline Earth ; Metals, Heavy
Language	English
Publishing date	2019-10-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-019-01909-x
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Article: Repositioning of pentoxifylline as an immunomodulator and regulator of the renin-angiotensin system in the treatment of COVID-19

Maldonado, Valente / Loza-Mejía, Marco A / Chávez-Alderete, Jaime

Med Hypotheses

Abstract	Pentoxifylline (PTX) is a phosphodiesterase inhibitor that increases cyclic adenosine monophosphate levels, which in turn activate protein kinase, leading to a reduction in the synthesis of proinflammatory cytokines to ultimately influence the renin-angiotensin system (RAS) in vitro by inhibiting angiotensin 1 receptor (AT1R) expression. The rheological, anti-inflammatory, and renin-angiotensin axis properties of PTX highlight this drug as a therapeutic treatment alternative for patients with COVID-19 by helping reduce the production of the inflammatory cytokines without deleterious effects on the immune system to delay viral clearance. Moreover, PTX can restore the balance of the immune response, reduce damage to the endothelium and alveolar epithelial cells, improve circulation, and prevent microvascular thrombosis. There is further evidence that PTX can improve ventilatory parameters. Therefore, we propose repositioning PTX in the treatment of COVID-19. The main advantage of repositioning PTX is that it is an affordable drug that is already available worldwide with an established safety profile, further offering the possibility of immediately analysing the result of its use and associated success rates. Another advantage is that PTX selectively reduces the concentration of TNF-α mRNA in cells, which, in the case of an acute infectious state such as COVID-19, would seem to offer a more strategic approach.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #591493
Database	COVID19

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Article ; Online: Fibrinolytic Activity of Circulating Microvesicles Is Associated with Progression of Breast Cancer.

Valente-Acosta, Benjamín / Flores-García, Mirthala / González-Zárate, Georgina / Gerson-Cwilich, Raquel / Maldonado-Méndez, Marai / Juárez-Vega, Guillermo / Anglés-Cano, Eduardo / Peña-Díaz, Aurora de la

The Tohoku journal of experimental medicine

2020 Volume 250, Issue 2, Page(s) 121–128

Abstract: The fibrinolytic system plays an important role in breast cancer, favoring progression through extracellular-matrix degradation, angiogenesis, apoptosis and cellular proliferation. The expression of urokinase-type plasminogen activator (uPA) in breast ... ...

Abstract	The fibrinolytic system plays an important role in breast cancer, favoring progression through extracellular-matrix degradation, angiogenesis, apoptosis and cellular proliferation. The expression of urokinase-type plasminogen activator (uPA) in breast cancer tissue is widely recognized as an unfavorable prognostic factor. However, fibrinolytic activity associated with uPA cannot be reliably measured in the blood because of the rapid inhibition of uPA by plasminogen activator inhibitor-1 (PAI-1). By contrast, circulating microvesicles (Mvs) in peripheral blood protect bound enzymes from inhibition. Mvs are extracellular vesicles, released from various types of cells, and their size fluctuates between 100 and 1,000 nm. Mvs carry DNA, RNA, miRNA, and proteins, thereby serving as a source of horizontal communication between cells. We investigated whether fibrinolytic activity on circulating Mvs reflects breast cancer progression. The study population consisted of 13 patients with breast cancer and 13 healthy women. The cancer patients included 4 patients in remission, 3 patients with locally advanced cancer, and 6 with metastatic disease. Mvs were isolated from peripheral blood, quantified by a protein concentration method, and their fibrinolytic potential was measured by their capacity to generate plasmin. Although the quantity of Mvs found in patients with cancer and healthy individuals was similar, plasmin generated on Mvs was twice the amount in patients with metastasis than in healthy women (P < 0.05), underlying the value of this distinctive parameter. The data suggest that in breast cancer patients, higher fibrinolytic activity of circulating Mvs could be related to progression and metastasis of breast cancer.
MeSH term(s)	Adult ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell-Derived Microparticles/metabolism ; Disease Progression ; Female ; Fibrinolysin/metabolism ; Fibrinolysis ; Fluorescence ; Humans ; Middle Aged ; Urokinase-Type Plasminogen Activator/metabolism
Chemical Substances	Fibrinolysin (EC 3.4.21.7) ; Urokinase-Type Plasminogen Activator (EC 3.4.21.73)
Language	English
Publishing date	2020-02-27
Publishing country	Japan
Document type	Journal Article
ZDB-ID	123477-8
ISSN	1349-3329 ; 0040-8727
ISSN (online)	1349-3329
ISSN	0040-8727
DOI	10.1620/tjem.250.121
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Article ; Online: Necrotic carpal tunnel syndrome in a child.

Maldonado García, César / Valente Duarte de Sousa, Isabel Cristina / López Cepeda, Larissa

Pediatric dermatology

2014 Volume 31, Issue 4, Page(s) 500–503

Abstract: Median nerve entrapment at the wrist level causes carpal tunnel syndrome (CTS). Although frequent in adults, CTS is a rare entity in children. Bouvier described an exceptional necrotic variant in 1979 in which skin, nail, and bone lesions are typical. We ...

Abstract	Median nerve entrapment at the wrist level causes carpal tunnel syndrome (CTS). Although frequent in adults, CTS is a rare entity in children. Bouvier described an exceptional necrotic variant in 1979 in which skin, nail, and bone lesions are typical. We report the case of a 10-year-old child with necrotic CTS secondary to trauma. To our knowledge, this is the first case reported in a child.
MeSH term(s)	Carpal Tunnel Syndrome/diagnosis ; Carpal Tunnel Syndrome/etiology ; Carpal Tunnel Syndrome/surgery ; Child ; Decompression, Surgical ; Humans ; Male ; Necrosis ; Wounds and Injuries/complications
Language	English
Publishing date	2014-07
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	605539-4
ISSN	1525-1470 ; 0736-8046
ISSN (online)	1525-1470
ISSN	0736-8046
DOI	10.1111/pde.12066
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Article: Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration.

Schiff, Michael / Weinblatt, Michael E / Valente, Robert / Citera, Gustavo / Maldonado, Michael / Massarotti, Elena / Yazici, Yusuf / Fleischmann, Roy

RMD open

2016 Volume 2, Issue 1, Page(s) e000210

Abstract: Objectives: To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial.: Methods: Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As ... ...

Abstract	Objectives: To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial. Methods: Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI <10, SDAI <11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs >6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated. Results: A total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (>6 months) across multiple clinical measures. Conclusions: Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses. Trial registration number: NCT00929864, Post-results.
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article
ZDB-ID	2812592-7
ISSN	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2015-000210
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Article: Could biological tissue preservation methods change chemical elements proportion measured by energy dispersive X-ray spectroscopy?

Ladeira, Luiz Carlos Maia / dos Santos, Eliziária Cardoso / Valente, Gilmar Edilberto / da Silva, Janaina / Santos, Talita Amorim / dos Santos Costa Maldonado, Izabel Regina

Biological trace element research. 2020 July, v. 196, no. 1

2020

Abstract	Energy dispersive X-ray spectroscopy (EDS) is a powerful technical tool used in the biomedical field to investigate the proportion of chemical elements of interest in research, such as heavy metal bioaccumulation and the enzymatic cofactors and nanoparticle therapy in various pathologies. However, the correct evaluation of the proportion of the elements is subject to some factors, including the method of sample preservation. In this study, we seek to investigate the effect of biological tissue preservation methods on the proportion of chemical elements obtained by the EDS methodology. For such, we used EDS to measure the proportion of chemical elements with biomedical interest in preserved livers, using three common methods for preserving biological tissues: (a) freezing, (b) paraformaldehyde fixative solution, and (c) Karnovsky solution. We found an increased level of sodium and reduced contents of potassium and copper in samples fixed in fixative solutions, when compared to frozen samples (p < 0.05). Our data indicate that preservation methods can change the proportion of chemical elements in biological samples, when measured by EDS. Frozen preservation should be preferred to retain the actual chemical content of samples and allow a correct assessment of the proportion of their elements.
Keywords	bioaccumulation ; copper ; energy-dispersive X-ray analysis ; freezing ; heavy metals ; liver ; nanoparticles ; potassium ; sodium ; therapeutics
Language	English
Dates of publication	2020-07
Size	p. 168-172.
Publishing place	Springer US
Document type	Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-019-01909-x
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Pentoxifylline decreases serum LDH levels and increases lymphocyte count in COVID-19 patients: Results from an external pilot study.

Maldonado, Valente / Hernandez-Ramírez, Claudia / Oliva-Pérez, Eniel Alonso / Sánchez-Martínez, César Omar / Pimentel-González, Jorge Fabián / Molina-Sánchez, José Raúl / Jiménez-Villalba, Yeimmy Zuyenn / Chávez-Alderete, Jaime / Loza-Mejía, Marco A

International immunopharmacology

2020 Volume 90, Page(s) 107209

Abstract: We have previously hypothesized that pentoxifylline could be beneficial for the treatment of COVID-19 given its potential to restore the immune response equilibrium, reduce the impact of the disease on the endothelium and alveolar epithelial cells, and ... ...

Abstract	We have previously hypothesized that pentoxifylline could be beneficial for the treatment of COVID-19 given its potential to restore the immune response equilibrium, reduce the impact of the disease on the endothelium and alveolar epithelial cells, and improve the circulatory function.Serum lactate dehydrogenase (LDH) and lymphocyte count are accessible biomarkers that correlate with the severity of COVID-19, the need for hospitalization, and mortality, reflecting the host immune response's contribution to the seriousness of SARS-CoV-2 infection. We carried out this external pilot study on 38 patients with moderate and severe COVID-19 to test the effect pentoxifylline on parameters such as LDH, lymphocyte count, days of hospitalization, mortality, and proportion of patients requiring intubation. Twenty-six patients were randomized to receive 400 mg of pentoxifylline t.i.d. plus standard therapy (pentoxifylline group), while the rest received the standard treatment (control group). Linear regression models were built for statistically significant parameters. Pentoxifylline treatment was associated with a 64.25% increase (CI95% 11.83, 116.68) in lymphocyte count and a 29.61% decrease (CI95% 15.11, 44.10) in serum LDH. Although a trend towards reduced days of hospitalization, mortality, and proportion of patients requiring intubation was observed, no statistically significant difference was found for these parameters. Our findings open the possibility of pentoxifylline being repositioned as a drug for COVID-19 treatment with the advantages of a proven safety profile, availability, and no risk of immunosuppression; however, this evidence needs to be confirmed in a pragmatic randomized controlled trial.
MeSH term(s)	Aged ; Biomarkers/blood ; COVID-19/blood ; COVID-19/drug therapy ; COVID-19/immunology ; Drug Repositioning ; Female ; Humans ; L-Lactate Dehydrogenase/blood ; Lymphocyte Count ; Male ; Middle Aged ; Pentoxifylline/pharmacology ; Pentoxifylline/therapeutic use ; Pilot Projects ; SARS-CoV-2
Chemical Substances	Biomarkers ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; Pentoxifylline (SD6QCT3TSU)
Language	English
Publishing date	2020-11-26
Publishing country	Netherlands
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2020.107209
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