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  1. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. 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- ... ...

    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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  3. 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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  4. Article: Risk of Pulmonary Fibrosis and Persistent Symptoms Post-COVID-19 in a Cohort of Outpatient Health Workers

    Fernández-Plata, Rosario / Higuera-Iglesias, Anjarath-Lorena / Torres-Espíndola, Luz María / Aquino-Gálvez, Arnoldo / Velázquez Cruz, Rafael / Camarena, Ángel / Chávez Alderete, Jaime / Romo García, Javier / Alvarado-Vásquez, Noé / Martínez Briseño, David / Castillejos-López, Manuel / Group, Research Working

    Viruses. 2022 Aug. 23, v. 14, no. 9

    2022  

    Abstract: Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A ... ...

    Abstract Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. Results: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5–3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. Conclusions: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; chi-square distribution ; gastrointestinal system ; multivariate analysis ; pneumonia ; prospective studies ; pulmonary fibrosis ; risk ; viruses
    Language English
    Dates of publication 2022-0823
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14091843
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Risk of Pulmonary Fibrosis and Persistent Symptoms Post-COVID-19 in a Cohort of Outpatient Health Workers.

    Fernández-Plata, Rosario / Higuera-Iglesias, Anjarath-Lorena / Torres-Espíndola, Luz María / Aquino-Gálvez, Arnoldo / Velázquez Cruz, Rafael / Camarena, Ángel / Chávez Alderete, Jaime / Romo García, Javier / Alvarado-Vásquez, Noé / Martínez Briseño, David / Castillejos-López, Manuel / Group, Research Working

    Viruses

    2022  Volume 14, Issue 9

    Abstract: Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A ... ...

    Abstract Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. Results: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5−3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. Conclusions: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.
    MeSH term(s) COVID-19/complications ; Humans ; Outpatients ; Prospective Studies ; Pulmonary Fibrosis/epidemiology ; SARS-CoV-2
    Language English
    Publishing date 2022-08-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14091843
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Salivary concentrations of cytokines and other analytes in healthy children.

    Chávez-Alderete, Jaime / Gochicoa-Rangel, Laura / Del-Río-Hidalgo, Rodrigo / Guerrero-Zúñiga, Selene / Mora-Romero, Uri / Benítez-Pérez, Rosaura / Rodríguez-Moreno, Luis / Torre-Bouscoulet, Luis / Vargas, Mario H

    Cytokine

    2020  Volume 138, Page(s) 155379

    Abstract: Background: Blood has been the usual biological fluid for measuring analytes, but there is mounting evidence that saliva may be also useful for detecting cytokines in a noninvasive way. Thus, in this study we aimed to determine concentration of ... ...

    Abstract Background: Blood has been the usual biological fluid for measuring analytes, but there is mounting evidence that saliva may be also useful for detecting cytokines in a noninvasive way. Thus, in this study we aimed to determine concentration of cytokines and other analytes in saliva from a population of healthy children.
    Methods: We collected un-stimulated whole saliva samples from clinically healthy children, and concentration of 17 cytokines and 12 other analytes were measured in supernatants. All values were adjusted by albumin content and were log-transformed before multivariate statistical analysis.
    Results: We included 114 children (53.5% females) between 6.0 and 11.9 years old. The highest concentrations (medians, pg/µg albumin) were seen for visfatin (183.70) and adiponectin (162.26) and the lowest for IL-13 and IL-2 (~0.003). Albumin concentration was associated with age (r
    Conclusions: Herein, we provided concentration values for 29 analytes in saliva from healthy children that may be useful as preliminary reference framework in the clinical research setting.
    MeSH term(s) Adiponectin/biosynthesis ; Age Factors ; Body Height ; C-Peptide/biosynthesis ; Child ; Cytokines/biosynthesis ; Cytokines/metabolism ; Female ; Ghrelin/biosynthesis ; Glucagon/biosynthesis ; Glucagon-Like Peptide 1/biosynthesis ; Humans ; Insulin/metabolism ; Interleukin-13/biosynthesis ; Interleukin-2/biosynthesis ; Leptin/biosynthesis ; Male ; Multivariate Analysis ; Nicotinamide Phosphoribosyltransferase/biosynthesis ; Reference Values ; Saliva/metabolism
    Chemical Substances ADIPOQ protein, human ; Adiponectin ; C-Peptide ; Cytokines ; Ghrelin ; IL13 protein, human ; IL2 protein, human ; Insulin ; Interleukin-13 ; Interleukin-2 ; LEP protein, human ; Leptin ; Glucagon-Like Peptide 1 (89750-14-1) ; Glucagon (9007-92-5) ; Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12) ; nicotinamide phosphoribosyltransferase, human (EC 2.4.2.12)
    Language English
    Publishing date 2020-12-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2020.155379
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2840: Show issues Location:
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  7. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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