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  1. Article: COVID-19: Pandemic in Ecuador: a health disparities perspective.

    Toulkeridis, Theofilos / Seqqat, Rachid / Torres A, Marbel / Ortiz-Prado, Esteban / Debut, Alexis

    Revista de salud publica (Bogota, Colombia)

    2023  Volume 22, Issue 3, Page(s) 304–308

    Abstract: Background: The global COVID-19 pandemic initiated in Ecuador with the patient zero in February 2020 and since more than 40,000 persons have been tested positive to the virus, leaving some 3,500 deceased, while approximately about 10,500 persons above ... ...

    Abstract Background: The global COVID-19 pandemic initiated in Ecuador with the patient zero in February 2020 and since more than 40,000 persons have been tested positive to the virus, leaving some 3,500 deceased, while approximately about 10,500 persons above annual average numbers died within March to May. A strict lockdown was applied by mid-March, which resulted to a severe economic crisis in the country. Although during the lockdown.
    Objective: Our study postulates, that persons who are most likely to be infected during such secondary wave will be people who have already health issues to which we count besides the known ones, especially those who are already suffer by the distribution of volcanic ashes, as such pyroclastic material is known to affect lunges and thyroids. occurred a notable decrease in the number of new cases, the spread of the infection was already massive, untechnical, political and economic decisions will certainly lead to continuous wave of infections for months.
    Methods: A descriptive ecological study of information related to COVID-19 infection at a national level using official data from the Minister of Public Health and volcanic ash fall by geographical area in Ecuador.
    Results: The mortality rate per canton indicated that those with lower attack rates are the ones with highest mortality rate. For instance, Portovelo (21.3/100,000), Playas (18.4/100,000), Santa Rosa (15.8/100,000), Suscal (15.3/100,000) and Penipe (14.3/100,000) reported the highest mortality rate per 100,000 people. The main distribution of such volcanic material is within the central to northern area of the Highlands and Inter-Andean Valley of Ecuador, due to the analysis of some 7394 satellite images of the last 21 years.
    Conclusions: We conclude that areas with high vulnerabilities are also most susceptible to develop COVID-19. Such areas with their respective populations will be affected above average and shall be protected in particular within the presently starting during possible second wave of infection.
    MeSH term(s) Humans ; COVID-19/epidemiology ; Ecuador/epidemiology ; Pandemics ; Communicable Disease Control ; Public Health
    Language English
    Publishing date 2023-01-18
    Publishing country Colombia
    Document type Journal Article
    ZDB-ID 2060572-9
    ISSN 0124-0064
    ISSN 0124-0064
    DOI 10.15446/rsap.V22n3.88102
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Silver nanoparticles as a potential treatment against SARS-CoV-2: A review.

    Pilaquinga, Fernanda / Morey, Jeroni / Torres, Marbel / Seqqat, Rachid / Piña, María de Las Nieves

    Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology

    2021  Volume 13, Issue 5, Page(s) e1707

    Abstract: Several human coronaviruses (HCoVs) are distinguished by the ability to generate epidemics or pandemics, with their corresponding diseases characterized by severe respiratory illness, such as that which occurs in severe acute respiratory syndrome (SARS- ... ...

    Abstract Several human coronaviruses (HCoVs) are distinguished by the ability to generate epidemics or pandemics, with their corresponding diseases characterized by severe respiratory illness, such as that which occurs in severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and, today, in SARS-CoV-2, an outbreak that has struck explosively and uncontrollably beginning in December 2019 and has claimed the lives of more than 1.9 M people worldwide as of January 2021. The development of vaccines has taken one year, which is why it is necessary to investigate whether some already-existing alternatives that have been successfully developed in recent years can mitigate the pandemic's advance. Silver nanoparticles (AgNPs) have proved effective in antiviral action. Thus, in this review, several in vitro and in vivo studies of the effect of AgNPs on viruses that cause respiratory diseases are analyzed and discussed to promote an understanding of the possible interaction of AgNPs with SARS-CoV-2. The study focuses on several in vivo toxicological studies of AgNPs and a dose extrapolation to humans to determine the chief avenue of exposure. It can be concluded that the use of AgNPs as a possible treatment for SARS-CoV-2 could be viable, based on comparing the virus' behavior to that of similar viruses in in vivo studies, and that the suggested route of administration in terms of least degree of adverse effects is inhalation. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.
    MeSH term(s) COVID-19/therapy ; Humans ; Metal Nanoparticles/therapeutic use ; Pandemics ; SARS-CoV-2/drug effects ; Silver
    Chemical Substances Silver (3M4G523W1G)
    Language English
    Publishing date 2021-02-27
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2502698-7
    ISSN 1939-0041 ; 1939-5116
    ISSN (online) 1939-0041
    ISSN 1939-5116
    DOI 10.1002/wnan.1707
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: COVID-19

    Toulkeridis, Theofilos / Seqqat, Rachid / Torres Arias, Marbel / Ortiz-Prado, Esteban / Debut, Alexis

    Revista de Salud Pública; Vol. 22 No.; 1-5 ; Revista de Salud Pública; Vol. 22 Núm. 3 (2020); 1-5 ; 2539-3596 ; 0124-0064

    Pandemic in Ecuador: a health disparities perspective ; COVID-19: pandemia en Ecuador desde una perspectiva de las disparidades de salud

    2020  Volume 3

    Abstract: The global COVID-19 pandemic initiated in Ecuador with the patient zero in February 2020 and since more than 40,000 persons have been tested positive to the virus, leaving some 3,500 deceased, while approximately about 10,500 persons above annual average ...

    Abstract The global COVID-19 pandemic initiated in Ecuador with the patient zero in February 2020 and since more than 40,000 persons have been tested positive to the virus, leaving some 3,500 deceased, while approximately about 10,500 persons above annual average numbers died within March to May. A strict lockdown was applied by mid-March, which resulted to a severe economic crisis in the country. Although during the lockdown occurred a notable decrease in the number of new cases, the spread of the infection was already massive, untechnical, political and economic decisions will certainly lead to continuous wave of infections for months.Objective Our study postulates, that persons who are most likely to be infected during such secondary wave will be people who have already health issues to which we count besides the known ones, especially those who are already suffer by the distribution of volcanic ashes, as such pyroclastic material is known to affect lunges and thyroids.Methods A descriptive ecological study of information related to COVID-19 infection at a national level using official data from the Minister of Public Health and volcanic ash fall by geographical area in Ecuador.Results The mortality rate per canton indicated that those with lower attack rates are the ones with highest mortality rate. For instance, Portovelo (21.3/100,000), Playas (18.4/100,000), Santa Rosa (15.8/100,000), Suscal (15.3/100,000) and Penipe (14.3/100,000) reported the highest mortality rate per 100,000 people. The main distribution of such volcanic material is within the central to northern area of the Highlands and Inter-Andean Valley of Ecuador, due to the analysis of some 7394 satellite images of the last 21 years.Conclusions We conclude that areas with high vulnerabilities are also most susceptible to develop COVID-19. Such areas with their respective populations will be affected above average and shall be protected in particular within the presently starting during possible second wave of infection.

    La pandemia de COVID-19 inició en Ecuador en febrero de 2020. Desde el inicio más de 40 000 personas han sido oficialmente diagnosticadas con el virus, que ha dejado al menos 3 500 fallecidas, mientras que aproximadamente unas 10 500 personas por encima del promedio anual murieron entre marzo y mayo de 2020. A mediados de marzo se aplicó el confinamiento absoluto en el país, lo que provocó una grave crisis económica y social en Ecuador. Aunque el bloqueo produjo una reducción en el número de casos, la infección estaba propagada ya entre la comunidad y los diagnósticos aumentaron notable debido a decisiones políticas y económicas, que, sin lugar a duda, conducirán a oleadas posteriores de infección por incluso meses.Objetivo Nuestro estudio postula que las personas que tienen más probabilidades de infectarse durante dicha ola secundaria serán las personas que ya tengan problemas de salud. A la vez, proponemos que aquellos pobladores que ya están sufriendo por la caída de cenizas volcánicas y flujos piroclásticos pueden tener más riesgo tal como lo describimos en casos relacionados con cáncer de tiroides y ceniza.Métodos Es un estudio ecológico descriptivo de la información relacionada con la infección por COVID-19 a nivel nacional, utilizando datos oficiales de contagio del Ministerio de Salud Pública y caída de cenizas volcánicas por área geográfica en Ecuador.Resultados La tasa de mortalidad por cantón indicó que aquellos con tasas de ataque más bajas son los que tienen la tasa de mortalidad más alta. Por ejemplo, Portovelo (21,3/100.000), Playas (18,4/100.000), Santa Rosa (15,8/100 000), Suscal (15,3/100 000) y Penipe (14,3/100 000) registraron la tasa de mortalidad más alta por cada 100 000 personas. La principal distribución de dicho material volcánico se encuentra dentro de la zona centro-norte de la Sierra y Valle Interandino del Ecuador, debido al análisis de unas 7 394 imágenes satelitales de los últimos 21 años.Conclusiones Concluimos que las áreas con alta vulnerabilidad también son más susceptibles a desarrollar COVID-19. Tales áreas con sus respectivas poblaciones se verán afectadas por encima de la media y estarán protegidas, en particular, dentro del inicio actual durante una posible segunda ola de infección.
    Keywords Covid19 ; cinza vulcanica ; vulnerabilidade pulmonar ; segunda onda de infecção ; Saúde pública ; epidemiologia ; vulcanologia ; prevenção ; Salud publica ; epidemiología ; vulcanología prevención ; Public health ; epidemiology ; volcanology ; prevention ; covid19
    Language English
    Publishing date 2020-11-05
    Publisher Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Instituto de Salud Pública
    Publishing country co
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Volcanic Ash as a Precursor for SARS-CoV-2 Infection Among Susceptible Populations in Ecuador: A Satellite Imaging and Excess Mortality-Based Analysis.

    Toulkeridis, Theofilos / Seqqat, Rachid / Torres Arias, Marbel / Salazar-Martinez, Rodolfo / Ortiz-Prado, Esteban / Chunga, Scarlet / Vizuete, Karla / Heredia-R, Marco / Debut, Alexis

    Disaster medicine and public health preparedness

    2021  , Page(s) 1–13

    Abstract: The global coronavirus disease 2019 (COVID-19) pandemic has altered entire nations and their health systems. The greatest impact of the pandemic has been seen among vulnerable populations, such as those with comorbidities like heart diseases, kidney ... ...

    Abstract The global coronavirus disease 2019 (COVID-19) pandemic has altered entire nations and their health systems. The greatest impact of the pandemic has been seen among vulnerable populations, such as those with comorbidities like heart diseases, kidney failure, obesity, or those with worse health determinants such as unemployment and poverty. In the current study, we are proposing previous exposure to fine-grained volcanic ashes as a risk factor for developing COVID-19. Based on several previous studies it has been known since the mid 1980s of the past century that volcanic ash is most likely an accelerating factor to suffer from different types of cancer, including lung or thyroid cancer. Our study postulates, that people who are most likely to be infected during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) widespread wave will be those with comorbidities that are related to previous exposure to volcanic ashes. We have explored 8703 satellite images from the past 21 y of available data from the National Oceanic and Atmospheric Administration (NOAA) database and correlated them with the data from the national institute of health statistics in Ecuador. Additionally, we provide more realistic numbers of fatalities due to the virus based on excess mortality data of 2020-2021, when compared with previous years. This study would be a very first of its kind combining social and spatial distribution of COVID-19 infections and volcanic ash distribution. The results and implications of our study will also help countries to identify such aforementioned vulnerable parts of the society, if the given geodynamic and volcanic settings are similar.
    Language English
    Publishing date 2021-05-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2375268-3
    ISSN 1938-744X ; 1935-7893
    ISSN (online) 1938-744X
    ISSN 1935-7893
    DOI 10.1017/dmp.2021.154
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: In vitro evaluation of silver nanoparticles cytotoxicity on Hepatic cancer (Hep-G2) cell line and their antioxidant activity: Green approach for fabrication and application.

    Kumar, Brajesh / Smita, Kumari / Seqqat, Rachid / Benalcazar, Karen / Grijalva, Marcelo / Cumbal, Luis

    Journal of photochemistry and photobiology. B, Biology

    2016  Volume 159, Page(s) 8–13

    Abstract: In this article, biosynthesis of silver nanoparticles (AgNPs) using Andean Mora (Rubus glaucus Benth.) leaf has been reported. Different analytical techniques including UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy ...

    Abstract In this article, biosynthesis of silver nanoparticles (AgNPs) using Andean Mora (Rubus glaucus Benth.) leaf has been reported. Different analytical techniques including UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used for the characterization of AgNPs. The initial appearance of color change with the intense surface plasmon resonance (SPR) bands around 440-455 in UV-visible spectra revealing the formation of AgNPs. The TEM image showed the AgNPs to be anisotropic, quasi-spherical in shape with sizes in the range of 12-50nm. On the other hand, XRD studies revealed the formation of face-centered cubic structure for AgNPs. The surface modified AgNPs showed no cytotoxicity at the concentration ranging from 0.01μM to 1.0μM on the Hepatic cancer (Hep-G2) cell line and observed antioxidant efficacy >70% at the concentration 0.05mM/0.20mL against 1, 1-diphenyl-2-picrylhydrazyl. From the results obtained it is suggested that AgNPs could be used effectively in future drug delivery systems and other biomedical concerns.
    MeSH term(s) Antioxidants/pharmacology ; Cell Proliferation ; Drug Screening Assays, Antitumor ; Hep G2 Cells ; Humans ; Metal Nanoparticles/chemistry ; Microscopy, Electron, Transmission ; Silver/chemistry ; Spectrum Analysis/methods ; X-Ray Diffraction
    Chemical Substances Antioxidants ; Silver (3M4G523W1G)
    Language English
    Publishing date 2016-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 623022-2
    ISSN 1873-2682 ; 1011-1344
    ISSN (online) 1873-2682
    ISSN 1011-1344
    DOI 10.1016/j.jphotobiol.2016.03.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Loss of Protease-Activated Receptor 4 Prevents Inflammation Resolution and Predisposes the Heart to Cardiac Rupture After Myocardial Infarction.

    Kolpakov, Mikhail A / Guo, Xinji / Rafiq, Khadija / Vlasenko, Liudmila / Hooshdaran, Bahman / Seqqat, Rachid / Wang, Tao / Fan, Xiaoxuan / Tilley, Douglas G / Kostyak, John C / Kunapuli, Satya P / Houser, Steven R / Sabri, Abdelkarim

    Circulation

    2020  Volume 142, Issue 8, Page(s) 758–775

    Abstract: Background: Cardiac rupture is a major lethal complication of acute myocardial infarction (MI). Despite significant advances in reperfusion strategies, mortality from cardiac rupture remains high. Studies suggest that cardiac rupture can be accelerated ... ...

    Abstract Background: Cardiac rupture is a major lethal complication of acute myocardial infarction (MI). Despite significant advances in reperfusion strategies, mortality from cardiac rupture remains high. Studies suggest that cardiac rupture can be accelerated by thrombolytic therapy, but the relevance of this risk factor remains controversial.
    Methods: We analyzed protease-activated receptor 4 (Par4) expression in mouse hearts with MI and investigated the effects of Par4 deletion on cardiac remodeling and function after MI by echocardiography, quantitative immunohistochemistry, and flow cytometry.
    Results: Par4 mRNA and protein levels were increased in mouse hearts after MI and in isolated cardiomyocytes in response to hypertrophic and inflammatory stimuli. Par4-deficient mice showed less myocyte apoptosis, reduced infarct size, and improved functional recovery after acute MI relative to wild-type (WT). Conversely, Par4
    Conclusions: These findings reveal essential roles of Par4 in neutrophil apoptosis and inflammation resolution during myocardial healing and point to Par4 inhibition as a potential therapy that should be limited to the acute phases of ischemic insult and avoided for long-term treatment after MI.
    MeSH term(s) Animals ; Female ; Gene Expression Regulation ; Heart Rupture/etiology ; Heart Rupture/genetics ; Heart Rupture/metabolism ; Heart Rupture/prevention & control ; Inflammation/genetics ; Inflammation/metabolism ; Inflammation/prevention & control ; Male ; Mice ; Mice, Knockout ; Myocardial Infarction/classification ; Myocardial Infarction/genetics ; Myocardial Infarction/metabolism ; Myocardial Infarction/prevention & control ; Myocardium/metabolism ; Receptors, Thrombin/biosynthesis ; Receptors, Thrombin/deficiency
    Chemical Substances Receptors, Thrombin ; protease-activated receptor 4 (JWE1M73YZN)
    Language English
    Publishing date 2020-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.119.044340
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Angiotensin type 1a receptor-deficient mice develop diabetes-induced cardiac dysfunction, which is prevented by renin-angiotensin system inhibitors.

    Yong, Qian Chen / Thomas, Candice M / Seqqat, Rachid / Chandel, Niketa / Baker, Kenneth M / Kumar, Rajesh

    Cardiovascular diabetology

    2013  Volume 12, Page(s) 169

    Abstract: Background: Diabetes-induced organ damage is significantly associated with the activation of the renin-angiotensin system (RAS). Recently, several studies have demonstrated a change in the RAS from an extracellular to an intracellular system, in several ...

    Abstract Background: Diabetes-induced organ damage is significantly associated with the activation of the renin-angiotensin system (RAS). Recently, several studies have demonstrated a change in the RAS from an extracellular to an intracellular system, in several cell types, in response to high ambient glucose levels. In cardiac myocytes, intracellular angiotensin (ANG) II synthesis and actions are ACE and AT1 independent, respectively. However, a role of this system in diabetes-induced organ damage is not clear.
    Methods: To determine a role of the intracellular ANG II in diabetic cardiomyopathy, we induced diabetes using streptozotocin in AT1a receptor deficient (AT1a-KO) mice to exclude any effects of extracellular ANG II. Further, diabetic animals were treated with a renin inhibitor aliskiren, an ACE inhibitor benazeprilat, and an AT1 receptor blocker valsartan.
    Results: AT1a-KO mice developed significant diastolic and systolic dysfunction following 10 wks of diabetes, as determined by echocardiography. All three drugs prevented the development of cardiac dysfunction in these animals, without affecting blood pressure or glucose levels. A significant down regulation of components of the kallikrein-kinin system (KKS) was observed in diabetic animals, which was largely prevented by benazeprilat and valsartan, while aliskiren normalized kininogen expression.
    Conclusions: These data indicated that the AT1a receptor, thus extracellular ANG II, are not required for the development of diabetic cardiomyopathy. The KKS might contribute to the beneficial effects of benazeprilat and valsartan in diabetic cardiomyopathy. A role of intracellular ANG II is suggested by the inhibitory effects of aliskiren, which needs confirmation in future studies.
    MeSH term(s) Amides/pharmacology ; Angiotensin II/physiology ; Angiotensin II Type 1 Receptor Blockers/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Animals ; Benzazepines/pharmacology ; Cells, Cultured ; Diabetes Mellitus, Experimental/metabolism ; Diabetic Cardiomyopathies/diagnostic imaging ; Diabetic Cardiomyopathies/genetics ; Diabetic Cardiomyopathies/metabolism ; Disease Models, Animal ; Down-Regulation ; Fumarates/pharmacology ; Kallikreins/genetics ; Kallikreins/metabolism ; Kininogens/genetics ; Kininogens/metabolism ; Kinins/genetics ; Kinins/metabolism ; Mice ; Mice, Knockout ; Myocytes, Cardiac/metabolism ; Receptor, Angiotensin, Type 1/genetics ; Receptor, Angiotensin, Type 1/physiology ; Renin/antagonists & inhibitors ; Renin-Angiotensin System/physiology ; Tetrazoles/pharmacology ; Ultrasonography ; Valine/analogs & derivatives ; Valine/pharmacology ; Valsartan
    Chemical Substances Agtr1a protein, mouse ; Amides ; Angiotensin II Type 1 Receptor Blockers ; Angiotensin-Converting Enzyme Inhibitors ; Benzazepines ; Fumarates ; Kininogens ; Kinins ; Receptor, Angiotensin, Type 1 ; Tetrazoles ; Angiotensin II (11128-99-7) ; aliskiren (502FWN4Q32) ; Valsartan (80M03YXJ7I) ; Kallikreins (EC 3.4.21.-) ; Renin (EC 3.4.23.15) ; Valine (HG18B9YRS7) ; benazeprilat (JRM708L703)
    Language English
    Publishing date 2013-11-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1475-2840
    ISSN (online) 1475-2840
    DOI 10.1186/1475-2840-12-169
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Inhibition of nuclear factor κB regresses cardiac hypertrophy by modulating the expression of extracellular matrix and adhesion molecules

    Kumar, Sandeep / Seqqat, Rachid / Chigurupati, Sravanthi / Kumar, Rajesh / Baker, Kenneth M / Young, David / Sen, Subha / Gupta, Sudhiranjan

    Free Radical Biology and Medicine. 2011 Jan. 1, v. 50, no. 1

    2011  

    Abstract: Myocardial remodeling denotes a chronic pathological condition of dysfunctional myocardium that occurs in cardiac hypertrophy (CH) and heart failure (HF). Reactive oxygen species (ROS) are major initiators of excessive collagen and fibronectin deposition ...

    Abstract Myocardial remodeling denotes a chronic pathological condition of dysfunctional myocardium that occurs in cardiac hypertrophy (CH) and heart failure (HF). Reactive oxygen species (ROS) are major initiators of excessive collagen and fibronectin deposition in cardiac fibrosis. Increased production of ROS and nuclear factor κB (NF-κB) activation provide a strong link between oxidative stress and extracellular matrix (ECM) remodeling in cardiac hypertrophy. The protective inhibitory actions of pyrrolidine dithiocarbamate (PDTC), a pharmacological inhibitor of NF-κB and a potent antioxidant, make this a good agent to evaluate the role of inhibition of NF-κB and prevention of excessive ECM deposition in maladaptive cardiac remodeling during HF. In this report, we used a transgenic mouse model (Myo-Tg) that has cardiac-specific overexpression of myotrophin. This overexpression of myotrophin in the Myo-Tg model directs ECM deposition and increased NF-κB activity, which result in CH and ultimately HF. Using the Myo-Tg model, our data showed upregulation of profibrotic genes (including collagen types I and III, connective tissue growth factor, and fibronectin) in Myo-Tg mice, compared to wild-type mice, during the progression of CH. Pharmacological inhibition of NF-κB by PDTC in the Myo-Tg mice resulted in a significant reduction in cardiac mass, NF-κB activity, and profibrotic gene expression and improved cardiac function. To the best of our knowledge, this is the first report of ECM regulation by inhibition of NF-κB activation by PDTC. The study highlights the importance of the NF-κB signaling pathway and therapeutic benefits of PDTC treatment in cardiac remodeling.
    Keywords adhesion ; animal models ; antioxidants ; cardiac output ; collagen ; extracellular matrix ; fibronectins ; fibrosis ; gene expression regulation ; gene overexpression ; genes ; genetically modified organisms ; heart failure ; hypertrophy ; mice ; myocardium ; oxidative stress ; reactive oxygen species ; signal transduction ; transcription factor NF-kappa B
    Language English
    Dates of publication 2011-0101
    Size p. 206-215.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 807032-5
    ISSN 1873-4596 ; 0891-5849
    ISSN (online) 1873-4596
    ISSN 0891-5849
    DOI 10.1016/j.freeradbiomed.2010.10.711
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Cardiac-specific genetic inhibition of nuclear factor-κB prevents right ventricular hypertrophy induced by monocrotaline.

    Kumar, Sandeep / Wei, Chuanyu / Thomas, Candice M / Kim, Il-Kwon / Seqqat, Rachid / Kumar, Rajesh / Baker, Kenneth M / Jones, W Keith / Gupta, Sudhiranjan

    American journal of physiology. Heart and circulatory physiology

    2012  Volume 302, Issue 8, Page(s) H1655–66

    Abstract: Uncontrolled pulmonary arterial hypertension (PAH) results in right ventricular (RV) hypertrophy (RVH), progressive RV failure, and low cardiac output leading to increased morbidity and mortality (McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, ...

    Abstract Uncontrolled pulmonary arterial hypertension (PAH) results in right ventricular (RV) hypertrophy (RVH), progressive RV failure, and low cardiac output leading to increased morbidity and mortality (McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. J Am Coll Cardiol 53: 1573-1619, 2009). Although the exact figures of its prevalence are difficult to obtain because of the diversity of identifiable causes, it is estimated that the incidence of pulmonary hypertension is seven to nine cases per million persons in the general population and is most prevalent in the age group of 20-40, occurring more commonly in women than in men (ratio: 1.7 to 1; Rubin LJ. N Engl J Med 336: 111-117, 1997). PAH is characterized by dyspnea, chest pain, and syncope. Unfortunately, there is no cure for this disease and medical regimens are limited (Simon MA. Curr Opin Crit Care 16: 237-243, 2010). PAH leads to adverse remodeling that results in RVH, progressive right heart failure, low cardiac output, and ultimately death if left untreated (Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. J Am Coll Cardiol 43: 13S-24S, 2004; Humbert M, Sitbon O, Simonneau G. N Engl J Med 351: 1425-1436, 2004. LaRaia AV, Waxman AB. South Med J 100: 393-399, 2007). As there are no direct tools to assess the onset and progression of PAH and RVH, the disease is often detected in later stages marked by full-blown RVH, with the outcome predominantly determined by the level of increased afterload (D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Ann Intern Med 115: 343-349, 1991; Sandoval J, Bauerle O, Palomar A, Gomez A, Martinez-Guerra ML, Beltran M, Guerrero ML. Validation of a prognostic equation Circulation 89: 1733-1744, 1994). Various studies have been performed to assess the genetic, biochemical, and morphological components that contribute to PAH. Despite major advances in the understanding of the pathogenesis of PAH, the molecular mechanism(s) by which PAH promotes RVH and cardiac failure still remains elusive. Of all the mechanisms involved in the pathogenesis, inflammation and oxidative stress remain the core of the etiology of PAH that leads to development of RVH (Dorfmüller P, Perros F, Balabanian K, Humbert M. Eur Respir J 22: 358-363, 2003).
    MeSH term(s) Animals ; Blotting, Western ; Cell Adhesion Molecules/biosynthesis ; Cytokines/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Fluorescent Antibody Technique ; Heart/physiology ; Hypertension, Pulmonary/chemically induced ; Hypertension, Pulmonary/physiopathology ; Hypertrophy, Right Ventricular/chemically induced ; Hypertrophy, Right Ventricular/genetics ; Hypertrophy, Right Ventricular/prevention & control ; I-kappa B Proteins/physiology ; Inflammation/pathology ; Male ; Mice ; Monocrotaline ; Myocardium/metabolism ; Myocardium/pathology ; NF-KappaB Inhibitor alpha ; NF-kappa B/genetics ; Poisons ; RNA/biosynthesis ; RNA/isolation & purification ; Real-Time Polymerase Chain Reaction ; Signal Transduction/physiology ; Ventricular Remodeling/drug effects
    Chemical Substances Cell Adhesion Molecules ; Cytokines ; I-kappa B Proteins ; NF-kappa B ; Nfkbia protein, mouse ; Poisons ; NF-KappaB Inhibitor alpha (139874-52-5) ; RNA (63231-63-0) ; Monocrotaline (73077K8HYV)
    Language English
    Publishing date 2012-01-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00756.2011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Direct renin inhibition prevents cardiac dysfunction in a diabetic mouse model: comparison with an angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor.

    Thomas, Candice M / Yong, Qian Chen / Seqqat, Rachid / Chandel, Niketa / Feldman, David L / Baker, Kenneth M / Kumar, Rajesh

    Clinical science (London, England : 1979)

    2012  Volume 124, Issue 8, Page(s) 529–541

    Abstract: Hyperglycaemia up-regulates intracellular AngII (angiotensin II) production in cardiac myocytes, effects of which are blocked more effectively by renin inhibition than ARBs (angiotensin receptor blockers) or ACEis (angiotensin-converting enzyme ... ...

    Abstract Hyperglycaemia up-regulates intracellular AngII (angiotensin II) production in cardiac myocytes, effects of which are blocked more effectively by renin inhibition than ARBs (angiotensin receptor blockers) or ACEis (angiotensin-converting enzyme inhibitors). In the present study, we determined whether renin inhibition is more effective at preventing diabetic cardiomyopathy than an ARB or ACEi. Diabetes was induced in adult mice for 10 weeks by STZ (streptozotocin). Diabetic mice were treated with insulin, aliskiren (a renin inhibitor), benazeprilat (an ACEi) or valsartan (an ARB) via subcutaneous mini-pumps. Significant impairment in diastolic and systolic cardiac functions was observed in diabetic mice, which was completely prevented by all three RAS (renin-angiotensin system) inhibitors. Hyperglycaemia significantly increased cardiac oxidative stress and circulating inflammatory cytokines, which were blocked by aliskiren and benazeprilat, whereas valsartan was partially effective. Diabetes increased cardiac PRR (prorenin receptor) expression and nuclear translocation of PLZF (promyelocytic zinc finger protein), which was completely prevented by aliskiren and valsartan, and partially by benazeprilat. Renin inhibition provided similar protection of cardiac function to ARBs and ACEis. Activation of PLZF by PRR represented a novel mechanism in diabetic cardiomyopathy. Differential effects of the three agents on oxidative stress, cytokines and PRR expression suggested subtle differences in their mechanisms of action.
    MeSH term(s) Amides/administration & dosage ; Angiotensin Receptor Antagonists/administration & dosage ; Angiotensin-Converting Enzyme Inhibitors/administration & dosage ; Animals ; Benzazepines/administration & dosage ; Blood Pressure/drug effects ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/enzymology ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/physiopathology ; Fumarates/administration & dosage ; Heart/drug effects ; Heart/physiopathology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Myocardium/enzymology ; Oxidative Stress/drug effects ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Renin/antagonists & inhibitors ; Renin/metabolism ; Tetrazoles/administration & dosage ; Valine/administration & dosage ; Valine/analogs & derivatives ; Valsartan
    Chemical Substances Amides ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Benzazepines ; Fumarates ; Receptors, Cell Surface ; Tetrazoles ; prorenin receptor ; aliskiren (502FWN4Q32) ; Valsartan (80M03YXJ7I) ; Renin (EC 3.4.23.15) ; Valine (HG18B9YRS7) ; benazeprilat (JRM708L703)
    Language English
    Publishing date 2012-11-01
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20120448
    Database MEDical Literature Analysis and Retrieval System OnLINE

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