scholarly journals COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection

2021 ◽  
Vol 14 (1) ◽  
pp. 71
Author(s):  
Katarzyna Kotfis ◽  
Kacper Lechowicz ◽  
Sylwester Drożdżal ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Tomasz K. Wojdacz ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Potential ◽  
Severe Pneumonia ◽  
Therapeutic Benefit ◽  
World Health ◽  
Therapeutic Effects ◽  
Severe Acute Respiratory Infection ◽  
Dual Action ◽  
Health Organization ◽  
Transmembrane Serine Protease

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin–angiotensin–aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.

scholarly journals Targeting CD146 with a 64Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas

2015 ◽  
Vol 112 (47) ◽  
pp. E6525-E6534 ◽  
Author(s):  
Yunan Yang ◽  
Reinier Hernandez ◽  
Jun Rao ◽  
Li Yin ◽  
Yazhuo Qu ◽  
...  
Keyword(s):  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
World Health ◽  
Positive Staining ◽  
Therapeutic Effects ◽  
Clinical Value ◽  
Positron Emission ◽  
Resected Tumor ◽  
Health Organization

Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positron-emission tomography (PET) imaging of orthotopic GBM models. 64Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high-contrast PET images of small tumor nodules (∼2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (χ2 = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors.

scholarly journals A review of post infectious pulmonary fibrosis in the era of COVID-19 and potential treatment options

2021 ◽  
Vol 9 (40) ◽  
pp. 37-46
Author(s):  
Medha Ghose ◽  
Maehali Patel
Keyword(s):  
Risk Factors ◽  
Pulmonary Fibrosis ◽  
Treatment Options ◽  
World Health ◽  
Potential Treatment ◽  
Pulmonary Injury ◽  
The World ◽  
Health Organization ◽  
Post Infectious

On March 11, 2020, the World Health Organization (WHO) released a statement characterizing COVID-19 as a pandemic that has, as of October 2020, caused almost 36 million confirmed global cases and over 1 million deaths. One of the long-term complications suggested by researchers is fibrosis. It has been hypothesized that the combination of ongoing pulmonary injury caused by COVID-19 and the inability to promptly repair damage results in interstitial matrix widening and eventual compression and destruction of alveoli and capillaries. Here we focus on pathogenesis, risk factors, different infectious causes of fibrosis along with COVID-19, and potential treatment options that might reduce its effects. Key words: COVID-19, pulmonary fibrosis, mechanism, treatment

scholarly journals Safety and Efficacy of Chloroquine/Hydroxychloroquine in SARS-CoV-2 Infection

2021 ◽  
Vol 33 (8) ◽  
pp. 1718-1722
Author(s):  
Alberto Boretti
Keyword(s):  
Case Fatality Rate ◽  
Case Fatality ◽  
Severe Pneumonia ◽  
World Health ◽  
Fatality Rate ◽  
Late Infection ◽  
Western Countries ◽  
Asymptomatic Patients ◽  
Overwhelming Evidence ◽  
Health Organization

This work summarizes the available evidence of the use of chloroquine/hydroxychloroquine (CQ/HCQ) in SARS-CoV-2 infection. Most of the published works indicate CQ/HCQ is likely effective against SARS-CoV-2 infection, almost 100% in prophylaxis and mild-medium severity cases and 60% in late infection cases. The percentage of positive works is larger if those works conducted under a probable conflict of interest are excluded from the list. Despite this overwhelming evidence from independent studies, the use of CQ/HCQ is currently limited or prevented in many western countries, based on a very singular examination of the science. The case of a work published in late May 2020, despite being openly defective and then retracted, prompted the World Health Organization (WHO) to ban the use of CQ/HCQ. This position has not yet rectified, thanks to the results of the not less questionable RECOVERY trial, where very sick patients were administered more than double the dose, over more than double the time, recommended for asymptomatic patients in current protocols of other countries, where CQ/HCQ are used for asymptomatic and mild but not severe pneumonia critically ill patients. While the case fatality rate does not depend only on therapies, it is finally shown based on the number of cases and fatalities per million and the case fatality rate as the western countries enforcing the ban on CQ/HCQ did not perform better, but much worse, than other countries, also because of therapies.

scholarly journals What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2018 ◽  
Author(s):  
Francesca Salamanna ◽  
Veronica Borsari ◽  
Deyanira Contartese ◽  
Viviana Costa ◽  
Gianluca Giavaresi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Bone Metastases ◽  
Metastatic Breast ◽  
World Health ◽  
Therapeutic Effects ◽  
Preclinical Studies ◽  
Functional Roles ◽  
Novel Strategy ◽  
Health Organization

Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast cancer to bone are still fragmented. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science Core Collection) to identify preclinical reports, and in three clinical registers (ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register) to identify clinical trials, from 2008 to 2019. Sixty-seven preclinical studies and 11 clinical trials were recognized as eligible. Although preclinical studies identified specific key ILs which promote breast cancer bone metastases, which have pro-metastatic effects (e.g., IL-6, IL-8, IL-1β, IL-11), and whose inhibition also shows potential preclinical therapeutic effects, the clinical trials focused principally on ILs (IL-2 and IL-12), which have an anti-metastatic effect and a potential to generate a localized and systemic antitumor response. However, these clinical trials are yet to post any results or conclusions. This inconsistency indicates that further studies are necessary to further develop the understanding of cellular and molecular relations, as well as signaling pathways, both up- and downstream of ILs, which could represent a novel strategy to treat tumors that are resistant to standard care therapies for patients affected by breast cancer bone disease.

scholarly journals Incidence and Risk Factors for Severe Pneumonia in Children Hospitalized with Pneumonia in Ujjain, India

2020 ◽  
Vol 17 (13) ◽  
pp. 4637
Author(s):  
Sunil Kumar Kasundriya ◽  
Mamta Dhaneria ◽  
Aditya Mathur ◽  
Ashish Pathak
Keyword(s):  
Risk Factors ◽  
Public Health Problem ◽  
Severe Pneumonia ◽  
World Health ◽  
Major Public Health Problem ◽  
Open Defecation ◽  
History Of ◽  
Poor Ventilation ◽  
Acyanotic Congenital Heart Disease ◽  
Health Organization

Childhood pneumonia is a major public health problem. The aim of this prospective hospital-based study is to determine the incidence and risk factors for community-acquired severe pneumonia in children in Ujjain, India. The study includes 270 children, 161 (60%) boys and 109 (40%) girls, aged between 2 months and 5 years with World Health Organization defined and radiologically confirmed severe pneumonia. Considering the 270 children, 64% (95% confidence interval (CI) 57.9–69.4) have severe pneumonia. The following are identified as risk factors for severe pneumonia from the generalized logistic regression model: Born premature (adjusted odds ratio (AOR) 7.50; 95% CI 2.22–25.31; p = 0.001); history of measles (AOR 6.35; 95% CI 1.73–23.30; p = 0.005); incomplete vaccination (AOR 2.66; 95% CI 1.09–6.48; p = 0.031); acyanotic congenital heart disease (AOR 9.21; 95% CI 2.29–36.99; p = 0.002); home treatment tried (AOR 3.84; 95% CI 1.42–10.39; p = 0.008); living in a kuchha house (AOR 3.89; 95% CI 1.51–10.01; p = 0.027); overcrowding (AOR 4.50; 95% CI 1.75–11.51; p = 0.002);poor ventilation in living area (AOR 16.37; 95% CI 4.67–57.38; p < 0.001); and practicing open defecation (AOR 16.92; 95% CI 4.95–57.85; p < 0.001). Awareness of these risk factors can reduce mortality due to severe pneumonia.

scholarly journals Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic

2020 ◽  
Vol 11 ◽  
Author(s):  
Concetta Di Natale ◽  
Sara La Manna ◽  
Ilaria De Benedictis ◽  
Paola Brandi ◽  
Daniela Marasco
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Severe Pneumonia ◽  
World Health ◽  
Primary Host ◽  
Viral Pathogen ◽  
Drug Candidates ◽  
Health Organization ◽  
Spread Of Infection

At the end of December 2019, an epidemic form of respiratory tract infection now named COVID-19 emerged in Wuhan, China. It is caused by a newly identified viral pathogen, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which can cause severe pneumonia and acute respiratory distress syndrome. On January 30, 2020, due to the rapid spread of infection, COVID-19 was declared as a global health emergency by the World Health Organization. Coronaviruses are enveloped RNA viruses belonging to the family of Coronaviridae, which are able to infect birds, humans and other mammals. The majority of human coronavirus infections are mild although already in 2003 and in 2012, the epidemics of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV), respectively, were characterized by a high mortality rate. In this regard, many efforts have been made to develop therapeutic strategies against human CoV infections but, unfortunately, drug candidates have shown efficacy only into in vitro studies, limiting their use against COVID-19 infection. Actually, no treatment has been approved in humans against SARS-CoV-2, and therefore there is an urgent need of a suitable vaccine to tackle this health issue. However, the puzzled scenario of biological features of the virus and its interaction with human immune response, represent a challenge for vaccine development. As expected, in hundreds of research laboratories there is a running out of breath to explore different strategies to obtain a safe and quickly spreadable vaccine; and among others, the peptide-based approach represents a turning point as peptides have demonstrated unique features of selectivity and specificity toward specific targets. Peptide-based vaccines imply the identification of different epitopes both on human cells and virus capsid and the design of peptide/peptidomimetics able to counteract the primary host-pathogen interaction, in order to induce a specific host immune response. SARS-CoV-2 immunogenic regions are mainly distributed, as well as for other coronaviruses, across structural areas such as spike, envelope, membrane or nucleocapsid proteins. Herein, we aim to highlight the molecular basis of the infection and recent peptide-based vaccines strategies to fight the COVID-19 pandemic including their delivery systems.

scholarly journals Probiotic Products in Canada with Clinical Evidence: What Can Gastroenterologists Recommend?

2008 ◽  
Vol 22 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Gregor Reid ◽  
Kingsley Anukam ◽  
Tara Koyama
Keyword(s):  
United States Of America ◽  
Clinical Evidence ◽  
Health Benefit ◽  
The United States ◽  
World Health ◽  
Therapeutic Effects ◽  
The Us ◽  
Health Organization ◽  
Health Canada

Probiotics, defined as ‘live microorganisms, which when administered in adequate amounts, confer a health benefit on the host’, are finally becoming an option for gastroenterologists in Canada, after being available for many years in Japan, Europe and the United States of America. Unfortunately, Health Canada and the US Food and Drug Administration have not controlled the use of the term ‘probiotic’ or put into place United Nations and World Health Organization guidelines. The net result is that a host of products called ‘probiotics’ are available but are not truly probiotic. The aim of the present review was to discuss the rationale for probiotics in gastroenterology, and specifically examine which products are options for physicians in Canada, and which ones patients might be using. It is hoped that by clarifying what probiotics are, and the strengths and limitations of their use, specialists will be better placed to make recommendations on the role of these products in patient care. In due course, more clinically documented probiotics will emerge, some with therapeutic effects based on a better understanding of disease processes.

scholarly journals An atypical case: RT-PCR-negative, sero-positive covid-19 patient

Pneumologia ◽  
2020 ◽  
Vol 69 (2) ◽  
pp. 107-114
Author(s):  
William Suriady ◽  
Andika Chandra Putra ◽  
Wiwien Heru Wiyono ◽  
Mohammad Fahmi Alatas ◽  
Bettia Bermawi ◽  
...  
Keyword(s):  
False Negative ◽  
Severe Pneumonia ◽  
World Health ◽  
Diagnostic Process ◽  
The Novel ◽  
Rt Pcr ◽  
Atypical Case ◽  
Polymerase Chain ◽  
Novel Coronavirus ◽  
Health Organization

Abstract The novel coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has become a public health emergency of international concern. The first confirmed COVID-19 case in Indonesia was announced on 2 March 2020, and later on, 11,192 confirmed cases were reported as of 3 May. The World Health Organization has stated that performing a real-time reverse transcription–polymerase chain reaction (RT-PCR) specific for SARS-CoV-2 on specimens from the upper and the lower respiratory tracts, especially nasopharyngeal and oropharyngeal swabs, is the standard diagnostic procedure for COVID-19. In Indonesia, we also use other diagnostic tests, such as rapid antibody tests specific for SARS-CoV-2. Herein, we report an atypical case of COVID-19 and describe the diagnostic process, the clinical course, with progression to severe pneumonia on Week 3 of illness and the case management. We also try to highlight the possibility of false-negative RT-PCR tests.

scholarly journals Modeling the COVID-19 outbreaks and the effectiveness of the containment measures adopted across countries

2020 ◽  
Author(s):  
Edward De Brouwer ◽  
Daniele Raimondi ◽  
Yves Moreau
Keyword(s):  
Herd Immunity ◽  
Case Fatality ◽  
Severe Pneumonia ◽  
Optimal Level ◽  
World Health ◽  
Reproduction Ratio ◽  
The Public ◽  
Global Pandemic ◽  
Containment Measures ◽  
Health Organization

AbstractOn March 11, 2020, the World Health Organization declared the COVID-19 outbreak, originally started in China, a global pandemic. Since then, the outbreak has indeed spread across all continents, threatening the public health of numerous countries. Although the Case Fatality Rate (CFR) of COVID-19 is relatively low when optimal level of healthcare is granted to the patients, the high percentage of severe cases developing severe pneumonia and thus requiring respiratory support is worryingly high, and could lead to a rapid saturation of Intensive Care Units (ICUs). To overcome this risk, most countries enacted COVID-19 containment measures. In this study, we use a Bayesian SEIR epidemiological model to perform a parametric regression over the COVID-19 outbreaks data in China, Italy, Belgium, and Spain, and estimate the effect of the containment measures on the basic reproduction ratio R0.We find that the effect of these measures is detectable, but tends to be gradual, and that a progressive strengthening of these measures usually reduces the R0 below 1, granting a decay of the outbreak. We also discuss the biases and inconsistencies present in the publicly available data on COVID-19 cases, providing an estimate for the actual number of cases in Italy on March 12, 2020. Lastly, despite the data and model’s limitations, we argue that the idea of “flattening the curve” to reach herd immunity is likely to be unfeasible.

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