scholarly journals Autophagy in Zika Virus Infection: A Possible Therapeutic Target to Counteract Viral Replication

2019 ◽  
Vol 20 (5) ◽  
pp. 1048 ◽  
Author(s):  
Rossella Gratton ◽  
Almerinda Agrelli ◽  
Paola Tricarico ◽  
Lucas Brandão ◽  
Sergio Crovella
Keyword(s):  
Public Health ◽  
Viral Replication ◽  
Zika Virus ◽  
Health Concern ◽  
Mtor Signaling Pathway ◽  
Catabolic Pathway ◽  
Public Health Concern ◽  
Zikv Infection ◽  
Fundamental Process

Zika virus (ZIKV) still constitutes a public health concern, however, no vaccines or therapies are currently approved for treatment. A fundamental process involved in ZIKV infection is autophagy, a cellular catabolic pathway delivering cytoplasmic cargo to the lysosome for degradation—considered as a primordial form of innate immunity against invading microorganisms. ZIKV is thought to inhibit the Akt-mTOR signaling pathway, which causes aberrant activation of autophagy promoting viral replication and propagation. It is therefore appealing to study the role of autophagic molecular effectors during viral infection to identify potential targets for anti-ZIKV therapeutic intervention.

scholarly journals Zika virus is transmitted in neural progenitor cells via cell-to-cell spread and infection is inhibited by the autophagy inducer trehalose

2020 ◽  
pp. JVI.02024-20
Author(s):  
Alex E Clark ◽  
Zhe Zhu ◽  
Florian Krach ◽  
Jeremy N Rich ◽  
Gene W. Yeo ◽  
...  
Keyword(s):  
Viral Replication ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neutralizing Antibody ◽  
Neural Progenitor ◽  
Health Concern ◽  
Free Virus ◽  
Zikv Infection ◽  
Infected Cells

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes congenital Zika syndrome and neurological symptoms in some adults. There are currently no approved treatments or vaccines for ZIKV, and exploration of therapies targeting host processes could avoid viral development of drug resistance. The purpose of our study was to determine if the non-toxic and widely used disaccharide trehalose, which showed antiviral activity against Human Cytomegalovirus (HCMV) in our previous work, could restrict ZIKV infection in clinically relevant neural progenitor cells (NPCs). Trehalose is known to induce autophagy, the degradation and recycling of cellular components. Whether autophagy is proviral or antiviral for ZIKV is controversial and depends on cell type and specific conditions used to activate or inhibit autophagy. We show here that trehalose treatment of NPCs infected with recent ZIKV isolates from Panama and Puerto Rico significantly reduces viral replication and spread. In addition, we demonstrate that ZIKV infection in NPCs spreads primarily cell-to-cell as an expanding infectious center, and NPCs are infected via contact with infected cells far more efficiently than by cell-free virus. Importantly, ZIKV was able to spread in NPCs in the presence of neutralizing antibody.Importance Zika virus causes birth defects and can lead to neurological disease in adults. While infection rates are currently low, ZIKV remains a public health concern with no treatment or vaccine available. Targeting a cellular pathway to inhibit viral replication is a potential treatment strategy that avoids development of antiviral resistance. We demonstrate in this study that the non-toxic autophagy-inducing disaccharide trehalose reduces spread and output of ZIKV in infected neural progenitor cells (NPCs), the major cells infected in the fetus. We show that ZIKV spreads cell-to-cell in NPCs as an infectious center and that NPCs are more permissive to infection by contact with infected cells than by cell-free virus. We find that neutralizing antibody does not prevent the spread of the infection in NPCs. These results are significant in demonstrating anti-ZIKV activity of trehalose and in clarifying the primary means of Zika virus spread in clinically relevant target cells.

scholarly journals Zika Virus: New Clinical Syndromes and Its Emergence in the Western Hemisphere

2016 ◽  
Vol 90 (10) ◽  
pp. 4864-4875 ◽  
Author(s):  
Helen M. Lazear ◽  
Michael S. Diamond
Keyword(s):  
Zika Virus ◽  
Antiviral Agents ◽  
Western Hemisphere ◽  
Health Concern ◽  
Global Public Health ◽  
Public Health Concern ◽  
Zikv Infection ◽  
Clinical Complications ◽  
Clinical Syndromes ◽  
Potential Interactions

Zika virus (ZIKV) had remained a relatively obscure flavivirus until a recent series of outbreaks accompanied by unexpectedly severe clinical complications brought this virus into the spotlight as causing an infection of global public health concern. In this review, we discuss the history and epidemiology of ZIKV infection, recent outbreaks in Oceania and the emergence of ZIKV in the Western Hemisphere, newly ascribed complications of ZIKV infection, including Guillain-Barré syndrome and microcephaly, potential interactions between ZIKV and dengue virus, and the prospects for the development of antiviral agents and vaccines.

Impact of the Opioid/Fentanyl Epidemic on the Toxicology Laboratory’s Workload: The CMCVAMC Experience

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S90-S90
Author(s):  
Jeffrey Petersen ◽  
Thomas George ◽  
Darshana Jhala
Keyword(s):  
Public Health ◽  
Clinical Care ◽  
Health Concern ◽  
Fiscal Year ◽  
Opioid Epidemic ◽  
Public Health Concern ◽  
Significant Public Health Concern ◽  
Significant Public Health ◽  
Gas Chromatography Mass Spectroscopy

Abstract Introduction Opiates have long been used by both the population at large and the veteran population as a drug of abuse. However, recently, fentanyl—a synthetic opioid—has risen in prominence in this opioid drug abuse epidemic as a drug used by suppliers to “cut” heroin, to masquerade for another opiate, or for direct usage. As this is a recent phenomenon, the new increasing need to test for fentanyl for clinical reasons has a major impact on the toxicology laboratory’s workload. Method Quality assurance/improvement data were obtained to determine the number of fentanyl tests by gas chromatography/mass spectroscopy (GC/MS) performed by the toxicology laboratory since quarter 1 of 2011 (October-December 2010) to quarter 1 of 2018 (October-December 2017). The numbers of tests required for clinical care in each quarter were tabulated and compared in a graph. Quarters for each year begin and end in October. Results The total number of GC/MS tests for fentanyl needed for clinical care has been drastically increasing recently. From 2011 to 2015, the yearly number of tests clinically needed has ranged from 83 to 92. In 2016, the total number of clinically needed tests for fentanyl spiked to 167 and by fiscal year 2017 included 1,108 fentanyl GC/MS tests. The last examined quarter (quarter 1 of fiscal year 2018) included 527 tests, which is more than the highest number from 2017 (377 in quarter 4 of 2017). Conclusion The increasing use of fentanyl in the opioid epidemic appears to have played a role in significantly increasing the clinical need to test for fentanyl by GC/MS, increasing the volume by over 10 to 15 times. The role of fentanyl in the opioid epidemic remains a significant public health concern.

Endothelial dysfunction induced by cadmium and mercury and its relationship to hypertension

2021 ◽  
Vol 17 ◽  
Author(s):  
Airton Cunha Martins ◽  
Alessanda Antunes Dos Santos ◽  
Ana Carolina B. Almeida Lopes ◽  
Anatoly V. Skalny ◽  
Michael Aschner ◽  
...  
Keyword(s):  
Public Health ◽  
Nitric Oxide ◽  
Heavy Metals ◽  
Endothelial Dysfunction ◽  
Toxic Elements ◽  
Health Concern ◽  
Public Health Concern ◽  
Important Public Health ◽  
Nitric Oxide Signaling

: Hypertension is an important public health concern that affects millions globally, leading to a large number of morbidities and fatalities. The etiology of hypertension is complex and multifactorial, and it involves environmental factors including heavy metals. Indeed, cadmium and mercury are toxic elements commonly distributed in the environment which contribute to hypertension. We aimed to assess the role of cadmium and mercury-induced endothelial dysfunction in the development of hypertension. A narrative review was carried out through database searches. In this review, we discussed the critical roles of cadmium and mercury in the etiology of hypertension and provide new insights into potential mechanisms of their effect, focusing primarily on endothelial dysfunction. Although, the mechanisms by which cadmium and mercury induce hypertension have yet to be completely elucidated, evidence for both implicates impaired nitric oxide signaling in their hypertensive etiology.

scholarly journals The Role of Sarcopenic Obesity in Cancer and Cardiovascular Disease: A Synthesis of the Evidence on Pathophysiological Aspects and Clinical Implications

2021 ◽  
Vol 22 (9) ◽  
pp. 4339
Author(s):  
Erika Aparecida Silveira ◽  
Rômulo Roosevelt da Silva Filho ◽  
Maria Claudia Bernardes Spexoto ◽  
Fahimeh Haghighatdoost ◽  
Nizal Sarrafzadegan ◽  
...  
Keyword(s):  
Public Health ◽  
Cardiovascular Disease ◽  
Older Adults ◽  
High Risk ◽  
Sarcopenic Obesity ◽  
Health Concern ◽  
Clinical Implications ◽  
Public Health Concern ◽  
Epidemiological Evidence

Obesity is globally a serious public health concern and is associated with a high risk of cardiovascular disease (CVD) and various types of cancers. It is important to evaluate various types of obesity, such as visceral and sarcopenic obesity. The evidence on the associated risk of CVD, cancer and sarcopenic obesity, including pathophysiological aspects, occurrence, clinical implications and survival, needs further investigation. Sarcopenic obesity is a relatively new term. It is a clinical condition that primarily affects older adults. There are several endocrine-hormonal, metabolic and lifestyle aspects involved in the occurrence of sarcopenic obesity that affect pathophysiological aspects that, in turn, contribute to CVD and neoplasms. However, there is no available evidence on the role of sarcopenic obesity in the occurrence of CVD and cancer and its pathophysiological interplay. Therefore, this review aims to describe the pathophysiological aspects and the clinical and epidemiological evidence on the role of sarcopenic obesity related to the occurrence and mortality risk of various types of cancer and cardiovascular disease. This literature review highlights the need for further research on sarcopenic obesity to demonstrate the interrelation of these various associations.

scholarly journals Role of Gas6, TAM receptors ligand, in the pathogenesis of Zika virus infection

2019 ◽  
Author(s):  
Leticia Cristina S. Monteiro ◽  
João Luiz da Silva Filho ◽  
Jose Luiz Proença Modena ◽  
Fabio T. M. Costa
Keyword(s):  
Public Health ◽  
Virus Infection ◽  
Zika Virus ◽  
Zikv Infection ◽  
Neurological Sequelae ◽  
Tam Receptors ◽  
The World ◽  
Public Health Challenge

Zika virus (ZIKV) represents a public health challenge to Brazil and the rest of the world, especially because ZIKV infection has been linked to neurological sequelae, such as congenital fetal syndrome. Here, we aim to verify the role of Gas6 in the pathogenesis of ZIKV infection, by evaluating the expression of Gas6 and TAM receptors in patients infected by the virus with different degrees of disease severity, and infection of different human cells in vitro.

scholarly journals Gambling as a public health issue: The critical role of the local environment

2009 ◽  
pp. 66 ◽  
Author(s):  
David Marshall
Keyword(s):  
Public Health ◽  
Critical Role ◽  
Local Environment ◽  
Health Concern ◽  
Public Health Issue ◽  
Health Issues ◽  
Gambling Activity ◽  
Public Health Concern ◽  
Contextual Environment

This paper discusses gambling as a public health concern and outlines why local circumstances are central to such concerns. Using the framework of compositional and contextual factors to frame discussions, it is argued that the local circumstances of individuals and communities are critical to whether gambling activity is problematic. Unlike other similar public health issues for which there are clear parameters defining what is a problem and how severe the problem is, it is argued here that gambling-related problems are determined almost entirely by the circumstances in which the activity is occurring. As such, strategies designed to prevent or minimise gambling-related problems should target the local contextual environment and not just focus on the gamblers themselves, as has tended to occur to date.

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