Nanomedicine as a Potential Tool against Monkeypox.

Human monkeypox is a rare viral zoonosis that was first identified in 1970; since then, this infectious disease has been marked as endemic in central and western Africa. The disease has always been considered rare and self-limiting; however, recent worldwide reports of several cases suggest otherwise. Especially with monkeypox being recognized as the most important orthopoxvirus infection in humans in the smallpox post-eradication era, its spread across the globe marks a new epidemic. Currently, there is no proven treatment for human monkeypox, and questions about the necessity of developing a vaccine persist. Notably, if we are to take lessons from the COVID-19 pandemic, developing a nanomedicine-based preventative strategy might be prudent, particularly with the rapid growth of the use of nanotechnology and nanomaterials in medical research. Unfortunately, the collected data in this area is limited, dispersed, and often incomplete. Therefore, this review aims to trace all reported nanomedicine approaches made in the monkeypox area and to suggest possible directions that could be further investigated to develop a counteractive strategy against emerging and existing viruses that could diminish this epidemic and prevent it from becoming a potential pandemic, especially with the world still recovering from the COVID-19 pandemic.NAM is a recipient of the Early Career Research Award (ECRA; ECRA03-006-3-004) from the Qatar National Research Fund (QNRF), and the L’Oréal-UNESCO for Women in Science Middle East Regional Young Talents ward 2021. This work was supported by the Ministry of Health, Rome-Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste–Italy (RC 47/20)

Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine : novel explanation of cardiovascular side effects associated with anti-inflammatory drugs

© 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.BACKGROUND: Cardiovascular side effects associated with cyclooxygenase-2 inhibitor drugs dominate clinical concern. Cyclooxygenase-2 is expressed in the renal medulla where inhibition causes fluid retention and increased blood pressure. However, the mechanisms linking cyclooxygenase-2 inhibition and cardiovascular events are unknown and no biomarkers have been identified.METHODS AND RESULTS: Transcriptome analysis of wild-type and cyclooxygenase-2(-/-) mouse tissues revealed 1 gene altered in the heart and aorta, but >1000 genes altered in the renal medulla, including those regulating the endogenous nitric oxide synthase inhibitors asymmetrical dimethylarginine (ADMA) and monomethyl-l-arginine. Cyclo-oxygenase-2(-/-) mice had increased plasma levels of ADMA and monomethyl-l-arginine and reduced endothelial nitric oxide responses. These genes and methylarginines were not similarly altered in mice lacking prostacyclin receptors. Wild-type mice or human volunteers taking cyclooxygenase-2 inhibitors also showed increased plasma ADMA. Endothelial nitric oxide is cardio-protective, reducing thrombosis and atherosclerosis. Consequently, increased ADMA is associated with cardiovascular disease. Thus, our study identifies ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction with nonsteroidal anti-inflammatory drug usage.CONCLUSIONS: We identify the endogenous endothelial nitric oxide synthase inhibitor ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction.Peer reviewedFinal Published versio

Studying COX-2 in the cardiovascular system using a transcriptomic approach

At the time of starting my thesis there were no agreed mechanisms that could explain how cyclooxygenase (COX)-2 protects the cardiovascular system and no ‘hypothesis generating’ approaches done to try to find new answers. I have used transcriptomics, to come up with targets for this problem. I used microarray and RNA-seq on the following experimental models; (i) tissue from COX-1/COX-2 knockout mice, (ii) wildtype mice treated with the COX-2 inhibitor paracoxib and (iii) whole blood from healthy male volunteers after taking the COX-2 inhibitor celecoxib. Transcriptomic data was also analysed from online databases including (i) Open TG-GATEs and (ii) Human Protein Atlas. Altered transcriprt lists generated using GeneSpring and StrandNGS where analysed using manual curation, g:Profiler and GeneOntology.org databases and using Gene Set Enrichment Analysis. No transcripts were altered in aorta, heart, kidney, blood or brain from COX-1 knock out mice but >260 transcripts were altered (>1.5 fold) in the renal medulla of COX-2 knockout mice or wildtype mice where COX-2 was blocked with paracoxib with expression of four cardiovascular genes, namely, Agxt2, Edn1, Cd34 and Ptgds being similarly altered in both approaches. Transcripts were also altered in blood of humans taking celecoxib or COX-2 knockout mice, although in blood it was transcripts associated with inflammation and interferon pathways that came up. As an unexpected observation, it was found that expression of the oncogene Rgl1 was down regulated in all tissues from the COX-2 knockout mice. Since drugs that block COX-2 also prevent cancer the Rgl1 hit was explored using human cancer cells. This work helps us understand new ways that COX-2 protects the cardiovascular system and causes cancer. Finally, after more tests, the pathways I found could be used to help identify and treat people at risk of having heart attacks when they take pain killers that work by blocking COX-2.Open Acces

ACE-I Angioedema: Accurate Clinical Diagnosis May Prevent Epinephrine-Induced Harm

Introduction: Upper airway angioedema is a life-threatening emergency department (ED) presentation with increasing incidence. Angiotensin-converting enzyme inhibitor induced angioedema (AAE) is a non-mast cell mediated etiology of angioedema. Accurate diagnosis by clinical examination can optimize patient management and reduce morbidity from inappropriate treatment with epinephrine. The aim of this study is to describe the incidence of angioedema subtypes and the management of AAE. We evaluate the appropriateness of treatments and highlight preventable iatrogenic morbidity.Methods: We conducted a retrospective chart review of consecutive angioedema patients presenting to two tertiary care EDs between July 2007 and March 2012.Results: Of 1,702 medical records screened, 527 were included. The cause of angioedema was identified in 48.8% (n=257) of cases. The most common identifiable etiology was AAE (33.1%, n=85), with a 60.0% male predominance. The most common AAE management strategies included diphenhydramine (63.5%, n=54), corticosteroids (50.6%, n=43) and ranitidine (31.8%, n=27). Epinephrine was administered in 21.2% (n=18) of AAE patients, five of whom received repeated doses. Four AAE patients required admission (4.7%) and one required endotracheal intubation. Epinephrine induced morbidity in two patients, causing myocardial ischemia or dysrhythmia shortly after administration.Conclusion: AAE is the most common identifiable etiology of angioedema and can be accurately diagnosed by physical examination. It is easily confused with anaphylaxis and mismanaged with antihistamines, corticosteroids and epinephrine. There is little physiologic rationale for epinephrine use in AAE and much risk. Improved clinical differentiation of mast cell and non-mast cell mediated angioedema can optimize patient management

Long Term Effects of the Administration of Quisqualic Acid into the Substantia Nigra of Rats

Previous in vitro studies in rat hippocampal slices have demonstrated that the non-NMDA receptor and mGluR agonist, quisqualic acid (QUIS) causes sensitization of pyramidal cell neurons which persists for hours following the removal of QUIS from the extracellular medium. This effect is not blocked by antagonists of either non-NMDA receptors but is blocked by non-transportable inhibitors of the cystine/glutamate exchanger, System xc-. Based on these studies, we hypothesized that QUIS may trigger a slowly developing neurodegeneration. In this study, QUIS and/or S-4-carboxyphenylglycine (CPG), a non-transportable inhibitor of system xc- was injected into the substantia nigra of rats. The rats’ motor performance, anxiety, and spatial learning were tested for 25 weeks post-injection. QUIS injections into the substantia nigra led to changes in performance in the Morris Water Maze five months following injection. QUIS-treated rats traveled a greater distance and took longer to find a hidden platform than did rats not treated with QUIS. However, there were no other motor effects observed as a result of QUIS treatment. QUIS had no effect on performance on the Rotarod task or the hanging wire task. There also was no reliable effect of QUIS on gate or risk taking behavior. These results indicate that central administration of QUIS into the substantia nigra has minimal effects on the behavior of rats. Previous studies in which QUIS was injected into the hippocampus led to changes in spatial learning ability, as predicted, five months following QUIS injection. However, the results from the substantia nigra-injected rats suggest there may be fewer neurons in this region of the brain, unlike the hippocampus, which are susceptible to QUIS excitotoxicity

Stress, Anxiety, and Depression in Pre-Clinical Medical Students: Prevalence and Association with Sleep Disorders

Our aim was to assess sleep quality in different subgroups of preclinical medical students, and then to identify specific lifestyle factors, academic and social factors as well as Corona virus related factors that were associated with poor sleeping quality and poor psychological health. Study participants were all medical students at King Saud University of Medical Sciences in the first and second years (648 students), and the study was conducted from December 2021 to January 2022. We administered the survey on paper as well as online. We used three types of questionnaires in this study. The first was a self-administered questionnaire, the second was a validated Insomnia Severity Index (ISI) for finding sleeping problems, and the third was a validated DASS 10 for determining Depression, Anxiety, and Stress. A total of 361 pre-clinical medical students consisted of 146 (40.4%) males and 215 (59.5%) females. The majority of the students, 246 (68.1%), were in their second year. Furthermore, in the current study, students who had poor academic performance (15.8%), satisfactory academic performance (21.3%), or good academic performance (30.7%) had significant sleeping problems found (χ2 = 19.4; p = 0.001), among them poor academic performance students 21.6%, satisfactory academic performance students (29.3%), and good academic performance students (29.3%) had moderate to severe levelled sleeping problems. Similarly, poor, satisfactory, and good academic performers experienced the highest levels of anxiety (poor = 21.5%; satisfactory = 22.1%; and good = 22.8%); stress (poor = 22.4%; satisfactory = 25.2%; and good = 22.4%); and depression (poor = 40.5%; satisfactory = 40.5%; and good = 11.9%). The majority of students (64.8%) reported that during the pandemic crisis their anxiety levels were high. Additionally, students reported significantly high sleeping issues (χ2 = 10.6; p = 0.001) and also serious psychological issues (Anxiety = 34.9 (0.000); Stress = 32.5 (0.000); and Depression = 5.42 (0.01)). There was a high prevalence of sleep issues, anxiety, stress, and depression among the pre-clinical medical students, with significantly higher sleeping disorders, anxiety, stress, and depression levels among those medical students who struggle with their academic performances, poor lifestyle factor, and poor Social and COVID management

Microwave technology for food applications

This chapter aims at introducing basic features of dielectric heating and to present the applications in the food industry. Based on a literature survey of recent works, many examples are given to highlight the main advantages of the microwave (MW) technology in food processing. The case of most processes involving heating is addressed. From another point of view, the environmental impacts, regulations, and safety aspects are discussed. Little data concerning the environmental impact of dielectric heating in the food industry are available. Therefore beyond assessing some particular points, a general methodology is presented which should be followed to obtain reliable results. Finally, some industrial examples are presented and future trends for the MW technique are given