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2021 ◽  
Vol 23 (1) ◽  
pp. 49
Author(s):  
Zoi Skaperda ◽  
Fotios Tekos ◽  
Periklis Vardakas ◽  
Charitini Nepka ◽  
Demetrios Kouretas

Cellular adaptive mechanisms emerging after exposure to low levels of toxic agents or stressful stimuli comprise an important biological feature that has gained considerable scientific interest. Investigations of low-dose exposures to diverse chemical compounds signify the non-linear mode of action in the exposed cell or organism at such dose levels in contrast to the classic detrimental effects induced at higher ones, a phenomenon usually referred to as hormesis. The resulting phenotype is a beneficial effect that tests our physiology within the limits of our homeostatic adaptations. Therefore, doses below the region of adverse responses are of particular interest and are specified as the hormetic gain zone. The manifestation of redox adaptations aiming to prevent from disturbances of redox homeostasis represent an area of particular interest in hormetic responses, observed after exposure not only to stressors but also to compounds of natural origin, such as phytochemicals. Findings from previous studies on several agents demonstrate the heterogeneity of the specific zone in terms of the molecular events occurring. Major factors deeply involved in these biphasic phenomena are the bioactive compound per se, the dose level, the duration of exposure, the cell, tissue or even organ exposed to and, of course, the biomarker examined. In the end, the molecular fate is a complex toxicological event, based on beneficial and detrimental effects, which, however, are poorly understood to date.


Toxics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 334
Author(s):  
Raluca Elena Ginghina ◽  
Adriana Elena Bratu ◽  
Gabriela Toader ◽  
Andreea Elena Moldovan ◽  
Tudor Viorel Tiganescu ◽  
...  

This paper comprises an extensive study on the evaluation of decontamination efficiency of three types of reactive organic suspensions (based on nanosized adsorbents) on two real chemical warfare agents: soman (GD) and sulfur mustard (HD). Three types of nanoparticles (ZnO, TiO2, and zeolite) were employed in the decontamination formulations, for enhancing the degradation of the toxic agents. The efficacy of each decontamination solution was investigated by means of GC-MS analysis, considering the initial concentration of toxic agent and the residual toxic concentration, measured at different time intervals, until the completion of the decontamination process. The conversion of the two chemical warfare agents (HD and GD) into their decontamination products was also monitored for 24 h.


BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e053028
Author(s):  
Liqaa Raffee ◽  
Hamza M Daradkeh ◽  
Khaled Alawneh ◽  
Aida I Al-Fwadleh ◽  
Moath Darweesh ◽  
...  

ObjectivesTo describe the effect of the COVID-19 lockdown in Jordan (21 March 2020–21 May 2020) on the incidence and patterns of toxic exposures and poisoning as compared with the same period from the previous year (21 March 2019–21 May 2019).DesignA retrospective descriptive study.MethodsCall data sourced from Pharmacy One Poison Center from the lockdown period (21 March 2020–21 May 2020) and the same period during 2019 (21 March 2019–21 May 2019) were revised. In addition, a database was established and analysed.ResultsWe noticed that not only did calls increased, but there was also a noticeable change in call patterns. Calls increased by 91% (544 vs 285 calls) during the lockdown period. Drugs were the most common among types of exposure, and the most prevalent route of exposure was ingestion. There was a notable increase in ocular exposure by 550% (13 vs 2 cases). The majority of exposures were at home and there were no occupational exposures. We found an increase in household cleaner exposure among males and an increase in alcohol exposure in females. Children aged below 5 years are the most affected. Even though there is an increase in the total number of cases, severe cases decreased.ConclusionThe lockdown effect on rates of toxic exposures was prominent, whether through the increase in calls or the change in patterns. As people spent more time at home, their exposure to toxic agents increased. Furthermore, cleaning recommendations led to the misuse of cleaning and disinfectant products, increasing exposures related to abating the COVID-19 infection.


2021 ◽  
Author(s):  
Theophilus Clavell Davies

Abstract The term diseases of unknown aetiology (DUA) or idiopathic diseases refers to diseases that are of uncertain or unknown cause or origin. Among plausible geoenvironmental (co-)factors in causation of DUA, this article focusses on the entry of trace elements, including metals and metalloids into biological systems, and their involvement in humoral and cellular immune responses, representing potentially toxic agents with implications as co-factors for certain DUA. Several trace elements/metals/metalloids (micronutrients) play vital roles as cofactors for essential enzymes and antioxidant molecules, thus, conferring protection against disease. However, inborn errors of trace element/metal/metalloid metabolisms can occur to produce toxicity, such as when there are basic defects in the element transport mechanism. Ultimately, it is the amount of trace element, metal or metalloid that is taken up, its mode of accumulation in human tissues, and related geomedical attributes such as the chemical form and bioavailability that decisively determine whether the exerted effects are toxic or beneficial. Several case descriptions of DUA that are common worldwide are given to illustrate our knowledge so far of how trace element/metal/metalloid interactions in the immune system may engender its dysregulation and be implicated as causal co-factors of DUA.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2511-2511
Author(s):  
Tiffany Guan ◽  
Mimi Lo ◽  
Rebecca Young ◽  
Fouad Boulbol ◽  
Hanson Mouanoutoua ◽  
...  

Abstract Background: Brentuximab vedotin (Bv) is an anti-CD30 antibody conjugated via a protease-cleavable linker to the anti-microtubule agent monomethyl auristatin E (MMAE). It is FDA approved for the treatment of classic Hodgkin lymphoma (cHL) and CD30-expressing T-cell lymphomas in both upfront and relapsed/refractory (R/R) settings. The most common side effects in the original registration trials (ECHELON-1, ECHELON-2, AETHERA) include peripheral neuropathy and cytopenias. With its expanded use in real world settings, it is imperative to identify less-established adverse events which may also result in dose delays or reductions. Pulmonary toxicity is a rare but potentially life-threatening side effect of Bv, but few studies have characterized this toxicity in the adult and pediatric populations. Here, we characterize the incidence and risk factors of developing Bv-associated pulmonary toxicity in patients with lymphoma. Methods: We conducted a multicenter, retrospective, descriptive study of patients receiving Bv at University of California San Francisco Health in San Francisco, CA and Community Medical Center in Fresno, CA. Adult and pediatric patients were included if they received at least one dose of Bv between June 1, 2015 and September 30, 2020. Retrospective chart review was conducted to identify patients who developed respiratory symptoms concerning for Bv-induced pneumonitis. Past medical history, smoking history, and prior administration of pulmonary toxic agents were collected to assess for risk factors contributing to Bv-associated pulmonary toxicity. Respiratory symptoms were classified as likely related, possibly related, or not related to Bv. Patients were identified to have pulmonary toxicities likely related to Bv if they satisfied the following criteria: development of respiratory symptoms with a temporal relation to Bv, suggestive chest imaging or pulmonary function tests (PFTs), rule out of other etiologies including infectious causes, and relief of symptoms with steroid treatment and/or Bv discontinuation at the physician's discretion. Patients were identified to have pulmonary toxicities possibly related to Bv if they satisfied the following criteria: development of respiratory symptoms with a temporal relation to Bv, equivocal chest imaging or PFTs, inability to fully rule out other etiologies, and relief of symptoms with steroid treatment or Bv discontinuation at the physician's discretion. Data is reported using descriptive statistics. A consort flow diagram of the selection process is depicted in Figure 1. Results: A total of 123 patients were reviewed, of whom 27 were excluded due to pregnancy, prisoner status, or not having received Bv during the study period. 96 patients were included in the final analysis. Baseline characteristics are captured in Table 1. Following Bv administration, 19 of the 96 patients developed pulmonary symptoms (dry cough, shortness of breath, dyspnea on exertion, chest pain, or hypoxic respiratory failure not justified by a competing process). Based on the prespecified definitions, we identified four patients (4.2%) who developed respiratory symptoms concerning for Bv-induced toxicity. The mean age of the four patients was 51 (range 28-76) and one patient was female. One patient received Bv in the upfront setting for cHL, one had R/R cHL, and the remaining two had anaplastic large cell lymphoma (ALCL). One patient previously received pulmonary toxic agents (gemcitabine and carmustine) and two patients had a history of tobacco use. The cumulative doses of Bv the four patients received prior to developing respiratory symptoms ranged from 8.8 to 30.4 mg/kg (6-21 cycles). Three patients were classified as likely related based on supportive findings on chest imaging or PFTs and one patient was classified as possibly related given lack of definitive evidence to differentiate between pneumonitis and disease progression. Three of the four patients developed symptoms requiring steroid treatment and two required Bv dose reduction and/or discontinuation. Conclusions: This study is an effort to raise awareness of the incidence of Bv-induced pulmonary toxicity and describe the potential risk factors associated with this adverse event. Further real world studies in larger and diverse patient populations are necessary to better characterize the incidence and risk factors associated with Bv-associated pulmonary toxicities. Figure 1 Figure 1. Disclosures Lo: EUSA Pharma: Consultancy; Oncopeptides: Consultancy. Ai: Kymria, Kite, ADC Therapeutics, BeiGene: Consultancy. Abdulhaq: BMS, Alexion, Oncopeptides, Morphosys, Pfizer, Norvartis: Honoraria; Oncopeptides, Alexion, Amgen: Speakers Bureau; Morphosys, BMS, Amgen: Membership on an entity's Board of Directors or advisory committees. Fakhri: Loxo/Lilly: Research Funding.


2021 ◽  
Vol 124 ◽  
pp. 102727
Author(s):  
Clodoveo Ferri ◽  
Maria-Cristina Arcangeletti ◽  
Elisabetta Caselli ◽  
Krystyna Zakrzewska ◽  
Clara Maccari ◽  
...  

2021 ◽  
Author(s):  
Satoshi Watanabe ◽  
Yuta Nihongaki ◽  
Kie Itoh ◽  
Shigeki Watanabe ◽  
Takanari Inoue

Organelles vitally achieve multifaceted functions to maintain cellular homeostasis. Genetic and pharmacological approaches to manipulate individual organelles are powerful in probing their physiological roles. However, many of them are either slow in action, limited to certain organelles, or rely on toxic agents. Here, we designed a generalizable molecular tool utilizing phospholipase A/acyltransferases (PLAATs) for rapid induction of organelle defunctionalization via remodeling of the membrane phospholipid composition. In particular, we identified a minimal, fully catalytic PLAAT with no unfavorable side effects. Chemically-induced translocation of the engineered PLAAT to the mitochondria surface resulted in their rapid deformation in a phospholipase activity dependent manner, followed by loss of luminal proteins as well as dissipated membrane potential, thus invalidating the functionality. To demonstrate wide applicability, we then adapted the molecular tool in peroxisomes, and observed leakage of matrix-resident functional proteins. The technique was compatible with optogenetic control, viral delivery and operation in primary neuronal cultures. Due to such versatility, the PLAAT strategy should present a novel utility in organelle biology of diverse contexts.


2021 ◽  
Vol 14 (10) ◽  
pp. e245165
Author(s):  
Nicola Magnavita ◽  
Maria Teresa Congedo ◽  
Reparata Rosa Di Prinzio ◽  
Angela Iuliano

Apart from the risk of accidents, war theatres present a hazard related to numerous long-lasting toxic agents. For 10 years, a >60-year-old male journalist worked in war theatres in the Far and Near East where he was exposed to asbestos and other toxic substances (metals, silica, clays, polycyclic aromatic hydrocarbons and other organic substances) contained in dust and smoke of destroyed buildings. More than 15 years later, he developed a mucoepidermoid carcinoma of the soft palate and, subsequently, a pleural malignant mesothelioma. The safety of war journalists should focus not only on preventing the risk of being killed, but also on providing protection from toxic and carcinogenic agents. Exposure to substances released during the destruction of buildings can also pose a carcinogenic risk for survivors.


2021 ◽  
pp. 00399-2021
Author(s):  
Letizia Traversi ◽  
Marc Miravitlles ◽  
Miguel Angel Martinez-Garcia ◽  
Michal Shteinberg ◽  
Apostolos Bossios ◽  
...  

IntroductionThe coexistence of chronic obstructive pulmonary disease (COPD) and bronchiectasis (BE) seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians.MethodsWe conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD-BE association”.A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and gender distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds.ResultsA-hundred-and-two (72.3%) out of 141 invited experts participated the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD-BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry (FEV1/FVC<0.7), (3) at least two characteristic symptoms (cough, expectoration, dyspnoea, fatigue, frequent infections) and (4) current or past exposure to smoke (≥10 pack-years) or other toxic agents (biomass, etc.)”. These criteria form the acronym “ROSE” (Radiology, Obstruction, Symptoms, Exposure).ConclusionsThe Delphi process formulated a European consensus definition of “COPD-BE association”. We hope this definition will have broad applicability across clinical practice and research in the future.


2021 ◽  
Vol 22 (18) ◽  
pp. 10086
Author(s):  
Giovanna De Simone ◽  
Alessandra di Masi ◽  
Paolo Ascenzi

Human serum albumin (HSA) is the most abundant protein in plasma, contributing actively to oncotic pressure maintenance and fluid distribution between body compartments. HSA acts as the main carrier of fatty acids, recognizes metal ions, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays esterase, enolase, glucuronidase, and peroxidase (pseudo)-enzymatic activities. HSA-based catalysis is physiologically relevant, affecting the metabolism of endogenous and exogenous compounds including proteins, lipids, cholesterol, reactive oxygen species (ROS), and drugs. Catalytic properties of HSA are modulated by allosteric effectors, competitive inhibitors, chemical modifications, pathological conditions, and aging. HSA displays anti-oxidant properties and is critical for plasma detoxification from toxic agents and for pro-drugs activation. The enzymatic properties of HSA can be also exploited by chemical industries as a scaffold to produce libraries of catalysts with improved proficiency and stereoselectivity for water decontamination from poisonous agents and environmental contaminants, in the so called “green chemistry” field. Here, an overview of the intrinsic and metal dependent (pseudo-)enzymatic properties of HSA is reported to highlight the roles played by this multifaced protein.


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