BackgroundMicroparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human.ObjectiveTo evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs.MethodA panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA).ResultsThe results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM2.5 (IQR=64.9 μg·m−3) at prior 18 h and NO (IQR=40.5 μg·m−3) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05).ConclusionShort-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.
A key event in the process of rat but not human liver carcinogenesis caused by constitutive androstane receptor activators such as phenobarbital (PB) is hepatocyte proliferation, but the mechanism(s) underpinning this response is not fully understood. Previously we showed that rat liver microtissues (LiMTs) can recapitulate a PB-induced hepatocyte proliferation response (1). In this follow up study we used our microTMA technology coupled with transcriptomics and immunofluorescence (IF) staining to elucidate mechanisms of rat liver carcinogenesis in this model. We performed gene set enrichment analysis (GSEA) on transcriptomics data generated from laser microdissected liver microtissue microTMA FFPE sections from control and PB-treated LiMTs against custom liver cell proliferation and constitutive androstane receptor (CAR) activation signatures (2) and found that the former signature was significantly (q<0.25) enriched in rat but not human LiMT differentially expressed gene lists. This process also identified the cell proliferation gene nucleophosmin 1 (NPM1) as being significantly induced (p < 0.05) in rat but not human LiMTs. IF staining of parallel microTMA FFPE sections coupled with quantitative image analysis confirmed that the NPM1 protein was induced by PB treatment in rat but not human liver microtissues after 24 and 48 hrs PB treatment. In conclusion we have identified induction of nuclear NPM1 expression as an early event in PB-induced rat hepatocyte cell proliferation.
Abstract Introduction Since 2012, DRC adopted WHO recommendations for the malaria treatment with artemisinin-based drugs. Medication errors are defined as “a failure in the treatment process that results in, or has the potential to result in, harm to the patient”. Medication errors are a major public health problem and one of the leading causes of death in the United States. The impact of medical errors can have severe consequences on children due to physiological features of children. Objectives To identify, describe, and propose actionable strategies to address medication errors during malaria treatment in children with adverse effects in the DRC. Methods This is a cross-sectional study of the ADR reports of children (< 18 years old) in the DRC recorded in VigiBase®, the WHO pharmacovigilance database, from 2010 to February 2018. Five treatment process criteria (choice of treatment, dosage, duration, timing and route of administration) were selected to identify medication errors. Results Medication errors accounted for 65,9% of the 851 cases retrieved from VigiBase®. Children aged 2–11 years represented 55.2% of the study population. The choice of treatment, duration and dosage were the main prescription criteria for deviations. Discussion The availability of alternative formulations, self-medication and inadequate dosage forms are factors contributing to medication errors. The information available in VigiBase® did not allow us to evaluate the overall process of malaria management. Pharmacovigilance must be consolidated to raise awareness among consumers and providers and to ensure more effective monitoring. Conclusion Non-compliance with national guidelines for the management of malaria is important in DRC. Our study amply demonstrates the need to strengthen the four pillars of the WHO’s third global challenge, “Medication without harm”, to reduce medication errors. This study advocates a significant mobilisation of resources for the training of health professionals and the strengthening of pharmacovigilance. Field studies on the management of malaria in children should be conducted to quantify drug errors.
The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.
Kuldip Upadhyay, Rakesh Balachandar, Bhavani Shankara Bagepally
et al.
A recent systematic review reported very high pooled estimates of blood lead levels (BLLs) for Indian children. Current study aimed at systematically pooling the BLLs of Indian children (aged ≤ 14 years). Further, explore the time trend of BLLs with respect to implementing the ban on the use of Pb-petrol (i.e.2000) and a decade later (2010). Observational studies documenting the BLL in Indian children (aged ≤ 14 years) from PubMed-Medline, Scopus, and Embase digital databases from inception to August 2024 were systematically reviewed. Detailed protocol is available at PROSPERO (ID: CRD42022382835). Pooled mean BLL was estimated using the random-effects model and conventional-I2 statistics to assess the heterogeneity, while the Newcastle Ottawa Scale for bias assessment. Sub-group, sensitivity, and meta-regression analyses were performed where data permitted. Observations from 65 reports (51 original studies) revealed pooled BLL of 10.4 (95 % CI: 9.55–11.2) µg/dL with a trend of gradual reduction during the last 3 decades. Subgroup analysis revealed the high risk (with known Pb exposure) children had BLL of 14.3 (12.3–16.2) µg/dL, while that of the low risk (no known Pb exposure) is 8.71 (7.71–9.71) µg/dL. Only the low risk group exhibited a time trend of a gradual reduction in BLL. Notably, the review observed high heterogeneity. A progressive decline in Pb burden with respect to the national ban on leaded petrol was observed. However, present observations emphasize remedial actions toward non-occupational Pb exposure particularly among high risk Pb group, such as periodic BLL surveys.
Christian Ebere Enyoh, Tochukwu Oluwatosin Maduka, Miho Suzuki
et al.
Emerging pharmaceutical pollutants like ciprofloxacin (CIP) and ibuprofen (IBU) are frequently detected in aquatic environments, posing risks to ecosystems and human health. Since pollutants rarely exist alone in the environment, understanding the thermal stability and degradation kinetics of these compounds, especially in mixtures, is crucial for developing effective removal strategies. This study therefore investigates the thermal stability and degradation kinetics of CIP and IBU, under different heating rates. Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) were employed to examine the thermal behavior of these compounds individually and in mixture (CIP + IBU) at heating rates of 10, 20, and 30 °C/min. The kinetics of thermal degradation were analyzed using both model-fitting (Coats–Redfern (CR)) and model-free (Kissinger–Akahira–Sunose (KAS), Flynn–Wall–Ozawa (FWO), and Friedman (FR)) methods. The results showed distinct degradation patterns, with CIP decomposing between 280 and 550 °C and IBU between 152 and 350 °C, while the mixture exhibited multistep decomposition in the 157–500 °C range. The CR model indicated first-order kinetics as a better fit for the degradation (except for IBU). Furthermore, CIP exhibits higher thermal stability and activation energy compared to IBU, with the KAS model yielding activation energies of 58.09 kJ/mol for CIP, 11.37 kJ/mol for IBU, and 41.09 kJ/mol for CIP + IBU mixture. The CIP + IBU mixture generally showed intermediate thermal properties, suggesting synergistic and antagonistic interactions between the compounds. Thermodynamic parameters (Δ<i>H</i>°, Δ<i>G</i>°, Δ<i>S</i>°) were calculated, revealing non-spontaneous, endothermic processes for all samples (except in the FWO method) with a decrease in molecular disorder and positive Δ<i>G</i>° values across all models and heating rates. The study found that higher heating rates led to less thermodynamically favorable conditions for degradation. These findings provide important information concerning the thermal behavior of these pharmaceutical pollutants, which can inform strategies for their removal from the environment and the development of more effective waste-treatment processes.
Chromium a heavy metal present in the effluent of the industries causes accumulation of toxicity in water. Chromium commonly has Cr (III) and Cr (VI), two oxidation states, in which hexavalent form causes more health issues to human, other species and environment. The increased anthropogenic effects, especially tannery industrial effluent contributes the higher percentage of chromium accumulation. Removal of heavy metal can be attributed to many aspects, conventionally the physio-chemical methods which superseded by biological means of remediation. Chromium resistant microbes can be used to remove metal ions of chromium from the effluent, as this can be considered an eco-friendly approach. The microbial accession of nanoparticles synthesis is being focused, due to its accuracy and specificity in results. Mycoremediation grabbed attention as fungal absorbance efficiency and the surface-mechanism of heavy metal ions correlates each other. Current study in-depth indulges the base to core mechanism of mycoremediation of chromium ions from different effluents. Fungal-assisted mechanism of chromium ions have insists to be fewer, which may gain attention by enhancing the methodology of removal of chromium ions. This study focuses on improvement of fungal strain and pave-way, to improvise the study with immobilization technique which renders usage of the adsorbents redundant usage and applications, substantially with the low-cost polymeric material alginate is given more importance for immobilization technique. Alginate apart from low-cost adsorbent, is an excellent support for fungal producing nanoparticles which would provide wide-cast and an extraordinary adsorbent material.
Abstract Active compounds were usually incorporated into biopolymer films to enhance their properties. The tensile strength (TS) and elongation at break (EAB) of the gelatin composite films increased along with the addition of ε‐polylysine (ε‐PL) and zinc oxide nanoparticles (nano‐ZnO). When the concentrations of ε‐PL and nano‐ZnO were 4% and 0.5%, TS and EAB reached to the maximum which were 53.98 ± 2.61 MPa and 16.05 ± 1.76%. The water vapor permeability, water solubility, and water content of the composite films decreased from 2.01 ± 0.04 10−10 g m−1 Pa−1 s−1 to 1.56 ± 0.07 × 10−10 g m−1 Pa−1 s−1, from 45.23 ± 1.54% to 31.39 ± 1.24% and from 23.89 ± 1.41% to 17.34 ± 2.61%, respectively, compared with gelatin film. The light barrier capacity of the composite film was improved. The surface of the film was relatively smooth, and the cross‐section was overall flat. FTIR results indicated that no chemical reaction occurred among ε‐PL, nano‐ZnO and gelatin. The chemical structure of the films remained unchanged throughout the heat‐sealing process. Moreover, the gelatin films containing ε‐PL and nano‐ZnO showed excellent antibacterial activity. Our findings suggest that the gelatin composite films with antibacterial property hold promise for the application in food packaging materials.
Food processing and manufacture, Toxicology. Poisons
Maria Laura Schirripa, Letizia Gnetti, Edda Emanuela Guareschi
Tadalafil is an inhibitor of the enzyme human cyclic guanosine monophosphate–specific phosphodiesterase, type 5 (PDE-5). A mild vasodilator, it is primarily used for the treatment of erectile dysfunction (ED), an increasingly common condition. Other clinical uses include benign prostatic hyperplasia and pulmonary arterial hypertension. Adverse events are rare. Absolute contraindications include serious cardiac disease. Despite the widespread use of tadalafil, very little is known about any associations with lethal cases in forensic pathology, with related post-mortem redistribution phenomena and toxicology. This study presents a forensic case with possible contribution of tadalafil to the cause of death. Furthermore, an overview of tadalafil and a discussion on its relevance in the forensic practice are discussed. The administration of tadalafil might act as a concurrent cause, or contributing factor, to lethal cardiogenic shock in subjects with cardiac disease.
Endirlik Burcu Ünlü, Eken Ayşe, Canpınar Hande
et al.
The aim of this study was to investigate oxidative stress induced by perfluorooctanoic acid (PFOA) in the brain and liver tissues of Balb/c mice as well as protective effects of taurine and coenzyme Q10 (CoQ10) in both organs. For this purpose, animals were treated with PFOA (15 and 30 mg/kg) orally and their lipid peroxidation, total glutathione levels (GSH), and antioxidant enzyme activities measured and both tissues analysed for histopathological changes. Our results showed a dose-dependent decrease in body weight and increase in relative brain and liver weights, PFOA-induced lipid peroxidation and reduced glutathione peroxidase (GPx) activity in the brain tissue, and changes in GSH levels, GPx, superoxide dismutase (Cu-Zn SOD), and catalase (CAT) activities in the liver tissue. Pre-treatment with taurine or CoQ10 provided protection against PFOA-induced Cu-Zn SOD reduction in the liver tissue. Our findings evidence the depleting effect of PFOA on antioxidative systems and confirm that PFOA exerts its (neuro)toxicity through oxidative stress, but further research is needed to identify the exact toxicity mechanisms, especially in the brain.
BackgroundCoal workers' pneumoconiosis (CWP) is a serious occupational disease. Whether ferroptosis, a form of necrotic regulated cell death, is involved in coal dust induced mouse models of CWP needs further survey. ObjectiveThis experiment is designed to elucidate the role of ferroptosis in the formation of CWP induced by coal dust in mice. MethodsC57BL/6J mice were randomly assigned to a saline group or a CWP group, with eight mice in each group. The mice were treated with 0.1 mL normal saline or 0.1 mL coal dust suspensions (50g·L-1) via intra-tracheal instillation. HE staining and Masson staining were used to show lung injury and lung fibrosis. Iron concentration in mouse lung tissues was measured using iron assay kit. Lipid peroxidation was estimated in lung tissues by malondialdehyde (MDA) concentration and immunofluorescence intensity, and the ratio of glutathione (GSH) to L-glutathione oxidized (GSSG). Western blotting and real-time fluorescence-based quantitative PCR were used to test protein and mRNA expression levels of glutathione peroxidase 4 (GPX4) and ferritin in mice. ResultsCoal dust injured pulmonary structure, thickened alveolar wall, and caused collagen deposition and infiltration of inflammatory cells in the CWP group. The iron concentration in the CWP group [(10.75 ± 5.42) mg·L−1] was higher than that in the saline group [(1.14 ± 0.37) mg·L−1] (P < 0.01). The MDA concentration in the CWP group [(37.32 ± 12.18) μmol·L−1] was higher than that in the saline group [(18.70 ± 8.22) μmol·L−1] (P <0.01). The immunofluorescence intensity of MDA in the CWP group was stronger than that in the saline group. The GSH/GSSG ratio decreased in CWP treated mice (1.50 ± 1.70) compared with the normal saline treated ones (4.95 ± 2.86) (P < 0.01). Compared with the saline group (38.84 ± 15.61 for GPX4, 225.90 ± 54.34 for ferritin), the relative expression levels of GPX4 and ferritin mRNA in the CWP group were downregulated (14.29 ± 7.21 for GPX4, 106.70 ± 36.70 for ferritin) (P < 0.01). Compared with the saline group (1.47 ± 0.54 for GPX4, 1.73 ± 0.34 for ferritin), the relative expression levels of GPX4 and ferritin protein in the CWP group were also downregulated (0.92 ± 0.22 for GPX4, 0.97 ± 0.09 for ferritin) (P < 0.05). ConclusionFerroptosis may be involved in the formation of coal workers' pneumoconiosis induced by coal dust in mice.
Somayeh Esmaeili, Mahya Asadi, Mahmoud Mosaddegh
et al.
Background: Cancer is the second cause of death in developed countries. Colon and breast cancers are among the most prevalent ones. Research focusing on finding new natural products with fewer side effects to fight cancer is increasing. Objectives: The present study aimed to evaluate the cytotoxicity of Centaurea albonitens Turrill methanol extract and its fractions against colon and breast cancer cell lines and a normal cell line of bovine kidney cells. Methods: The methanol extract and petroleum ether, chloroform and aqueous fractions were provided from the aerial parts of C. albonitens by maceration method in three days. Each day the solvent was refreshed. Colon (HT-29) and breast (MCF-7) cell lines were treated with the extract/fractions for 48 h for evaluating the cytotoxic activity by MTT assay. The apoptotic induction potential was also evaluated with the Hoechst 33258 staining method. Results: The most considerable effect was reported from the chloroform fraction with IC50 values of 25.6 and 25.1 μg/mL in MCF-7 and HT-29 cells, respectively. In Hoechst staining, condensed chromatin of the apoptotic cells was observed in both cell lines. Conclusion: Centaurea albonites can be suggested for further cancer research studies.
Violaine Sironval, Mihaly Palmai-Pallag, Rita Vanbever
et al.
Abstract Background Li-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2 (LCO), one of the most used cathode material, induces inflammatory and fibrotic lung responses in mice. LCO also stabilizes hypoxia-inducible factor (HIF) -1α, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1α as determinants of toxicity, and evaluated their predictive value for the lung toxicity of LIB particles in in vitro assays. Results By testing a set of 5 selected LIB particles (LCO, LiNiMnCoO2, LiNiCoAlO2) with different cobalt and nickel contents, we found a positive correlation between their in vivo lung inflammatory activity, and (i) Co and Ni particle content and their bioaccessibility and (ii) the stabilization of HIF-1α in the lung. Inhibition of HIF-1α with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1β deficient mice, HIF-1α was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1α stabilization induced by LIB particles in BEAS-2B cells correlated with the intensity of lung inflammation induced by the same particles in vivo. Conclusions We conclude that HIF-1α, stabilized in lung cells by released Co and Ni ions, is a mechanism-based biomarker of lung inflammatory responses induced by LIB particles containing Co/Ni. Documenting the Co/Ni content of LIB particles, their bioaccessibility and their capacity to stabilize HIF-1α in vitro can be used to predict the lung inflammatory potential of LIB particles.
Background: Salvia multicaulis Vahl. a medicinal plant belonging to the Lamiaceae family, has an extensive application in native and traditional medicine.
Objective: This research was conducted to investigate diversity of morphophysiological traits and content of essential oil, phenol and flavonoid of Salvia multicaulis ecotypes in different districts of Hamedan province, Iran.
Methods: In this study, 11 ecotypes of Salvia multicaulis were collected from different districts of Hamedan Province at the full flowering stage in spring 2016 and were evaluated for their morphophysiological and phytochemical characteristics. The classification of ecotypes was done on the basis of phytochemical and morphophysiological traits by cluster analysis and correlations among quantitative traits was also conducted by Pearson method.
Results: Result showed that the essential oil content had positive significant correlation with plant height, inflorescence length, dry matter of flowering branche and essential oil yield. Also there was a positive significant correlation between essential oil yield with receptacle length, flower fresh and dry matter and plant dry matter. The heighes dry weight of flowering branch and flower was related to ecotypes of Lashkardar and west of Hamedan, respectively. The maximum plant dry weight was belong to Yelfan ecotype. The most essential oil content was related to Lashkardar and west of Hamedan ecotypes. Also, the highest content of phenol and flavonoid related to Vehnan ecotype. According to the cluster analysis, 11 ecotypes were divided into two groups.
Conclusion: The evaluation of morphophysiological and phytochemical traits showed that there was a considerable variation among different ecotypes of Salvia multicaulis in respect of morphophysiological and phytochemical characteristics.
Background: Hyssop (Hyssopus officinalis L.) is herbaceous perennial plants of Lamiaceae family grown in Europe, the Middle East, Asia, and Northern Africa.
Objective: In this research, the effect of harvesting time was studied on essential oil, photosynthetic pigment, and some morphological characteristics of hyssop.
Methods: A Field experiment was carried out during 2015/2016 at the Research farm of Payam Noor University of Marand, Iran. The experimental design was laid out as randomized complete block design with three replicates. The three harvesting time (pre-flowering, beginning of flowering and full flowering stages) were arranged in experimental plots.
Results: Results indicated that the percentage of essential oil varied for 0.459 to 0.618 in different stage of plant growth. Hyssop essential oil yields increased with time and the highest value of measured traits included plant high, stem diameter, number of secondary and flowering branches, dry weight, chlorophyll (a, b and total), carotenoid, total anthocyanins and total flavonoids was obtained for collected plants in full flowering stage.
Conclusion: Overall, the harvesting in full flowering stage was the best time in respect of essential oils content and morphological characteristics in hyssop.
Paraquat is one of the most widely used herbicides in the world and is highly toxic to humans and animals. In this study, we developed a serum metabolomic method based on GC/MS to evaluate the effects of acute paraquat poisoning on rats. Pattern recognition analysis, including both principal component analysis and partial least squares-discriminate analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the level of octadecanoic acid, L-serine, L-threonine, L-valine, and glycerol in the acute paraquat poisoning group (36 mg/kg) increased, while the levels of hexadecanoic acid, D-galactose, and decanoic acid decreased. These findings provide an overview of systematic responses to paraquat exposure and metabolomic insight into the toxicological mechanism of paraquat. Our results indicate that metabolomic methods based on GC/MS may be useful to elucidate the mechanism of acute paraquat poisoning through the exploration of biomarkers.
Abstract Acute pesticide poisoning is an important public health problem worldwide and accounts for a significant number of deaths occurring each year. Most of these fatalities are due to poisoning with organophosphorus insecticides which are an integral part of agriculture within this region of Asia. Due to their very high intrinsic toxicity, continuous efforts are being made to develop newer pesticides of low toxicity and high potency. Invariably such compounds are released into the market without appropriate data on direct human toxicity. Human toxicity is often extrapolated from toxicological studies in animals, the relevance of which remains poorly defined. Imidacloprid is a neonicotinoid insecticide belonging to the chloronicotinyl nitroguanidine chemical family. It acts on the nervous system through an acetylcholine receptor blockade and is considered nontoxic to humans based on the available literature. It is routinely used to kill fleas present on pet animals, termites and bees. This study reports a case that presented with severe gastrointestinal symptoms along with respiratory distress and neuropsychiatric features following accidental inhalational exposure to imidacloprid. The patient recovered from the effects of the poisoning with supportive and symptomatic treatment. As far as this research is concerned, this is the first report of acute inhalational intoxication with imidacloprid in India.