Potential Acute Toxicity Research Articles

Advanced oxidation process of valsartan by activated peroxymonosulfate: Chemical characterization and ecotoxicological effects of its byproducts

In recent years, the antihypertensive drug Valsartan (VAL) has been detected in surface waters up to concentrations of 6300 ng/L, due to its high consumption and its mostly unchanged excretion. Moreover, wastewater treatment plants fail to completely mineralize/transform it, as evidenced by findings of up to 3800 ng/L in some effluents. In this paper, the possible degradation of VAL was evaluated through Fenton-like reaction with activation of peroxymonosulfate in the presence of Fe(II) under neutral conditions. Fourteen degradation byproducts were isolated and completely identified by both nuclear magnetic resonance and mass spectrometry, five of which were discovered for the first time, and a mechanism of their formation was proposed. Furthermore, the potential acute and chronic toxicity of valsartan and its byproducts in the aquatic environment were evaluated in key organisms of the freshwater trophic chain belonging to producers and consumers, the alga Raphidocelis subcapitata and the rotifer Brachionus calyciflorus, respectively. Acute effects occurred at concentrations in the order of tens/hundreds of mg/L, far from those of environmental concern. As regards chronic effects, algae were not particularly affected by the parent compound and its derivatives, while rotifers were less affected by derivatives (effective concentrations at units/tens of μg/L) compared to valsartan (effective concentrations at hundreds of ng/L).

Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode.

Understanding the metabolism of pharmaceutical compounds is a fundamental prerequisite for ensuring their safety and efficacy in clinical use. However, conventional methods for monitoring drug metabolism often come with the drawbacks of being time-consuming and costly. In an ongoing quest for innovative approaches, the application of electrochemistry in metabolism studies has gained prominence as a promising approach for the synthesis and analysis of drug transformation products. In this study, we investigated the hepatic metabolism of voriconazole, an antifungal medication, by utilizing human liver microsomes (HLM) assay coupled with LC-MS. Based on the obtained results, the electrochemical parameters were optimized to simulate the biotransformation reactions. Among the various electrodes tested, the chemometric analysis revealed that the iron(II) phthalocyanine electrode was the most effective in catalyzing the formation of all hepatic voriconazole metabolites. These findings exemplify the potential of phthalocyanine electrodes as an efficient and cost-effective tool for simulating the intricate metabolic processes involved in drug biotransformation, offering new possibilities in the field of pharmaceutical research. Additionally, in silico analysis showed that two detected metabolites may exhibit significantly higher acute toxicity and mutagenic potential than the parent compound.

In Vivo Acute Toxicity and Therapeutic Potential of a Synthetic Peptide, DP1 in a Staphylococcus aureus Infected Murine Wound Excision Model.

Bacterial infections at the surgical sites are one of the most prevalent skin infections that impair the healing mechanism. They account for about 20% of all types of infections and lead to approximately 75% of surgical-site infection-associated mortality. Several antibiotics, such as cephalosporins, fluoroquinolones, quinolones, penicillin, sulfonamides, etc., that are used to treat such wound infections not only counter infections but also disrupt the normal flora. Moreover, antibiotics, when used for a prolonged duration, may impair the formation of new blood vessels, delay collagen production, or inhibit the migration of certain cells involved in wound repair, leading to an impaired healing process. Therefore, there is a dire need for alternate therapeutic approaches against such infections. Antimicrobial peptides have gained considerable attention as a promising strategy to counter these pathogens and prevent the spread of infection. Recently, we have reported a designed peptide, DP1, and its broad-spectrum in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria. In the present study, in vivo acute toxicity of DP1 was evaluated and even at a high dose (20mg/kg body weight) of DP1, a 100% survival of mice was observed. Subsequently, a Staphylococcus aureus-infected murine wound excision model was established to assess the wound healing efficacy of DP1. The study revealed significant wound healing vis-a-vis attenuated S. aureus bioburden at the wound site and also controlled the oxidative stress depicting anti-oxidant activity as well. Healing of the infected wounds was also verified by histopathological examination. Based on the results of this study, it can be concluded that DP1 improves wound resolution despite infections and promotes the healing mechanism. Hence, DP1 holds compelling potential as a novel antimicrobial drug that requires further explorations in clinical platforms.

Adsorptive removal of ciprofloxacin from simulated wastewater using crosslinked starch ester: Isotherms, kinetics, thermodynamics, modeling, and simulation for continuous operation

The rise in fluoroquinolone concentrations in wastewater caused significant concern due to their potential acute toxicity to living organisms. A novel eco-friendly adsorbent, crosslinked potato starch ester, was used to remove ciprofloxacin from a simulated aqueous solution by a batch adsorption process and used its obtained parameters to solve mathematical modeling. With a maximum adsorption capacity of 243.90 mg/g, the ciprofloxacin adsorption on crosslinked potato starch ester was suitable for the Langmuir isotherm model. The kinetics of ciprofloxacin adsorption showed that the pseudo-first-order kinetic model was a good fit for the adsorption process. Thermodynamic parameters exhibited that ciprofloxacin adsorption onto crosslinked potato starch ester was exothermic, achievable, and spontaneous. Finally, the process is simulated under various operating conditions using the mathematical model of a fixed bed continuous adsorption column. According to the results, under optimal operation conditions of inlet fluid velocity, particle size, bed height, and initial ciprofloxacin concentration with values 0.002 m/s, 1.2 mm, 0.2 m, and 143.4 mg/L, respectively, the highest dynamic adsorption capacity was 18.75 mg/g.

Evaluation of Acute Dermal Toxicity of Hibiscus Leaves as Simplicial Ointment on Albino Rats

Hibiscus is a plant that has been shown to contain substances that may be used as sunscreen to protect the skin from UV radiation. In terms of their potential as sunscreens, flavonoids, tannins, and quinone chemicals are crucial because they are antioxidants that can reduce the negative effects of UV radiation and boost photoprotective activity. This study aimed to investigate the acute dermal toxicity potential of hibiscus leaves simplicial ointment 40% on female albino rats. The evaluation method refered to The OECD Guideline for Testing of Chemicals – No. Test: 402, Acute Dermal Toxicity-Fixed Doses Procedure. Based on the Globally Harmonized System compared to this study reported that acute dermal median lethal dose (LD50) was > 2000 mg/kg. It can be concluded that hibiscus leaves simplicial ointment 40% has safe to apply topically and doesn't produce acute skin toxicity.

The application of acute oral toxicity computational models in dangerous goods classification.

Acute oral toxicity (AOT) data inform the acute toxicity potential of a compound and guides occupational safety and transportation practices. AOT data enable the categorization of a chemical into the appropriate AOT Globally Harmonized System (GHS) category based on the severity of the hazard. AOT data are also utilized to identify compounds that are Dangerous Goods (DGs) and subsequent transportation guidance for shipping of these hazardous materials. Proper identification of DGs is challenging for novel compounds that lack data. It is not feasible to err on the side of caution for all compounds lacking AOT data and to designate them as DGs, as shipping a compound as a DG has cost, resource, and time implications. With the wealth of available historical AOT data, AOT testing approaches are evolving, and in silico AOT models are emerging as tools that can be utilized with confidence to assess the acute toxicity potential of de novo molecules. Such approaches align with the 3R principles, offering a reduction or even replacement of traditional in vivo testing methods and can also be leveraged for product stewardship purposes. Utilizing proprietary historical in vivo AOT data for 210 pharmaceutical compounds (PCs), we evaluated the performance of two established in silico AOT programs: the Leadscope AOT Model Suite and the Collaborative Acute Toxicity Modeling Suite. These models accurately identified 94% and 97% compounds that were not DGs (GHS categories 4, 5, and not classified (NC)) suggesting that the models are fit-for-purpose in identifying PCs with low acute oral toxicity potential (LD50 >300mg/kg). Utilization of these models to identify compounds that are not DGs can enable them to be de-prioritized for in vivo testing. This manuscript provides a detailed evaluation and assessment of the two models and recommends the most suitable applications of such models.

Exploration of the anti-diabetic potential of hydro-ethanolic leaf extract of Koenigia polystachya L.: an edible wild plant from Northeastern India

BackgroundGlobally, medicinal plants are used to treat diseases like diabetes. The present study evaluates the possible antioxidant, acute oral toxicity, the in-vitro and in-vivo antidiabetic potential of the hydro-ethanolic leaf extract of Koenigia polystachya (HELeKP) against beta-cell damage in experimentally induced diabetes mellitus. The DPPH (2,2-diphenyl-1-picrylhydrazine), ABTS [2,2′-azino bis-(3-ethylbenzothiazoline-6-sulfonic acid)], H2O2 (Hydrogen peroxide), superoxide radical scavenging activity and NO (Nitric oxide) assay estimated the in-vitro antioxidant assay of HELeKP. The acute oral toxicity study was evaluated per the OECD (Organization for Economic Cooperation and Development) test guidelines 425. Diabetes was stimulated in rats with a single dose of Streptozotocin (STZ), and after confirmation of diabetes, HELeKP was given orally for 21 days. Blood/serum samples were gathered and examined for biochemical changes, while tissue samples were evaluated for histopathological alterations.ResultsThe IC50 value of the HELeKP for all the anti-oxidant assays confirms the free radical scavenging activity. The data on acute oral toxicity revealed that the HELeKP used in the study was comparatively very safe. The outcomes of the in-vivo study suggested that the extract significantly reduced (p < 0.001) the fasting glucose level in STZ-induced diabetic rats. Furthermore, the lipid profile level was significantly normalized (p < 0.01, p < 0.001) in diabetic rats. The histopathological observation of the pancreas in HELeKP-treated rats showed significant beta-cell restoration.ConclusionsBased on the outcomes of this study, the HELeKP-treated rats have significant free radical scavenging and anti-diabetic potential. Therefore, it can be recommended as a beneficial functional vegetable for consumption.

Acute oral toxicity of Cannabis sativa L. co-products in mice

Cannabis sativa L. commonly known as ‘Kif’, is a medicinal plant belonging to the Cannabaceae family (Cannabis genus). It is used in traditional folk medicine to treat several diseases. The recent legalization of cannabis use for medicinal, cosmetic, and industrial purpose in Morocco (law 13.21), has enabled us to assess the potential acute toxicity of extract from its female plant co-products in Swiss mice. In this experimentation, 3 different extraction methods (maceration, decoction, and sonication) were used to determine the efficacy of cannabis extracts and investigate their acute toxicity in mice over a period of 14 days. Decoction showed the highest efficacy (19.7%), followed by maceration (16.2%), and finally sonication (5.4%). Regarding the toxicity results of the oral gavage administration dose at 2,000 mg kg-1, there were no recorded deaths and no changes in the internal organs (kidneys and liver) between treated and control groups of both male and female mice. We also found that body weight of female mice treated by decoction and maceration extracts decreased significantly compared to those treated with sonication extract throughout the experimental period, when treated and untreated male mice show no significant changes (p-value &lt; 0.05). Our findings suggest that the LD50 may be greater than 2.000 mg kg-1. Nevertheless, the extracts showed signs of low-level toxicity such as drowsiness, hypoactivity, and tachycardia. Further studies to determine the phytochemical composition of the three extracts of C. sativa and assess the chronic and sub-chronic toxicity should be carried out.

L-glutamic acid-g-poly hydroxyethyl methacrylate nanoparticles: acute and sub-acute toxicity and biodistribution potential in mice.

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD50 was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.

Effects of Zinc Oxide Nanoparticle Exposure on Human Glial Cells and Zebrafish Embryos.

Zinc oxide nanoparticles (ZnO NPs) are among the most widely used nanomaterials. They have multiple applications in cosmetics, textiles, paints, electronics and, recently, also in biomedicine. This extensive use of ZnO NPs notably increases the probability that both humans and wildlife are subjected to undesirable effects. Despite being among the most studied NPs from a toxicological point of view, much remains unknown about their ecotoxicological effects or how they may affect specific cell types, such as cells of the central nervous system. The main objective of this work was to investigate the effects of ZnO NPs on human glial cells and zebrafish embryo development and to explore the role of the released Zn2+ ions in these effects. The effects on cell viability on human A172 glial cells were assessed with an MTT assay and morphological analysis. The potential acute and developmental toxicity was assessed employing zebrafish (Danio rerio) embryos. To determine the role of Zn2+ ions in the in vitro and in vivo observed effects, we measured their release from ZnO NPs with flame atomic absorption spectrometry. Then, cells and zebrafish embryos were treated with a water-soluble salt (zinc sulfate) at concentrations that equal the number of Zn2+ ions released by the tested concentrations of ZnO NPs. Exposure to ZnO NPs induced morphological alterations and a significant decrease in cell viability depending on the concentration and duration of treatment, even after removing the overestimation due to NP interference. Although there were no signs of acute toxicity in zebrafish embryos, a decrease in hatching was detected after exposure to the highest ZnO NP concentrations tested. The ability of ZnO NPs to release Zn2+ ions into the medium in a concentration-dependent manner was confirmed. Zn2+ ions did not seem entirely responsible for the effects observed in the glial cells, but they were likely responsible for the decrease in zebrafish hatching rate. The results obtained in this work contribute to the knowledge of the toxicological potential of ZnO NPs.

Acute Toxicity of Ethanol Extract and A Fraction Of Sansevieria Trifasciata Prain Using The Brine Shrimp Lethality Test (BSLT)

Sansevieria trifasciata Prain plants are simple to grow in Indonesia and have therapeutic potential. The potential toxicity effect present in medicinal plants is important to be identified for safety assurance. The objective of this study is to identify the potential acute toxicity of leaves ethanol extract and fraction of snake plants (S.trifasciata). This study used the Brine Shrimp Lethality Test (BSLT) method. S. trifasciata leaves are extracted with ethanol by maceration. The ethanol extract was then fractionated using n-hexane, ethyl acetate, and n-butanol solvents. Extract and fraction S. trifasciata leaves with concentrations of 1000, 500, 100, 50, and 10 µg/ml were exposed to Artemia salina (L.). larvae for 24 hours. The level of toxicity is determined based on LC50 obtained based on the number of dead larvae, through probit analysis. The ethanol extract and the fraction of S.trifasciata leaves are active cytotoxic characterized by LC50 of 251,187 ppm for the ethanol extract, 116,950 ppm for the n-hexane fraction, 76,033 ppm for the ethyl acetate fraction, 20,230 ppm for the n-butanol fraction and 34,751 for the remaining fraction. The ethanol extract, n-hexane fraction, ethyl acetate fraction, and the remaining fraction were categorized as toxic, while the n-butanol fraction was categorized as very toxic.

Defective TiO2 Nanotube Arrays for Efficient Photoelectrochemical Degradation of Organic Pollutants.

Oxygen vacancies (OVs) are one of the most critical factors that enhance the electrical and catalytic characteristics of metal oxide-based photoelectrodes. In this work, a simple procedure was applied to prepare reduced TiO2 nanotube arrays (NTAs) (TiO2-x) via a one-step reduction method using NaBH4. A series of characterization techniques were used to study the structural, optical, and electronic properties of TiO2-x NTAs. X-ray photoelectron spectroscopy confirmed the presence of defects in TiO2-x NTAs. Photoacoustic measurements were used to estimate the electron-trap density in the NTAs. Photoelectrochemical studies show that the photocurrent density of TiO2-x NTAs was nearly 3 times higher than that of pristine TiO2. It was found that increasing OVs in TiO2 affects the surface recombination centers, enhances electrical conductivity, and improves charge transport. For the first time, a TiO2-x photoanode was used in the photoelectrochemical (PEC) degradation of a textile dye (basic blue 41, B41) and ibuprofen (IBF) pharmaceutical using in situ generated reactive chlorine species (RCS). Liquid chromatography coupled with mass spectrometry was used to study the mechanisms for the degradation of B41 and IBF. Phytotoxicity tests of B41 and IBF solutions were performed using Lepidium sativum L. to evaluate the potential acute toxicity before and after the PEC treatment. The present work provides efficient PEC degradation of the B41 dye and IBF in the presence of RCS without generating harmful products.

Oncological and functional outcomes of transoral surgery compared with non-surgical management in small-volume oropharyngeal cancer: a systematic review protocol.

The objective of this systematic review is to investigate oncological and functional outcomes following primary transoral surgery compared with non-surgical management in patients with small-volume (T1-2, N0-2) oropharyngeal cancer. The incidence of oropharyngeal cancer is rising. Transoral surgery was introduced to provide a minimally invasive treatment option for patients with small-volume oropharyngeal cancer and to avoid the morbidity that results from open surgery and the potential acute and late toxicities of chemoradiotherapy. The review will include all studies on adult patients with small-volume oropharyngeal cancer managed by transoral surgery or non-surgical management with radiotherapy and/or chemotherapy. All patients must have undergone treatment with curative intent. Participants who underwent palliative treatment will be excluded. This review will follow the JBI methodology for systematic reviews of effectiveness. Eligible study designs will include randomized controlled trials, quasi-experimental studies, and prospective or retrospective cohort studies. Databases to be searched will include PubMed, Embase, CINAHL, Cochrane CENTRAL, and multiple trial registries from 1972. Titles and abstracts will be reviewed, and full-text articles will be retrieved if they meet the inclusion criteria. All eligible studies will be critically appraised by 2 independent reviewers using the appropriate JBI tools for experimental and observational designs. Where possible, outcome data from studies will be pooled with statistical meta-analysis to compare both oncological and functional outcomes between the two groups. All time to event to data will be converted to a common metric for oncological outcomes. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be followed to assess the certainty of findings. PROSPERO CRD4202235209.

Disinfection byproducts of iopamidol, iohexol, diatrizoate and their distinct acute toxicity on Scenedesmus sp., Daphnia magna and Danio rerio

The COVID-19 pandemic resulted in increasing the usage of iodinated contrast media (ICM), and thus an increase in the prevalence of ICM-contaminated wastewater. While ICM is generally safe, this has the potential to be problematic because as medical wastewater is treated and disinfected, various ICM-derived disinfection byproducts (DBPs) may be generated and released into the environment. However, little information was available about whether ICM-derived DBPs are toxic to aquatic organisms. In this study, the degradation of three typical ICM (iopamidol, iohexol, diatrizoate) at initial concentration of 10 μM and 100 μM in chlorination and peracetic acid without or with NH4+ was investigated, and the potential acute toxicity of treated disinfected water containing potential ICM-derived DBPs on Daphnia magna, Scenedesmus sp. and Danio rerio was tested. The degradation results suggested that only iopamidol was significantly degraded (level of degradation >98%) by chlorination, and the degradation rate of iohexol and diatrizoate were significantly increased in chlorination with NH4+. All three ICM were not degraded in peracetic acid. The toxicity analysis results indicate that only the disinfected water of iopamidol and iohexol by chlorination with NH4+ were toxic to at least one aquatic organism. These results highlighted that the potential ecological risk of ICM-contained medical wastewater by chlorination with NH4+ should not be neglected, and peracetic acid may be an environment-friendly alternative for the disinfection of wastewater containing ICM.

Short-term toxicity assessment of combined use of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in vitro and in vivo.

A combination of zidovudine (AZT), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus, and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P<0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P<0.05); the relative weights of the liver, kidney, spleen, and brain increased (P<0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The hemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P<0.05). The total protein, albumin, cholesterol, and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P<0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P<0.05). The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.

Formation characteristics and acute toxicity assessment of THMs and HAcAms from DOM and its different fractions in source water during chlorination and chloramination

The formation characteristics of trihalomethanes (THMs) and haloacetamides (HAcAms) from dissolved organic matter and its fractions were investigated during chlorine-based disinfection processes. The relationships between water quality parameters, fluorescence parameters, and the formation levels of THMs and HAcAms were analyzed. The fractions contributing most to the acute toxicity were identified. The trichloromethane (TCM) generation level (72 h) generally followed the order of Cl2 > NH2Cl > NHCl2 process. The NHCl2 process was superior to the NH2Cl process in controlling TCM formation. Hydrophobic acidic substance (HOA), hydrophobic neutral substance (HON), and hydrophilic substance (HIS) were identified as primary precursors of 2,2-dichloroacetamide and trichloroacetamide during chlorination and chloramination. The formation of TCM mainly resulted from HOA, HON and HIS fractions relatively uniformly, while HOA and HIS fractions contributed more to the formation of bromodichloromethane and dibromomonochloromethane. UV254 could be used as an alternative indicator for the amount of ΣTHMs formed during chlorination and chloramination processes. Dissolved organic nitrogen was a potential precursor of 2,2-dichloroacetamide during chlorination process. The fractions with the highest potential acute toxicity after the chlorination were water-dependent.

Acute Toxicity Testing and Phytochemical Screening of Hydromethanolic Leaf Extract of Maerua angolensis on Albino Wistar Rats

Maerua angolensis leaves have been used traditionally for the treatment of several ailments which include but not limited to anaemia, jaundice, arthritis, insomnia, liver diseases and neurological disorders. Despite its widespread use and several reported beneficial uses, there is a paucity of data on its toxicity potential. This study was therefore designed to evaluate the phytochemical constituents and acute toxicity potential of hydromethanolic leaf extract of Maerua angolensis on albino wistar rats. Phytochemical screening was carried out using a standard procedure for the identification of phytochemicals as described in the literatures. Acute toxicity determination was done in two phases (using Lorke‟s method). In the first phase, the rats were divided into three groups of three rats each and were administered 10mg/kg, 100mg/kg and 1000mg/kg body weight of the hydromethanolic leaf extract of Maerua angolensis respectively. In the second phase, the rats were divided into three groups of one rat each and were administered 1600mg/kg, 2900mg/kg and 5000mg/kg body weight of the hydromethanolic leaf extract of Maerua angolensis respectively. Phytochemical screening revealed that the hydromethanolic leaf extract of Maerua angolensis contains flavonoids, cardiac glycosides, saponins, tannins and terpenoids. The rats did not show any signs or symptoms of toxicity following the administration of the extract during both phases. Therefore, it could be concluded that Maerua angolensis leaves contain essential constituents needed in the treatment and management of various ailments and are also safe for use as the LD50 was &gt;5000mg/kg supporting its folkloric use in disease management.

Combining Contamination Indices and Multivariate Statistical Analysis for Metal Pollution Evaluation during the Last Century in Lacustrine Sediments of Lacu Sărat Lake, Romania.

Integrated study of both water and sediment in lakes provides important information regarding the human impact on the environment. The current work is focused on the correlation between age, source, composition, and degree of human intervention over the last 178 years and health impact of sediments from Lacu Sărat Lake (Romania), one of the most important balneo-climateric resorts in the country. The novelty relies on the fact that this is the first time the temporal patterns of metal contamination and the human health effects associated with the metal exposure from sediment core samples have been assessed. The sediment contamination status was determined by evaluating several indices, such as the enrichment factor, geo-accumulation index, metal pollution index, and potential ecological risk index, etc. Results showed a significant accumulation of Cd, Cr, As and Ni and a major contribution of Pb, Zn, Cd, Hg, Cr as well as Cu to the potential acute toxicity. The sediment quality guidelines emphasized a risk concerning the life and proper development of benthic organisms in Lacu Sărat Lake. Moreover, the incidental ingestion lifetime carcinogenic risk values for As and Cr suggest a potential risk of developing cancer. A strong human impact was observed especially between 1950 and 1990, which can be attributed to the rapid economic growth and intensive industrial development strategies pursued by the communist political regime in Romania.

Stereotactic body radiation therapy for colorectal cancer liver metastases.

The management of colorectal cancer liver metastases requires a multidisciplinary approach, which may incorporate systemic therapy, surgery, or local ablative therapies. Stereotactic body radiation therapy (SBRT) is a non-invasive highly conformal radiation technique that enables the delivery of large doses of radiation in a few fractions to well-defined targets using image-guidance and motion management. For selected patients with colorectal cancer liver metastases, stereotactic body radiation therapy can be delivered safely, with excellent long-term local control and overall survival. The purpose of this clinical practice review is to review the background, indications, and treatment details of stereotactic body radiation therapy for the treatment of colorectal liver metastases. SBRT for colorectal cancer liver metastases may be considered for patients with oligometastatic colorectal cancer in combination with surgery or other locally ablative therapies; for patients who are not candidates for surgical resection; or after failure of resection or other ablative therapies. When planning SBRT both a computed tomography and magnetic resonance imaging simulation may be obtained, where feasible, for target delineation. One or 3 fraction SBRT can be considered for lesions away from the central liver and luminal organs at risk, whereas 5 fraction SBRT is preferred otherwise. Image-guidance and motion management strategies are essential components of liver SBRT and will guide the creation of relevant internal and planning target volume margins. For lesions in close proximity to or overlapping with organs-at-risk, the balance between adequate local control and potential for cure with potential acute and late toxicity must be carefully considered.

Pulicaria dysenterica (L.) Bernh.—Rightfully Earned Name? Identification and Biological Activity of New 3-Methoxycuminyl Esters from P. dysenterica Essential Oil

Motivated by the ethnopharmacological use of Pulicaria dysenterica, in the present study, the antimicrobial potential of the extracted essential oil was investigated against a panel of eighteen microorganism strains. Additionally, anti-acetylcholinesterase and antispasmodic (isolated rat distal colon) activities, general acute toxicity (Artemia salina model), and immunomodulatory properties (cytotoxicity on isolated mouse macrophages) were studied. Detailed analyses of the essential oil led to the identification of 3-methoxycuminyl 2-methylbutanoate (a new natural product) and 3-methoxycuminyl 3-methylbutanoate (a rare natural product). The obtained esters and intermediates in the synthesis of the starting alcohol (3-methoxycuminol) were subjected to a battery of 1D- and 2D-NMR experiments. The synthesized esters were additionally characterized by GC-MS, IR, and UV-Vis. The synthesized compounds (ten in total) were biologically tested in the same way as the extracted P. dysenterica essential oil. The obtained low acute toxicity and promising antimicrobial potential suggest that the P. dysenterica essential oil might partially explain the ethnopharmacological application of P. dysenterica plant material for the treatment of gastrointestinal infections.