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The article focuses on difficulties in biomonitoration of occupational exposure to antineoplastic drugs. Topics include the research group of the UFRGS Toxicology Laboratory has carried out studies in populations exposed to different xenobiotics, and the other parameters such as cariorexis, karyolysis and pycnosis were in fact not evaluated, characterizing a limitation of the study.

Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC–MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC–MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 min. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision coefficient of variations% were <20%, and bias was within ± 20%. Only 4 of the 95 analytes presented significant ionization suppression or enhancement (>25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%) and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential for understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies. [ABSTRACT FROM AUTHOR]

Over the last decades, new psychoactive substances (NPSs) have established a new pattern of drug synthesis and distribution. These compounds brought with them several challenges, including their analytical determination by known methodologies, the uncertainty of their toxicological effects, and the possible approaches used for control. In Brazil, the control of NPS started with a nominal list of proscribed compounds. But the variety of substances was so large that other strategies were implemented. Generic legislation was created as several groups began to emerge, such as phenethylamines, synthetic cathinones, and synthetic cannabinoids. The legislation also began to include salts and isomers of all listed substances and precursor chemical ingredients or plants that may be used to produce them. Those substances are known for the unpredictability of their effects, causing a wide range of symptoms, including seizures, aggression, and acute psychosis. Users under effect represent a high risk for themselves and others. In this study, we present an overview of the timeline in which NPSs were detected in Brazilian territory and the legislative approaches. A complete literature search was performed using PubMed, Scopus, the World Wide Web and Brazilian governmental websites employing relevant keywords such as NPS, legislation, and Brazil. Even with the high volume of legislative measures, the race against NPS intoxication cases and apprehensions continues to be fierce. There are limitations in the process of detection, identification, and prohibition of the substances in the country that demand a multifactorial approach, stronger public health measures, scientific research, as well as harm reduction strategies. Nevertheless, the Brazilian scenario on NPS arrival reflects a worldwide problem faced by many countries. In conclusion, it is stated that the use of multiple legislative strategies such as prohibition lists and generic controls can provide for better regulation of the NPS problem. However, this issue needs to be addressed by multiple organizations, including police departments and the public health system, and that effort needs to be coordinated and standardized for all Brazilian Federal states. [ABSTRACT FROM AUTHOR]

Background: PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) acts by applying aerosolized chemotherapy in the peritoneal cavity, enhancing tissue penetration of chemotherapeutic agents. This method of chemotherapy delivery still raises several concerns related to the operating room's environmental exposure, arousing discussions related to the occupational risks of this technique. This work aims to demonstrate the pattern of aerosolization distribution in the absence of safety mechanisms in an operating room. Materials and Methods: A cross-sectional experimental work of 31 aerosol applications was carried out. Aerosolization was performed with a 1% aqueous solution of caffeine Cellulose. Nitrate membranes were used to capture the concentration of caffeine in different sites within the operating room for 5 periods of fixed exposure times. Results: 930 samples are obtained in 31 rounds of aerosolization. Comparing the changes in concentration per minute between the different time intervals. There were statistically significant differences between the 0-2 minutes interval and the 15-30 interval (P<0.001). Surgeon site shows a significant difference between the times (P=0.010). There were no difference between changes in concentrations in the time intervals for the anesthetist site (P=0.094). At the injector site, there is a statistically significant difference (P<0.001). The time assessment between 30-35 exposure showed a median of 0. Conclusion: The study pointed out that the moment of greatest risk of contamination of the surgical environment occurs during aerosolization, especially during the first 15 minutes after the start of aerosolization. The sites that were most exposed to contamination were the patient, the surgeon and the injector, respectively. [ABSTRACT FROM AUTHOR]

People are exposed to pesticides through food, drinking water, and the environment. These compounds are associated with several disorders, such as inflammatory diseases, rheumatoid arthritis, cancer, and a condition related to metabolic syndrome. The immunotoxicants or immunotoxic compounds can cause a wide variety of effects on immune function, altering humoral immunity and cell-mediated immunity, resulting in adverse effects to the body. Here, immune system disorders are highlighted because they are closely linked to multiple organs, including the nervous, endocrine, reproductive, cardiovascular, and respiratory systems, leading to transient or permanent changes. Therefore, this study reviewed the mechanisms involved in the immunotoxicity of fungicides, herbicides, and insecticides in cells, animals, and humans in the past 11 years. According to the studies analyzed, the pesticides interfere with innate and adaptive immune functions, but the effects observed mainly on cellular and humoral immunity were highlighted. These compounds affected specific immune cells, causing apoptosis, changes in factor nuclear kappa B (NF-κB) expression, pro-inflammatory factors interleukin 6 (IL-6), interleukin 8 (IL-8), interferon-gamma (IFN-γ), chemokines (CXCL-c1c), and anti-inflammatory factor, such as interleukin 10 (IL-10). To verify the threats of these compounds, new evaluations with immunotoxicological biomarkers are necessary. Pesticides interfere with the innate and adaptive immune response. Cells, animals and human studies demonstrate the immunotoxicity of pesticides in the cellular and humoral immune response. Fungicides, herbicides, and insecticides alter the immune system by various mechanisms, such as pro-inflammatory and anti-inflammatory factors. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is a potentially fatal disease categorized as a neglected public health issue for not receiving the appropriate attention from national and international health authorities. The most affected people by this problem usually live in poor rural communities, where medical resources are often sparse and, in some instances, there is even a scarcity of serum therapy. The administration of the appropriate antivenom is the only specific treatment available, however it has limited efficacy against venom-induced local effects. In this scenario, various plant species are used as local first aid for the treatment of snakebite accidents in Brazil, and some of them can effectively inhibit lethality, neurotoxicity, hemorrhage, and venom enzymes activities. This review compiles a list of plants used in the treatment of snakebites in Brazil, focusing on the native Brazilian species registered in the databases Pubmed, Scielo, Scopus and Google Scholar. All these searches were limited to peer-reviewed journals written in English, with the exception of a few articles written in Portuguese. The most cited native plant species were Casearia sylvestris Sw., Eclipta prostrata (L.) L., Mikania glomerata Spreng., Schizolobium parahyba (Vell.) S.F.Blake and Dipteryx alata Vogel, all used to decrease the severity of toxic signs, inhibit proteolytic and hemorrhagic activities, thus increasing survival time and neutralizing myotoxicity effects. Different active compounds showing important activity against the snake venoms and their toxins include flavonoids, alkaloids and tannins. Although some limitations to the experimental studies with medicinal plants were observed, including lack of comparison with control drugs and unknown active extracts compounds, species with anti-venom characteristics are effective and considered as candidates for the development of adjuvants in the treatment of snake envenomation. Further studies on the chemistry and pharmacology of traditionally used plant species will help to understand the role that snakebite herbal remedies may display in local medical health systems. It might also contribute to the development of alternative or complementary treatments to reduce the number of severe disabilities and deaths. [Display omitted] • Snakebite envenoming is a serious disease and a neglected public health issue. • Plant species are used as local first aid for the treatment of snakebite accidents. • There were 8 native plant species that were the most cited. • The plant compounds inhibited protein destruction and hemorrhagic activity. [ABSTRACT FROM AUTHOR]

Hypothermic storage has been proposed as a method to reduce bacterial loads and promoting prudent use of antibiotics. Reducing temperature, however, can lead to cold shock damage and oxidative stress in boar semen. This study verified the effect of L-cysteine on the quality of semen stored at 5 °C for 120 h. Twenty-one normospermic ejaculates were diluted in Beltsville Thawing Solution into five treatments: Positive control (Pos_Cont, storage at 17 °C without L-cysteine) and groups with 0, 0.5, 1, and 2 mmol/L of L-cysteine supplementation stored at 5 °C. Variables were analyzed as repeated measures, considering treatment, storage time, and interaction as main factors. The effects of different L-cysteine concentrations were also evaluated using polynomial orthogonal contrasts. Sperm motility and pH were higher in the Pos_Cont compared to the groups stored at 5 °C (P < 0.05). In polynomial orthogonal contrast models, total motility was affected by the interaction between L-cysteine and storage time (P = 0.04), with a linear increase in motility when increasing the amount of L-cysteine at 72 and 120 h. Progressive motility increased quadratically as the L-cysteine reached 1 mmol/L (P < 0.01). In the thermoresistance test at 120 h, sperm motility increased quadratically up to an L-cysteine dose of 1 mmol/L (P < 0.05). Sulfhydryl content linearly increased with L-cysteine supplementation (P = 0.01), with no effect on intracellular ROS and sperm lipid peroxidation (P ≥ 0.06) in 5ºC-stored doses. In conclusion, L-cysteine supplementation has a positive effect on sperm motility up to 120 h of storage at 5 °C. • Hypothermic storage reduces sperm motilities in BTS extender. • L-cysteine helps to maintain the sperm motilities in semen doses stored at 5 ºC. • The pH of semen doses is affected by storage temperature. • Supplementation with L-cysteine does not change the pH of semen doses. • L-cysteine does not affect the oxidative status in boar spermatozoa at 5 ºC. [ABSTRACT FROM AUTHOR]

The neonicotinoid imidacloprid was promoted in the market because of widespread resistance to other insecticides, plus its low mammalian impact and higher specific toxicity towards insects. This study aimed to evaluate the immunomodulatory effect of imidacloprid on macrophages. RAW 264.7 cells were incubated to 0–4000 mg/L of imidacloprid for 24 and 96 h. Imidacloprid presented a concentration-dependent cytotoxicity after 24 h and 96 h incubation for MTT reduction (3-(4,5-dimethyl-thiazol-2-yl)− 2,5-diphenyltetrazolium bromide) (EC 50 519.6 and 324.6 mg/L, respectively) and Neutral Red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) assays (EC 50 1139.0 and 324.2 mg/L, respectively). Moreover, imidacloprid decreased the cells' inflammatory response and promoted a mitochondrial depolarization. The complex II and succinate dehydrogenase (SDH) activities in RAW 264.7 cells incubated with imidacloprid increased more at 24 h. These results suggest that imidacloprid exerts an immunomodulatory effect and mitochondria can act as regulator of innate immune responses in the cytotoxicity mediated by the insecticide in RAW 264.7 cells. [Display omitted] • A commercial formulation of imidacloprid impaired the inflammatory response in RAW 264.7 cells; • The immunotoxic effects were associated with long term exposure to imidacloprid; • The mitochondria is a primary target of imidacloprid cytotoxicity. [ABSTRACT FROM AUTHOR]

The diagnostic methods in an emergency scenario must be simple, fast, and efficient to provide an effectiveness and efficient treatment, thus reducing the consequences of exposure. Considering the sample analysis, the protein precipitation combined with LC-MS/MS has been shown to be a good strategy for the simultaneous determination of compounds of toxicological interest, such as medicines and drugs of abuse. In this study, a rapid and simple multi-analyte method was developed and validated for the quantification of 57 pharmaceuticals and illicit drugs in plasma samples. Sample pre-treatment consists of protein precipitation of 50 µL of the sample with 240 µL of organic solvent mixture (MeOH:ACN, 3:1, v/v), centrifugation, and injection into the LC-MS/MS, with a chromatographic run time of 7 min. The method was validated considering lower limit of quantification (LLOQ), interferences, linearity, precision, accuracy, dilution integrity, carryover, and matrix effect. The LLOQs ranged from 5 to 20 ng/mL and all analytes were linear (r 2 >0.99) in the tested concentration ranges. The method proved to be precise and accurate, presenting QC concentrations for all analytes within acceptable limits by the guideline used (CV % ≤20 % and bias ± 20 %). The developed method was successfully applied in 470 plasma samples of real cases of poisoning. A total of 80 % of the samples were positive for at least one substance, with acetaminophen (32.1 %), diazepam (25.1 %), and lidocaine (18.9 %) being the most detected. The most prevalent exposure circumstance among the cases was suicide attempt. The most frequent age groups were young adults between 20 and 29 years old and children under 5 years old. The methodology developed proved to be efficient in the simultaneous determination of 57 substances of toxicological interest, contributing to a correct diagnosis and, consequently, to the most appropriate management and treatment of the intoxicated patient. Furthermore, it is possible to observe the most commonly involved toxic agents in the Rio Grande do Sul, southern Brazil, helping to trace a profile of the poisoning patient, important in toxicovigilance actions. • A fast and simple LC-MS/MS screening of the 57 pharmaceutical and illicit drugs. • A quick, inexpensive, and efficient sample preparation that is easy to implement. • The method was successfully applied to 470 samples of poisoned patients. • 80 % of the samples were positive for at least one of the investigated substances. • A poisoning profile of a Brazilian state was observed based on toxicological analysis. [ABSTRACT FROM AUTHOR]

The transgenic soy monoculture demands supplementation with pesticides. The aim of this study was to evaluate the individual and mixture effects of fipronil, glyphosate and imidacloprid in human HepG2 cells. Cytotoxicity was evaluated after 48-h incubations through MTT reduction and neutral red uptake assays. Free radicals production, mitochondrial membrane potential, DNA damage, and release of liver enzymes were also evaluated. Data obtained for individual agents were used to compute the additivity expectations for two mixtures of definite composition (one equipotent mixture, based in the EC 50 values achieved in the MTT assay; the other one based in the acceptable daily intake of each pesticide), using the models of concentration addition and independent action. The EC 50 values for fipronil, glyphosate and imidacloprid were 37.59, 41.13, and 663.66 mg/L, respectively. The mixtures of pesticides elicited significant synergistic effects (p < 0.05), which were greater than the expected by both addictive predictions. Decreased in mitochondrial membrane potential and increased in the transaminases enzymatic activities were observed. As they occur simultaneously, interactions between pesticides, even at non-effective single levels, can reverberate in significant deleterious effects, justifying the need for a more realistic approach in safety evaluations to better predict the effects to human health. • Fipronil, glyphosate, and imidacloprid acted synergistically on toxicity. • Fipronil and glyphosate disrupt the mitochondrial membrane potential. • Fipronil, glyphosate, and their mixtures increase liver enzymes activities. [ABSTRACT FROM AUTHOR]

Imidacloprid (IMI) is a neonicotinoid insecticide employed worldwide for crop protection. IMI's mode of action occurs through the agonism of postsynaptic nicotinic acetylcholine receptors (nAChRs), with high specificity for insect nAChRs although there are reports of mammals' toxicity. Studies on IMI's neurotoxicity are not conclusive; therefore, the aim of this study was to evaluate the subchronic toxic effects of an IMI based commercial pesticide on rats. Adult male Wistar rats received an IMI suspension via the oral route at doses of 1.5, 5, and 15 mg/kg for 45 consecutive days. IMI caused an increase in rearing and time spent at the periphery in the locomotor activity test and a decrease in time spent to finish the OX maze task (p < 0.05; ANOVA/Bonferroni). In blood, there was a decrease in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (p < 0.05; ANOVA/Bonferroni) and an increase in serum butyrylcholinesterase activity (p < 0.001; ANOVA/Bonferroni). Therefore, subchronic administration of an IMI-based-pesticide caused behavioral and systemic impairments in rats. • Imidacloprid increased rearing in rats. • Imidacloprid increased time spent at the periphery in the locomotor activity test. • Imidacloprid decreased the time spent to finish the OX maze task. • Imidacloprid decreased mean corpuscular hemoglobin in rats. • Imidacloprid increased serum butyrylcholinesterase in rats. [ABSTRACT FROM AUTHOR]

The use of the anthelmintic levamisole as a cocaine adulterant has been increasing worldwide. Complications caused by this association include systemic vasculitis, agranulocytosis, neutropenia, tissue necrosis, pulmonary hemorrhage, and renal injury. Data about toxicity of levamisole are scarce, therefore the aim of this study was to evaluate the acute and subchronic toxic effects of levamisole in rats. Male Wistar rats received saline or levamisole by intraperitoneal route at the doses of 12, 24 and 36 mg/kg in the acute toxicity test; and at 3, 6 and 12 mg/kg in the subchronic toxicity test. Toxicity was evaluated using behavioral, cognitive, renal, hematological, biochemical and histopathological parameters. Acute administration of levamisole caused behavioral and histopathological alterations. Subchronic administration caused behavioral, cognitive and hematological alterations (p < 0.0001 and p < 0.05, respectively), impairment of liver and kidney functions (p < 0.05), and changes of antioxidant defenses (p ≤ 0.0001). Both administrations produced toxic effects of clinical relevance, which make levamisole a dangerous cutting agent. Furthermore, the knowledge of these effects can contribute to the correct diagnosis and treatment of cocaine dependents with unusual systemic alterations. • The use of levamisole as a cocaine adulterant increased worldwide. • Several complications are associated with the concomitant use of these substances. • Data about the toxicology of levamisole are scarce. • Acute and subchronic administration of levamisole can cause toxic effects in rats. [ABSTRACT FROM AUTHOR]