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In Candida albicans, Cdr1 pumps azole drugs out of the cells to reduce intracellular accumulation at detrimental concentrations, leading to azole-drug resistance. Milbemycin oxime, a veterinary anti-parasitic drug, strongly and specifically inhibits Cdr1. However, how Cdr1 recognizes and exports azole drugs, and how milbemycin oxime inhibits Cdr1 remain unclear. Here, we report three cryo-EM structures of Cdr1 in distinct states: the apo state (Cdr1Apo), fluconazole-bound state (Cdr1Flu), and milbemycin oxime-inhibited state (Cdr1Mil). Both the fluconazole substrate and the milbemycin oxime inhibitor are primarily recognized within the central cavity of Cdr1 through hydrophobic interactions. The fluconazole is suggested to be exported from the binding site into the environment through a lateral pathway driven by TM2, TM5, TM8 and TM11. Our findings uncover the inhibitory mechanism of milbemycin oxime, which inhibits Cdr1 through competition, hindering export, and obstructing substrate entry. These discoveries advance our understanding of Cdr1-mediated azole resistance in C. albicans and provide the foundation for the development of innovative antifungal drugs targeting Cdr1 to combat azole-drug resistance. Candida albicans Cdr1 pumps azole antifungal drugs out of the cell, driving drug resistance. Here, the authors determine the mechanism of Cdr1-mediated fluconazole resistance and milbemycin oxime inhibition, providing a foundation for future drug discovery efforts. [ABSTRACT FROM AUTHOR]

Drug residues that contaminate food and water represent a serious concern for human health. The major concerns regard the possible irrational use of these contaminants, since this might increase the amplitude of exposure. Multiple sources contribute to the overall exposure to contaminants, including agriculture, domestic use, personal, public and veterinary healthcare, increasing the possible origin of contamination. In this review, we focus on crop pesticides and veterinary drug residues because of their extensive use in modern agriculture and farming, which ensures food production and security for the ever-growing population around the world. We discuss crop pesticides and veterinary drug residues with respect to their worldwide distribution and impacts, with special attention on their harmful effects on human reproduction and embryo development, as well as their link to epigenetic alterations, leading to intergenerational and transgenerational diseases. Among the contaminants, the most commonly implicated in causing such disorders are organophosphates, glyphosate and antibiotics, with tetracyclines being the most frequently reported. This review highlights the importance of finding new management strategies for pesticides and veterinary drugs. Moreover, due to the still limited knowledge on inter- and transgenerational effects of these contaminants, we underlie the need to strengthen research in this field, so as to better clarify the specific effects of each contaminant and their long-term impact. [ABSTRACT FROM AUTHOR]

Introduction: Theileria orientalis, an economically significant tick-borne hemoparasite, infects cattle globally. The T. orientalis Ikeda genotype, transmitted by Haemaphysalis longicornis ticks, is associated with clinical manifestations characterized by anemia, abortions, and mortality, although subclinical infections prevail. Despite the common occurrence of subclinical infections, therapeutic interventions targeting T. orientalis Ikeda in such cases are currently lacking, impeding effective parasite control measures. To address this critical knowledge gap, we assessed the efficacy of buparvaquone (BPQ) in eliminating the T. orientalis Ikeda, US isolate, in sub-clinically infected cattle. Methods: Twelve sub-clinically infected calves, identified by the presence of T. orientalis in peripheral blood alongside the absence of fever and anemia, were enrolled in the study. Six calves received two treatments of the BPQ label dose (2.5mg/kg) at a 48-h interval, while additional three calves received the drug at a dosage of 6mg/kg following the same regimen. Three untreated calves served as controls. Results and discussion: Endpoint and quantitative PCR analyses revealed that BPQ exerted a transient effect on T. orientalis parasitemia. Parasites remained undetectable in peripheral blood until weeks 4 and 11 post-treatment in animals administered 2.5 mg/kg and 6 mg/kg of BPQ, respectively. Intriguingly, following recrudescence, administering 6 mg/kg to animals previously treated with 2.5 mg/kg did not result in a reduction in parasite load. Pharmacokinetic analysis data suggested that escalating the dosage led to a less than proportional increase in serum concentrations of BPQ. Moreover, a significant yet reversible decrease (p < 0.05) in blood urea nitrogen was observed in animals treated with the drug, irrespective of the dosage. Despite parasitemia relapse, animals treated with 6 mg/kg BPQ exhibited a noteworthy decrease (p < 0.05) in IgG levels specific to the T. orientalis major piroplasm surface protein compared to controls and animals treated with 2.5 mg/kg of the drug. Conclusion: BPQ did not demonstrate efficacy in clearing subclinical T. orientalis Ikeda infection. Future investigations are warranted to explore innovative therapeutic modalities that, in synergy with vaccines and diagnostic assays, can facilitate the development of comprehensive programs aimed at controlling and eradicating this parasite. [ABSTRACT FROM AUTHOR]

Background: Addressing critical veterinary drugs, especially drugs with solubility problems like albendazole, and their implications for therapeutic efficacy, in-vitro dissolution studies can indeed provide valuable insights into how different brands of albendazole boluses perform under standardized conditions, helping to assess their dissolution profiles and potential bioavailability. Methods: Six brands of albendazole 300 mg boluses were collected from December 2020 to May 2021 G.C. The laboratory work was conducted from December 2020 to May 2021 in the National Animal Products and Veterinary Drugs and Feed Quality Assessment Centre (APVD-FQAC) laboratories. The collected brands from government veterinary clinics and private veterinary shops were subjected to model independent and dependent parameters. The dissolution test was conducted according to the USP monograph. Results: The study found that none of the six brands met the requirements of the dissolution test, as their API release was less than 80% within the specified 60-minute timeframe according to USP standards. Model independence indicated that only one brand (Alb002 = 3.72) achieved a difference factor of ≤ 15%. The remaining four brands (4/6) did not meet this criterion. However, the similarity factor (f2) revealed that all five brands (5/6) were comparable to the comparator products, with f2 values of 50%. The mean dissolution time results confirmed that three brands (3/6) had the highest dissolution rate and the fastest onset of action. The model-dependent kinetics indicated that the Weibull and Korsemeyer-Peppas models were the best fit for the release of drug substances. Conclusion: The study highlights issues with albendazole boluses' quality, highlighting the need for national in-vitro dissolution studies. These recommendations could improve quality control, streamline regulatory frameworks, and offer practical, cost-effective methods for evaluating drug efficacy and safety, ensuring veterinary pharmaceuticals meet safety and efficacy standards. [ABSTRACT FROM AUTHOR]

Livestock and poultry meat consumption play an important role in the dietary structure of Chinese residents. However, the extent of residues of veterinary drugs and heavy metal contamination in livestock and poultry meat and their by-products within Hunan province is not extensively studied. This survey aimed to fill this gap by assessing the presence of 76 veterinary drug residues in Hunan province. Additionally, heavy metals in pork and pig liver were also assessed. The obtained findings suggest that residues of veterinary drugs are still present in livestock and poultry meat, as well as their by-products, within Hunan province. However, the contamination of heavy metals remained within the food safety limits. These results underscore the significance of establishing more refined criteria for assessing human exposure, taking into account factors such as consumption patterns, product varieties and chemical compounds of interest. [ABSTRACT FROM AUTHOR]

Pesticides and veterinary drugs are widely employed to support food production. Assessing potential risks associated with the dietary consumption of pesticide and veterinary drug residues is, however, essential. Potential risks depend on the toxicity degree of the analyzed residue and population exposure levels. Human populations are exposed to numerous chemical substances through different pathways with varying exposure times, leading to increased health risks when compared to exposure to individual chemicals. Cumulative exposure assessments usually assess combined exposures to multiple chemicals through multiple exposure pathways. In this sense, this comprehensive review aims to provide insights into cumulative dietary pesticide and veterinary drug residue exposures. The main methodologies, strategies, and legislation employed by international agencies to this end are discussed. A review concerning articles that apply existing methodologies and approaches, as well as the challenges in this context faced by Brazil is also presented. As this is a critical issue not only for Brazilian public health but also for the global community, regulatory agencies should prioritize formulating regulations that incorporate exposure assessments regarding the simultaneous presence of residues and contaminants in foodstuffs. [ABSTRACT FROM AUTHOR]

Neonicotinoids are insecticides used worldwide in phytosanitary and biocidal products and veterinary pharmaceuticals. Recently, some restrictions and bans have been imposed due to their adverse effects on nontarget invertebrates, including pollinators. Although they may have direct and indirect effects on wild vertebrates, few studies have assessed exposure to these compounds in wild birds, so our knowledge remains limited. In the present pilot study we have assessed the prevalence of seven neonicotinoid insecticides and some of their metabolites in whole blood samples from 19 European roller (Coracias garrulus) nestlings and five adult common kestrels (Falco tinnunculus) in an area treated with neonicotinoids to control the palm weevil (Rynchophorus ferrugineus) in southeastern Spain. One European roller nestling born in a palm tree was positive for thiamethoxam, with a concentration of 2.26 ng mL−1, but no residues of neonicotinoids or their metabolites were found in adult common kestrels. Future studies are needed to elucidate potential exposure to neonicotinoids at different times of the year. To our knowledge, this is the first report of the presence of thiamethoxam residues in whole blood of a wild bird species after its ban in Spain. Environ Toxicol Chem 2024;43:1836–1843. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Humans are exposed to a cocktail of food-related and environmental contaminants, potentially contributing to the etiology of chronic diseases. Better characterizing the "exposome" is a challenging task and requires broad human biomonitoring (HBM). Veterinary drugs (VDs)/antibiotics, widely used and regulated in food and animal production, however, are typically not yet included in exposomics workflows. Therefore, in this work, a previously established multianalyte liquid chromatography-tandem mass spectrometry (LC-MS/MS) method covering >80 diverse xenobiotics was expanded by >40 VDs/antibiotics and pesticides. It was investigated if the generic workflow allowed for the successful integration of a high number of new analytes in a proof-of-principle study. The expanded method was successfully in-house validated and specificity, matrix effects, linearity, intra- and inter-day precision, accuracy, limits of quantification, and detection were evaluated. The optimized method demonstrated satisfactory recovery (81–120%) for most of the added analytes with acceptable RSDs (<20%) at three spiking levels. The majority of VDs/antibiotics and pesticides (69%) showed matrix effects within a range of 50–140%. Moreover, sensitivity was excellent with median LODs and LOQs of 0.10 ng/mL and 0.31 ng/mL, respectively. In total, the expanded method can be used to detect and quantify more than 120 highly diverse analytes in a single analytical run. To the best of the authors' knowledge, this work represents the first targeted biomonitoring method integrating VDs with various other classes of pollutants including plasticizers, PFAS, bisphenols, mycotoxins, and personal care products. It demonstrates the potential to expand targeted multianalyte methods towards additional groups of potentially toxic chemicals. [ABSTRACT FROM AUTHOR]

Veterinary medications are constantly being used for the diagnosis, treatment, and prevention of diseases in livestock. However, untreated veterinary drug active compounds are interminably discharged into numerous water bodies and terrestrial ecosystems, during production procedures, improper disposal of empty containers, unused medication or animal feed, and treatment procedures. This exhaustive review describes the different pathways through which veterinary medications enter the environment, discussing the role of agricultural practices and improper disposal methods. The detrimental effects of veterinary drug compounds on aquatic and terrestrial ecosystems are elaborated with examples of specific veterinary drugs and their known impacts. This review also aims to detail the mechanisms by which microbes degrade veterinary drug compounds as well as highlighting successful case studies and recent advancements in microbe-based bioremediation. It also elaborates on microbial electrochemical technologies as an eco-friendly solution for removing pharmaceutical pollutants from wastewater. Lastly, we have summarized potential innovations and challenges in implementing bioremediation on a large scale under the section prospects and advancements in this field. [ABSTRACT FROM AUTHOR]

Pathogens such as Plasmodium , Babesia , and Theileria invade and multiply within host red blood cells, leading to the pathological consequences of malaria, babesiosis, and theileriosis. Establishing continuous in vitro culture systems and suitable animal models is crucial for studying these pathogens. This review spotlights the Babesia duncani in culture-in mouse (ICIM) model as a promising resource for advancing research on the biology, pathogenicity, and virulence of intraerythrocytic parasites. The model offers practical benefits, encompassing well-defined culture conditions, ease of manipulation, and a well-annotated genome. Moreover, B. duncani serves as a surrogate system for drug discovery, facilitating the evaluation of new antiparasitic drugs in vitro and in animals, elucidating their modes of action, and uncovering potential resistance mechanisms. The B. duncani ICIM model thus emerges as a multifaceted tool with profound implications, promising advancements in our understanding of parasitic biology and shaping the development of future therapies. [ABSTRACT FROM AUTHOR]

With the increase in life expectancy, aging has emerged as a significant health concern. Due to its various mechanisms of action, cardiometabolic drugs are often repurposed for other indications, including aging. This systematic review analyzed and highlighted the repositioning potential of cardiometabolic drugs to increase lifespan as an aging parameter in animal studies and supplemented by information from current clinical trial registries. Systematic searching in animal studies was performed based on PICO: "animal," "cardiometabolic drug," and "lifespan." All clinical trial registries were also searched from the WHO International Clinical Trial Registry Platform (ICTRP). Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan. Systematic Review Registration: crd.york.ac.uk/prospero/display_record.php?RecordID=457358, identifier: CRD42023457358. [ABSTRACT FROM AUTHOR]

Purpose: Serotonin (5-HT3) receptor antagonists are promising agents for treatment of neuropathic pain. However, insufficient drug exposure at the central nervous system (CNS) might result in lack of efficacy. The goal of this study was to evaluate the impact of administration of a Pgp inhibitor (tariquidar) on ondansetron exposure in the brain, spinal cord, and cerebrospinal fluid in a wild-type rat model. Methods: Ondansetron (10 mg/kg) and tariquidar (7.5 mg/kg) were administered intravenously, plasma and tissue samples were collected and analyzed by HPLC. A mathematical model with brain, spinal cord, cerebrospinal fluid and two systemic disposition compartments was developed to describe the data. Results: The results demonstrate that tariquidar at 7.5 mg/kg resulted in a complete inhibition of Pgp efflux of ondansetron in the brain and spinal cord. The compartmental model successfully captured pharmacokinetics of ondansetron in wild type and Pgp knockout (KO) animals receiving the drug alone or in wild type animals receiving the ondansetron and tariquidar combination. Conclusions: The study provided important quantitative information on enhancement of CNS exposure to ondansetron using co-administration of Pgp Inhibitor in a rat model, which will be further utilized in conducting a clinical study. Tariquidar co-administration resulted in ondansetron CNS exposure comparable to observed in Pgp KO rats. Results also highlighted the effect of tariquidar on plasma disposition of ondansetron, which may not be dependent on Pgp inhibition, and should be evaluated in future studies. [ABSTRACT FROM AUTHOR]

In the postantibiotic era, the pathogenicity and resistance of pathogens have increased, leading to an increase in intestinal inflammatory disease. Bacterial infections remain the leading cause of animal mortality. With increasing resistance to antibiotics, there has been a significant decrease in resistance to both inflammation and disease in animals, thus decreasing production efficiency and increasing production costs. These side effects have serious consequences and have detracted from the development of China's pig industry. Microcin C7 (McC7) demonstrates potent antibacterial activity against a broad spectrum of pathogens, stable physicochemical properties, and low toxicity, reducing the likelihood of resistance development. Thus, McC7 has received increasing attention as a potential clinical antibacterial and immunomodulatory agent. McC7 has the potential to serve as a new generation of antibiotic substitutes; however, its commercial applications in the livestock and poultry industry have been limited. In this review, we summarize and discuss the biosynthesis, biochemical properties, structural characteristics, mechanism of action, and immune strategies of McC7. We also describe the ability of McC7 to improve intestinal health. Our aim in this study was to provide a theoretical basis for the application of McC7 as a new feed additive or new veterinary drug in the livestock and poultry breeding industry, thus providing a new strategy for alleviating resistance through feed and mitigating drug resistance. Furthermore, this review provides insight into the new functions and anti-infection mechanisms of bacteriocin peptides and proposes crucial ideas for the research, product development, and application of bacteriocin peptides in different fields, such as the food and medical industries. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the level of anxiolysis achieved by alprazolam and gabapentin in hospitalized cats prior to elective ovariohysterectomy and to evaluate the sedative effects of these agents. ANIMALS 60 client-owned female cats classified as American Society of Anesthesiologists physical status 1, admitted for elective ovariohysterectomy at a veterinary teaching hospital. METHODS The cats were prospectively and randomly allocated into 3 groups. Ninety minutes before evaluation, group G received gabapentin (100 mg/cat), group A received alprazolam (0.125 mg/cat), and group P received no medication (placebo). Stress, enclosure activity, and sedation scores were blindly evaluated. RESULTS Stress scores were similar in cats treated with gabapentin and alprazolam and gabapentin-treated cats had significantly lower stress score than those of the placebo group. Enclosure activity levels did not differ among the groups. Additionally, gabapentin and alprazolam resulted in similar sedation levels 90 minutes after treatment, which differed significantly compared to placebo. CLINICAL RELEVANCE The results of this study suggest that gabapentin provides similar anxiolysis in cats to that of alprazolam when evaluated 90 minutes after administration. Although no difference was noted in sedation levels between gabapentin and alprazolam. both induced deeper sedation than placebo. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is a One Health issue and a major threat to animal and human health. Antibiotic use (ABU) drives AMR development, and several hotspots for ABU, and AMR, in livestock have been identified in Southeast Asia, including Vietnam. There are often multiple drivers of ABU at farms, and to identify all of them there is a need to look beyond farm level. Objectives: The overall aim of this study was to identify routines and/or competencies, related to antibiotic sales, among veterinary drug shop workers that may be improved in order to decrease the medically non‐rational use of antibiotics in livestock production. Methods: A questionnaire‐based survey was conducted at 50 veterinary drug shops in northern Vietnam. Results: Results showed high education and knowledge levels. According to the respondents, antibiotic treatment advice was almost always provided to the farmers, and the recommended treatment was most commonly based on recommendations for the specific disease. However, farmers had almost never had their animals properly diagnosed. Antibiotics were the most sold drug category, penicillins being the most common. Several broad‐spectrum antibiotics were also quite frequently sold. Further, >50% of respondents recommended antibiotics for disease prevention. Conclusions: Even though education and knowledge levels might be high, several challenges can prevent drug shop workers from contributing to more prudent ABU at farms, for example, lack of proper diagnosis, commercial interests and individual farmer motives, often in combination with poor compliance to regulations. [ABSTRACT FROM AUTHOR]

Background The presence of veterinary drug residues in food-producing animals and animal products is regulated through the enforcement of maximum residue limits (MRLs). To answer the need of the food sector to monitor these substances in a wide range of food commodities, stakeholders at AOAC INTERNATIONAL identified the need for a reliable confirmatory screening method. Such a qualitative approach is required for compliance checking and to support product release in manufacturing. Objective Data were collected from five independent laboratories that applied the First Action Official Method   2020.04 to demonstrate adequate performance under reproducibility conditions. The probability of detection (POD) was calculated in blank test samples and test samples spiked at the screening target concentration (STC) level, with the objective to achieve PODs ≤10% and ≥90%, respectively. Additionally, the effectiveness of the screening method was evaluated by participating in 92 proficiency tests. Methods Four streams were optimized to screen for 152 veterinary drug residues by LC–MS/MS in a wide variety of food commodities including milk-based ingredients and related products (e.g. milk fractions, infant formula, infant cereals, and baby foods), meat- and fish-based ingredients and related products (fresh, powdered, cooked, infant cereals, and baby foods), and other ingredients based on eggs, animal fat, and animal byproducts. The four streams covered 105 antibiotic residues, anti-inflammatory and antiparasitic agents (stream A), 23 beta-lactams (stream B), 14 aminoglycosides (stream C), and 10 tetracyclines (Stream D). Results The multilaboratory validation led to PODs at the STC ≥94% and PODs in the blank ≤9%. Further application of the multilaboratory validated method to 92 proficiency tests provided more than 99% satisfactory submitted results (n  = 784). Conclusion The interlaboratory reproducibility determined for this method met the acceptance criteria defined in AOAC Standard Method Performance Requirement (SMPR®) 2018.010. Highlights AOAC has approved the method for Final Action status. [ABSTRACT FROM AUTHOR]

Background The topical veterinary drug product containing fipronil and permethrin provides an effective repellent protection and high insecticidal efficacy for dogs. Objective The objective of this study was to develop a stability-indicating high-performance liquid chromatography (HPLC) method for simultaneous detection and quantification of fipronil, permethrin, their key degradation products, and butylated hydroxytoluene (BHT) in a topical drug product. Method The two active ingredients, their degradation products, and the antioxidant (BHT) were separated by a gradient elution on a Phenomenex Kinetex C18 column (150 × 3 mm, 2.6 µm particle size) maintained at 37°C with H2O “acetonitrile “isopropyl alcohol “85% H3PO4 (65.5 + 32.5 + 4/0.0053, v/v/v/v) as mobile phase A and acetonitrile (100%) as mobile phase B. The flow rate was 0.9 mL/min, and analytes were detected and quantified at 235 nm. Results The specificity of the method was demonstrated by adequate separation of fipronil, permethrin, their degradation products, and BHT in the forced degraded finished product. The linearity of the method was demonstrated in the range of 0.2% to 150% of target analytical concentration of both active ingredients and 50% to 150% for BHT. Excellent recoveries of fipronil, permethrin, and BHT in placebo spiked active ingredient solutions in the linearity range showed sufficient accuracy of the method. The LOQ and LOD of the method were determined to be 0.2% and 0.07% of the analytical concentration. A robustness study did not identify any critical parameter that adversely affected the separation and quantification. Conclusions Here, we report the development and validation of a robust, stability-indicating HPLC method for identification and assay of fipronil, permethrin, and BHT, including estimation of fipronil's and permethrin's degradation products in a topical drug product for dogs. Highlights The new HPLC method permits the acquisition of data for all analytes of interest for a topical finished drug product containing fipronil, permethrin, and BHT. [ABSTRACT FROM AUTHOR]

A method for the determination of 106 pesticides, 74 veterinary drugs, 10 mycotoxins, and 18 persistent organic pollutants in livestock and poultry meat was developed and validated in the present study. The meat was extracted with acetonitrile under citric acid caching and purified using the multi-plug filtration clean-up (m-PFC) column. The components were separated using liquid chromatography on a C18 column and then eluted using a gradient of the aqueous solutions of acetonitrile and 0.1% formic acid (containing 2 mmol/L ammonium acetate) as the mobile phase. The mass spectrometry analysis was performed next using two electrospraying scan modes—the positive ion mode and the negative ion mode, and multiple reaction monitoring (MRM) modes. The results revealed that all 208 target analytes exhibited good linearity in their respective linear ranges, with the correlation coefficient of each analyte above 0.9953 and the corresponding limits of quantification (LOQs) in the range of 0.1–9.8 µg/kg. The average recovery values of 189 targets at three different spiked levels of low, medium, and high ranged from 70.1 to 120.0%, and the corresponding values of relative standard deviation (RSD) ranged from 1.3 to 15.0%, respectively. The remaining 19 targets exhibited the average recovery values [at three different spiked levels of low, medium, and high] ranging from 18.6 to 58.9%, with the corresponding RSD values ranging from 1.5 to 11.3%. The developed method was applied to 132 batches of livestock and poultry meat, and nine pesticides and seven veterinary drugs were detected in the concentration range of 0.1–24.8 µg/kg. These results suggested that the developed method is simple, reliable, reproducible, and suitable for the determination of pesticides, veterinary drugs, mycotoxins, and persistent organic pollutants in livestock and poultry meat. [ABSTRACT FROM AUTHOR]

Beginning in the mid‐1990s, populations of three species of Gyps vultures declined by more than 97% in South Asia in little more than a decade, caused by unintentional poisoning by the non‐steroidal anti‐inflammatory drug (NSAID) diclofenac. This led to a ban on the veterinary use of the drug, and establishment of conservation breeding programmes, throughout the region. Once much of Nepal had been confirmed as being free from diclofenac, beginning in 2017 White‐rumped Vultures Gyps bengalensis were released from the captive breeding population. A total of 99 birds (n = 50 wild and n = 49 released) were fitted with GPS transmitters between 2017 and 2022 and monitored daily. Tag fixes suggesting death or ill‐health were followed up and dead vultures were retrieved for post‐mortem analysis. The estimated annual survival of wild adult vultures was 0.974 (95% confidence interval [CI] 0.910–0.997), while that of wild subadults was 0.880 (95% CI 0.721–0.966). Survival rates of released birds were lower than those of wild birds, being 0.644 (95% CI 0.490–0.778) for adults and 0.758 (95% CI 0.579–0.887) for subadults. Post‐mortem analysis of dead vultures indicated several possible causes of death, including predation, infection and electrocution. There was no evidence that any birds died of NSAID poisoning. The high survival rates of wild birds, especially adults, and the lack of evidence for NSAID‐caused mortality, suggest that vulture habitat in the Nepal Vulture Safe Zone is free from diclofenac and that other hazards are sufficiently infrequent to allow the vulture population to recover. The lower survival of released birds compared with their wild counterparts suggests a need to improve the conservation breeding programme and release protocol. [ABSTRACT FROM AUTHOR]

Milk, as a widely consumed nutrient‐rich food, is crucial for bone health, growth, and overall nutrition. The persistent application of veterinary drugs for controlling diseases and heightening milk yield has imparted substantial repercussions on human health and environmental ecosystems. Due to the high demand, fresh consumption, complex composition of milk, and the potential adverse impacts of drug residues, advanced greener analytical methods are necessitated. Among them, functional materials‐based analytical methods attract wide concerns. The magnetic molecularly imprinted polymers (MMIPs), as a kind of typical functional material, possess excellent greenification characteristics and potencies, and they are easily integrated into various detection technologies, which have offered green approaches toward analytes such as veterinary drugs in milk. Despite their increasing applications and great potential, MMIPs' use in dairy matrices remains underexplored, especially regarding ecological sustainability. This work reviews recent advances in MMIPs' synthesis and application as efficient sorbents for veterinary drug extraction in milk followed by chromatographic analysis. The uniqueness and effectiveness of MMIPs in real milk samples are evaluated, current limitations are addressed, and greenification opportunities are proposed. MMIPs show promise in revolutionizing green analytical procedures for veterinary drug detection, aligning with the environmental goals of modern food production systems. [ABSTRACT FROM AUTHOR]

The use of human and veterinary drugs has led to the accumulation of pharmaceuticals in various aquatic environments at progressively increasing levels, exhibiting strong ecological risks. Metformin is widely used as a first-line prescription drug for the treatment of type 2 diabetes mellitus as well as a livestock drug. Unlike other drugs, metformin is not metabolized in the body, and almost all of its intake is excreted and released into the aquatic environment via urine and feces, causing adverse effects on aquatic ecosystems. This review provides an overview of the occurrence and detection of metformin in the aquatic environment and its toxic effects on different aquatic organisms (fish, daphnia, rotifers, chlorella). Metformin has been documented in a variety of aqueous environments such as wastewater, surface water, and groundwater as well as drinking water. The wide distribution of metformin in the aqueous environment calls for the development of more accurate detection methods. This paper reviews detection methods for metformin in the aqueous environment and evaluates their advantages and disadvantages. Toxicity studies have shown that metformin can cause adverse reactions in fish, such as oxidative stress, genotoxicity, disruption of intestinal flora, and morphological alterations; it also affects the growth and reproduction of small aquatic organisms. Knowledge gaps in the field of metformin research were assessed, and future research priorities were identified. [ABSTRACT FROM AUTHOR]

The application of biosolids, manure, and slurry onto agricultural soils and the growing use of treated wastewater in agriculture result in the introduction of human and veterinary pharmaceuticals to the environment. Once in the soil environment, pharmaceuticals may be taken up by crops, resulting in consequent human exposure to pharmaceutical residues. The potential side effects of pharmaceuticals administered in human medicine are widely documented; however, far less is known regarding the risks that arise from incidental dietary exposure. The aim of this study was to evaluate human exposure to pharmaceutical residues in crops and assess the associated risk to health for a range of pharmaceuticals frequently detected in soils. Estimated concentrations of carbamazepine, oxytetracycline, sulfamethoxazole, trimethoprim, and tetracycline in soil were used in conjunction with plant uptake and crop consumption data to estimate daily exposures to each compound. Exposure concentrations were compared to Acceptable Daily Intakes (ADIs) to determine the level of risk. Generally, exposure concentrations were lower than ADIs. The exceptions were carbamazepine, and trimethoprim and sulfamethoxazole under conservative, worst-case scenarios, where a potential risk to human health was predicted. Future research therefore needs to prioritize investigation into the health effects following exposure to these compounds from consumption of contaminated crops. [ABSTRACT FROM AUTHOR]

ABSTRACT: The use of veterinary drugs is of similar importance to that of human drugs in addressing health challenges. In this context, pharmaceuticals and their metabolites inevitably enter soil and water in unknown quantities. Therefore, this study collects and analyzes drug data from 2020 for 50 dairy farms located in Germany. The most frequently used substance group is antibiotics (40.13%), followed by antiphlogistics (18.86%), antiparasitics (13.09%), and hormones (9.29%). Treatment frequencies record the number of days per year on which an average animal on a farm was treated with a substance. The calculated values range from 0.94 to 21.69 d/yr and are distributed heterogeneously across farms. In this study, on average, a cow was treated on 6 d in 2020: 2.34 d with antibiotics, 1.07 d with antiphlogistics, 0.76 d with antiparasitics, and 0.41 d with hormones. In addition to individual farm management practices, other factors are related to treatment frequency. Farms with a veterinary care contract used more hormonal substances than farms without a care contract. In addition, higher milk yield coincides with more frequent treatments with antiphlogistic or hormonal substances. Other related factors include grazing, longevity, farm size, and use of a claw bath. Our study represents an important first step in describing the amounts and determinants of veterinary drugs used in livestock farming. Such insights on magnitudes and farm parameters are essential to estimate potential environmental effects and derive strategies to reduce veterinary drug use.

This work compares the electroanalytical performance of two electroanalytical systems based on (1) the glassy carbon electrode (GCE), and (2) the electrified liquid–liquid interface (eLLI), for the detection of fluoroquinolone antibiotic–danofloxacin (DANO). Our aim was to define the optimal conditions to detect the chosen analyte with two employed systems, extract a number of electroanalytical parameters, study the mechanism of the charge transfer reactions (oxidation at GCE and ion transfer across the eLLI), and to provide physicochemical constants for DANO. Detection of the chosen analyte was also performed in the spiked milk samples. To the best of our knowledge, this is the first work that directly compares the electroanalytical parameters obtained with solid electrode (in this case GCE) and eLLI. We have found that for DANO the latter provides better electroanalytical parameters (lower LOD and LOQ) as well as good selectivity when the milk was analyzed. [ABSTRACT FROM AUTHOR]

Background: Subclinical mastitis in camels, an inflammation of the udder without visible signs, can reduce milk quality and raise bacteria levels. Regular monitoring of camel milk is crucial for consumer safety. Methods: A cross sectional study was conducted in Jigjiga city, Ethiopia to investigate the prevalence and characteristics of subclinical mastitis in she- camels. The study included 244 lactating she-camels from three privately- owned camel dairy farms, and a questionnaire survey was conducted with 60 camel owners. Results: The overall prevalence of subclinical mastitis in she-camels was 10.6% (26/244), with no significant difference among the studied dairy farms. Risk factors that influenced the result of California Mastitis Test (CMT) included age and udder and leg hygiene. The study revealed that S. aureus was the most prevalent bacterium among the isolated bacteria, with a prevalence rate of 34.5%. This was followed by S. agalactiae, S. dysgalactiae, and Pasteurella multocida, with prevalence rates of 29.8, 19.4, and 16.2%, respectively. Among the isolated bacteria, 84.5% were sensitive to Erythromycin, 60% to Streptomycin, 44.7% to Oxytetracycline, and 36.7% to Tetracycline. Interviews with camel owners revealed that 66.7% used mixed herd grazing methods and reported feed shortage. Treatment practices for sick camels included modern veterinary drugs, traditional medicines, or a combination of both. The owners of camel dairy farms did not maintain proper hygiene practices during milking, such as not using soap when washing hands. Conclusion: Addressing camel mastitis necessitates access to alternative drugs, comprehensive herder training, and enhanced management practices. [ABSTRACT FROM AUTHOR]

Background: Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs. Objective: To determine the potential for HCO‐ethoxylate‐containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO‐25, ‐40, ‐60 and ‐80). Animals: Four healthy male laboratory dogs. Materials and Methods: We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre‐treatment with an antihistamine. Results: All HCO‐ethoxylate‐containing drugs caused a wheal‐and‐flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO‐ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO‐60‐induced reaction was suppressed by an oral antihistamine. Conclusions and Clinical Relevance: The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision‐making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect. [ABSTRACT FROM AUTHOR]

Soil is one of the main destinations for pesticides and veterinary drugs used in agriculture and animal production. The negative consequences of the accumulation of these compounds in the environment make it important to monitor these compounds in the soil. In this study, we compared different extraction procedures using solvent shaking, ultrasound, or QuEChERS, and their combinations, for the simultaneous determination of 75 pesticide and seven veterinary drug residues in agricultural soil by ultra-high performance liquid chromatography coupled to serial mass spectrometry (UHPLC–MS/MS). The method using QuEChERS combined with shaking showed the best results for soil using the addition of water, followed by extraction with acetonitrile acidified with acetic acid and shaking in a shaker. For partitioning, anhydrous magnesium sulfate and anhydrous sodium acetate were used. The extract was centrifuged, filtered, and diluted (1:4, v/v) in water for determination by UHPLC–MS/MS. Method validation showed adequate accuracy and precision results, with recoveries between 70 and 120% and RSD ≤ 20% for the vast majority of the compounds evaluated at the spike levels of 10, 25, 50, and 100 μg kg−1. The method limits of detection (LOD) and quantification (LOQ) ranged from 3.0 to 7.5 μg kg−1 and from 10 to 25 μg kg−1, respectively. The method was applied to different agricultural soil samples and proved to be efficient for routine analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Carvacrol and thymol are the primary constituents of oregano essential oil (OEO) and possess significant antibacterial, antiviral, and antifungal properties. Recent research has showcased the potent antioxidant, anti-inflammatory, antidiabetic, and cancer-inhibiting effects of OEO. The properties of OEO hold potential implications for the livestock and veterinary industries. This manuscript aims to evaluate the utility of OEO in the domains of animal husbandry and veterinary medicine. With a growing global concern over food safety and animal welfare issues, the livestock and veterinary industries are undergoing unprecedented changes. These changes have not only brought challenges within each industry, but also brought unprecedented opportunities for development. In this context, the search for natural and safe products that can effectively replace traditional veterinary drugs has become an important research direction in the fields of animal husbandry and veterinary medicine. Oregano essential oil (OEO), as a natural extract, is gradually emerging in the fields of animal husbandry and veterinary medicine with its unique antibacterial, antioxidant, and multiple other biological activities. OEO not only has a wide antibacterial spectrum, effectively fighting against a variety of pathogenic microorganisms, but also, because of its natural properties, helps us to avoid traditional veterinary drugs that may bring drug residues or cause drug resistance problems. This indicates OEO has great application potential in animal disease treatment, animal growth promotion, and animal welfare improvement. At present, the application of OEO in the fields of animal husbandry and veterinary medicine has achieved preliminary results. Studies have shown that adding OEO to animal feed can significantly improve the growth performance and health status of animals and reduce the occurrence of disease. At the same time, pharmacokinetic studies in animals show that the absorption, distribution, metabolism, and excretion processes of OEO in animals shows good bioavailability. In summary, oregano essential oil (OEO), as a substitute for natural veterinary drugs with broad application prospects, is gradually becoming a research hotspot in the field of animal husbandry and veterinary medicine. In the future, we look forward to further tapping the potential of OEO through more research and practice and making greater contributions to the sustainable development of the livestock and veterinary industries. [ABSTRACT FROM AUTHOR]

Lack of data on drug secretion in human milk is a concern for safe use of drugs during postpartum. Clinical studies are often difficult to perform; despite substantial improvements in computational methodologies such as physiologically based pharmacokinetic modelling, there is limited clinical data to validate such models for many drugs. Various factors that are likely to impact milk to plasma ratio were identified. A literature search was performed to gather available data on milk composition, total volume of milk produced per day, milk pH, haematocrit, and renal blood flow and glomerular filtration rate in various animal models. BLAST nucleotide and protein tools were used to evaluate the similarities between humans and animals in the expression and predominance of selected drug transporters, metabolic enzymes, and blood proteins. A multistep analysis of all the potential variables affecting drug secretion was considered to identify most appropriate animal model. The practicality of using the animal in a lab setting was also considered. Donkeys and goats were identified as the most suitable animals for studying drug secretion in milk and future studies should be performed in goats and donkeys to validate the preliminary observations. [ABSTRACT FROM AUTHOR]

Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a dangerous human risk. In this review, we aim to highlight the sources, occurrence, human exposure pathways, and human health effects of drug residues in food-animal products. Following the usage of veterinary medications, pharmacologically active compounds known as drug residues can be found in food, the environment, or animals. They can cause major health concerns to people, including antibiotic resistance development, the development of cancer, teratogenic effects, hypersensitivity, and disruption of normal intestinal flora. Drug residues in animal products can originate from variety of sources, including water or food contamination, extra-label drug use, and ignoring drug withdrawal periods. This review also examines how humans can be exposed to drug residues through drinking water, food, air, and dust, and discusses various analytical techniques for identifying these residues in food. Furthermore, we suggest some potential solutions to prevent or reduce drug residues in animal products and human exposure pathways, such as implementing withdrawal periods, monitoring programs, education campaigns, and new technologies that are crucial for safeguarding public health. This review underscores the urgency of addressing veterinary drug residues as a significant and emerging public health threat, calling for collaborative efforts from researchers, policymakers, and industry stakeholders to develop sustainable solutions that ensure the safety of the global food supply chain. [ABSTRACT FROM AUTHOR]

Using the Design of Experiments methodology (Response-Surface Methodology and Derringer's Desirability Function), a simple, fast and robust RP-HPLC method was developed for the analysis of enrofloxacin (EFC), its impurity A (fluoroquinolonic acid, FQ) and impurity B (ciprofloxacin, CPX). Gradient elution of samples was performed on a Zorbax Eclipse XDB C18 column (150 × 4.6 mm, 3.5 μm) with a mobile phase consisting of 32 mM phosphate buffer pH 3.5 – methanol (0 min-19.6% methanol; 15.5 min-19.6% methanol; 29.5 min-80% methanol; 30 min-19.6% methanol; 35 min-19.6% methanol), delivered at a flow rate of 1.5 mL min−1, wavelength of detection 278 nm (for EFX and CFX) and 265 nm for FQ. A good linear response was achieved in the range 15–35 μg mL−1 (EFX) and LOQ-150% for impurities (CFX and FQ). Other validation parameters were also tested: precision, accuracy, sensitivity and robustness. The developed method was shown to be simple, practical and suitable for the analysis of EFC and its impurities (CPX, FQ) in veterinary drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: Seizures are commonly noted in dogs and cats and should prompt immediate veterinary assessment and care in first time seizure patients or patients with multiple or ongoing seizures. All animals presenting for seizures should be evaluated to ensure they are not in imminent danger of death, to confirm that the episode noted at home was a seizure, and to look for the underlying causes of seizures. In certain situations, animals with seizures require immediate anticonvulsant medications and possibly in-hospital therapy and monitoring. This review presents a stepwise approach for veterinarians evaluating patients presenting for seizures. Seizures are a common presentation seen in small animal practices. Seizures require prompt management including initial interventions for triage, stabilization, and treatment with first-line anticonvulsant (AC) drugs like benzodiazepines. Concurrently, ruling out metabolic or extracranial causes with point-of-care diagnostics can help guide further diagnostics and treatments. Analysis of the history and a physical exam are also necessary to rule out common "look-alikes" that require specific diagnostic workup and treatments. Typically, causes of seizures can be grouped into intracranial and extracranial causes, with the latter being easier to diagnose with commonly available tests. This review presents a systematic approach to the diagnosis and treatment of single seizures, cluster seizures, and status epilepticus in dogs and cats. [ABSTRACT FROM AUTHOR]

Narcotic Detection Dogs (NDDs) are essential tools in the fight against drug trafficking, acting with high precision and improving efficiency at border posts. When trained efficiently, these dogs can detect a great variety of compounds, such as cocaine, marijuana and its derivatives, and synthetic drugs, among others. Most of the knowledge on canine detection processes and efficiency has been determined in experimentally controlled conditions, but narcotic seizures detected by dogs in realistic anti-drug operations have not yet been critically determined in a Country with continental dimensions such as Brazil. This study aimed to evaluate the data set concerning the performance, operations, efficiency, and success rate of NDDs used by the Brazilian Customs Authority (Aduana) in the fight against drug trafficking. Narcotic seizure rates increased in luggage and packages detected by NDDs working at border crossings from 2010 to 2020, with an estimated value of over US$ 2 billion in losses to the cocaine drug trafficking business. NDD units also increased most narcotic groups seized in the same period. The number of NDDs and anti-drug operations, and Customs Border Post (CBP) influenced the rates of drugs seized. NDDs provided an increase of 3,157 kg/animal of drugs seized for every new dog introduced into the inspection systems. [ABSTRACT FROM AUTHOR]

Patients with opioid use disorder experience high rates of relapse during recovery, despite successful completion of rehabilitation programs. A key factor contributing to this problem is the long-lasting nature of drug-seeking behavior associated with opioid use. We modeled this behavior in a rat drug self-administration paradigm in which drug-seeking is higher after extended abstinence than during the acute abstinence phase. The goal of this study was to determine the contribution of discrete or discriminative drug cues and drug dosage to time-dependent increases in drug-seeking. We examined heroin-seeking after 2 or 21 days of abstinence from two different self-administration cue-context environments using high or low doses of heroin and matched animals for their drug intake history. When lower dosages of heroin are used in discriminative or discrete cue protocols, drug intake history contributed to drug-seeking after abstinence, regardless of abstinence length. Incubation of opioid craving at higher dosages paired with discrete drug cues was not dependent on drug intake. Thus, interactions between drug cues and drug dosage uniquely determined conditions permissible for incubation of heroin craving. Understanding factors that contribute to long-lasting opioid-seeking can provide essential insight into environmental stimuli and drug-taking patterns that promote relapse after periods of successful abstinence. [ABSTRACT FROM AUTHOR]

Three newly synthesized triphenyltin(IV) compounds, Ph3SnL1 (L1− = 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoato), Ph3SnL2 (L2− = 2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato), and Ph3SnL3 (L3− = 2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato), were characterized by elemental microanalysis, FT-IR spectroscopy and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. A single X-ray diffraction study indicates that compounds Ph3SnL1 and Ph3SnL2 exhibit a 1D zig-zag chain polymeric structure, which in the case of Ph3SnL2 is additionally stabilized by π-interactions. In addition, the synthesized compounds were further examined using density functional theory and natural bond orbital analysis. The compounds have been evaluated for their in vitro anticancer activity against three human cell lines: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three murine cell lines: 4T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the nanomolar range, indicating that these compounds possess better anticancer activity than cisplatin. The study of the effect of the newly developed drug Ph3SnL1 showed its plasticity in achieving an antitumor effect in vitro, which depends on the specificity of the phenotype and the redox status of the malignant cell line and ranges from the initiation of apoptotic cell death to the induction of differentiation to a more mature cell form. In the syngeneic model of murine melanoma, Ph3SnL1 showed the potential to reduce the tumor volume similar to cisplatin, but in a well-tolerated form and with low systemic toxicity, representing a significant advantage over the conventional drug. [ABSTRACT FROM AUTHOR]

A pharmaceutical warehouse is part of the pharmaceutical supply chain and is essential to maintaining the quality and efficacy of veterinary pharmaceuticals for successful animal health service delivery. However, poor storage conditions, improper handling, and inappropriate use and disposal constitute challenges for veterinary supplies in animal health services. Therefore, this study aimed to assess the existing practices and challenges in warehouse management in government veterinary clinics and private veterinary drug wholesalers in Ethiopia. A cross-sectional study was conducted on 37 veterinary health facilities in four selected zones (south Gondar, west Gondar, central Gondar, and west Gojam zones) and Bahir Dar administrative city. Zones were selected using a simple random sampling technique. Data was collected using a structured questionnaire, pre-defined and tested observational checklists, and semi-structured interview guides. Descriptive statistics were used to analyze the quantitative data, while qualitative data was analyzed using a thematic approach. The study revealed the presence of poor stock management practices, such as the absence of standard operating procedures for warehouse activities in ~59.5% of facilities surveyed. In none of the surveyed facilities, bin cards and system software utilization were satisfactory. The absence of disposal guidelines was detected in 83.8% of the facilities, and the practice of timely disposal of expired drugs was not satisfactory. Compared to the government veterinary clinics, private veterinary drug wholesalers had better storage practices (86.25%) following theoretical recommendations. The storage conditions in government clinics were rated poor at 48.3% (>80%, which is the limit to the acceptable rate for good storage conditions). The challenges of inadequate infrastructure, a lack of qualified staff, problems with the availability and affordability of pharmaceutical products, insufficient regulatory practice, and budget constraints were identified. A holistic approach involving related stakeholders should be followed to improve the existing challenges and the sector's efficiency. [ABSTRACT FROM AUTHOR]

Funding: This project was supported with funds from the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Program Award number i01 BX003312 (M.K.R.). M.K.R. is a recipient of a VA Research Career Scientist Award (14S-RCS001). Research reported in this publication was also supported by the US National Institutes of Health under award numbers R01AI100569 and R01AI141412 (M.K.R.) and by the US Department of Defense Peer Reviewed Medical Research Program (PR181134) (M.K.R.). This work was also funded by VA Merit Review Award BX004522 to JSD from the US Department of Veterans Affairs Biomedical Laboratory Research and Development. The National Science Foundation provided instrument funding for the BioAnalytical Mass Spectrometry Facility at Portland State University (NSF, MRI 1828573), which was used to generate HRMS analytical measurements. [ABSTRACT FROM AUTHOR]

Every year, new compounds contained in consumer products, such as detergents, paints, products for personal hygiene, and drugs for human and veterinary use, are identified in wastewater and are added to the list of molecules that need monitoring. These compounds are indicated with the term emerging contaminants (or Contaminants of Emerging Concern, CECs) since they are potentially dangerous for the environment and human health. To date, among the most widely used methodologies for the removal of CECs from the aquatic environment, adsorption processes play a role of primary importance, as they have proven to be characterized by high removal efficiency, low operating and management costs, and an absence of undesirable by-products. In this paper, the adsorption of ibuprofen (IBU), a nonsteroidal anti-inflammatory drug widely used for treating inflammation or pain, was performed for the first time using two different types of geopolymer-based materials, i.e., a metakaolin-based (GMK) and an organic–inorganic hybrid (GMK-S) geopolymer. The proposed adsorbing matrices are characterized by a low environmental footprint and have been easily obtained as powders or as highly porous filters by direct foaming operated directly into the adsorption column. Preliminary results demonstrated that these materials can be effectively used for the removal of ibuprofen from contaminated water (showing a concentration decrease of IBU up to about 29% in batch, while an IBU removal percentage of about 90% has been reached in continuous), thus suggesting their potential practical application. [ABSTRACT FROM AUTHOR]

The application of veterinary drugs has brought great economic benefits, but its unreasonable application has also caused a series of safety problems. The study aimed to establish methods that will provide accurate quantitative information for the monitoring of veterinary drug residues in animal‐derived foods. Selecting nine veterinary drugs in four categories, the study combined quick, easy, cheap, effective, rugged, and safe technology with high‐performance liquid chromatography (HPLC) to detect multiple veterinary drugs in animal foods simultaneously. The study established two rapid, efficient, and accurate HPLC‐diode array detection methods to achieve the simultaneous detection of nitroimidazoles and β‐adrenergic agonists, and the simultaneous detection of benzimidazoles and diethylstilbestrol. The limit of detection of the former was 1.36–2.05 μg/kg and the latter 0.42–0.72 μg/kg. Then the two methods were used to detect veterinary drug residues in 297 animal foods from 10 categories to investigate the drug residues. For the seven banned drugs, the detection rates ranged from 1.35% to 7.41%. And for the two restricted drugs, the over‐standard rates were 4.38% and 0.00%. [ABSTRACT FROM AUTHOR]

The use of veterinary drugs is of similar importance to that of human drugs in addressing health challenges. In this context, pharmaceuticals and their metabolites inevitably enter soil and water in unknown quantities. Therefore, this study collects and analyzes drug data from 2020 for 50 dairy farms located in Germany. The most frequently used substance group is antibiotics (40.13%), followed by antiphlogistics (18.86%), antiparasitics (13.09%), and hormones (9.29%). Treatment frequencies record the number of days per year on which an average animal on a farm was treated with a substance. The calculated values range from 0.94 to 21.69 d/yr and are distributed heterogeneously across farms. In this study, on average, a cow was treated on 6 d in 2020: 2.34 d with antibiotics, 1.07 d with antiphlogistics, 0.76 d with antiparasitics, and 0.41 d with hormones. In addition to individual farm management practices, other factors are related to treatment frequency. Farms with a veterinary care contract used more hormonal substances than farms without a care contract. In addition, higher milk yield coincides with more frequent treatments with antiphlogistic or hormonal substances. Other related factors include grazing, longevity, farm size, and use of a claw bath. Our study represents an important first step in describing the amounts and determinants of veterinary drugs used in livestock farming. Such insights on magnitudes and farm parameters are essential to estimate potential environmental effects and derive strategies to reduce veterinary drug use. [ABSTRACT FROM AUTHOR]

An analytical method was developed for the screening of 172 veterinary drugs in traditional Chinese medicine Galli Gigerii Endothelium Corneum by high-performance liquid chromatography tandem mass spectrometry. The samples were pretreated by a modified QuEChERS method. A Zorbax Eclipse plus C18 column (1.8 μm, 3.0 × 150 mm2, Agilent) was used for the separation of analytes by gradient elution. All analytes were detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. Good linearity with R  ≥ 0.99 was exhibited for all analytes within the respective range. The recoveries of all monitored analytes ranged from 55.4 to 127.6% at three spiked levels (limit of quantitation—LOQ, 2-fold LOQ, 10-fold LOQ), with relative standard deviations <17.8%. The estimated LOQ levels were 0.2–20 μg/kg. The application of this method provides a reference for the safety control of traditional Chinese medicines. [ABSTRACT FROM AUTHOR]

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3–5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and β-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold. [ABSTRACT FROM AUTHOR]

Background: Antibiotics are commonly used drugs in farm animals for therapeutic, prophylactic and diagnosis purposes. As a result of the use of antibiotics in livestock, residues of antibiotics may be present in animal‐derived foods, especially in meat. This study aimed at determining the antibiotic residues in cattle slaughtered at Nekemte municipal abattoir and assessing the knowledge, attitude and practice (KAP) level of the community about antibiotic residue in food of cattle origin. Materials and methods: A cross‐sectional study was conducted on randomly selected kidney and muscle samples slaughtered at Nekemte municipal abattoir. The samples were collected aseptically and analysed using liquid chromatography mass spectrometer. In addition the KAP of cattle handlers, butcher men and meat users were collected using structured questionnaire. The data was analysed by SPSS and intercooled Stata version 7.0, 2001. Results: Results are presented as percentages and frequency distributions in tabular and graphical form. From 120 individuals interviewed, only 25.83% knew about withdrawal time and had limited knowledge on effect of antibiotic residue on human health, whereas about 47.5% did not heard about antibiotic residue in meat. Tetracycline was detected in all the sampled meat 60 (100%), whereas oxytetracycline residues were detected in half 15 (50%) of the samples. In the current study doxycycline, sulphadiazine, penicillin G and enrofloxacin were not detected in all samples. Oxytetracycline residue levels ranged from 0.00 to 463.35 µg/kg for the kidney and 0.00 to 354.55 µg/kg for muscle samples. About 10% of kidney and 3.33% muscle samples collected had oxytetracycline residues above maximum residue limits. Conclusion: In general, the study revealed that oxytetracycline residues were prevalent among antimicrobial residues analysed from the study area. The study indicated the presence of high antimicrobial residue and hence exposes for antimicrobial resistance of pathogens warranting coordinated effort to mitigate its health effect on the animal and hence human being. [ABSTRACT FROM AUTHOR]

The presence of human and veterinary pharmaceuticals (PhACs) in the environment poses potential risks. To comprehensively assess these risks, robust multiresidual analytical methods are essential for determining a broad spectrum of PhAC classes in various environmental compartments (soil, plants, and soil organisms). This study optimized extraction methods for analyzing over 40 PhACs from various matrices, including soil, lettuce, and earthworms. A four-step ultrasonic extraction method with varying extraction conditions and subsequent solid phase extraction was developed for soil samples. QuEChERS methods were optimized for extracting PhACs from lettuce and earthworm samples, addressing a literature gap in these less-studied matrices. The quantification of PhACs in soil, lettuce, and earthworm extracts was performed using a single LC–MS/MS method. Following thorough method validation, earthworms and lettuce were exposed to a mixture of 27 pharmaceuticals in a soil environment. The method validation results demonstrated the robustness of these methods for a broad spectrum of PhACs. Specifically, 29 out of 42 PhACs were extracted with an average efficiency > 50% and RSD < 30% from the soil; 40 out of 42 PhACs exhibited average efficiency > 50% and %RSD < 30% from the earthworms, while 39 out of 42 PhACs showed average efficiency > 50% and RSD < 30% from the lettuce. Exposure experiments confirmed the viability of these methods for quantifying a diverse range of PhACs in different environmental compartments. This study presents three thoroughly validated methods for determining more than 40 PhACs in diverse matrices, enabling a comprehensive assessment of PhAC dissemination in the environment. [ABSTRACT FROM AUTHOR]

Biologists and veterinarians rely on dart projectors to inject animals with drugs, take biopsies from specimens, or inject tracking chips. Firearms, air guns, and other launchers are limited in their ability to precisely control the kinetic energy of a projectile, which can injure the animal if too high. In order to improve the safety of remote drug delivery, a lidar-modulated electromagnetic launcher and a soft drug delivery dart were prototyped. A single-stage revolver coilgun and soft dart were designed and tested at distances up to 8 m. With a coil efficiency of 2.25%, the launcher could consistently deliver a projectile at a controlled kinetic energy of 1.00 ± 0.006 J and an uncontrolled kinetic energy of 2.66 ± 0.076 J. Although modifications to charging time, sensors, and electronics could improve performance, our launcher performed at the required level at the necessary distances. The precision achieved with commercial components enables many other applications, from law enforcement to manufacturing. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus suis (S. suis) is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against S. suis. In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against S. suis and withdrawal intervals. Methods: The PBPK model of ADP injection can predict drug concentrations in plasma, liver, kidney, muscle, and fat. A semi-mechanistic pharmacodynamic (PD) model, including susceptible subpopulation and resistant subpopulation, is successfully developed by a nonlinear mixed-effect model to evaluate antibacterial effects. An integrated PBPK/PD model is conducted to predict the time-course of bacterial count change and resistance development under different ADP dosages. Results: ADP injection, administrated at 20 mg/kg with 12 intervals for 3 consecutive days, can exert an excellent antibacterial effect while avoiding resistance emergence. The withdrawal interval at the recommended dosage regimen is determined as 18 days to ensure food safety. Discussion: This study suggests that the PBPK/PD model can be applied as an effective tool for the antibacterial effect and safety evaluation of novel veterinary drugs. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) poses a serious global threat to human and animal health. In the context of antimicrobial usage (AMU) in livestock production, veterinarians are key stakeholders. However, there is a lack of comprehensive situational analysis regarding the current Knowledge, Attitudes, and Practices (KAP) among veterinarians concerning AMU and AMR in poultry production in Nepal. Methods: The primary objective of this study was to evaluate the situation of AMU and KAP regarding AMU and AMR of among poultry practitioner veterinarians in Nepal. A total of 327 respondents from 56 districts across seven provinces participated. Demographic information and AMU situation were collected and analyzed using descriptive statistics, and factors affecting KAP on AMU and AMR were performed using logistic regression analysis. Results: Nearly half of veterinarians (49.2%) were from Bagmati, followed by Lumbini (16.5%) and Gandaki (8.9%) provinces. Most of the respondents (85.0%) identified themselves as male with a mean age of 31.9± 7.8years, with a range of 24-74years. A large proportion of veterinarians held a master's degree (43.8%). Regarding reasons for AMR, 51.1% of them attributed it to the irrational use of antimicrobials. Other identified reasons for AMR, including over-the-counter sales (27.8%), low-dose administration (12.3%), and low-quality antimicrobials (6.7%). Based on antibiotic prescription rates, most veterinarians (50.8%) prescribed antimicrobials at a rate of 20-40%, while 25.9% prescribed at a rate of less than 20.0 and 18.9% at a rate of 40-60%. Approximately 89.0% of veterinarians agreed that vaccination could reduce the use of antimicrobials in poultry, and 75.6% preferred narrow-spectrum antimicrobials than broad-spectrum antimicrobials. A combination of broad-spectrum antimicrobials such as colistin with amoxicillin, gentamicin, tylosin, and tetracycline was commonly used in poultry production. Discussion: In logistic regression analysis, it was observed that veterinarians aged 45-60 years demonstrated significantly higher levels of knowledge concerning AMU and AMR (p = 0.02) compared to those in the 24-30 age group. This study indicates that the need for robust regulatory mechanisms in veterinary drug administration and increased awareness among veterinarians to address the AMR issue livestock production. [ABSTRACT FROM AUTHOR]

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug. [ABSTRACT FROM AUTHOR]