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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]

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 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]

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]

Avilamycins, which possess potent inhibitory activity against Gram-positive bacteria, are a group of oligosaccharide antibiotics produced by Streptomyces viridochromogenes. Among these structurally related oligosaccharide antibiotics, avilamycin A serves as the main bioactive component in veterinary drugs and animal feed additives, which differs from avilamycin C only in the redox state of the two-carbon branched-chain of the terminal octose moiety. However, the mechanisms underlying assembly and modification of the oligosaccharide chain to diversify individual avilamycins remain poorly understood. Here, we report that AviZ1, an aldo-keto reductase in the avilamycin pathway, can catalyze the redox conversion between avilamycins A and C. Remarkably, the ratio of these two components produced by AviZ1 depends on the utilization of specific redox cofactors, namely NADH/NAD+ or NADPH/NADP+. These findings are inspired by gene disruption and complementation experiments and are further supported by in vitro enzymatic activity assays, kinetic analyses, and cofactor affinity studies on AviZ1-catalyzed redox reactions. Additionally, the results from sequence analysis, structure prediction, and site-directed mutagenesis of AviZ1 validate it as an NADH/NAD+-favored aldo-keto reductase that primarily oxidizes avilamycin C to form avilamycin A by utilizing abundant NAD+ in vivo. Building upon the biological function and catalytic activity of AviZ1, overexpressing AviZ1 in S. viridochromogenes is thus effective to improve the yield and proportion of avilamycin A in the fermentation profile of avilamycins. This study represents, to our knowledge, the first characterization of biochemical reactions involved in avilamycin biosynthesis and contributes to the construction of high-performance strains with industrial value. IMPORTANCE Avilamycins are a group of oligosaccharide antibiotics produced by Streptomyces viridochromogenes, which can be used as veterinary drugs and animal feed additives. Avilamycin A is the most bioactive component, differing from avilamycin C only in the redox state of the two-carbon branched-chain of the terminal octose moiety. Currently, the biosynthetic pathway of avilamycins is not clear. Here, we report that AviZ1, an aldo-keto reductase in the avilamycin pathway, can catalyze the redox conversion between avilamycins A and C. More importantly, AviZ1 exhibits a unique NADH/NAD+ preference, allowing it to efficiently catalyze the oxidation of avilamycin C to form avilamycin A using abundant NAD+ in cells. Thus, overexpressing AviZ1 in S. viridochromogenes is effective to improve the yield and proportion of avilamycin A in the fermentation profile of avilamycins. This study serves as an enzymological guide for rational strain design, and the resulting high-performance strains have significant industrial value. [ABSTRACT FROM AUTHOR]

Objective To understand the detection of four prohibited veterinary drugs of fresh and live freshwater fish sold in Guangzhou by analyzing the test data from risk monitoring and supervision sampling, so as to provide reference basis for food safety supervision. Methods Through the Guangzhou Food Safety Risk Monitoring system and the Food Safety Supervision and Inspection Public Information report of Guangzhou Market Administration, the test results of fresh water fish samples col-lected from supermarkets, markets, and online e-commerce in Guangzhou from 2017 to 2021 were obtained. The detection of nitrofuran drugs, chloramphenicol, sodium pentachloro phenate, and malachite green drugs were analyzed. Results The total detection rate of banned veterinary drugs in risk monitoring samples was 35.3% (84/238), and that in supervised sampling samples was 3.10% (118/3 806). The banned veterinary drugs with high detection rates of the two data sources were different. The risk monitoring rates of chloramphenicol and sodium pentachloro phenate were 17.23% (41/238) and 17.23% (41/238), respectively, and that of malachite green was 2.18% (83/3 806). The drug detection rate of the samples collected by risk monitoring in the network e-commerce link was Al.50% (19/40), which was the highest among all sampling links. The results of the two data sources showed that the detection rate of banned veterinary drugs in the wholesale market was high: 47.37% (18/38) and 4.13% (5/121), respectively. Conclusion The results of data analysis from the two sources complement each other and jointly reveal the problem of banned veterinary drug residues in fresh freshwater fish sold in Guangzhou from 2017 to 2021. It is suggested that the relevant departments pay more attention to the illegal use of chloramphenicol, sodium pentachloro phenate, and malachite green drugs. [ABSTRACT FROM AUTHOR]

Supply chain issues disrupt veterinary care and cause downstream consequences that alter the practice of veterinary medicine. Antimicrobials are just 1 class of pharmaceuticals that have been impacted by supply chain issues over the last couple of years. Since February 2021, 2 sponsors/manufacturers of penicillin products have reported shortages in the active pharmaceutical ingredient. With the release of the 2021 Summary Report on Antimicrobials Sold or Distributed for Use in Food-Producing Animals by the FDA, a key finding was a 19% decrease in penicillin sales and distribution from 2020 to 2021. Herein, we provide our clinicians' professional perspective regarding how drug shortages, specifically that of penicillin, might contribute to misconstrued patterns in antimicrobial use and what can be done by veterinarians and the FDA to minimize the impact of an antimicrobial drug shortage on animal health and well-being. [ABSTRACT FROM AUTHOR]

Brazil plays an important role in ensuring its position on the international market by assuring high food safety standards for its products, and all products should meet the requirements for residues from veterinary drugs and contaminants in animal products. Statutory monitoring provides insights into the compliance of the Brazilian industry regarding these legal requirements. The objective of this study was to provide insight into the safety of Brazilian animal products by reporting the occurrence of residues from veterinary drugs and contaminants according to an analysis of an 11-year report published by the Brazilian Ministry of Agriculture, Livestock and Food Supply (MAPA). Between 2010 and 2021, 166,647 samples from animal-derived products were analyzed in Brazil, and 624 of those samples were non-compliant (0.37%) exceeding maximum residue limits (>MRLs) or showed the presence of prohibited substances. The most common types of substances found in the non-compliant samples were heavy metals, parasiticides, and antimicrobials, accounting for 82% of all documents from the MAPA. Among Brazilian products, the challenge related to occurrence of substances varied across the food supply chain, with highest incidence rates observed in the fish chain, followed by eggs, milk, equids, sheep/goat, honey, bovine, swine, and broilers chains in decreasing order. Considering the type of substance, heavy metals were found to be more prevalent in fish products, mainly arsenic in wild fish. The prevalence of contaminants and heavy metals decreased, while that of veterinary drugs increased in Brazilian products from 2010 to 2021. From these results, it can be concluded that the number of accidental incidents including those associated with environmental contaminants decreased over the last decade, opposed to those involving human adversaries and deliberate illegal actions, such as the abuse of veterinary drugs, increased. Future monitoring plans need to take this paradigm shift into account. [ABSTRACT FROM AUTHOR]

Marbofloxacin (MBF) was once widely used as a veterinary drug to control diseases in animals. MBF residues in animal food endanger human health. In the present study, an immunochromatographic strip assay (ICSA) utilizing a competitive principle was developed to rapidly detect MBF in beef samples. The 50% inhibitory concentration (IC50) and the limit of detection (LOD) of the ICSAs were 2.5 ng/mL and 0.5 ng/mL, respectively. The cross-reactivity (CR) of the MBF ICSAs to Ofloxacin (OFL), enrofloxacin (ENR), norfloxacin (NOR), and Ciprofloxacin (CIP) were 60.98%, 32.05%, 22.94%, and 23.58%, respectively. The CR for difloxacin (DIF) and sarafloxacin (SAR) was less than 0.1%. The recovery rates of MBF in spiked beef samples ranged from 82.0% to 90.4%. The intra-assay and interassay coefficients of variation (CVs) were below 10%. In addition, when the same authentic beef samples were detected in a side-by-side comparison between the ICSAs and HPLC‒MS, no statistically significant difference was observed. Therefore, the proposed ICSAs can be a useful tool for monitoring MBF residues in beef samples in a qualitative and quantitative manner. [ABSTRACT FROM AUTHOR]

Estimating antibiotic consumption in animals is fundamental to guiding decision-making and research on controlling the emergence and spread of antibiotic-resistant bacteria in humans, animals, and the environment. This study aimed to establish importation trends of antibiotics for veterinary use in Rwanda between 2019 and 2021. Data was collected from the Rwanda Food and Drugs Authority's database. Quantities of imported antibiotic active ingredients were computed using the information extracted from the issued import licenses. These quantities were subsequently adjusted per animal biomass. In total, 35,291.4 kg of antibiotics were imported into Rwanda between 2019 and 2021, with an annual mean of 11,763.8 ± 1,486.9 kg. The adjustment of imported quantities of antibiotics per animal biomass revealed that 29.1 mg/kg, 24.3 mg/kg, and 30.3 mg/kg were imported in 2019, 2020, and 2021 respectively. A slight but not statistically significant decline in antibiotic importation was noted in 2020 (p-value = 0.547). Most of the imported antibiotics were indicated to be used in food-producing animals (35,253.8 kg or 99.9% of the imported antibiotics). Tetracyclines (17,768.6 kg or 50.3%), followed by sulfonamides (7,865.0 kg or 22.3%) and aminoglycosides (4,071.1 kg or 11.5%), were the most imported antibiotics over the studied period. It was noted that 78.9% of the imported antibiotics were categorized as highly important antimicrobials for human medicine. This study established a generalized overview of the importation of antibiotics for veterinary use in Rwanda. These results can serve as guidance for the control of antibiotic misuse. They can be used to make a correlation between antibiotic importation, antibiotic consumption, and the occurrence of antibiotic resistance in the country. [ABSTRACT FROM AUTHOR]

Marbofloxacin (MB) is a newly developed fluoroquinolone antibiotic used especially as a veterinary drug. It may be regarded as the improved version of enrofloxacin owing to its antibacterial activity, enhanced bioavailability, and pharmacokinetic–pharmacodynamic (PK–PD) properties. In this study, nine heavy rare-earth ions (Y, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were selected in light of their potential antibacterial activity and satisfactory biosafety to afford the corresponding rare-earth metal complexes of MB: the MB–Ln series. Their chemical structures and coordination patterns were characterized using IR spectroscopy, HRMS, TGA, and X-ray single-crystal diffraction analysis. Our results confirmed that all the MB–Ln complexes yielded the coincident coordination modes with four MB ligands coordinating to the Ln(III) center. In vitro antibacterial screening on five typical bacteria strains revealed that the MB–Ln complexes exhibited antibacterial activities comparable with MB, as indicated by the MIC/MBC values, in which Escherichia coli and Salmonella typhi were the most sensitive ones to MB–Ln. Furthermore, the MB–Ln complexes were found to be much less toxic in vivo than MB, as suggested by the evaluated LD50 (50% lethal dose) values. All the MB–Ln series complexes fell in the LD50 range of 5000–15 000 mg kg−1, while the LD50 value of MB was only 1294 mg kg−1. Furthermore, MB–Lu, as the selected representative of MB–Ln, could effectively inhibit the activity of DNA gyrase, the same as MB, suggesting the primary antibacterial mechanism of the MB–Ln series. The results demonstrated the good prospects and potential of metal-based veterinary drugs with better drug performance. [ABSTRACT FROM AUTHOR]

The article describes changes in pharmacy law at the turn of the year 2023/2024. Two legislative amendments were passed, the Agreement Implementation Act 2024 and the restructuring of the veterinary medicine sector. The changes affect, among other things, the binding of drug supply in hospitals to the recommendations of an evaluation board. Adjustments were made to the veterinary medicine law in accordance with Union regulations. The revised veterinary medicine law does not bring about major changes for pharmacies, except for the permissibility of dispensing drugs by veterinary home pharmacies to other veterinary home pharmacies in small quantities. [Extracted from the article]

For at least two reasons, the current transgenic animal models of Alzheimer's disease (AD) appear to be patently inadequate. They may be useful in many respects, the AD models; however, they are not. First, they are incapable of developing the full spectrum of the AD pathology. Second, they respond spectacularly well to drugs that are completely ineffective in the treatment of symptomatic AD. These observations indicate that both the transgenic animal models and the drugs faithfully reflect the theory that guided the design and development of both, the amyloid cascade hypothesis (ACH), and that both are inadequate because their underlying theory is. This conclusion necessitated the formulation of a new, all-encompassing theory of conventional AD—the ACH2.0. The two principal attributes of the ACH2.0 are the following. One, in conventional AD, the agent that causes the disease and drives its pathology is the intraneuronal amyloid-β (iAβ) produced in two distinctly different pathways. Two, following the commencement of AD, the bulk of Aβ is generated independently of Aβ protein precursor (AβPP) and is retained inside the neuron as iAβ. Within the framework of the ACH2.0, AβPP-derived iAβ accumulates physiologically in a lifelong process. It cannot reach levels required to support the progression of AD; it does, however, cause the disease. Indeed, conventional AD occurs if and when the levels of AβPP-derived iAβ cross the critical threshold, elicit the neuronal integrated stress response (ISR), and trigger the activation of the AβPP-independent iAβ generation pathway; the disease commences only when this pathway is operational. The iAβ produced in this pathway reaches levels sufficient to drive the AD pathology; it also propagates its own production and thus sustains the activity of the pathway and perpetuates its operation. The present study analyzes the reason underlying the evident inadequacy of the current transgenic animal models of AD. It concludes that they model, in fact, not Alzheimer's disease but rather the effects of the neuronal ISR sustained by AβPP-derived iAβ, that this is due to the lack of the operational AβPP-independent iAβ production pathway, and that this mechanism must be incorporated into any successful AD model faithfully emulating the disease. The study dissects the plausible molecular mechanisms of the AβPP-independent iAβ production and the pathways leading to their activation, and introduces the concept of conventional versus unconventional Alzheimer's disease. It also proposes the path forward, posits the principles of design of productive transgenic animal models of the disease, and describes the molecular details of their construction. [ABSTRACT FROM AUTHOR]

Studies have reported health risks associated with seafood contamination, but few data exist on levels in commercially available seafood in the US. To better understand, the magnitude of foodborne exposure and identify vulnerable populations in the US, we measured concentrations of veterinary drugs, persistent organic pollutants (POPs) (polycyclic aromatic hydrocarbons [PAHs], polybrominated diphenyl ethers [PBDEs] and polychlorinated biphenyls [PCBs]), and legacy and current-use pesticides in 46 seafood samples purchased from retail outlets. Measured levels were used to estimate risk based on available maximum residue limits (MRLs) and toxic equivalence (TEQ) factors for analytes. Only seventeen of the 445 analytes were detected, at low substance frequencies. However, half of the samples tested positive for one or more analyte, with total concentrations ranging from below the limit of detection (LOD) to as high as 156 µg/kg wet weight. Based on the risk assessment for individual pesticides and veterinary drugs, the hazard quotients (HQ) were all <1, indicating no risk. However, for the sum of PCB126 and PCB167, two dioxin-like PCBs detected in our samples, the TEQ was nearly two orders of magnitude higher than the WHO limits in one catfish sample. Moreover, vulnerable groups with higher rates of consumption of specific fish types may face higher risks. [ABSTRACT FROM AUTHOR]

• Fetuses might be more susceptible to prenatal amoxicillin exposure (PAmE) than mothers. • PAmE induced abnormal fetal development with organ-, stage- and course-differences. • Most obvious changes in fetuses were in high-dose, late-pregnancy and multi-course. • There were sex differences in fetal developmental and functional changes caused by PAmE. • Male fetuses were more affected by PAmE during mid-/late-pregnancy than females. Amoxicillin, a widely used antibiotic in human and veterinary pharmaceuticals, is now considered as an "emerging contaminant" because it exists widespreadly in the environment and brings a series of adverse outcomes. Currently, systematic studies about the developmental toxicity of amoxicillin are still lacking. We explored the potential effects of amoxicillin exposure on pregnancy outcomes, maternal/fetal serum phenotypes, and fetal multiple organ development in mice, at different doses (75, 150, 300 mg/(kg·day)) during late-pregnancy, or at a dose of 300 mg/(kg·day) during different stages (mid-/late-pregnancy) and courses (single-/multi-course). Results showed that prenatal amoxicillin exposure (PAmE) had no significant influence on the body weights of dams, but it could inhibit the physical development and reduce the survival rate of fetuses, especially during the mid-pregnancy. Meanwhile, PAmE altered multiple maternal/fetal serum phenotypes, especially in fetuses. Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis, long bone/cartilage and hippocampal development, and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis, and the order of severity might be gonad (testis, ovary) > liver > others. Further analysis found that PAmE-induced multi-organ developmental and functional alterations had differences in stages, courses and fetal gender, and the most obvious changes might be in high-dose, late-pregnancy and multi-course, but there was no typical rule of a dose-response relationship. In conclusion, this study confirmed that PAmE could cause abnormal development and multi-organ function alterations, which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm. [Display omitted] [ABSTRACT FROM AUTHOR]

There is an urgent need to find new solutions for the global dilemma of increasing antibiotic resistance in humans and animals. Modifying the performance of existing antibiotics using the nanocarrier drug delivery system (DDS) is a good option considering economic costs, labor costs, and time investment compared to the development of new antibiotics. Numerous studies on nanomedicine carriers that can be used for humans are available in the literature, but relatively few studies have been reported specifically for veterinary pharmaceutical products. Polymer-based nano-DDS are becoming a research hotspot in the pharmaceutical industry owing to their advantages, such as stability and modifiability. This review presents current research progress on polymer-based nanodelivery systems for veterinary antimicrobial drugs, focusing on the role of polymeric materials in enhancing drug performance. The use of polymer-based nanoformulations improves treatment compliance in livestock and companion animals, thereby reducing the workload of managers. Although promising advances have been made, many obstacles remain to be addressed before nanoformulations can be used in a clinical setting. Some crucial issues currently facing this field, including toxicity, quality control, and mass production, are discussed in this review. With the continuous optimization of nanotechnology, polymer-based DDS has shown its potential in reducing antibiotic resistance to veterinary medicines. [ABSTRACT FROM AUTHOR]

A combination of sample screening and subsequent confirmatory detection of contaminants represents an optimal strategy for routine analysis in implementing food safety monitoring programs. We propose ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry for the multicomponent determination of a wide range of veterinary drugs and their metabolite residues with minimal sample preparation. Isotopic dilution was employed to mitigate matrix effects. The procedure proposed in this study enables the simultaneous identification and assessment of residual levels of 214 veterinary drugs at limits of detection of 0.1–10.0 ng/g with a significantly shortened analysis time (40–50 min) and reduced cost. [ABSTRACT FROM AUTHOR]

Nowadays, incorrect apply of antibiotics to treat infections in honey has led to health risks for humans and antibiotic resistance. Current systematic review and meta-analysis conducted to study antibiotic residues in honey. Data were obtained through searching the databases, including Scopus, Web of Science, PubMed, and other internal databases. The pooled concentration of antibiotic residues was 5.032 (µg/kg) that ranged from 4.72 to 5.33 (µg/kg). The ranking of antibiotics concentration was found in order of fluoroquinolone (8.59 µg/kg) > tetracycline (5.68 µg/kg) > sulfonamides (5.54 µg/kg) > macrolides (4.19µg/kg), respectively. Liquid chromatography–mass spectrometry (LC–MS) method (37.9.7%), high-performance liquid chromatography (HPLC) method (34.4%), and enzyme-linked immunosorbent assay (ELISA) method (27.5.8%) were the most used methods in various studies. In order to avoid contamination, proper use of antibiotics, placement of hives at a suitable distance from agricultural environment, and regular control of antibiotic residues in honey seems to be necessary. [ABSTRACT FROM AUTHOR]

Although filtration is one of the most common steps in sample preparation for chemical analysis, filter membrane materials can leach contaminants and/or retain some analytes in the filtered solutions. In multiclass, multiresidue analysis of veterinary drugs, it is challenging to find one type of filter membrane that does not retain at least some of the analytes before injection in ultrahigh‐performance liquid chromatography‐tandem mass spectrometry (UHPLC‐MS/MS). In this study, different filter membranes were tested for use in UHPLC‐MS/MS analysis of 183 diverse drugs in bovine muscle, kidney, and liver tissues. Membranes evaluated consisted of polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF), polyethersulfone, nylon, and regenerated cellulose. Drug classes represented among the analytes included β‐agonists, β‐lactams, anthelmintics, macrolides, tetracyclines, sulfonamides, tranquilizers, (fluoro)quinolones, anti‐inflammatories, nitroimidazoles, coccidiostats, phenicols, and others. Although the presence of a matrix helped reduce the binding of analytes on surface active sites, all of the filter types partially retained at least some of the drugs in the final extracts. In testing by flow‐injection analysis, all of the membrane filters were also observed to leach interfering components. Ultimately, filtration was avoided altogether in the final sample preparation approach known as the quick, easy, cheap, effective, rugged, safe, efficient, and robust (QuEChERSER) mega‐method, and ultracentrifugation was chosen as an alternative. [ABSTRACT FROM AUTHOR]

Purpose: The data acquisition of drug metabolism analysis requires a lot of time and animal resources. However, there are often many deviations in the results of pharmacokinetic analysis. Conventional methods cannot measure the blood drug concentration data in multiple tissues at the same time, and the data is obtained by in vitro measurement, which produces time errors, in vitro data errors, and individual differences between animals. In the analysis of pharmacokinetic parameters, it will seriously affect the pass rate of clinical trials of R&D drugs and the accuracy of the dosing schedule. To the best of our knowledge, we have not found the study of in vivo blood drug concentration using multi-channel equipment. Therefore, the purpose of this paper is to build a set of multi-organ monitoring and analysis instruments for synchronously monitoring the metabolism of drugs in various tissues of small animals, so as to obtain real in vivo data of blood drug concentration in real time. Procedures: Using the fluorescence properties and laser-induced fluorescence principle of drugs, we designed six channels to monitor the changes of fluorescence-labeled drugs in their main metabolic organs, a multi-channel calibration method was proposed to improve the accuracy of the time-division multiplexing, the real-time collection of drug concentration in vivo is realized, and the drug metabolism curve in vivo can be observed. Results: The instrument satisfies the collection of small doses of drugs such as microgram; the detection sensitivity can reach 10 ng/ml, and can monitor and collect the drug metabolism of multiple small animal tissues at the same time, which greatly reduces the use of animals, reduces the differences between individuals, and reduces consumption cost and improve the detection efficiency of parameters, and obtain data information that is closer to the real biology. Conclusion: The real-time continuous monitoring and data collection of the drug metabolism in the plasma of living small animals and the important organs such as kidney, liver, and spleen were realized. The research and development of new drugs and clinical research have higher practical value. [ABSTRACT FROM AUTHOR]

High-resolution mass spectrometry (HRMS) has become an important tool for monitoring chemical residues in food, but the time and effort required to evaluate the large amount of data generated by HRMS can be a limiting factor in the widespread application of this tool. Suspect screening, i.e., searching HRMS data against large compound databases or mass lists, represents a practical compromise between using HRMS data to only look for target compounds and performing full non-target analysis. Several different approaches for suspect screening using HRMS data were tested using data from shrimp and eel spiked with veterinary drugs and pesticides as well as from imported aquaculture samples. Most of the analytes (>70%) in the spiked samples were detected and identified by searching against compound databases. To query larger databases and on-line resources such as mzCloud, it was necessary to use software capable of differential analysis and selective filtering, such as Compound Discoverer. Using selective filtering, the number of compounds detected in fish sample extracts could be reduced from tens of thousands to a few hundred by subtracting method blanks and comparing to matrix blank extracts. This smaller list of potential compounds could be further evaluated and compared to available databases and libraries. Analysis of imported aquaculture samples resulted in detection of unexpected contaminants including the dewormer levamisole, the insecticide buprofezin, and potentially the plant alkaloid ricinine. [ABSTRACT FROM AUTHOR]

A freeze-dried bovine muscle–certified reference material (CRM), known as BOTS-1 (DOI: https://doi.org/10.4224/crm.2018.bots-1), containing incurred residues of commonly used veterinary drugs was produced and certified for the mass fraction of eight veterinary drug residues. Value assignment was carried out using liquid chromatography tandem mass spectrometry (LC–MS/MS) methods in conjunction with isotope dilution and standard addition approaches involving stable isotope internal standards. Data from the National Research Council of Canada (NRC), Canadian Food Inspection Agency (CFIA), United States Department of Agriculture (USDA), and the Federal Office of Consumer Protection and Food Safety in Germany (BVL) were used for value assignment. Results for two drug residues were also obtained through an international inter-laboratory comparison CCQM-K141/P178 organized under the auspices of the International Bureau of Weights and Measures (BIPM). Quantitative NMR (1H-qNMR) was used to characterize primary standards of all veterinary drugs certified. The certified mass fractions of the veterinary drug residues were 490 ± 100 µg/kg for chlorpromazine, 44 ± 4.4 µg/kg for ciprofloxacin, 3.3 ± 1.4 µg/kg for clenbuterol, 9.5 ± 0.8 µg/kg for dexamethasone, 57 ± 4.8 µg/kg for enrofloxacin, 3.0 ± 0.4 µg/kg for meloxicam, 12.4 ± 1.2 µg/kg for ractopamine, and 2290 ± 120 µg/kg for sulfadiazine with expanded uncertainties quoted (95% confidence) which include the effects due to between-bottle inhomogeneity, instability during long-term storage and transportation, and characterization. [ABSTRACT FROM AUTHOR]

Human babesiosis is a potentially fatal tick-borne disease caused by intraerythrocytic Babesia parasites. The emergence of resistance to recommended therapies highlights the need for new and more effective treatments. Here we demonstrate that the 8-aminoquinoline antimalarial drug tafenoquine inhibits the growth of different Babesia species in vitro, is highly effective against Babesia microti and Babesia duncani in mice and protects animals from lethal infection caused by atovaquone-sensitive and -resistant B. duncani strains. We further show that a combination of tafenoquine and atovaquone achieves cure with no recrudescence in both models of human babesiosis. Interestingly, elimination of B. duncani infection in animals following drug treatment also confers immunity to subsequent challenge. Altogether, the data demonstrate superior efficacy of tafenoquine plus atovaquone combination over current therapies for the treatment of human babesiosis and highlight its potential in providing protective immunity against Babesia following parasite clearance. [ABSTRACT FROM AUTHOR]

Background: Salinomycin, an antibiotic, have potential as a veterinary drug for fish due to its anti-parasitic activity against several fish parasites. Thus the residual levels of salinomycin in muscles of two significant aquaculture species in Korea, olive flounder and black rockfish, were analyzed using HPLC-MS-MS. Results: The proper method to analyze the residual salinomycin in fish muscles using LC-MS-MS was settled and the method was validated according to CODEX guidelines. The residues in three distinct groups for two fish species were analyzed using the matrix match calibration curves at points of five different times following oral administration. After oral administration, salinomycin rapidly breaks down in both olive flounder and black rockfish. After 7th days, the average residue in all groups of two fish spp. decreased below limit of quantitation (LOQ). Conclusion: Due to low residue levels in fish muscles, salinomycin may therefore be a treatment that is safe for both fish and humans. This result could contribute to establishment of MRL (minimal residual limit) for approval of salinomycin for use in aquaculture. [ABSTRACT FROM AUTHOR]

Background: Clostridium perfringens (CP) is an emerging anaerobic pathogen that can aggravate severe fatal infections in different hosts and livestock. Aim: This paper was designed to monitor the antibacterial efficacy of Moringa oleifera (M. oleifera) plant against different CP isolates of variant toxin genotypes comparing that with commercial antibiotics in the veterinary field. Methods: A total of 200 examined fecal, intestinal, and liver samples from cattle, sheep, and goat were investigated bacteriologically and biochemically for CP. Then, the isolates were examined by polymerase chain reaction (PCR) for toxin gene typing. Thereafter, the antimicrobial susceptibility testing as well as the antibacterial efficacy of M. oleifera were evaluated and statistically analyzed against recovered isolates. Results: The prevalence rate of CP was 51% (102/200); of which 54.5% was from cattle, 50% from sheep, and 40% from goat. Moreover, all CP isolates were highly resistant to tetracycline and lincomycin drugs; meanwhile, they were of the least resistance against ciprofloxacin (8.3%–16.7%), cefotaxime (16.7%–25%), and gentamycin (26.7%– 33.3%). For M. oleifera, high antibacterial efficacy with greater inhibition zones of the plant was recorded with its oil (20–24 mm) and ethanolic extracts (16–20 mm) against CP than the aqueous extract (≤ 10 mm). A good correlation was stated between M. oleifera oil and toxin type of CP isolates particularly type A followed by D and B types. Interestingly, the oil and ethanolic extracts of M. oleifera gave higher antibacterial efficacy than most commercial antibiotics against the recovered isolates. Conclusion: This study highlighted the potent antibacterial properties of M. oleifera for suppressing CP infections in farm animals. Hence, more investigations on M. oleifera are suggested to support its use as a medical herbal plant substituting antibiotics hazards and resistance problems worldwide. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the survival to discharge rate of rabbits with gastrointestinal obstructions treated with lidocaine constant rate infusion (CRI) and other factors associated with survival. ANIMALS Cases of gastrointestinal obstruction in rabbits (n = 56, including 64 events) that had presented to a veterinary teaching hospital from 2012 to 2021. METHODS This was a retrospective study in which data on rabbits with evidence of gastrointestinal obstruction were extracted from veterinary teaching hospital medical records over a 9-year period. Systemic lidocaine treatment, breed, sex, age, temperature at presentation, blood glucose at presentation, and time to discharge or death were evaluated with univariate and multivariate logistic regression to identify factors significantly associated with survival to hospitai discharge in rabbits with gastrointestinal obstruction. RESULTS Comparatively, 89.7% of rabbits treated with lidocaine CRI (n = 39) survived to hospital discharge, while only 56% of rabbits that were not treated with lidocaine CRI (25) survived. In the final multivariate analysis, 2 factors were associated with survival to discharge: rabbits treated with systemic lidocaine and male rabbits had increased odds of survival compared to those not treated with systemic lidocaine and female rabbits, respectively. CLINICAL RELEVANCE Results demonstrated that rabbits with gastrointestinal obstruction and treated with a lidocaine CRI were more likely to survive compared to rabbits not treated with lidocaine CRI. [ABSTRACT FROM AUTHOR]

The 2023 International African Swine Fever Workshop (IASFW) took place in Beijing, China, on 18–20 September 2023. It was jointly organized by the U.S.-China Center for Animal Health (USCCAH) at Kansas State University (KSU) and the Chinese Veterinary Drug Association (CVDA) and sponsored by the United States Department of Agriculture Foreign Agricultural Service (USDA-FAS), Harbin Veterinary Research Institute, and Zoetis Inc. The objective of this workshop was to provide a platform for ASF researchers around the world to unite and share their knowledge and expertise on ASF control and prevention. A total of 24 outstanding ASF research scientists and experts from 10 countries attended this meeting. The workshop included presentations on current ASF research, opportunities for scientific collaboration, and discussions of lessons and experiences learned from China/Asia, Africa, and Europe. This article summarizes the meeting highlights and presents some critical issues that need to be addressed for ASF control and prevention in the future. [ABSTRACT FROM AUTHOR]

In recent decades, microphysiological constructs and systems (MPCs and MPSs) have undergone significant development, ranging from self‐organized organoids to high‐throughput organ‐on‐a‐chip platforms. Advances in biomaterials, bioinks, 3D bioprinting, micro/nanofabrication, and sensor technologies have contributed to diverse and innovative biofabrication tactics. MPCs and MPSs, particularly tissue chips relevant to absorption, distribution, metabolism, excretion, and toxicity, have demonstrated potential as precise, efficient, and economical alternatives to animal models for drug discovery and personalized medicine. However, current approaches mainly focus on the in vitro recapitulation of the human anatomical structure and physiological‐biochemical indices at a single or a few simple levels. This review highlights the recent remarkable progress in MPC and MPS models and their applications. The challenges that must be addressed to assess the reliability, quantify the techniques, and utilize the fidelity of the models are also discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Deep amplicon sequencing of levamisole (LEV)-resistant S168T in Haemonchus spp. from Australia was undertaken. • A new approach was developed, enabling nemabiome and multi-drug surveillance in field populations. • Mixed amplicon sequencing was equivalent to individual amplicon sequencing. • LEV-resistant S168T was present in most ovine and caprine Australian field isolates. Anthelmintic-resistant parasitic nematodes present a significant threat to sustainable livestock production worldwide. The ability to detect the emergence of anthelmintic resistance at an early stage, and therefore determine which drugs remain most effective, is crucial for minimising production losses. Despite many years of research into the molecular basis of anthelmintic resistance, no molecular-based tools are commercially available for the diagnosis of resistance as it emerges in field settings. We describe a mixed deep amplicon sequencing approach to determine the frequency of the levamisole (LEV)-resistant single nucleotide polymorphism (SNP) within arc -8 exon 4 (S168T) in Haemonchus spp., coupled with benzimidazole (BZ)-resistant SNPs within β -tubulin isotype-1 and the internal transcribed spacer-2 (ITS-2) nemabiome. This constitutes the first known multi-drug and multi-species molecular diagnostic developed for helminths of veterinary importance. Of the ovine, bovine, caprine and camelid Australian field isolates we tested, S168T was detected in the majority of Haemonchus spp. populations from sheep and goats, but rarely at a frequency greater than 16%; an arbitrary threshold we set based on whole genome sequencing (WGS) of LEV-resistant Haemonchus contortus GWBII. Overall, BZ resistance was far more prevalent in Haemonchus spp. than LEV resistance, confirming that LEV is still an effective anthelmintic class for small ruminants in New South Wales, Australia. The mixed amplicon metabarcoding approach described herein paves the way towards the use of large scale sequencing as a surveillance technology in the field, the results of which can be translated into evidence-based recommendations for the livestock sector. [ABSTRACT FROM AUTHOR]

To investigate veterinarians' experience and perception of the risk of veterinary prescription medication (VPM) misuse and abuse by the public and veterinary professionals and to determine the clinical context in which respondent veterinarians prescribed certain VPMs. Anonymous online voluntary survey. A total of 361 of 7126 veterinarians registered as practicing in the UK, who provided e-mail contact details to the Royal College of Veterinary Surgeons Knowledge for participation in research. Respondents included general practitioners, with or without further qualifications, and European specialists, covering charity, private or academic small, large or mixed animal practice. The anonymous online survey, open from September to December 2021, posed 27 questions regarding personal experience and perception of VPM misuse or abuse, including which VPMs were considered most at risk of abuse by clients or veterinary staff. Thematic analysis was performed on free-text sections. The participation rate was 5% (361/7126), and the completion rate 60% (216/361 respondents). Of these, 88% of respondents somewhat agreed, agreed or strongly agreed that some VPMs were at risk of abuse. A third (29.9%; 107/358) had suspected an owner of taking VPMs, and one fifth (20.1%; 72/358) had suspected veterinary staff. Perceptions regarding the likelihood of public VPM abuse ranged from not suspecting a problem to having first-hand experience. Drugs considered most at risk of owner abuse were opioids, benzodiazepines and gabapentin, and those for veterinary staff were opioids, benzodiazepines and ketamine. Numerous 'red flags' prompting suspicion of VPM abuse were identified alongside ways of mitigating risk. Veterinarians in the UK reported varied experiences with, awareness of, and attitudes towards VPM abuse by the public and veterinary staff. Although not quantified, the UK veterinary industry could be a source of abusable drugs. [ABSTRACT FROM AUTHOR]

Background: The link between the reckless use of antimicrobials with the increasing development of multidrugresistant strains of antibiotics is well established. To control the spread of antimicrobial resistance (AMR), action plans, recommendations and guidelines on the prudent use of antibiotics have been developed for food-producing animals and companion animals but appear to be lacking in exotic pets due to the scarcity of data and information on the use of antibiotics in these species. Aim: The purpose of this study is to bring qualitative and quantitative data regarding the use of antimicrobials in exotic pets in a veterinary center in southern Brazil, seeking to measure the consumption of these animals to determine and guide future actions to combat AMR. Methods: A retrospective observational study was conducted by surveying 2,190 open care records in a specialized clinic of wildlife medicine in 2018. Data evaluation was performed in a descriptive, qualitative, and quantitative way, and the analysis of antimicrobial consumption was performed by calculating the daily dose/g of animal ml/day/kg by animal order, condition and active principle, adaptation to DDDVet. For statistical analysis, Levene´s, ANOVA followed by Tukey´s tests were used. Results: Approximately 57% (1250/2190) of the visits made use of one or more antimicrobials in the treatment of animals referred to the clinic. Of these, 67% (n = 839) were birds, 26% (n = 327) were mammals, and 7% (n = 84) were reptiles. In 2018, the total consumption of antimicrobials prescribed was 2.21 l for a total biomass of 129.24 kg. The relation between the dosages of the main antimicrobials used and the conditions treated showed that there is no variation between the treatments by disease and by animal class, due to the great variation within each group. Conclusion: The antimicrobial prescription in exotic pets requires a multifaceted and dynamic approach applied to safeguard the efficacy of the antimicrobials, optimizing consumption, minimizing the emergence of AMR and other possible adverse effects, and considering the physiological differences present within each species. The doses between the different classes and conditions do not obtain a significant difference, reflected in a possible nonstandardization of the dosages used, requiring further investigation of the recommended dosages for each animal species, avoiding the over or underdosing of these drugs. It is worth highlighting that professionals must always make rational use of antimicrobials in these species. [ABSTRACT FROM AUTHOR]

Understanding antibiotic use in dairy systems is critical to guide antimicrobial stewardship programs. We investigated antibiotic use practices in small-holder dairy farms, antibiotic quality, and antimicrobial resistance (AMR) awareness among veterinary drug retailers in a mixed farming community in the central Kenyan highlands. Data were collected from 248 dairy farms and 72 veterinary drug stores between February 2020 and October 2021. A scale was developed to measure knowledge about AMR and antibiotic use using item response theory, and regression models were used to evaluate factors associated with antibiotic use and AMR knowledge. The active pharmaceutical ingredient (API) content of 27 antibiotic samples was determined using high-performance liquid chromatography (HPLC). The presence and levels of 11 antibiotic residues in 108 milk samples collected from the study farms were also investigated using liquid chromatography tandem mass spectrometry (LC–MS/MS). Almost all farms (98.8%, n = 244) reported using antibiotics at least once in the last year, mostly for therapeutic reasons (35.5%). The most used antibiotics were tetracycline (30.6%), penicillin (16.7%), and sulfonamide (9.4%), either individually or in combination, and predominantly in the injectable form. Larger farm size (OR = 1.02, p < 0.001) and history of vaccination use (OR = 1.17, p < 0.001) were significantly associated with a higher frequency of antibiotic use. Drug retailers who advised on animal treatments had a significantly higher mean knowledge scores than those who only sold drugs. We found that 44.4% (12/27) of the tested antibiotics did not meet the United States Pharmacopeial test specifications (percentage of label claim). We detected nine antibiotics in milk, including oxytetracycline, sulfamethoxazole, and trimethoprim. However, only three samples exceeded the maximum residue limits set by the Codex Alimentarius Commission. Our findings indicate that antibiotics of poor quality are accessible and used in small-holder dairy systems, which can be found in milk. These results will aid future investigations on how to promote sustainable antibiotic use practices in dairy systems. [ABSTRACT FROM AUTHOR]

Selenium nanoparticles (Se NPs) have a number of unique properties that determine the use of the resulting nanomaterials in various fields. The focus of this paper is the stabilization of Se NPs with cetyltrimethylammonium chloride (CTAC). Se NPs were obtained by chemical reduction in an aqueous medium. The influence of the concentration of precursors and synthesis conditions on the size of Se NPs and the process of micelle formation was established. Transmission electron microscopy was used to study the morphology of Se NPs. The influence of the pH of the medium and the concentration of ions in the sol on the stability of Se micelles was studied. According to the results of this study, the concentration of positively charged ions has a greater effect on the particle size in the positive Se NPs sol than in the negative Se NPs sol. The potential antibacterial and fungicidal properties of the samples were studied on Escherichia coli, Micrococcus luteus and Mucor. Concentrations of Se NPs stabilized with CTAC with potential bactericidal and fungicidal effects were discovered. Considering the revealed potential antimicrobial activity, the synthesized Se NPs-CTAC molecular complex can be further studied and applied in the development of veterinary drugs, pharmaceuticals, and cosmetics. [ABSTRACT FROM AUTHOR]

The veterinary drug nitrofurazone (5‐nitro‐2‐furaldehyde semicarbazone) exhibits excellent antimicrobial properties but its application in food‐producing animals is prohibited. The illegal use of nitrofurazone is regularly monitored by food regulatory agencies. Currently, semicarbazide (SEM) is used as a marker of nitrofurazone exposure. However, the use of SEM as a marker of nitrofurazone is under scrutiny after evidence of a high incidence of false positive tests. To overcome the current dilemma, it is necessary to identify a nitrofurazone‐specific marker analyte which requires conducting nitrofurazone metabolism studies in food‐producing animals. The use of carbon‐14 labeled nitrofurazone would facilitate metabolism studies and structural elucidation of nitrofurazone metabolites of possible utility as a marker compound. In the present work, a synthetic method is described to procure radiolabeled nitrofurazone that incorporates 14C‐ carbon at the semicarbazide moiety. The method incorporates 14C‐carbon via employing readily available and more economically affordable [14C]‐urea compared with [14C]‐semicarbazide. To the best of our knowledge, there is no report on the synthesis of 5‐nitro‐2‐furaldehyde [14C]‐semicarbazone from 14C‐urea. The developed method involves monoamination of [14C]‐urea followed by a condensation reaction with 5‐nitro‐2‐furaldehyde to produce 5‐nitro‐2‐furaldehyde [14C]‐semicarbazone in 85% yield with greater than 98% radiochemical purity. [ABSTRACT FROM AUTHOR]

Simple Summary: Chlorpheniramine hydrochloride (ROBH) is a synthetic anticoccidial drug in global aquaculture. The abuse and inappropriate use of ROBH may result in mortality in animals and drug residues in foodborne animals. Mass balance studies not only provide insights into the drug disposal process in animals, but also provide information on the metabolite composition and elimination pathways, leading to the identification of pharmacological metabolites. However, there are no related reports of mass balance studies for ROBH in fish. In addition to prodrugs, ROBH may include PCBA and PCHA as major metabolites. Therefore, this study was conducted to monitor ROBH levels and possible metabolites in Channel catfish (Ictalurus punctatus) to provide a theoretical basis for the development of maximum residue limits (MRLs) for ROBH in aquatic animals. This study aims to determine the mass balance of chlorpheniramine hydrochloride (ROBH) in the body of Channel catfish (Ictalurus punctatus). ROBH was administered orally at a dose of 20 mg/kg; following drug administration, the water samples were collected at predetermined time points (12, 24, 48, 72, 96, 120, 144, and 168 h), the experimental fish were executed after the water samples were obtained at 168 h, and the tissue samples were collected separately from the bones. The water and tissue samples were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC–MS/MS) for concentrations of ROBH and its potential major metabolites, 4-chlorohippuric acid (PCHA) and 4-chlorobenzoic acid (PCBA). The tissue samples were prepared using a modified QuEChERS procedure; the water samples were prepared using a liquid–liquid extraction (LLE) procedure. The results show that the recovery rate of ROBH in fish is very low, less than 2% of the total amount of the drug, and the recovery in water can reach 80.7% of the total amount of the drug. The content of PCBA accounted for 42.4% of the total amount of the drug; the content of ROBH accounted for 38.3% of the total amount of the drug. The content of PCHA accounted for less than 1% of the total amount of the drug. The results show that, after a single administration, ROBH is rapidly metabolized in vivo and excreted in the form of ROBH as well as metabolite PCBA. ROBH and PCBA can be used as the main targets for the metabolism detection of ROBH in Channel catfish. [ABSTRACT FROM AUTHOR]

Embryofetal toxicity studies are conducted to support inclusion of women of childbearing potential in clinical trials and to support labeling for the marketed pharmaceutical product. For biopharmaceuticals, which frequently lack activity in the rodent or rabbit, the nonhuman primate is the standard model to evaluate embryofetal toxicity. These studies have become increasingly challenging to conduct due to the small number of facilities capable of performing them and a shortage of sexually mature monkeys. The low number of animals per group and the high rate of spontaneous abortion in cynomolgus monkeys further complicate interpretation of the data. Recent FDA guidance has proposed a weight of evidence (WoE) approach to support product labeling for reproductive toxicity of products intended to be used for the treatment of cancer (Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations), an approach that has also supported the approval of biotherapeutics for non-cancer indications. Considerations to determine the appropriateness and content of a WoE approach to support product labeling for embryofetal risk include known class effects in humans; findings from genetically modified animals with or without drug administration; information from surrogate compounds; literature-based assessments about the developmental role of the pharmaceutical target; and the anticipated exposure during embryofetal development. This paper summarizes the content of a session presented at the 42nd annual meeting at the American College of Toxicology, which explored the conditions under which alternative approaches may be appropriate to support product labeling for reproductive risk, and how sponsors can best justify the use of this approach. [ABSTRACT FROM AUTHOR]

This study investigated various qualitative and quantitative indices of antimicrobial use (AMU) in companion animals (CAs) at a Veterinary Teaching Hospital (VTH-A) and its annex (VTH- B) from 2019 to 2021. For 694 documented animals, antimicrobial administrations (AADs) were 5, 278 times, of which 98.8% (5217) and 1.2% (61) were in dogs and cats respectively. At the VTH- A, oxytetracycline (1185 times, 22.5%) was mostly administered in dogs and metronidazole (26 times, 0.5%) in cats. Similarly, at VTH- B, oxytetracycline was administered 895 times (17.0%) in dogs while amoxicillin was given 7 times (0.1%) in cats. The prescription diversity (PD) was estimated at 0.73 and 0.82 in VTH-A and VTH-B respectively. The quantity of antimicrobials (AMs) used was 10.1 kg (A, 6.2 kg and B, 3.9 kg). Oxytetracycline administrations and quantity of metronidazole (P < 0.0001) were higher than other Active Ingredients (AIs). Furthermore, 16.5% of AIs were classified as Critically Important Antibiotics (CIA) with the highest priority, while enrofloxacin, ciprofloxacin, and azithromycin fell under the World Health Organisation (WHO) Watch group. The In-Depth Interview (IDI) indicated that the high frequency of oxytetracycline administrations was linked with being the first choice for blood parasite treatment by the clinicians at the hospital. The quantity of metronidazole used was perceived to be higher due to the clinicians' preference for the treatment of acute gastroenteritis, its wider dose range, and the frequency of administration (bi-daily). The study provides baseline data on AMU indices in CAs, for the development of antimicrobial stewardship (AMS) and communication training, and policy modifications to enhance antimicrobial therapy optimization in tertiary veterinary hospital care in Nigeria. [ABSTRACT FROM AUTHOR]

Analytical methods based on the mass balance approach were developed for the purity evaluation of tetracycline hydrochloride, a representative salt compound used in pure veterinary drug analysis. The purity assignment method was used to quantify individual classes of impurities via independent analytical techniques. The mass fraction of the free base or salt form contained in a high-purity organic compound with a hydrochloride salt can be determined. The chloride content by ion chromatography-conductivity detector (IC-CD) and general classes of impurities, including structurally related impurities by liquid chromatography–ultraviolet (LC-UV) detector, water by Karl Fischer (KF) coulometric titration, residual solvents by headspace sampler gas chromatography/mass spectrometry (HS-GC/MS), and non-volatiles by thermogravimetric analyzer (TGA), were considered to calculate the purity of the mass fraction. The chloride content of the salt compound can be considered the main impurity in the mass fraction of the free base in the salt compound. A purity assay using quantitative nuclear magnetic resonance (q-NMR) as a direct determination method was performed to confirm the results of the mass balance method. The assigned purities of the tetracycline free form and its salt form in mass fraction were (898.80 ± 1.60) mg/g and (972.65 ± 1.58) mg/g, respectively, which are traceable to the international system of units (SI). Thus, the procedure for evaluating the purity of the free base and salt forms in the salt compound is newly demonstrated in this study. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a vector-borne parasitic infection caused by the infective bite of female Phlebotomine sandflies. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic CL. The cytotoxic effect of Farnesol against L.major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L.major was also evaluated by flow cytometry. In the findings, promastigotes were reduced at 167μM. The mean numbers of L.major amastigotes in macrophages were significantly decreased on exposure to Farnesol at 172μM. In addition, Farnesol induced significant apoptosis dose-dependent on L.major promastigotes. In silico protein-ligand_binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of Farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potential of Farnesol alone or in combination with other conventional drugs in animal models. [ABSTRACT FROM AUTHOR]

Purpose: The differences between intestinal and systemic (hepatic and renal) P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) roles in drug disposition are difficult to define. Accordingly, we characterized Encequidar (ECD) as an intestinal P-gp and BCRP specific inhibitor to evaluate their role in drug disposition. Methods: We assessed the in vitro and in vivo inhibition potential of ECD towards human and animal P-gp and BCRP. Results: ECD is a potent inhibitor with a high degree of selectivity in inhibiting human P-gp (hP-gp) over human BCRP (hBCRP) (IC50s of 0.0058 ± 0.0006 vs. > 10 µM, respectively). In contrast, ECD is a potent inhibitor of rat and cynomolgus monkey BCRP (IC50 ranged from 0.059 to 0.18 µM). While the AUC of IV paclitaxel (PTX) was significantly increased by elacridar (ELD) (P < 0.05) but not ECD in rats (15 mg/kg; PO) (2.55- vs. 0.93-fold), that of PO PTX was significantly elevated to a similar extent between the inhibitors (39.5- vs. 33.5-fold). Similarly, the AUC of PO sulfasalazine (SFZ) was dramatically increased by ELD and ECD (16.6- vs. 3.04-fold) although that of IV SFZ was not significantly affected by ELD and ECD in rats (1.18- vs. 1.06-fold). Finally, a comparable ECD-induced increase of the AUC of PO talinolol in cynomolgus monkeys was observed compared with ELD (2.14- vs. 2.12-fold). Conclusions: ECD may allow an in-depth appraisal of the role of intestinal efflux transporter(s) in drug disposition in animals and humans through local intestinal drug interactions. [ABSTRACT FROM AUTHOR]

In this study, a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method with using a reduced graphene oxide-modified melamine sponge (r-GO@MeS) as matrix purification material was developed for the determination of 35 veterinary drug residues in black chicken meat by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). First of all, the effects of metal chelating agents (Na2EDTA), dehydrating agents (MgSO4, Na2SO4) and acetic acid (HAc) addition (0%, 0.5%, 1%, 3%, 5%) on the extraction efficiency of veterinary drugs were thoroughly studied. According to the results, most of quinolones tended to chelate with magnesium ions, resulting in low recoveries of veterinary drugs in the extraction solution, while the appropriate addition of Na2EDTA and HAc could improve the overall drug recoveries. Therefore, 2.5 mL of 0.1 mmol/L Na2EDTA aqueous solution and 10 mL of 0.5% HAc-ACN were used as extraction solvents, with 2.0 g of anhydrous Na2SO4 and 0.5 g of NaCl as dehydrating agents. Then the effects of sponge dosages (sponge volume/extract volume of 0.45, 0.60, 0.75, 0.90, 1.05 cm³/mL) and different purification modes (dynamic cycles of 1, 5, 10, static time of 1, 5, 10 min) on the purification efficiency were investigated in terms of veterinary drug recoveries. The results showed that a moderate dosage of 0.75 cm³/mL and fast ten dynamic purification cycles tended to give out more acceptable recoveries for all drugs. The method validation results showed that the recoveries of all monitored drug were obtained in the range of 66.6%-118.8% with three different spiked levels of 50, 100, 150 μg/kg. The intra- and inter-day precisions were evaluated in terms of relative standard deviations (RSDs) by repeatability tests conducted on the same day or three consecutive days, which were acquired less than 13.8% and 14.6%, respectively. In the range of 5-200 μg/kg, good linearities were acquired with the correlation coefficients (R²) no less than 0.998. Additionally, the limits of detection (LODs) and quantitation (LOQs) were obtained in the range of 0.1-6 μg/kg and 0.3-15 μg/kg, respectively. By construction of matrix-matched curves and solvent curves, the matrix effect was calculated as -19.4%-19.8%, demonstrating an insignificant matrix effect by using the developed r-GO@MeS materials. Comparatively, the developed r-GO@MeS has the same or even better matrix purification effect as the other three commercial adsorption materials, such as PSA, GCB, C18. Furthermore, the purification process was achieved within several seconds by the quick and convenient soaking-squeezing cycles, and the matrix separation need no extra measures such as high-speed centrifugation and strong magnetic field assistance. This method has the advantages of speed, convenience and low cost, and shows great potential in the field of multi-residue detection of veterinary drugs. [ABSTRACT FROM AUTHOR]

Background: In clinical studies, psychedelics including psilocybin and D-lysergic acid diethylamide (LSD) demonstrate rapid and persistent antidepressant effects. Since the effective treatment with psychedelics is usually provided with psychotherapy, it is debatable whether their prolonged efficacy can be observed in infrahuman species. Preclinical reports on psychedelics' effects most often address their acute actions, and different tests and models provide inconsistent results. The goal of this study was to examine whether the treatment with psilocybin and/or LSD would demonstrate immediate and/or sustained antidepressant-like effects in the differential reinforcement of low-rate responding (DRL) schedule in rats. In contrast to the antidepressant screening tools, the DRL 72s test is known to detect antidepressants with high predictive validity as it differentiates clinically effective antidepressants from other psychoactive drugs in non-stressed animals. Methods: Adult male Sprague Dawley rats were injected over three consecutive days with psilocybin (1 mg/kg), LSD (0.08 mg/kg), or saline and then tested in DRL 72s for the following 4 weeks. Results: Treatment with psilocybin but not LSD demonstrated an immediate antidepressant-like effect, manifested as an increased number of reinforced presses and response efficiency. By contrast, neither of the drugs showed a long-term (up to 4 weeks following administration) antidepressant-like effect. Conclusions: Using DRL 72s schedule of reinforcement, we demonstrated the acute antidepressant-like effect of psilocybin but not of LSD, and failed to detect their persistent antidepressant-like efficacy. The present study suggests that the detection of long-lasting antidepressant-like activity in rats could be challenging and may require entirely novel behavioral methods. [ABSTRACT FROM AUTHOR]

Microbial colonization in veterinary stents poses a significant and concerning issue in veterinary medicine. Over time, these pathogens, particularly bacteria, can colonize the stent surfaces, leading to various complications. Two weeks following the stent insertion procedure, the colonization becomes observable, with the aggressiveness of bacterial growth directly correlating with the duration of stent placement. Such microbial colonization can result in infections and inflammations, compromising the stent's efficacy and, subsequently, the animal patient's overall well-being. Managing and mitigating the impact of these pathogens on veterinary stents is a crucial challenge that veterinarians and researchers are actively addressing to ensure the successful treatment and recovery of their animal patients. In addition, irritation of the tissue in the form of an inserted stent can lead to overgrowth of granulation tissue, leading to the closure of the stent lumen, as is most often the case in the trachea. Such serious complications after stent placement require improvements in the procedures used to date. In this review, antibacterial or antibiofilm strategies for several stents used in veterinary medicine have been discussed based on the current literature and the perspectives have been drawn. Various coating strategies such as coating with hydrogel, antibiotic, or other antimicrobial agents have been reviewed. [ABSTRACT FROM AUTHOR]

To evaluate the accuracy with which veterinary anaesthetists and nurses of different experience draw up small volumes of liquid. Prospective blinded randomized study. A group of seven European College of Veterinary Anaesthesia and Analgesia (ECVAA) diplomates, six ECVAA residents and six anaesthesia nurses participated in the study. For each participant, five target volumes between 0.01 and 1.0 mL were randomly allocated. They were drawn up 20 times in random order using a 1 mL syringe attached to a 23 gauge needle. A total of 1900 measurements were analysed. An investigator filled the syringe and needle dead space with water for injection before each experiment. The change in mass of the syringe once filled to the target volume was used to calculate the actual volume of liquid drawn up. Large errors were made with measurements < 0.04 mL, so they were excluded from the statistical analysis. There was a significant effect of the target volume (p < 0.001) and of the order (p < 0.01). For each mL increase in the target volume, the absolute error decreased by 4% and from the first to the hundredth withdrawal each participant's absolute error decreased by 1%. The target volume was underestimated in 52.3% of measurements, 42% were overestimated and 5.7% were on target. None of the between-subject predictor variables approached significance. Accuracy of veterinary anaesthetists and nurses in drawing up medications decreases as the target volume becomes smaller. Small veterinary patients receive small volumes of anaesthetic drugs with higher risks of overdosing compared with larger dogs. Years of experience and staff grade are not associated with greater accuracy. Large percentage errors may be seen with target volumes less than 0.04 mL. Dilutions are recommended for volumes > 0.19 mL in 1 mL syringe. [ABSTRACT FROM AUTHOR]

The ATP‐binding cassette transporter P‐glycoprotein (P‐gp) limits the oral bioavailability of many drugs. Although P‐gp has been well studied in humans and mice, little is known about the substrate specificities of many of its species orthologs. To address this, we performed in vitro analysis of P‐gp transporter function using HEK293 cells stably expressing human, ovine, porcine, canine, and feline P‐gp. We also employed a human physiologically based pharmacokinetic (PBPK) model to assess variations in digoxin exposure resulting from altered P‐gp function. Compared to human P‐gp, sheep P‐gp had significantly less digoxin efflux (2.3‐fold ±0.04 vs. 1.8‐fold ±0.03, p <.0001) and all species orthologs had significantly less quinidine efflux compared with human P‐gp (p <.05). Human P‐gp also had significantly greater efflux of talinolol compared to sheep and dog P‐gp (1.9‐fold ±0.04 vs. 1.6‐fold ±0.06, p =.003 and 1.6‐fold ±0.05, p =.0002, respectively). P‐gp expression protected all lines against paclitaxel‐induced toxicity, with sheep P‐gp being significantly less protective. The inhibitor verapamil demonstrated dose‐dependent inhibition of all P‐gp orthologs. Finally, a PBPK model showed digoxin exposure was sensitive to altered P‐gp activity. Overall, our study found that species differences in this major drug transporter exist and that the appropriate species ortholog of P‐gp should be evaluated during veterinary drug development. [ABSTRACT FROM AUTHOR]

This study investigated various qualitative and quantitative indices of antimicrobial use (AMU) in companion animals (CAs) at a Veterinary Teaching Hospital (VTH-A) and its annex (VTH- B) from 2019 to 2021. For 694 documented animals, antimicrobial administrations (AADs) were 5, 278 times, of which 98.8% (5217) and 1.2% (61) were in dogs and cats respectively. At the VTH- A, oxytetracycline (1185 times, 22.5%) was mostly administered in dogs and metronidazole (26 times, 0.5%) in cats. Similarly, at VTH- B, oxytetracycline was administered 895 times (17.0%) in dogs while amoxicillin was given 7 times (0.1%) in cats. The prescription diversity (PD) was estimated at 0.73 and 0.82 in VTH-A and VTH-B respectively. The quantity of antimicrobials (AMs) used was 10.1 kg (A, 6.2 kg and B, 3.9 kg). Oxytetracycline administrations and quantity of metronidazole (P < 0.0001) were higher than other Active Ingredients (AIs). Furthermore, 16.5% of AIs were classified as Critically Important Antibiotics (CIA) with the highest priority, while enrofloxacin, ciprofloxacin, and azithromycin fell under the World Health Organisation (WHO) Watch group. The In-Depth Interview (IDI) indicated that the high frequency of oxytetracycline administrations was linked with being the first choice for blood parasite treatment by the clinicians at the hospital. The quantity of metronidazole used was perceived to be higher due to the clinicians' preference for the treatment of acute gastroenteritis, its wider dose range, and the frequency of administration (bi-daily). The study provides baseline data on AMU indices in CAs, for the development of antimicrobial stewardship (AMS) and communication training, and policy modifications to enhance antimicrobial therapy optimization in tertiary veterinary hospital care in Nigeria. [ABSTRACT FROM AUTHOR]

Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis of antibiotics and pesticides in aquatic environments. To address this knowledge gap, a concise and sensitive analytical method is proposed in which three classes of human and veterinary drugs (sulfonamides, macrolides, and hormones) and two classes of pesticides (organophosphorus and neonicotinoids) are simultaneously extracted and determined in surface water. The solid-phase extraction column with Cleanert PEP-2 was preconditioned sequentially with 6 mL of methanol, ultrapure water, and citric acid buffer (pH 3.0) each for simultaneous extraction and further purification. The forty-seven target analytes were analysed by LC-MS/MS in positive and negative ion modes. The LC separation was performed using a Sigma-Aldrich C18 column with 0.1% formic acid in water and acetonitrile as a gradient eluting mobile phase in positive ion mode. The internal standard method was used to overcome the inevitable matrix effects in LC-MS/MS analysis. The matrix effects of most target analytes were in the range of 27–151%. The recoveries of forty analytes in the three concentrations (10, 50, and 100 ng L−1) of surface water spiked samples ranged from 41 to 127%. The method quantitative limits of the analytes were in the range of 0.40–5.49 ng L−1. Application of the method to analyze samples in the eight runoff outlets of the Pearl River Delta showed that some antibiotics and pesticides were detected, and the concentration of parathion was as high as 154 ng L−1. A powerful tool for quickly and efficiently screening for contaminants in surface water has been presented. [ABSTRACT FROM AUTHOR]

The research progress in matrix purification combined with liquid chromatography-mass spectrometry (LC-MS) method as well as their applications in determination of veterinary drugs in animal-derived foods was reviewed. Among various matrix purification methods, liquid liquid extraction (LLE), dispersed liquid liquid microextraction (DLLME), solid phase extraction (SPE), solid phase microextraction (SPME), dispersed solid phase extraction (DSPE), and magnetic solid phase extraction (MSPE) are mostly widely used in different animal derived foods such as meat, eggs, milk, and their products. However, there are still some limitations, such as weak matrix selectivity of LLE, limited applicability of DLLME, moderate purification efficiency DPSE, poor reproducibility of SPME, and time-consuming operation of SPE. In the future, the detection technology of veterinary drugs in various animal-derived foods could be further studied in terms of establishing simultaneous purification methods for various kinds of veterinary drugs, developing novel and efficient matrix-based purification materials, and enhancing convenience and automation in matrix purification process to meet the urgent needs in screening of multi-residues of veterinary drugs in animal-derived foods. [ABSTRACT FROM AUTHOR]