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We describe the case of a 27‐year‐old male, previously healthy though with a social history notable for recreational cocaine use, who developed bone marrow failure due to aplastic anemia (AA) with associated serous fat atrophy (SFA). After the SFA was corrected with nutritional supplementation, the patient underwent successful allogeneic, haploidentical stem cell transplantation with a regimen designed to treat AA. To our knowledge, this is the first case of hematopoietic stem cell transplantation (HSCT) performed following correction of SFA. Herein we propose our novel hypothesis that SFA, once resolved, is not a contraindication to stem cell transplantation, which we believe adds valuable insight toward an improved understanding of nutrition's role in HSCT. Additionally, the AA is thought to be toxin‐induced and specifically levamisole‐mediated after exposure to levamisole‐adulterated cocaine. We highlight potential connections between levamisole, AA, and SFA and call for further efforts to understand these relationships—especially as the use of levamisole as a cocaine adulterant continues to rise across the globe. [ABSTRACT FROM AUTHOR]

Background: The increasing diversity of psychoactive substances on the unregulated drug market poses significant health, psychological, and social risks to people who use drugs (PWUD). To address these risks, various harm reduction (HR) policies have been implemented, including drug checking services (DCS). Many analytical methods are used for DCS. While qualitative methods (e.g., thin layer chromatography, spectroscopy) are easier to implement, they are not as accurate as quantitative methods (e.g., LC-UV, LC-MS). Some HR programmes have implemented high-performance liquid chromatography coupled with UV detection (LC-UV). This article presents the cross-validation of this quantitative method with a reference liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) method. Methods: Drug samples were provided by PWUD to a DCS called DrugLab in Marseille, France. The samples were weighed and prepared through dissolution in methanol, followed by ultrasonic bathing. Samples were analysed onsite using LC-UV analysis. They were then subsequently analysed with the reference LC-HRMS method. The LC-UV instrument in DrugLab was calibrated after being purchased; analysis of standard solutions was routinely performed once a month and after maintenance operations. For the LC-HRMS instrument, calibration and quality control procedures followed European Medicines Agency (EMA) guidelines. Statistical analyses were conducted including Spearman correlation tests using IBM® SPSS® Statistics version 20. Results: A total of 102 samples representing different product classes and cutting agents were cross-validated. Differences between both analyses methods for each molecule analysed were ≤ 20%, with significant correlations between both methods' results for most substances. Notably, LC-HRMS provided lower concentration values for cocaine and acetaminophen, whereas it provided higher values for other substances. Correlations were significant for cocaine, ketamine, MDMA, heroin, amphetamine, caffeine, acetaminophen, and levamisole. Conclusions: This study demonstrates that the results provided by DrugLab were accurate and reliable, making LC-UV an adaptable, stable, and suitable analytical method for simple matrices like drugs in a DCS context. However, this cross validation does not guarantee accuracy over time. A proficiency test project in HR laboratories across France is currently under development in order to address potential drifts in LC-UV accuracy. [ABSTRACT FROM AUTHOR]

Background: The increasing diversity of psychoactive substances on the unregulated drug market poses significant health, psychological, and social risks to people who use drugs (PWUD). To address these risks, various harm reduction (HR) policies have been implemented, including drug checking services (DCS). Many analytical methods are used for DCS. While qualitative methods (e.g., thin layer chromatography, spectroscopy) are easier to implement, they are not as accurate as quantitative methods (e.g., LC-UV, LC-MS). Some HR programmes have implemented high-performance liquid chromatography coupled with UV detection (LC-UV). This article presents the cross-validation of this quantitative method with a reference liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) method. Methods: Drug samples were provided by PWUD to a DCS called DrugLab in Marseille, France. The samples were weighed and prepared through dissolution in methanol, followed by ultrasonic bathing. Samples were analysed onsite using LC-UV analysis. They were then subsequently analysed with the reference LC-HRMS method. The LC-UV instrument in DrugLab was calibrated after being purchased; analysis of standard solutions was routinely performed once a month and after maintenance operations. For the LC-HRMS instrument, calibration and quality control procedures followed European Medicines Agency (EMA) guidelines. Statistical analyses were conducted including Spearman correlation tests using IBM® SPSS® Statistics version 20. Results: A total of 102 samples representing different product classes and cutting agents were cross-validated. Differences between both analyses methods for each molecule analysed were ≤ 20%, with significant correlations between both methods' results for most substances. Notably, LC-HRMS provided lower concentration values for cocaine and acetaminophen, whereas it provided higher values for other substances. Correlations were significant for cocaine, ketamine, MDMA, heroin, amphetamine, caffeine, acetaminophen, and levamisole. Conclusions: This study demonstrates that the results provided by DrugLab were accurate and reliable, making LC-UV an adaptable, stable, and suitable analytical method for simple matrices like drugs in a DCS context. However, this cross validation does not guarantee accuracy over time. A proficiency test project in HR laboratories across France is currently under development in order to address potential drifts in LC-UV accuracy. [ABSTRACT FROM AUTHOR]

Introduction: Nephrotic syndrome (NS) is a common childhood glomerular disease. The most common presentation in paediatric population is the idiopathic syndrome (INS). Treatment with levamisole is effective in frequent re- lapsing and corticosteroid-dependent NS. Studies have reported mild and rarely severe side effects, which subside after treatment withdrawal. Results: We describe two clinical cases of frequently relapsing INS treated with levamisole that presented with cutaneous vasculitis with positive anti-neutrophil cytoplasmic antibodies. Both cases had skin lesions that disappeared after withdrawal of the drug, avoiding the use of other treatments with corticosteroids, immunomodulators and even amputations due to skin necrosis. Conclusions: It is important to know the possible complications of levamisole treatment in paediatric patients with INS to proceed with drug withdrawal for resolution. [ABSTRACT FROM AUTHOR]

Background: Levamisole is less expensive and has a better toxicity profile compared to other steroid sparing agents used in nephrotic syndrome. It has a plasma half-life of 2.0 to 5.6 hours, but is conventionally administered on alternate days. We aimed to assess whether daily levamisole is safe and more effective than standard alternate-day therapy in maintaining remission in children with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). Methods: An open-label randomized controlled trial was conducted in children with FR/SDNS. Group A received daily while Group B received alternate-day levamisole (2–3 mg/kg/dose) for 12 months. Prednisolone was tapered off by 3 months. Patients were monitored for relapses, further steroid requirement, and adverse effects. Results: A total of 190 children with FR/SDNS (94 in Group A and 96 in Group B) were analyzed. Sustained remission for 12 months was observed in 36% of Group A and 27% of Group B patients (p = 0.18). Numbers completing 12 months in the study were 67% in Group A and 56% in Group B (p = 0.13). Time to first relapse, persistent FR/SDNS, and withdrawal due to poor compliance were statistically similar in both groups, while relapse rate and cumulative steroid dosage were significantly lower in Group A compared to Group B (p = 0.03 and p = 0.02, respectively). The incidence of adverse effects was comparable in both groups, with reversible leucopenia and hepatic transaminitis being the commonest. Conclusions: Daily levamisole therapy was not superior to alternate-day therapy in maintaining sustained remission over 12 months. Nevertheless, relapse rate and cumulative steroid dosage were significantly lower without increased adverse effects. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

A new Co(II) complex, [Co(NCS)2(L)2] (1) has been synthesized based on levamisole (L) as a new ligand. Single‐crystal X‐ray diffraction analyses confirm that the Co(II) ion is having a distorted tetrahedral coordination geometry in the complex. Notably strong intramolecular S⋅⋅⋅S and S⋅⋅⋅N interactions has been confirmed by employing Quantum Theory of Atoms in Molecules (QTAIM). These intramolecular interactions occur among the sulfur and nitrogen atoms of the levamisole ligands and also the nitrogen atoms of the thiocyanate. Direct current (dc) magnetic analyses reveal presence of zero field splitting (ZFS) and large magnetic anisotropy on Co(II). Detailed ab initio ligand field theory calculations quantitatively predicted the magnitude of ZFS. Prominent field‐induced single‐ion magnet (SIM) behavior was observed for 1 from dynamic magnetization measurements. Slow magnetic relaxation follows an Orbach mechanism with the effective energy barrier Ueff=29.6 (7) K and relaxation time τo=1.4 (4)×10−9 s. [ABSTRACT FROM AUTHOR]

Drug-induced or associated vasculitis is a prevalent form of vasculitis that resembles primary idiopathic antineutrophil cytoplasmic autoantibody (ANCA) vasculitis (AAV). Cocaine is a diffuse psychostimulant drug and levamisole is a synthetic compound used to cut cocaine. Their abuse may result in a spectrum of autoimmune manifestations which could be categorized into three overlapping clinical pictures: cocaine-induced midline destructive lesion (CIMDL), levamisole-adulterated cocaine (LAC) vasculopathy/vasculitis, and cocaine-induced vasculitis (CIV). The mechanisms by which cocaine use leads to disorders resembling AAV are not well understood. Cocaine can cause autoimmune manifestations ranging from localized nasal lesions to systemic diseases, with neutrophils playing a key role through NETosis and ANCA development, which exacerbates immune responses and tissue damage. Diagnosing and treating these conditions becomes challenging when cocaine and levamisole abuse is not suspected, due to the differences and overlaps in clinical, diagnostic, therapeutic, and prognostic aspects compared to primary idiopathic vasculitides. [ABSTRACT FROM AUTHOR]

Levamisole is an anti-helminthic drug developed and introduced in veterinary medicine, and it has been used more frequently after the inclusion of its usage in human medicine regarding disorders with immunomodulatory properties. In recent years, it has started to attract attention since it has beneficial effects on the treatment of COVID-19 due to its immunomodulatory properties. To investigate the effects of levamisole on sexual behavior and the reproductive system in male rats, two groups were formed the vehicle (n = 10) and levamisole (n = 10) groups. The vehicle group was given purified water whereas the levamisole group was administered with levamisole (2 mg/kg) by oral gavage daily for 4 weeks. Levamisole treatment significantly increased the mount latency (ML, P < 0.001) as well as the intromission latency (IL, P < 0.01). It also significantly prolonged postejaculatory interval (PEI, P < 0.01), decreased copulatory rate (CR, P < 0.05), and sexual activity index (SAI, P < 0.05). It significantly decreased serum monoamine oxidase A (MAO-A) levels (P < 0.05). Additionally, levamisole induced disorganizations of germinal epithelial cells of seminiferous tubules, congestion, edema in the interstitial area, and metaphase arrest in some spermatocytes (P < 0.001), and it significantly increased the immunohistochemical expressions of apoptotic Bax and cytochrome c, which is crucial proapoptotic protein, in the testis (P < 0.001). Also, levamisole significantly upregulated the mRNA levels of the apoptosis-related key regulatory genes, including Bax (Bcl-2-associated X protein, P = 0.05) and Bax/Bcl-2 ratio (P < 0.01) in testis. The current research is the first to show that levamisole may decrease sexual performance, potency, sexual motivation, and libido and induce apoptosis in the testis. [ABSTRACT FROM AUTHOR]

Jun-Xiang Wang,1,&ast; Jia-Hui Zhang,1,&ast; Mu Guo,1,&ast; Wei-Rui Huang,1 Han-Lu Zheng,1 Yi-Qi Liao,1 Ying-Xue Yan,1 Zhao-Long Lin,1 Neng-Fu Qiu,1 Cui-Ting Dai,2 Xiang-Bin Yu,1 Yue Yu1 1School of Pharmacy & Fujian Center for New Drug Safety Evaluation, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Department of Pathology, The People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Yu; Xiang-Bin Yu, Email yyu@fjmu.edu.cn; yxb4666@fjmu.edu.cnIntroduction: Given the limitations and adverse effects of current rheumatoid arthritis (RA) treatments, there is an urgent need for safer and more effective therapeutic options. Levamisole (LVM) is a non-specific immunomodulator with potential for treating skin diseases, tumors, and autoimmune disorders. Recognizing LVM’s potential despite its controversial reputation, this study aimed to investigate its safety profile and therapeutic efficacy towards RA.Methods: To evaluate the potential toxicity of LVM, a 28-day oral administration was conducted in SD rats, assessing general toxicity and neurotoxicity using serum biochemical indicators, the Morris water maze test, transmission electron microscopy, and H&E staining. Subsequently, the therapeutic effects of LVM on RA were evaluated.Results: The results showed that 30 mg/kg LVM has promising therapeutic effects in the treatment of RA with negligible toxicity from 45 mg/kg to 180 mg/kg.Discussions: This study provides valuable preclinical data on the safety and efficacy of LVM, laying the groundwork for future clinical applications and potentially offering a safer and more effective treatment option for RA patients.Keywords: levamisole, general toxicity, neurotoxicity, rheumatoid arthritis

Abstract Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3–CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases.

Animal parasitic diseases cause major losses to the livestock industry and require constant monitoring and control. The purpose of this study was to monitor the livestock (calves, goats, sheep, pigs, dogs, chickens) for the presence of helminthic pathogens, to determine the therapeutic efficacy of levamisole-based preparations and the general toxicity of meat of experimental animals using the Colpoda steinii test culture. In 2020-2022, a considerable spread of invasive animal diseases was detected in the Kharkiv region of Ukraine. In a study of 3,500 calves, 1,000 (28.6%) were found to be persistently infected with nematodes with an intensity of 25.0-150.0 worm eggs per 1 g of faeces. In goats, the intensity of endoparasite infection ranged within 10.0-15.0 worm eggs per 1 g of faeces, while in sheep this figure reached 25.0 worm eggs per 1 g of faeces. In the study of faeces from pigs, 800 (34.8%) samples revealed the presence of helminth eggs, while mono-infestation was detected in 300 samples (37.5%). In the study of canine faeces, 10 (66.7%) positive samples were found. When examining the manure from chickens, 200 (44.4%) positive samples revealed the presence of helminth eggs. The use of levamisole dosage forms can reduce the extent of infection in animals by 50% as early as on Day 5. No worm eggs were detected in the faeces of animals from Day 14 to Day 30 of observation, and therefore the extensional efficacy of the studied products under modern conditions is 100%. Meat obtained from farm animals (pigs, calves, sheep) treated with levamisole-based preparations shows signs of general toxicity within 5...9 days after the use of the products: 5 days for pigs and 9 days for calves and sheep. At the same time, meat obtained from poultry (chickens) treated with levamisole-based preparations shows signs of general toxicity within 2 days after the end of the treatment course

Simple Summary: Parasitic infections, especially those caused by a particular group of roundworms called gastrointestinal nematodes, are one of the most important diseases of goats worldwide. The widespread and uncontrolled use of deworming drugs (anthelmintics) makes nematodes increasingly resistant, and this phenomenon is called anthelmintic resistance. Romania has one of the highest goat populations in Europe, but little is known about how widespread and resistant gastrointestinal parasites are in this country. That is why we decided to carry out this survey—to find out how Romanian farmers fight parasites in their goats and what their opinion is on the presence of parasites and the effectiveness of deworming drugs in their herds. Our findings are disappointing. Most farmers deworm goats when they think it is necessary, not when laboratory tests show that they really need it. Moreover, they use deworming drugs too often and at too low doses. Such practices are very likely to stimulate parasites to develop anthelmintic resistance, and only intensive education programs for farmers and veterinarians can stop this process. The widespread and uncontrolled use of anthelmintic products has contributed to the emergence of anthelmintic resistance (AR). This phenomenon globally threatens the productivity and welfare of small ruminants. A questionnaire consisting of 34 questions was handed to 234 goat farmers across Romania to gain insight into control practices against internal parasites and the farmers' perception of the parasitic infections present in their herds and the efficacy of anthelmintic treatments. The majority of farmers (88.5%) admitted they had never submitted fecal samples for parasitological laboratory analysis, and 77.4% had treated the animals on their own. In general, the farmers dewormed their goats based on visual body weight estimation. Prophylactic anthelmintic treatment was practiced by more than 85% of the farmers. A traditional control approach based on treating the entire herd at fixed time intervals is widespread among Romanian goat and sheep farmers. The most commonly used anthelmintic drugs in the previous 3 years (2021–2023) were benzimidazoles (85.5%) and macrocyclic lactones (81.6%). Poor anthelmintic efficacy was suspected by 14.5% of farmers, and the minority (18.0%) considered internal parasites as a problem in their herds. Regarding the farmers' perception of the presence of parasites, there was a significant level of uncertainty. This is the first survey carried out in Romanian goat herds, and it provides up-to-date information on practices aimed at controlling internal parasites. [ABSTRACT FROM AUTHOR]

Background: Levamisole is a commonly used steroid-sparing agent (SSA), but the reported incidence of antineutrophil cytoplasmic antibody (ANCA) positivity has been concerning. Methods: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA. Results: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6–9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15–30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months. Conclusions: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication. [ABSTRACT FROM AUTHOR]

Levamisole is an anthelmintic drug restricted to veterinary use but is currently detected as the most widely used cocaine cutting agent in European countries. Levamisole-adulterated cocaine has been linked to acute kidney injury, marked by a decrease in glomerular filtration rate, which involves reduced renal blood flow, but data on the alteration of renovascular response produced by levamisole are scarce. Renal arteries were isolated from healthy rabbits and used for isometric tension recording in organ baths and protein analysis. We provide evidence that depending on its concentration, levamisole modulates renovascular tone by acting as a non-selective α-adrenergic receptor blocker and down-regulates α1-adrenoceptor expression. Furthermore, levamisole impairs the endothelium-dependent relaxation induced by acetylcholine without modifying endothelial nitric oxide synthase (eNOS) expression. However, exposure to superoxide dismutase (SOD) partially prevents the impairment of ACh-induced relaxation by levamisole. This response is consistent with a down-regulation of SOD1 and an up-regulation of NADPH oxidase 4 (Nox4), suggesting that endothelial NO loss is due to increased local oxidative stress. Our findings demonstrate that levamisole can interfere with renal blood flow and the coordinated response to a vasodilator stimulus, which could worsen the deleterious consequences of cocaine use. EFS electric field stimulation, NA noradrenaline, AR adrenergic receptor, IP3 inositol 1, 4, 5-trisphosphate, cAMP cyclic adenosine monophosphate, mAChR muscarinic acetylcholine receptor, eNOS endothelial nitric oxide synthase, sGC soluble guanylyl cyclase, SOD superoxide dismutase, NOX4 NAPH oxidase 4 [ABSTRACT FROM AUTHOR]

Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3–CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases. [ABSTRACT FROM AUTHOR]

In current study, anti-parasitic properties of Nicotiana tabacum leaves (N. tabacum L.) and their traditional use in ethno-veterinary therapy were investigated using both in-vitro and in-vivo approaches. Crude aqueous extracts (CAE) of N. tabacum L. were used to evaluate in-vitro antiparasitic effect of Haemonchus (H.) placei that had been directly retrieved from the abomasum of cows. The nematodes' death or paralysis within three hours subsequent to being exposed to different quantities 25, 50 and 100 mg/ml of CAE proved to be statistically significant (P<0.05) indicator. Cattle infected with gastrointestinal nematodes, specifically H. placei, were orally administered with crude aqueous extracts (CAE) and crude methanolic extracts (CME) at gradually higher dosage of 1.0 and 3.0 gm/kg, respectively to evaluate in-vivo anthelmintic efficiency. When administered with 3.0 gm/kg of the body weight, CME showed an ideal decrease of 75.8 and 79.03% parasitic infection but CAE showed 48.88 and 51.11% reduction after 5 and 10 days of treatment, respectively (P<0.05). The overall reduction in eggs per gram was 98.68% in positive controls treated with levamisole HCl. Being an initial investigation of its kind in Pakistan, the outcomes suggested that N. tabacum L. have potential to be used as anti-parasitic agent in ethno-veterinary medication. [ABSTRACT FROM AUTHOR]

Objective: In this multicentric study involving three London hospitals, we compared ANCA‐positive and ANCA‐negative cocaine‐induced midline destructive lesions (CIMDL) patients to assess how presence of antineutrophil cytoplasmic antibodies (ANCA) may correlate with disease severity. Our secondary aims are to better classify etiology centered around ANCA positivity and, consequently, better disease management. Methods: A retrospective review was performed to identify patients with CIMDL seen between January 2019 and December 2022. Population data including age, sex, presentation, endoscopic findings, duration of cocaine use and active use of cocaine, type of treatment, laboratory (including ANCA serology), radiological, and histological findings were collected. Results: Forty CIMDL patients (25 male, median age of 42 years) were identified. The majority of them (72.5%) presented with either a septal perforation, a saddle nose deformity (22.5%), and/or a palatal fistula (20.0%). ANCA was positive in 71.1% of cases (66.7% p‐ANCA). No statistically significant differences in the general characteristics, type of treatment, laboratory results, radiological or histological findings were observed when comparing ANCA‐positive and ANCA‐negative CIMDL patients or when comparing p‐ANCA and c‐ANCA patients. Similarly, no statistically significant difference was obtained when comparing the pattern of distribution of lesions between the two groups. Conclusions: A large percentage of CIMDL patients showed positive ANCA test (71.1%) and in the majority of the cases a p‐ANCA pattern specifically targeting PR3 (p‐ANCA, PR3 + MPO‐). However, ANCA positivity or presence of a specific ANCA pattern was not associated with more severe presentation or more aggressive disease. Given its similarities to granulomatosis with polyangiitis (GPA), we recommend the use of the term "cocaine‐induced ENT pseudo‐GPA" instead of CIMDL. Level of Evidence: IV Laryngoscope, 134:2609–2616, 2024 [ABSTRACT FROM AUTHOR]

Animal parasitic diseases cause major losses to the livestock industry and require constant monitoring and control. The purpose of this study was to monitor the livestock (calves, goats, sheep, pigs, dogs, chickens) for the presence of helminthic pathogens, to determine the therapeutic efficacy of levamisole-based preparations and the general toxicity of meat of experimental animals using the Colpoda steinii test culture. In 2020-2022, a considerable spread of invasive animal diseases was detected in the Kharkiv region of Ukraine. In a study of 3,500 calves, 1,000 (28.6%) were found to be persistently infected with nematodes with an intensity of 25.0-150.0 worm eggs per 1 g of faeces. In goats, the intensity of endoparasite infection ranged within 10.0-15.0 worm eggs per 1 g of faeces, while in sheep this figure reached 25.0 worm eggs per 1 g of faeces. In the study of faeces from pigs, 800 (34.8%) samples revealed the presence of helminth eggs, while mono-infestation was detected in 300 samples (37.5%). In the study of canine faeces, 10 (66.7%) positive samples were found. When examining the manure from chickens, 200 (44.4%) positive samples revealed the presence of helminth eggs. The use of levamisole dosage forms can reduce the extent of infection in animals by 50% as early as on Day 5. No worm eggs were detected in the faeces of animals from Day 14 to Day 30 of observation, and therefore the extensional efficacy of the studied products under modern conditions is 100%. Meat obtained from farm animals (pigs, calves, sheep) treated with levamisole-based preparations shows signs of general toxicity within 5-9 days after the use of the products: 5 days for pigs and 9 days for calves and sheep. At the same time, meat obtained from poultry (chickens) treated with levamisole-based preparations shows signs of general toxicity within 2 days after the end of the treatment course. [ABSTRACT FROM AUTHOR]

For endoparasitic infestations of dogs, drugs based on levamisole hydrochloride are used. That is why the purpose of the work was to conduct a field study to evaluate the effectiveness of the studied drug “Levamizole O.L.KAR 10 %” and the reference drug “Levamizole-plus 10 %” against endoparasitic infestations of dogs of different breeds, ages, and sexes. According to the results of a parasitological examination of the dogs of the experimental and control groups, endoparasites established spontaneous damage, the causative agents of nematodes of the alimentary canal: species Toxocara canis with an intensity of invasion (II) from 110 to 180 eggs in one gram of feces (EGF) with an average intensity of invasion of 149.0 ± 5.62 EGF, species Toxascaris leonina with an intensity of invasion from 75 to 131 EGF with an average intensity of invasion of 104.4 ± 4.85 EGF and the species Ancylostoma caninum with an intensity of invasion from 48 to 92 EGF with an average intensity of invasion of 69.9 ± 3.71 EGF. Clinically, nematodes of the alimentary canal in dogs were manifested by poor appetite, depressed state, pallor of mucous membranes, mild diarrhea, vomiting, and weight loss observed in some animals. Based on the obtained results, it was established that the studied drug “Levamizol O.L.KAR 10 %” and the reference drug “Levamizol-plus 10 %” when deworming dogs have a pronounced nematodocidal effect against endoparasites of the alimentary canal, which are caused by the following species: Toxocara canis, Toxascaris leonine, Ancylostoma caninum. Thus, the effectiveness of the studied drug “Levamizol O.L.KAR 10 %” for spontaneous toxocariasis infestation in dogs on the seventh day after deworming was 93 %. The reference drug “Levamizol-plus 10 %” was 91 %, and on the 14th day after deworming the animals, the effectiveness of the drugs was 100 %. For spontaneous toxascarosis infestation in dogs, the efficacy of the studied drug “Levamizol O.L.KAR 10 %” on the seventh day after deworming was 95 %. The reference drug “Levamizol-plus 10 %” was 94.4%, and on the 14th day after deworming the animals, the effectiveness of the drugs was 100 %. Helminthological studies have established that for spontaneous hookworm infestation in dogs on the 7th and 14th day after deworming with the study drug and the comparison drug in the recommended doses, the effectiveness of veterinary drugs was 100 %. Field tests showed that the studied drug “Levamizol O.L.KAR 10 %” and the reference drug “Levamizol-plus 10 %” when administered once orally in the recommended doses of the manufacturer, are well tolerated by animals regardless of breed, age, sex, and body weight, not have a toxic effect on the body of animals and are effective against nematodes of the alimentary canal in dogs.

A novel group of biocidal compounds are the Crystal 3D (Cry) and Cytolytic (Cyt) proteins produced by Bacillus thuringiensis (Bt). Some Bt Cry proteins have a selective nematocidal activity, with Cry5B being the most studied. Cry5B kills nematode parasites by binding selectively to membrane glycosphingolipids, then forming pores in the cell membranes of the intestine leading to damage. Cry5B selectively targets multiple species of nematodes from different clades and has no effect against mammalian hosts. Levamisole is a cholinergic anthelmintic that acts by selectively opening L-subtype nicotinic acetylcholine receptor ion-channels (L-AChRs) that have been found on muscles of nematodes. A synergistic nematocidal interaction between levamisole and Cry5B at the whole-worm level has been described previously, but the location, mechanism and time-course of this synergism is not known. In this study we follow the timeline of the effects of levamisole and Cry5B on the Ca2+ levels in enterocyte cells in the intestine of Ascaris suum using fluorescence imaging. The peak Ca2+ responses to levamisole were observed after approximately 10 minutes while the peak responses to activated Cry5B were observed after approximately 80 minutes. When levamisole and Cry5B were applied simultaneously, we observed that the responses to Cry5B were bigger and occurred sooner than when it was applied by itself. It is proposed that the synergism is due to the cytoplasmic Ca2+ overload that is induced by the combination of levamisole opening Ca2+ permeable L-subtype nAChRs and the Ca2+ permeable Cry5B toxin pores produced in the enterocyte plasma membranes. The effect of levamisole potentiates and speeds the actions of Cry5B that gives rise to bigger Ca2+ overloads that accelerates cell-death of the enterocytes. Author summary: The neglected tropical diseases are a diverse set of infectious diseases which are common in low-income populations of Asia, Africa and the Americas. They include soil-transmitted helminth (STH) infections produced by the parasitic nematode Ascaris lumbricoides (= Ascaris suum). There are no effective vaccines, so mass drug administration (MDA) to control and prevent infection is the only practical option. With the limited number of anthelmintic drugs available for treatment, there is an increasing concern about the development of resistance. The use of combinations of anthelmintics, particularly if they are additive, is important for the delay of the onset of resistance. Here we describe synergistic interactions of levamisole and Cry5B mediated by Ca++ in A. suum intestine enterocytes. We have been able to make these new observations because of our access to A. suum parasites and development of our techniques for studying Ca++ signaling in the intestine of this nematode parasite, a site of the interaction of these two anthelmintic drugs. Our study provides new insights for development of effective STH combination therapies of anthelmintic drugs for slowing development of resistance with continued mass drug administration and understanding the nematode parasite intestine as a major target for combinations of anthelmintic drugs. [ABSTRACT FROM AUTHOR]

Introduction: Prohibited drugs in unregulated markets may be adulterated, resulting in increased risks for people who use drugs. This study investigated levels of drug adulteration and substitution of drugs purchased in Australia from cryptomarkets. Methods: Data were collected from a darknet forum called Test4Pay from 1 September 2022 to 23 August 2023. Posts were included if they reported the results of drug samples submitted by post to the Vancouver‐based Get Your Drugs Tested service, which uses Fourier‐transform infrared spectroscopy with immunoassay strip tests (fentanyl and benzodiazepines). Results: Of 103 samples, 65% contained only the advertised substance, 14% contained the advertised substance in combination with other psychoactive and/or potentially harmful substances and for 21%, the advertised substance was absent. Substances sold as MDMA, methamphetamine or heroin were consistently found to contain only the advertised substance, while substances sold as 2C‐B, alprazolam or ketamine were the most likely to be completely substituted. Only 4 samples sold as cocaine contained solely the advertised substance, with 13 containing cocaine with adulterants like lidocaine, creatine, levamisole and boric acid (n = 19). No fentanyl contamination was detected. Novel dissociatives and novel benzodiazepines were detected, as well as a nitazene compound. Discussion and Conclusions: Drug markets under prohibition continue to contain numerous unexpected substances, some of which can elevate risk of harm. Cryptomarkets are not immune to this problem, despite review systems, which should, in theory, make vendors more accountable for the quality of their stock. These findings demonstrate a need for expansion of local drug checking services in Australia. [ABSTRACT FROM AUTHOR]

To determine the concentration, in comparison with the maximum residue limit (MRL), of anthelmintic marker residues in the target tissues (liver and fat) of sheep treated concurrently with two oral drenches, one containing monepantel and abamectin and the other oxfendazole and levamisole. On day 0 of the study, 12 sheep (six male and six female; 8–9-months old) were dosed according to individual body weight determined the day prior. Zolvix Plus (dual-active oral drench containing 25 g/L monepantel and 2 g/L abamectin) was administered to all animals prior to administration of Scanda (dual-active oral drench containing 80 g/L levamisole hydrochloride and 45.3 g/L oxfendazole). Six sheep (three male and three female) were slaughtered 21 and 28 days after treatment and renal fat and liver samples were collected. Using validated methods, analyses for monepantel sulfone, abamectin, levamisole and oxfendazole (expressed as total fenbendazole sulfone following conversion of the combined concentrations of oxfendazole, fenbendazole and fenbendazole sulfone) were performed on liver samples while renal fat specimens were analysed for monepantel sulfone and abamectin residues only. Detected concentrations were compared to the established MRL in sheep for each analyte determined by the Ministry for Primary Industries. All residues detected in samples of liver and fat collected 21 and 28 days after treatment were below the MRL for each analyte. All liver samples collected on day 21 had detectable monepantel sulfone (mean 232 (min 110, max 388) μg/kg) and oxfendazole (mean 98.7 (min 51.3, max 165) μg/kg) residues below the MRL (5,000 and 500 μg/kg, respectively). Monepantel sulfone (mean 644 (min 242, max 1,119) μg/kg; MRL 7,000 μg/kg) residues were detected in 6/6 renal fat samples. Levamisole residues were detected in 3/6 livers (mean 40.0 (min 14.3, max 78.3) μg/kg; MRL 100 μg/kg), and abamectin residues in 1/6 livers (0.795 μg/kg; MRL 25 μg/kg) and 2/6 fat samples, (mean 0.987 (min 0.514, max 1.46) μg/kg; MRL 50 μg/kg) 21 days after treatment. These results suggest that concurrent administration of Zolvix Plus and Scanda to sheep is unlikely to result in an extended residue profile for any of the active ingredients, with all analytes measured being under the approved New Zealand MRL 21 days after treatment. This work was not completed in line with guidance for establishing official residue profiles, nor is it sufficient to propose a new withholding period. [ABSTRACT FROM AUTHOR]

Simple Summary: One of the biggest problems with sheep and goat farming is worms. These parasites impede the development of these animals and even lead to death. Currently, the dewormers used to control these parasites do not have the desired effect because worms have developed resistance. This study aimed to evaluate the effect of nanoemulsions that combine synthetic anthelmintics with carvacryl acetate on the worm Haemonchus contortus. Assessments were performed on the hatching of worm eggs and the development of larvae. Photomicrographs of the eggs were taken to show the effect of the different treatments. The best results were obtained with the combination of carvacryl acetate and thiabendazole and carvacryl acetate and thiabendazole encapsulated in sodium alginate. The results of this study allowed the reuse of anthelmintics such as benzimidazoles whose use was discontinued due to the development of anthelmintic resistance, when combined with natural and nanoencapsulated products. The present study aimed to evaluate the effect of nanoemulsions using combined synthetic anthelmintics, thiabendazole (TBZ), levamisole (LEV), and ivermectin (IVM), with carvacryl acetate (CA) against Haemonchus contortus, and also tested the presence and absence of alginate (ALG). The anthelmintic effect of the CA/TBZ nanoemulsion was evaluated in the egg hatch test (EHT). The effects of CA/IVM and CA/LEV nanoemulsions were evaluated in the larval development test (LDT). The emulsions CA/TBZ/ALG and CA/TBZ showed a multimodal profile, with most particles on the nanometric scale. The encapsulation efficiency in CA/TBZ/ALG was 80.25%, and that in CA/LEV/ALG was 89.73%. In the EHT, CA/TBZ and CA/TBZ/ALG showed mean combination indices (CIs) of 0.55 and 0.36, respectively, demonstrating synergism in both. In LDT, CA/IVM had an average CI of 0.75, and CA/LEV and CA/LEV/ALG showed CI values of 0.4 and 0.93, respectively. It was concluded that CA/TBZ showed a synergistic interaction, and CA/TBZ/ALG showed an enhanced effect. In addition, the matrix brought stability to the product, encouraging its improvement to obtain higher efficacy. [ABSTRACT FROM AUTHOR]

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The over-use of anti-parasitic compounds as a method of control has led to insufficient effectiveness and widespread drug resistance worldwide. The aim of this study was to investigate the efficacy of albendazole and levamisole as anti-parasitic agents in a lung worm control program in goat flocks. During 2021 and 2022, a total of 110 goats (age of four months and above) were randomly selected from 11 herds in the north-western region of Iran including Saanen breed (both sexes of the same age). The results indicated that 3.60, 50.80 and 41.90% were respectively infected with Dictyocaulus filaria, Muellerius capillaris and Proto-strongylus rufescens, and generally all the lung parasites in goats of this region were resistant to albendazole and levamisole. Due to clinical importance of D. filaria in goats, the molecular analysis of two samples was also done. Sequencing results showed that the identified parasites were 100% similar to the reference sequences registered in the GenBank®. The results of this research showed low level of these anthelmintics efficacy against Dictyocaulus and Muellerius. Generally, the lung parasites in goats of this region are resistant to albendazole and levamisole. The P. rufescens showed high resistance to these drugs. Totally, it can be concluded that the level of drug resistance varies in different parts of the world; but, the frequencies of drug resistance in different parts of the world are not the same, requiring more studies. [ABSTRACT FROM AUTHOR]

The electrochemical oxidation of levamisole, a glassy carbon electrode, was investigated over the pH range 2.0–10.0. Cyclic voltammetric investigations showed a single oxidation process was recorded, with a peak potential (Ep) shown to be pH-dependent in the range 5.0–8.0; between pH 2.0 and pH 5.0, and above pH 8.0, the Ep was found to be independent of pH, indicating apparent pKa values of 5.0 and 8.0. Peak currents were found to increase with increasing pH values. This voltammetric oxidation process was found to be consistent with a two-electron, two-proton oxidation to the corresponding sulfoxide. Based on these findings, the development of a of method based on the high-performance liquid chromatography separation of levamisole, with electrochemical detection being used for its determination, was explored. The chromatographic conditions required for the separation of levamisole were first investigated and optimized using UV detection. The conditions were identified as a 150 mm × 4.6 mm, 5 µm C18 column with a mobile phase consisting of 50% methanol, and 50%, 50 mM, pH 8.0 phosphate buffer. The technique of hydrodynamic voltammetry was applied to optimize the applied potential required for the determination of levamisole, identified as +2.3 V versus a stainless-steel pseudo-reference counter-electrode. Under the optimized conditions, levamisole exhibited a linear response of 1.00–20 mg/L (R2 = 0.999), with a detection limit of 0.27 mg/L. The possibility of determining levamisole in artificial urine was shown to be possible via simple dilution in the mobile phase. Mean recoveries of 99.7%, and 94.6%, with associated coefficients of variation of 8.2% and 10.2%, respectively, were obtained for 1.25 µg/mL (n = 5) and 2.50 µg/mL (n = 5). [ABSTRACT FROM AUTHOR]

A new series of amide functionality contained isoxazole-imidazo[2,1-b]thiazole (12a-j) were synthesized and their structures were characterized by analytical techniques. Further, all of the newly developed compounds 12a-j was assessed in vitro anticancer properties against a panel of four human cancer cell lines such as human breast cancer (MCF-7), human lung cancer (A549), human colon cancer (Colo-205) & human ovarian cancer (A2780) by using of MTT method. According to the results most of the compounds displayed good to moderate anticancer activity when compare with etoposide, which is used as positive control. Five compounds 12a, 12b, 12c, 12d and 12e showed most promising activities. Particularly, compound 12a displayed good activity on four cell lines.

Levamisole has been used as an effective immunomodulator. Levamisole has been used for nephrotic syndrome due to its immunostimulant, immunomodulating, and steroid-sparing effects. Common adverse effects of levamisole are gastrointestinal symptoms (nausea, abdominal cramps), and pyrexia. However, agranulocytosis or pancytopenia is also a rare but life-threatening complication of levamisole. This is a case report of a 5-year-old girl who had steroid-dependent nephrotic syndrome for which she was started on levamisole as per her weight, following which she had falling total leukocyte count levels on every visit. Thus, this case report emphasizes identifying this rare side effect and its management.

The aim of this study is to by converting albendazole and levamisole, which are antiparasitic drugs used in both humans and animals, into liposomal formulations under laboratory conditions. To ascertain the circumstance in practice, characterization studies were additionally conducted. The study was performed by modifying the hydration of the thin lipid film. Experiments were carried out with egg phosphatidylcholine, cholesterol, chloroform and methanol in different amounts. Albendazole and levamisole formulations were made with the substances used in liposomes. Zeta potential, polydispersity index, encapsulation efficiency, particle size measurements and scanning electron microscopy were performed as part of characterization studies. The results show that Lipo LVM has the smallest particle size value at 380.87 ± 19.52 nm, whereas Lipo LVM–PBS has the largest particle size value at 7236.67 ± 443.89 nm. Values for the polydispersity index fall between 0.527 and 0.896. Zeta potential levels, on the other hand, range from -7.6 mV to -46.8 mV. While this value was determined as -8.2 ± 0.4 mV in LD Lipo ABZ and -18.4 ± 0.6 mV in HD Lipo ABZ, respectively. Both HD Lipo ABZ and LD Lipo ABZ have polydispersity indices for ABZ of 0.529 ± 0.066 and 0.896 ± 0.085, respectively. It was found that the particle size rose as the desired amount of liposomal albendazole increased. It was found that the liposomization of albendazole was higher than that of levamisole. Albendazole and levamisole liposomal formulations were successfully developed in the investigation. By carrying out characterization studies, it was discovered that it may be employed in clinical trials. In the upcoming years, it is anticipated that continuous research in the field of nanotechnology will improve human and animal health and aid to more effectively control parasite infestations.

Levamisole effects on the biochemical, hematological, and Histopathological parameters on heat stress fish.40 Cyprinus carpio fish were distributed into 4 groups, raised in a glass aquarium, and provided with a basic diet for ten days. Control groups as G1 and three treated groups were tested G2 with the elevated water temperature at 30°C, G3 was treated with a concentrated dose of 125 mg/L of levamisole, and the water temperature was25°C. At the same time, G4 elevated water temperature to 30°C and treated with the same dose of levamisole. At the end of the experiment, all groups were euthanized. Blood samples were collected for packed cell volume, hemoglobin, mean corpuscular hemoglobin concentration, cortisol, glucose, immunoglobulin, albumin, and histopathological investing from all groups also done. The results showed that the G2 and G3 showed highly significant variation in the level of glucose and albumin in contrast to others, as well G4 showed highly significant variation in the level of the biochemical parameters, G4 showed a higher level of biological parameters changes in contrast to the other groups. At the same time, the hematological value was higher in the G3. The pathological alterations of G2, G3 and G4 represented vascular changes such as hemorrhagic congestion, disturbances of growth infiltration of inflammatory cell, necrosis, hyalin cast and dilution of bowman’s capsule; all these changes were graded as mild, moderate, and severe changes and were more severe in G2.Our results refer that immune stimulant agents enhance the biochemical and hematological parameters, but it leads to changes in the liver and kidney due to the effects of heat stress.

Antineutrophilic cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a condition characterized by vessel inflammation and may have a variety of etiologies. Among these, cocaine and its common adulterant, levamisole, have been described to contribute to the development of AAV with distinct cutaneous manifestations. Classically, these manifestations involve purpuric or necrotic lesions involving the ears, nose, and extremities. However, we present a case of cocaine‐induced AAV presenting with violaceous nodules on the dorsal hands in order to demonstrate that this condition may not always present with retiform purpura and skin necrosis. [ABSTRACT FROM AUTHOR]

This study conducted a literature review to investigate the immunomodulatory effect of levamisole in both humans and farm animals. The following procedure was followed for database searching: PubMed, Google Scholar, Web of Science, and Cochrane Library. All research works were updated to September 2022. The terms used in the literature search were included: ("levamisole" OR "immunity" OR "immune system") AND ("adjuvant" OR "fish" OR "poultry" OR "farm animal" OR "cattle" OR "sheep"). The current review enlightens the extensive potential of levamisole as an adjuvant immunotherapeutic agent and explains its divergent applications beyond its antiparasitic use as an adjuvant, dietary supplement, immunostimulant, antiviral, and anti-cancer drug in humans and farm animals. In the articles examined, various mechanisms have been proposed for levamisole immunoprotective effects, but hormonal alteration and stress hormone reduction are indicated as the main mechanisms in various animal species. [J Adv Vet Anim Res 2023; 10(4.000): 620-629]

Gastrointestinal nematodes pose a threat to animal health and affect farmers by negatively impacting farm management.

Dung beetles perform vital ecosystem functions, but their survival is threatened by parasiticide use in veterinary practices. Currently, it's unclear if parasiticides directly harm dung beetles or cause damage via secondary effects on crucial microbiome components. We investigated the impact of three commercial parasiticides (P1–levamisole and oxfendazole; P2–abamectin, levamisole and oxfendazole; P3–moxidectin) on Onthophagus binodis dung beetle gut and exoskeleton microbiomes. Dung beetles were subjected to parasiticides mixed with fresh dung for 14 days, and we used 16S rRNA genes to detect bacterial diversity changes. The tested parasiticides didn't alter dung beetle gut communities, but slightly affected the exoskeleton microbiota composition. No mortality difference was observed. Onthophagus binodis microbiomes are mainly diet-influenced, and their exoskeleton is more adaptable than their gut. Our study suggests that adjustable dung beetle microbiomes aren't susceptible to parasiticides due to their innate resilience. [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]

Levamisole (LVM) is considered an immunomodulatory agent that has the potential to treat various cancer and inflammation diseases. However, there is still much debate surrounding the toxicokinetic and toxicological information of LVM. Therefore, it is crucial to assess its toxicity to provide useful data for future human LVM risk assessments. In this study, a barrier environment was established under the guidance of good laboratory practice (GLP) at the Fujian Center for New Drug Safety Evaluation. Male beagle dogs were orally administered with 5, 15, and 30 mg/kg of LVM daily for four weeks. Toxicity assessment was based on various factors such as mortality, clinical signs, food and water consumption, body weight, body temperature, electrocardiogram, ophthalmological examination, hematology, serum biochemistry, organ/body coefficients, histopathological study, and toxicokinetic analysis. The results of this study showed that LVM did not exhibit any significant toxicological effects on beagle dogs at the exposure levels tested. A no observed adverse effect level (NOAEL) of LVM was set at 30 mg/kg/day for male beagle dogs, which is equivalent to a 12-fold clinical dose in humans. Moreover, the repeated exposure to LVM for four weeks did not lead to any bioaccumulation. These findings provide valuable insights for future human LVM risk assessments. [ABSTRACT FROM AUTHOR]

For endoparasitic infestations of dogs, drugs based on levamisole hydrochloride are used. That is why the purpose of the work was to conduct a field study to evaluate the effectiveness of the studied drug "Levamizole O.L.KAR 10 %" and the reference drug "Levamizole-plus 10 %" against endoparasitic infestations of dogs of different breeds, ages, and sexes. According to the results of a parasitological examination of the dogs of the experimental and control groups, endoparasites established spontaneous damage, the causative agents of nematodes of the alimentary canal: species Toxocara canis with an intensity of invasion (II) from 110 to 180 eggs in one gram of feces (EGF) with an average intensity of invasion of 149.0 ± 5.62 EGF, species Toxascaris leonina with an intensity of invasion from 75 to 131 EGF with an average intensity of invasion of 104.4 ± 4.85 EGF and the species Ancylostoma caninum with an intensity of invasion from 48 to 92 EGF with an average intensity of invasion of 69.9 ± 3.71 EGF. Clinically, nematodes of the alimentary canal in dogs were manifested by poor appetite, depressed state, pallor of mucous membranes, mild diarrhea, vomiting, and weight loss observed in some animals. Based on the obtained results, it was established that the studied drug "Levamizol O.L.KAR 10 %" and the reference drug "Levamizol-plus 10 %" when deworming dogs have a pronounced nematodocidal effect against endoparasites of the alimentary canal, which are caused by the following species: Toxocara canis, Toxascaris leonine, Ancylostoma caninum. Thus, the effectiveness of the studied drug "Levamizol O.L.KAR 10 %" for spontaneous toxocariasis infestation in dogs on the seventh day after deworming was 93 %. The reference drug "Levamizolplus 10 %" was 91 %, and on the 14th day after deworming the animals, the effectiveness of the drugs was 100 %. For spontaneous toxascarosis infestation in dogs, the efficacy of the studied drug "Levamizol O.L.KAR 10 %" on the seventh day after deworming was 95 %. The reference drug "Levamizol-plus 10 %" was 94.4%, and on the 14th day after deworming the animals, the effectiveness of the drugs was 100 %. Helminthological studies have established that for spontaneous hookworm infestation in dogs on the 7th and 14th day after deworming with the study drug and the comparison drug in the recommended doses, the effectiveness of veterinary drugs was 100 %. Field tests showed that the studied drug "Levamizol O.L.KAR 10 %" and the reference drug "Levamizol-plus 10 %" when administered once orally in the recommended doses of the manufacturer, are well tolerated by animals regardless of breed, age, sex, and body weight, not have a toxic effect on the body of animals and are effective against nematodes of the alimentary canal in dogs. [ABSTRACT FROM AUTHOR]

We have developed a new library of chalcone incorporated imidazo[2,1-b]thiazole derivatives (9a–9j) and their structures were determined for their analytical data. Further, all were screened for their anticancer profile towards a panel of human cancer cell lines like prostate cancer (PC3), lung cancer (A549), breast cancer (MCF-7), and ovarian cancer (A2780) by utilizing of MTT assay and etoposide used as standard reference drug. All compounds were displayed good to moderate anticancer properties on four cell lines with IC50 values ranges from 0.012 ± 0.0076 to 21.9 ± 8.24 µM, and standard showed IC50 values range from 1.38 ± 0.56 to 3.08 ± 0.135 µM, respectively. Amongst, five compounds 9a–9e were exhibited more strong anticancer activities. In which, compound 9a was demonstrated excellent anticancer activity. [ABSTRACT FROM AUTHOR]

Levamisole, an anthelmintic and immunostimulant drug, has been studied as a promising alternative for aquaculture use. While oral administration through feeding is the main route of administration in fish farming, no studies evaluating methods of levamisole incorporation into the feed have been reported so far. Therefore, this study aimed to evaluate potential procedures for levamisole incorporation in extruded fish feed using ethyl cellulose, gelatin, or vegetable oil, to avoid drug leaching to the water during the animal's medication. A suitable LC-MS/MS method was optimized (full factorial design), validated, and applied to evaluate the efficiency of the process, the homogeneity of the drug concentration, and the leaching rate. The method has been demonstrated to be selective, precise (RSD < 4.9%), accurate (recovery > 98.4%), and linear (r > 0.99, 125–750 mg kg−1). The incorporation procedures using the three coating agents showed high incorporation efficiency (70%) and a homogeneous drug concentration among the extruded feed pellets. A low levamisole leaching rate was verified in the feed prepared using the ethyl cellulose coating procedure (4.3% after 15 min of immersion in the water). On the other hand, fish feed coated with gelatin and oil resulted in a high leaching rate (30–35% after 15 min). Thus, this study shows that coating ethyl cellulose may be a promising procedure for levamisole incorporation in fish feed and with the potential to enhance its use in animal production while reducing environmental contamination. [ABSTRACT FROM AUTHOR]

Anti-helminthic drugs (Albendazole and Levamisole) trials were conducted on Indian Peafowls (n = 20) kept at Jallo Wildlife Park, Lahore, Pakistan for 15. Sampling was conducted on days 7 and 15 of treatments. The results showed that the WBC count was significantly (P < 0.05) higher in both samples in response to Levamisole treatment. Haemoglobin (HGB) and Mean Corpuscular Haemoglobin Concentration (MCHC) concentration increased significantly (P < 0.05) in response to both treatments; however, Mean Corpuscular Haemoglobin (MCH) decreased significantly (P < 0.05) in Albendazole-treated birds on both the sampling days compared to the control. Red Blood Cell Distribution Width-Standard Deviation (RDW-SD) decreased significantly (P < 0.05) in all treatment groups. On the other hand, the prevalence of eggs per gram (EPG) was reduced by 20% after the application of Levamisole on days 7 and 15. It was concluded that both drugs had significant effects on WBCs, HGB, MCH, MCHC and RDW-SD. [ABSTRACT FROM AUTHOR]

This study conducted a literature review to investigate the immunomodulatory effect of levamisole in both humans and farm animals. The following procedure was followed for database searching: PubMed, Google Scholar, Web of Science, and Cochrane Library. All research works were updated to September 2022. The terms used in the literature search were included: ("levamisole" OR "immunity" OR "immune system") AND ("adjuvant" OR "fish" OR "poultry" OR "farm animal" OR "cattle" OR "sheep"). The current review enlightens the extensive potential of levamisole as an adjuvant immunotherapeutic agent and explains its divergent applications beyond its antiparasitic use as an adjuvant, dietary supplement, immunostimulant, antiviral, and anti-cancer drug in humans and farm animals. In the articles examined, various mechanisms have been proposed for levamisole immunoprotective effects, but hormonal alteration and stress hormone reduction are indicated as the main mechanisms in various animal species. [ABSTRACT FROM AUTHOR]

Abstract Two simple and rapid chromatographic methods were developed and validated for the analysis of levamisole and triclabendazole simultaneously in pure and pharmaceutical products. The first method is thin-layer chromatography (TLC) with densitometry, and the second method is high-performance liquid chromatography with PDA detection (HPLC–PDA). A Hypersil BDS C18 column with dimensions of 4.6 × 150 mm and a particle size of 5 µm was used in the HPLC–PDA method. An isocratic condition was used to carry out the separation, and the mobile phase was made up of acetonitrile and a 0.03 M potassium dihydrogen phosphate buffer in double-distilled water. The ratio of the mobile phase preparation was 70:30 (v/v), and the flow rate was 1 mL/min. A wavelength of 215 nm was employed for analyte detection. Precoated silica gel 60 F254 aluminium plates were used for the TLC method's separation. Mobile phase was made of ethyl acetate, hexane, methanol, and ammonia (69:15:15:1) for the separation. The detection wavelength selected was 215 nm. According to the International Council for Harmonization (ICH) guidelines, the proposed methods were validated and it was found that the two chromatographic methods are accurate, precise, and linear for both compounds in the range of 3.75–37.5 and 6–60 mg/L for the HPLC method for levamisole and triclabendazole, respectively and in the range of 2–14 µg/spot for the TLC method. The developed methods greenness profile was assessed using AGREE and ComplexGAPI tools. Graphical Abstract

The widespread and uncontrolled use of anthelmintic products has contributed to the emergence of anthelmintic resistance (AR). This phenomenon globally threatens the productivity and welfare of small ruminants. A questionnaire consisting of 34 questions was handed to 234 goat farmers across Romania to gain insight into control practices against internal parasites and the farmers’ perception of the parasitic infections present in their herds and the efficacy of anthelmintic treatments. The majority of farmers (88.5%) admitted they had never submitted fecal samples for parasitological laboratory analysis, and 77.4% had treated the animals on their own. In general, the farmers dewormed their goats based on visual body weight estimation. Prophylactic anthelmintic treatment was practiced by more than 85% of the farmers. A traditional control approach based on treating the entire herd at fixed time intervals is widespread among Romanian goat and sheep farmers. The most commonly used anthelmintic drugs in the previous 3 years (2021–2023) were benzimidazoles (85.5%) and macrocyclic lactones (81.6%). Poor anthelmintic efficacy was suspected by 14.5% of farmers, and the minority (18.0%) considered internal parasites as a problem in their herds. Regarding the farmers’ perception of the presence of parasites, there was a significant level of uncertainty. This is the first survey carried out in Romanian goat herds, and it provides up-to-date information on practices aimed at controlling internal parasites.

The study's objectives were to investigate the acute toxicity and related biochemical effects of levamisole and ivermectin in mice. The 24 h oral median lethal dose (LD50) of levamisole was determined by the up-and-down method and was 155.5 mg/ kg of body weight. The treated mice showed signs of acute poisoning represented by excessive grooming, lacrimation, piloerection, straub tail, tachycardia, bulged eyes, tremor, convulsion and finally death within 24 h of treatment. The approximate lethal dose (ALD) of levamisole was 368 mg/kg, and the mice showed signs of poisoning similar to the previous signs of poisoning within 24 h of treatment. The 24 h oral LD50 of ivermectin was 115.2 mg/kg and the mice showed acute signs of poisoning, represented by excessive grooming, lacrimation, closed eyelids, piloerection, tachycardia, rapid respiration, depression, flat body appearance, paralysis and finally death within 24 h of treatment, while the approximate lethal dose of ivermectin was 121 mg/kg and also with the presence of severe poisoning signs as mentioned before. Non-lethal toxic doses of levamisole at 100 and 150 mg/kg and ivermectin at 75 and 100 mg/kg led to significant blood biochemical changes after 24 h of treatment, represented by a significant increase in the activity of the enzymes alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), and a significantly increased total bilirubin concentration in the blood plasma of mice. These results proved the presence of acute toxicity and biochemical effects of both anthelmintics levamisole and ivermectin even though they have wide safety margins.