暂无摘要。

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.

A simple and sensitive fluorescent probe has been developed and optimized to detect the non-intentional administration of levamisole (LVM). LVM is used as an anthelmintic therapy in cows, and hence, its residues appear in the drained milk until 60 hours after administering the drug. Meanwhile, levamisole is known to be an adulterant to cocaine and could be detected in addicts\' plasma samples. Owing to its severe side effects, including agranulocytosis, which is lethal in many cases, detection and quantification of LVM in milk and plasma samples are of utmost importance. Therefore, a sensitive and selective analytical method is required for this purpose. This work develops a highly fluorescent probe obtained through the reaction between LVM and erythrosine-B in an acidic medium, where the produced ion pair complex has been measured at 553 nm after excitation at 528 nm. The proposed method provides linearity over the concentration range of 0.5-2.0 μg mL-1 for LVM, with a corresponding detection and quantitation limit of 0.5 and 0.3 μg mL-1. Full validation was performed, permitting the application of the suggested method to perform simple extraction steps. All the applied procedures followed the guidelines offered by green analytical chemistry, where the Green Analytical Procedure Index (GAPI) assessed the greenness of the proposed tool, and the yielded pictograms proved the eco-friendliness of the offered tool.

暂无摘要。

Cocaine is a widely abused controlled substance. Cocaine use is associated with a myriad of side effects and a sequelae of consequences secondary to its harmful nature and potential adulterants, the most recently described and less known sequelae being leukoencephalopathy. In our case, we describe a 58-year-old male who presented to the ED with agitation and acute stroke-like symptoms with reported rapid onset. Cocaine induced toxic leukoencephalopathy is a diagnosis of exclusion, thus other etiologies of disease were ruled out in a full neurological and infectious workup; most importantly consisting of extensive brain imaging, alluding to the diagnosis of acute cocaine induced toxic leukoencephalopathy in an individual with a confirmed history of cocaine and cannabinoid abuse. Although there is no targeted therapy for the condition to our knowledge, we utilized a supportive approach to treatment in contrast to other reported treatment modalities which included the use of steroids, plasma exchange, and intravenous immunoglobulin. Furthermore, we describe the clinical evaluation and treatment throughout the patient\'s hospital course with his eventual marked improvement from initial presentation.

Street cocaine is often mixed with various substances that intensify its harmful effects. This paper proposes a framework to identify attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) intervals that best predict the concentration of adulterants in cocaine samples. Wavelengths are ranked according to their relevance through ReliefF and mRMR feature selection approaches, and an iterative process removes less relevant wavelengths based on the ranking suggested by each approach. Gaussian Process (GP) regression models are constructed after each wavelength removal and the prediction performance is evaluated using RMSE. The subset balancing a low RMSE value and a small percentage of retained wavelengths is chosen. The proposed framework was validated using a dataset consisting of 345 samples of cocaine with different amounts of levamisole, caffeine, phenacetin, and lidocaine. Averaged over the four adulterants, the GP regression coupled with the mRMR retained 1.07 % of the 662 original wavelengths, outperforming PLS and SVR regarding prediction performance.

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.

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.

The study aimed to assess the effects of a therapeutic bath of five different antiparasitic drugs, in different baths and durations: fenbendazole (25 mg l-1, 12 h and 2 × 12 h), formaldehyde (0.17 ml l-1, 15 min), ivermectin (0.031 mg l-1, 1 h), mebendazole (1 mg l-1, 12 h) and levamisole (50 mg l-1, 2 h and 3 × 1 h) on the reduction on the intensity and prevalence of a monogenean infection (Dactylogyrus anchoratus) in juvenile carp. The best effect on reducing the parasite number was achieved with the bath in formaldehyde (0.17 ml l-1, 15 min) and fenbendazole (25 mg l-1, 2 × 12 h with 24 h break), where the infection was reduced by more than 90%. Registered veterinary medicinal products (VMPs) with the active substance of fenbendazole can successfully replace the use of unregistered formaldehyde in the treatment of monogenean infections.

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.