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The use of ionophores as antiparasitic drugs plays an important role in US poultry production, especially in the broiler (Gallus gallus domesticus) industry. However, administered ionophores can pass through the bird's digestive system and appear in broiler litter, which, when applied to agricultural fields, can present an environmental hazard. Stacking (storing or stockpiling) broiler litter for some time might decrease the litter ionophore concentrations before land application. Because ionophores undergo abiotic hydrolysis at low pH, decreasing litter pH with acidic aluminum sulfate (alum) might also decrease ionophore concentrations. We assessed the change in ionophore concentrations in broiler litter in response to the length of time broiler litter was stored (stacking time) and alum addition. We spiked broiler litter with monensin and salinomycin, placed alum-amended litter (∼pH 4-5) and unamended litter (∼pH 8-9) into 1.8-m3 bins, and repeatedly sampled each bin for 112 d. Our findings showed that stacking broiler litter alone did not have an impact on monensin concentration, but it did slowly reduce salinomycin concentration by 55%. Adding alum to broiler litter reduced monensin concentration by approximately 20% relative to unamended litter, but it did not change salinomycin concentration. These results call for continued search for alternative strategies that could potentially reduce the concentration of ionophores in broiler litter before their application to agricultural soils. [ABSTRACT FROM AUTHOR]

Ionophore antibiotics (IPAs), one of the major groups of pharmaceuticals used in livestock industry, have been found to contaminate agricultural runoff and surface water via land application of animal manures as fertilizers. However, limited research has investigated the means to remove IPAs from water sources. This study investigates the degradation of IPAs by using ultraviolet (UV) photolysis and UV combined with hydrogen peroxide (UV/H2O2) advanced oxidation process (AOP) under low-pressure (LP) UV lamps in various water matrices. Three widely used (monensin, salinomycin, and narasin) and one model (nigericin) IPAs exhibit low light absorption in the UV range and degrade slowly at the light intensity of 3.36 ×10-6 Einstein-L-1-.s-1 under UV photolysis conditions. However, IPAs react with hydroxyl radicals produced by UV/H2O2 at fast reaction rates, with second-order reaction rate constants at (3.49-4.00) × 109 M-1--1. Water matrix constituents enhanced the removal of IPAs by UV photolysis but inhibited UV/H2O2 process. A steady-state kinetic model successfully predicts the impact of water constituents on IPA degradation by UV/H2O2 and determines the optimal H2O2 dose by considering both energy consumption and IPA removal. LC/MS analysis of reaction products reveals the initial transformation pathways of IPAs via hydrogen atom abstraction and peroxidation during UV/H2O2. This study is among the first to provide a comprehensive understanding of the degradation of IPAs via UV/H2O2 AOP [ABSTRACT FROM AUTHOR]

Veterinary anticoccidials, biochemically known as ionophores, are widely used in poultry feed at therapeutic levels to treat Coccidiosis and at sub-therapeutic levels for growth- promotion. Commonly used ionophores in the US poultry industry are monensin, salinomycin, lasalocid and narasin. There is an increasing concern regarding the persistence of these anticoccidials in the environment. However, little attention has been directed to methods development for quantitatively measuring ionophores in complex environmental matrices such as poultry litters that are land applied. Here, we describe a rapid and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based method developed for simultaneous quantification of monensin, lasalocid, salinomycin, and narasin in aged poultry litter samples. Results show significant level of monensin (97.8 ± 3.2 μg kg−1), lasalocid (19.2 ± 6.6 μg kg−1), salinomycin (70 ± 2.7 μg kg−1) and narasin (57.3 ± 2.6 μg kg−1) in poultry litter stored for over three years at < 5°C. Our findings indicate that even after several years of unmanaged storage of poultry litter, ionophores may continue to persist in this matrix, raising the possibility of prolonged release into the environment. [ABSTRACT FROM PUBLISHER]

The article presents a study on two microsized graphite sensors for potentiometric determination of cyclobenzaprine hydrochloride (CZ) in pure powder, tablets and plasma. It describes how the sensors were constructed by using 2-hydroxy propyl ß-cyclodextrin as an ionophore. The proposed method reportedly displayed useful analytical characteristics for determination of CZ in its pure powder form. The results were compared with those obtained by the U.S. Pharmacopeia method.

Residents of the area now occupied by the southwestern United States and northwestern Mexico have had to deal with coccidloidomycosis and complicating meningitis for >1500 years. The hundredth anniversary of the reporting of disseminated coccidloidomycosis has just passed. This year has the dubious distinction of being the hundredth anniversary of the first description of coccidioidal meningitis. Although intrathecal amphotericin B began to be used for therapy 50 years ago, and although we have benefited from azole therapy for >10 years, the morbidity and mortality associated with this all-too-common disease remain unacceptably high. This review wifi endeavor to discuss the pathogenic, pathophysiologic, clinical, laboratory, radiologic, and therapeutic features of meningitis secondary to Coccidioides infection. [ABSTRACT FROM AUTHOR]

Background: Potential differences in toxicity, potency and acquisition price among the liposomal amphotericin B formulations makes it unclear which agent is less costly when total resource consumption and treatment-associated costs are considered.Design: A retrospective cost-minimisation analysis in 51 patients was performed to compare the cost of amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AMB) from the hospital perspective. Costs ($US, 2001 values) were divided into level I (acquisition price only), level II (costs of all associated treatment, i.e. adverse events, failures, etc.) and level III (total fungal-related hospitalisation) costs.Results: No significant differences in patient demographics or length of therapy were apparent among those receiving ABLC or L-AMB. The clinical success rate in this population was similar between ABLC and L-AMB (53% vs 60%, p = 0.68), thus justifying the use of a cost-minimisation analysis. Among patients with baseline elevations in serum creatinine, 47% receiving ABLC and 10% receiving L-AMB experienced further increases in serum creatinine (p = 0.025). No differences in total treatment costs (level I, II, or III) were evident between patients receiving ABLC or L-AMB. When adjusted for duration of therapy, however, costs were significantly lower for ABLC than for L-AMB (level I: ABLC $US340 versus L-AMB $US435, p = 0.002; level II: ABLC $US361 versus L-AMB $US454, p = 0.027). The costs attributable to the prevention or treatment of adverse events were not different between the two treatments, and the economic outcome in this analysis was highly sensitive to the acquisition price and dosage of the lipid antifungal formulation. Two-way sensitivity analysis revealed that as long as the milligram price of L-AMB was greater than 135% of the milligram price of ABLC, ABLC remained the less costly formulation.Conclusion: In this patient population, total hospitalisation costs were not different between lipid antifungal formulations. However, after controlling for duration of therapy, ABLC was less costly than L-AMB, when considering acquisition costs of the lipid antifungal agent and costs associated with concomitant antifungal therapy and the treatment of adverse events or lipid failures, indicating that the acquisition price of these agents should be predictive of their cost differences. [ABSTRACT FROM AUTHOR]

Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families, including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (coxsackievirus, rhinovirus), flavirivuses (Zika virus), and coronaviruses (human coronavirus 229E [HCoV-229E] and Middle East respiratory syndrome CoV [MERS-CoV]). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication., (Copyright © 2020 American Society for Microbiology.)

The article reports on the sale of antimicrobials used in food-producing animals in 2009 based on the U.S. Food and Drug Administration's (FDA) review on these drugs and an analysis of the other issues. However, the Animal Health Institute (AHI) notes that the FDA figures on antimicrobials marketed are not associated with drug use. It also accounts ionophores for approximately 8.2 million pounds of the marketed or distributed microbials.

Purpose: The reliability of the preparation procedure for sphingosomal vincristine was studied. The effect of minor variations in the constitution conditions on the integrity of the drug product was also examined., Methods: Two studies were conducted. The laboratory study, which had two parts, was conducted to determine the effects of deliberately varying the constitution conditions, including such key parameters as incubation time and incubation temperature. In the field study, 20 pharmacists unfamiliar with sphingosomal vincristine were asked to constitute the product using the written instructions provided in the package insert as their sole guidance. All samples in both studies were evaluated by measuring key product characteristics, including free (un-encapsulated) vincristine sulfate, total vincristine sulfate, vincristine degradation products, and in vitro release rate. Vincristine loading into sphingosomes was considered acceptable if the percentage of free vincristine sulfate did not exceed 10%., Results: In the laboratory study, samples that were incubated at 60-75 degrees C for 5-60 minutes met all the acceptance criteria. However, acceptable loading was not achieved for samples that were incubated at 55 degrees C for 10 minutes or less. In the field study, all the pharmacist-prepared samples met the acceptance criteria, with the results for free vincristine sulfate demonstrating a high degree of statistical confidence in the reliability of the loading procedure., Conclusion: The recommended constitution procedure of sphingosomal vincristine from a three-vial kit can be reliably performed in pharmacies with a high degree of confidence. Small variations in temperature and incubation time had no effects on the quality of the product.