2-氯汞-4-硝基苯酚对人肌肌酸激酶巯基的修饰

本文用含汞试剂MNP修饰人肌肌酸激酶,结果表明,人肌肌酸激酶有6个可反应巯基。MNP首先修饰了一对与活力无关的非必需巯基,增大MNP摩尔比,则进一步修饰另外四个与活性有关的巯基。修饰酶的差吸收光谱、荧光光谱表明这三对巯基的微环境各不相同。其中第二对巯基很可能是位于活性部位的必需巯基,而第三对巯基则是由于第二对巯基,也就是必需巯基,被修饰后,微区构象发生改变而暴露出来的。比较MNP修饰人肌肌酸激酶、鸡胸脯肌肌酸激酶、兔肌肌酸激酶的结果,探讨了MNP对肌酸激酶的修饰以及人肌肌酸激酶可反应巯基的化学微环境。     

分光光度法测定血浆中黑色素含量的方法学研究

黑色素纳米材料(MNP)易与金属离子螯合,本文建立了分光光度法测定铁过载模型鼠血浆中MNP含量的方法,为MNP治疗铁过载提供基础。MNP标准溶液在200~800 nm波长范围内扫描呈全波谱吸收,选定490 nm波长为检测波长,且在5~100μg/m L浓度范围内线性关系良好。不同浓度的Fe3+对MNP吸收无影响。该方法快速、操作简便且重现性好,可有效用于血浆中MNP的含量测定。     

黄壤性稻田稗草发生特征及其对长期不同施肥的响应

研究长期不同施肥下黄壤性稻田稗草发生特征,明确稗草发生与长期不同施肥水稻产量和土壤性质变异的响应关系.基于农业部贵州耕地保育与农业环境科学观测试验站的一项连续23年不同施肥管理水稻试验,选取不施肥(CK)、单施氮肥(N)、磷钾肥(PK)、氮磷肥(NP)、氮钾肥(NK)、常量化肥(NPK)、1/4有机肥替代化肥(1/4MNP)、1/2有机肥替代化肥(1/2MNP)、单施有机肥(M)和常量有机肥化肥配施(MNPK)10个处理,采用田间调查法调查各处理稗草发生密度、单株穗数、总穗数、穗粒数、千粒重和穗粒重等植物学参数;采用方差分析明确不同处理稗草发生差异,采用直线拟合、相关分析和通径分析明确杂草发生特征对水稻产量和土壤性质的响应.结果表明: 长期不同施肥处理导致黄壤性稻田稗草发生特征显著变异,稗草的密度、单株穗数和总穗数均以MNPK处理最高,其次是1/4MNP处理.相较常量化肥处理,长期不施肥(CK)和不平衡施肥(N、PK、NK、NP)各处理稗草发生的密度显著降低,施用有机肥各处理(1/4MNP、1/2MNP、M、MNPK)稗草的单株穗数显著增加.稗草的发生密度和总穗数与水稻产量呈极显著的正相关性,拟合直线的决定系数分别为0.622和0.624.土壤有机质、全氮、全磷、碱解氮、有效磷和速效钾与稗草发生参数之间存在显著至极显著的相关性;通径分析表明,土壤全氮含量对稗草单株穗数发生有直接正效应,全磷含量是影响稗草密度和总穗数的主要因素,速效钾含量对穗粒数和穗粒重影响最大.长期不同施肥导致黄壤性稻田稗草发生特征变异,施用有机肥提高了稗草的发生密度、单株穗数和总穗数.土壤全磷含量是黄壤性稻田稗草密度和总穗数发生变异的直接影响因素.     

磁纳米散射探针暗场超灵敏检测具核梭杆菌

【背景】具核梭杆菌（Fusobacterium nucleatum）作为机会致病菌,能够引起许多感染性疾病,已被证实是促直肠癌发展的潜在重要危险因素,临床检测中亟需一种快速简单检测F. nucleatum的方法。【目的】通过建立一种磁纳米探针结合暗场显微镜直接观察计数的方法,可方便快速地检测样本中具核梭杆菌的数量。【方法】在磁纳米颗粒（magnetic nanoparticle,MNP）表面修饰制备的抗F. nucleatum抗体,构建一种特异性结合F. nucleatum的MNP探针。此外,比较MNP探针-暗场显微计数法与实时荧光定量PCR （qPCR）方法检测F. nucleatum的灵敏度。【结果】该方法的检测限可低至3.42×10¹ copies/μL,比qPCR的灵敏度高5倍左右。在实际样本的检测中,该方法与qPCR方法所检测F.nucleatum数量保持一致。【结论】本研究建立的方法用于检测F.nucleatum,操作简单、检测快速（约30 min）、灵敏且成本低,有应用于临床样本检测的前景。     

长期不同施肥对番茄根际土壤微生物功能多样性的影响

研究长期定位施肥对番茄根际土壤微生物群落功能多样性的影响,旨在为番茄根际生态过程中的调控提供科学依据和理论指导。以沈阳农业大学长期定位施肥基地的番茄根际土壤为研究对象,采用Biolog-ECO微平板法,分析了11个处理:N(单施氮肥)、K(单施钾肥)、P(单施磷肥)、NP(氮磷肥配施)、NPK(氮磷钾肥配施)、MN(有机肥配施氮肥)、MK(有机肥配施钾肥)、MP(有机肥配施磷肥)、MNP(有机肥配施氮磷肥)、MNPK(有机肥配施氮磷钾肥)、对照CK(不施肥)的土壤微生物群落功能多样性。结果表明:(1)配施有机肥能够显著提高土壤有机质、速效磷、速效钾和碱解氮的含量,氮肥的施入会降低根际土壤的pH,各处理间土壤理化性质的差异显著;(2)配施有机肥可以增强番茄根际土壤微生物对碳源的利用能力,提高微生物群落功能多样性,其中,MNP处理微生物对碳源利用能力最强,微生物活性最高。具体表现为:(1)长期施肥改变了土壤微生物对碳源的利用能力。配施有机肥处理的土壤微生物对6类碳源的总利用能力高于单施化肥处理,以MNP优势最明显;(2)在6类碳源中,氨基酸类碳源利用能力最强,酚酸类碳源利用能力最弱;(3)主成分分析表明,31种碳源对PC1贡献较大的有12种,对PC2贡献较大的有8种;(4)施加肥料的处理的Shannon指数、丰富度指数和优势度指数均高于不施肥的处理,但其均匀度下降。有机肥配施氮磷肥处理的Shannon指数、丰富度指数均显著高于其他处理。综合所有结果,以MNP的施肥较果最佳,能够呈现较高的根际土壤微生物功能多样性。     

长期施肥对黄土旱塬农田土壤有机磷组分及小麦产量的影响

研究长期施肥对黄土旱塬农田土壤有机磷组分及小麦产量的影响,可为提高磷素转化利用率及合理利用肥料提供理论支持。本研究依托长武旱塬农田生态系统长期(1984—2016年)定位试验站,选取不施肥(CK)、单施氮肥(N)、单施磷肥(P)、施氮磷肥(NP)、单施有机肥(M)、氮肥配施有机肥(MN)、磷肥配施有机肥(MP)、氮磷肥配施有机肥(MNP)8个处理,研究其对土壤有机磷组分、小麦产量和土壤性质的影响。结果表明: 长期施肥后土壤有机磷含量为244.7～429.1 mg·kg^-1,除N处理外,其余各处理有机磷含量比CK均显著增加了15.4%～47.9%。长期施用磷肥改变了黄土旱塬农田表层土壤(0～20 cm)各有机磷组分含量,MP、MNP处理显著提高了活性有机磷及中活性有机磷含量;N、P和NP处理显著降低了中稳性有机磷含量;N、P、NP、MN、MP、MNP处理均显著提高了高稳性有机磷含量。各处理土壤有机磷组分与总有机磷含量比值为:中活性有机磷>高稳性有机磷>活性有机磷>中稳性有机磷。长期施肥后,与CK相比,氮、磷肥配施,尤其是与有机肥配施,显著增加了小麦生物产量和籽粒产量。土壤指标中,有机质、速效磷和无机磷与小麦产量呈显著正相关。MP、M处理可以显著提高黄土旱塬黑垆土中的速效磷、总磷、总无机磷、活性有机磷和中活性有机磷含量,表明有机肥与磷肥配施可以提高该地区更容易被作物吸收的磷组分。总之,氮磷肥配施并配施有机肥可以提高该地区磷供给,对小麦增产有促进作用,对提高黄土旱塬地区土壤质量有重要意义。     

Cargo-encapsulated cells for drug delivery

正Synthetic micro-/nanoparticle (MNP) carriers, either organic or inorganic ones, have advanced considerably in recent years for drug delivery with the aim of enhancing drug solubility/stability, reducing systemic toxicity and increasing dosing at pathological sites (Chen and Liang, 2018; Xiang et al., 2018). Specially, the properties of MNPs, such as size,morphology, or surface groups, can be easily modulated to     

长期施肥条件下黄土高原黑垆土作物产量与土壤碳氮的关系

通过设置在黄土高原黑垆土区的长期定位试验系统,研究了长期施肥条件下作物产量与土壤碳氮的互馈关系.试验设不施肥(CK)、单施氮肥(N)、氮磷配施(NP)、秸秆与氮磷配施(SNP)、施有机肥(M)和有机肥与氮磷配施(MNP)6个处理.结果表明: 与对照相比,长期平衡施用化肥、单施有机肥、化肥与有机肥配合施用和秸秆还田配施化肥显著增加了作物产量及其稳定性, NP、SNP、M、MNP处理玉米和小麦产量分别增加92%、97%、93%、141%和147%、164%、139%、214%.NP处理玉米和小麦年均产量与当地常规施肥作物产量相当且稳定,小麦-玉米轮作体系施肥量为N 90 kg·hm^-2、P₂O₅ 75 kg·hm^-2能够满足作物需要.秸秆还田与隔年施磷相配合的SNP处理与NP处理作物产量相似,且可减少磷肥施用量50%.平衡施用化肥、有机肥、化肥与有机肥配施和秸秆还田配施化肥均可显著增加土壤有机碳含量,而施用化肥对土壤全氮含量影响不明显,综合所有处理,土壤有机碳和全氮含量呈显著正相关.不同处理土壤有机碳固存率在15%～41%.SNP处理土壤有机碳累积投入量增加1 t·hm^-2,土壤有机碳含量增加0.06 g·kg^-1,而CK、N、NP、M和MNP处理的增幅在0.12～0.15 g·kg^-1.玉米和小麦产量都与土壤全氮含量呈显著正相关,玉米产量随土壤有机碳含量的增加而增加,但小麦产量随土壤有机碳含量的增加先快速增加后趋于平稳,拐点出现在6.8 g·kg^-1.长期平衡施用化肥、有机肥、有机肥与化肥配合施用及秸秆还田配施化肥可显著增加黄土高原黑垆土土壤有机碳和全氮含量、作物产量和根茬还田量,根茬还田量的增加又进一步增加了土壤有机碳和全氮含量,形成了相互促进的互馈关系.     

长期不同施肥方式对黄潮土肥力特征的影响

依托黄潮土35 年长期定位试验,以2种土壤物理肥力指标、8种土壤化学肥力指标和5种土壤生物肥力指标进行主成分分析,最后将各主成分得分系统进行聚类分析.结果表明: 不同施肥方式对土壤肥力指标影响显著.施用有机肥处理(M、MN、MNP、MNPK)与NPK处理相比,土壤容重显著降低,而土壤孔隙度、有机质、全氮、碱解氮、全磷、有效磷、微生物生物量和过氧化氢酶、脲酶、碱性磷酸酶活性均显著增加;通过主成分分析可将原15个土壤指标降维,提取出2个主成分,反映了原信息量的85.5%,且无原变量丢失.土壤容重、孔隙度、有机质、全氮、碱解氮、全磷、有效磷、速效钾、微生物生物量、过氧化氢酶、脲酶、碱性磷酸酶、蔗糖酶活性在第1主成分上有较高因子负荷,全钾和pH在第2主成分上有较高因子负荷;以2个主成分得分为新指标进行聚类,得到长期不同施肥方式对黄潮土的培肥效果排序为MNPK＞MNP＞M、MN＞NPK＞N、NP＞CK.可见施用有机肥对黄潮土培肥效果更显著,以有机肥配施氮磷钾化肥方式效果最优.     

不同施肥对农田黑土微生物群落的影响

以未施肥(CK)和休闲(Fallow)处理为对照,研究黑土肥料定位站NP、NPK、MCK(有机肥)、MNP(有机肥 氮磷)、MNPK(有机肥 氮磷钾)等长期有机、无机肥施用对土壤基本理化性质、磷脂脂肪酸(PLFA)、酸(碱)性磷酸酶、微生物量碳或氮(SMBC或SMBN)等影响.结果表明,有机肥施用有效地提高了土壤有机质、总氮及速效氮、磷、钾等养分含量,显著地增加了SMBC(SMBN)和真菌、细菌的PLFA含量以及磷酸酶活力,极大地提高了土壤真菌/细菌比值;而长期NP或NPK处理不但未明显改善土壤养分状况,甚至抑制了磷酸酶活性及大多数菌群生长.总细菌PLFA与饱和脂肪酸或单烯脂肪酸与环化脂肪酸之间呈极显著正相关(p<0.01).PLFA主成分分析表明,有机肥与化肥处理微生物群落结构显著不同;个别PLFA载荷值分析表明,真菌脂肪酸易受无机肥施用影响,而G-菌或G 菌脂肪酸更易受有机肥影响.休闲处理高水平微生物活性与生物量的主要贡献者是黑土细菌群落而不是真菌.     

长期施肥对麦田土壤微生物垂直分布的影响

应用微量热法研究了长期轮作下麦田不同土层中的微生物活性, 以及施肥对微生物垂直分布的影响。结果表明, 微生物活性基本随深度的增加而下降; 随着土层加深, 可培养细菌菌落数减少, 且可培养细菌菌落数目与最大时间(Peak time)P_t值(表示从微生物生长开始到达到峰值的时间)呈负相关; 热功率(P)-时间(t)曲线由陡变缓, 由规则变得起伏不定, 侧翼变得更短, 峰高也降低; 不同土层的微生物生长速率常数(Microbial growth rate constant) µ、峰高(Peak height)P_h值变化明显, 基本随深度增加而减小。施肥土样和不施肥土样的曲线形状不同, 特别是上层土样施肥后的曲线明显比不施肥的曲线陡, 侧翼也明显变短; 施肥土样的µ和P_h值都大于不施肥土样, 且施肥土样的P_t都小于对照。这说明, 在不同的土壤深度有不同的微生物群落结构, 长期的施肥处理改变了土壤微生物的垂直分布特征。     

Changes in the subepithelial mesenchymal cell process meshwork in developing facial prominences in mouse embryos

We examined temporal and spatial changes in the subepithelial mesenchymal cell process meshwork (CPM) in normally developing medial (MNP) and lateral nasal prominences (LNP) in mouse embryos by light and scanning electron microscopy. Marked changes were found only in the MNP during the fusion of the MNP and LNP. The CPM density in the prospective fusion area of the MNP gradually increased as the epithelial surfaces approached each other, attained its maximum just before contact, and decreased after contact. The CPM density in the prospective fusion area of the LNP changed only slightly even when the epithelial surfaces approached each other. The increase in CPM density paralleled that in the density of mesenchymal cell bodies. The LNP grew more actively toward the line of fusion than did the MNP during the progressive fusion of the two prominences. A larger number of fusion-associated epithelial morphological changes--the appearance of superficial protruding cells and cell degeneration--occurred in the MNP than in the LNP. These findings suggest that the increased CPM density is closely related to the growth of the facial prominences and the fusion-associated epithelial morphology and that the CPM plays an important role in the epithelial-mesenchymal interaction during the formation of the upper lip and primary palate.     

ANTICANCER MEDICINES (DOXORUBICIN AND METHOTREXATE) CONJUGATED WITH MAGNETIC NANOPARTICLES FOR TARGETING DRUG DELIVERY THROUGH IRON

The uptake of iron is increased by cancer cells. Iron magnetic nanoparticles (MNP) can be used as a nanovehicle for immobilization of anticancer medicines and to integrate them at a target site. The anticancer medicines doxorubicin (DOX) and methotrexate (MTX) were immobilized separately and in combination onto MNP by a glutaraldehyde activation method and confirmed by magnetic nanoparticles linked immunosorbent assay (MagLISA) and Fourier-transform infrared (FTIR) spectroscopy. The phenol peaks of DOX and MTX at 2896.6 cm^?1 to 2912.5 cm^?1 in FTIR spectra of immobilized medicines indicated the conjugation. Affinity-purified anti-DOX and anti-MTX antibodies were used to evaluate the coupling of DOX and MTX onto MNP, and the binding was found 34.6% to 37.2% and 51.8% to 54.3% separately, respectively. The immobilization of DOX and MTX in combination onto MNP was 18% and 27%, respectively. HeLa and B cells were cultured with DOX-MNP, MTX-MNP, and DOX-MNP-MTX separately, and MagLISA indicated that the binding of DOX-MNP/MTX-MNP was 41.5% to 45% with HeLa cells and 20% to 26% with B cells. No significant difference was observed in binding of DOX-MNP-MTX with HeLa and B cells. Results also indicated that the release of medicines at pH 5.0 is more (39% to 44%) than at pH 7.4 (3.7% to 10.2%). Sixteen to 22% more killing effect was observed on HeLa cells than on B cells. In immunohistochemical staining, more deposition of brown color on HeLa cells than on B cells may be due to more expression of iron-binding sites on cancer cells. The dual property of MNP can be used for binding of medicines and for targeting drug delivery.     

Xanthine oxidoreductase promotes the inflammatory state of mononuclear phagocytes through effects on chemokine expression, peroxisome proliferator-activated receptor-{gamma} sumoylation, and HIF-1{alpha}

The protective effects of pharmacological inhibitors of xanthine oxidoreductase (XOR) have implicated XOR in many inflammatory diseases. Nonetheless, the role played by XOR during inflammation is poorly understood. We previously observed that inhibition of XOR within the inflammatory mononuclear phagocytes (MNP) prevented neutrophil recruitment during adoptive transfer demonstrating the role of XOR in MNP-mediated neutrophil recruitment. To further explore the role of XOR in the inflammatory state of MNP, we studied MNP isolated from inflammatory lungs combined with analyses of MNP cell lines. We demonstrated that XOR activity was increased in inflammatory MNP following insufflation of Th-1 cytokines in vivo and that activity was specifically increased by MNP differentiation. Inhibition of XOR reduced levels of CINC-1 secreted by MNP. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in purified rat lung MNP and MNP cell lines reflected both the presence of PPARγ isoforms and PPARγ SUMOylation, and XOR inhibitors increased levels of SUMO-PPARγ in MNP cell lines. Both ectopic overexpression of XOR cDNA and uric acid supplementation reduced SUMO-PPARγ in MNP cells. Levels of the M2 markers CD36, CD206, and arginase-1 were modulated by uric acid and oxonic acid, whereas siRNA to SUMO-1 or PIAS-1 also reduced arginase-1 in RAW264.7 cells. We also observed that HIF-1α was increased by XOR inhibitors in inflammatory MNP and in MNP cell lines. These data demonstrate that XOR promotes the inflammatory state of MNP through effects on chemokine expression, PPARγ SUMOylation, and HIF-1α and suggest that strategies for inhibiting XOR may be valuable in modulating lung inflammatory disorders.     

Mechanism of recovery from acute virus infection. IV. Questionable role of mononuclear phagocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice

After intravenous infection of mice with 10(3) infectious units (IU) the WE strain lymphocytic choriomeningitis (LCM) virus multiplied in the spleens (as in all other major organs), reaching more than 10(8) IU/g of tissue on days 4 to 5. Subsequently, the virus was quickly eliminated, being below detectability usually by day 10. During the time of virus clearance, the mononuclear phagocytes (MNP) of the spleen were activated as revealed by suppression of growth of Listeria monocytogenes and increase of cell-associated hydrolytic enzymes. In athymic nude mice, in whom the MNP system is assumed to be permanently activated, the virus replicated slightly but reproducibly less than in their euthymic counterparts. However, when the MNP were activated by Corynebacterium parvum, virus in spleens attained higher concentrations than in mice not so treated, and the rate of elimination was not altered. In mice whose MNP had been damaged by injection of dextran sulfate 500, the spleen virus titers were also increased, but the subsequent immune elimination was slightly delayed. Activation of spleen MNP was not evident at the time virus was rapidly cleared as a result of transfusion of LCM-immune T lymphocytes. Adoptive immunization was as successful in mice that had been pretreated with gamma-rays or cyclophosphamide, suggesting that replicating cells or their descendants, in particular monocytes, did not participate measurably in the process of elimination. Pretreatments of recipients with dextran sulfate 500 reduced the efficacy of transfused LCM-immune T lymphocytes, but this compound probably directly affected the cells. We interpret these findings to mean that the LCM virus in the mouse's spleen is controlled by a mechanism in which MNP do not play an essential role.     

Insulin-like 3 expression and fibrosis induction after intra-testicular injection of magnetic nanoparticles in rat testis and the ameliorative role of Echinacea purpurea extract

The World Health Organization has approved magnetic nanoparticles (MNP) for use as a contrast agent for magnetic resonance imaging or tumor hyperthermia treatment. MNP are toxic over time after intra-testicular injection. A clear strategy to ameliorate the toxic side effects of MNP in normal tissues after medical application has not yet been developed. We used an extract of Echinacea purpurea (EP) as a natural source of antioxidant and free radical scavenging product for detoxification of MNP in testicular tissues. MNP localization in the interstitial area of testicular tissue reduced the expression of insulin-like factor 3 (INSL3) proteins as well as serum testosterone levels. Further, MNP caused accumulation of both collagen and elastin in the interstitial area and increased the thickness of the tunica albuginea. Injection of MNP during administration of EP extract for short periods slightly reduced the toxic side effects of MNP. After extended exposure to EP extract, INSL3 expression and testosterone returned to near control levels. Also, collagen and elastin accumulation caused by MNP was reduced after extended exposure to EP extract. We believe that the ameliorative effect of EP extract is due to its antioxidant properties.     

A Critical Role for PDGFRα Signaling in Medial Nasal Process Development

The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.     

The role of mononuclear phagocytes in cardiac allograft rejection in the rat: I. Ultrastructural and cytochemical features

Mononuclear phagocytes (MNP) have been identified in rejecting rat cardiac allografts by morphological and cytochemical criteria. Their accumulation has been quantitated and their distribution within the graft recorded. Lymphocytes were the major infiltrating cell type present 3 days after transplantation, but by Day 5 and Day 7 there were 2.5 to 3 times as many MNP as lymphocytes. In the later stages (Days 6 and 7) many MNP were closely adjacent to myocardial cells and frequently possessed pseudopodia which were indenting the myocardial cell membrane. Allograft recipients given 750 rads γ-irradiation and reconstituted with thoracic duct lymphocytes rapidly rejected the graft. As many MNP were present in such grafts as in unmodified recipients. A potent antimacrophage serum did not prolong graft survival or alter the numbers of MNP within rejecting grafts. We conclude that MNP must be considered strong candidates for effector cells in allograft rejection and that satisfactory depletion techniques for MNP are not yet available.     

Monepantel-based anthelmintic combinations to optimize parasite control in cattle

Improvement in the use of existing anthelmintics is a high priority need for the pharmaco-parasitology research field, considering the magnitude and severity of anthelmintic resistance as an important issue in livestock production. In the work described here, monepantel (MNP) was given alone or co-administered with either macrocyclic lactone (ML) or benzimidazole (BZ) anthelmintics to calves naturally infected with ML- and BZ-resistant gastrointestinal (GI) nematodes on two different commercial cattle farms. Both pharmacokinetic (PK) and efficacy assessments were performed. On Farm A, male calves (n = 15 per group) were treated with either MNP orally (2.5 mg/kg), IVM s.c. (0.2 mg/kg), ricobendazole (RBZ) s.c. (3.75 mg/kg) or remained untreated. On Farm B, eight groups (n = 15) of male calves received treatment with either: MNP, abamectin (ABM, oral, 0.2 mg/kg), RBZ (s.c., 3.75 mg/kg), albendazole (ABZ, oral, 5 mg/kg), MNP+ABM, MNP+RBZ, MNP+ABZ (all at the above-mentioned routes and doses) or remained untreated. Seven animals from each treated group (Farm B) were randomly selected to perform the PK study. MNP and its metabolite monepantel sulphone (MNPSO₂) were the main analytes recovered in plasma after HPLC analysis. The combined treatments resulted in decreased systemic exposures to MNP parent drug compared with that observed after treatment with MNP alone (P < 0.05). However, the systemic availability of the main MNP metabolite (MNPSO₂) was unaffected by co-administration with either ABM, RBZ or ABZ. Efficacies of 98% (Farm A) and 99% (Farm B) demonstrated the high efficacy of MNP given alone (P < 0.05) against GI nematodes resistant to ML and BZ in cattle. While the ML (IVM, ABM) failed to control Haemonchus spp., Cooperia spp. and Ostertagia spp., MNP achieved 99% to 100% efficacy against those nematode species on both commercial farms. However, MNP alone failed to control Oesophagostomum spp. (60% efficacy) on Farm A. The co-administered treatments MNP+ABZ and MNP+RBZ reached a 100% reduction against all GI nematode genera. In conclusion, the oral treatment with MNP should be considered to deal with resistant nematode parasites in cattle. The use of MNP in combination with BZ compounds could be a valid strategy to extend its lifespan for use in cattle as well as to reverse its poor activity against Oesophagostomum spp.     

Nitrogen regulation of lignin peroxidase and manganese-dependent peroxidase production is independent of carbon and manganese regulation in Phanerochaete chrysosporium

In this study, a N-deregulated mutant (der8-5) of Phanerochaete chrysosporium was used as a tool to investigate the interrelationships between N, C, and Mn(II) regulation of LIP and MNP production in this organism. The results showed that LIP and MNP production by der8-5 was blocked in excess C medium but not in excess N medium. Furthermore, LIP and MNP production in this organism was subject to Mn(II) regulation regardless of the fact whether it is grown in low N medium or in high N medium. These and other results indicate that N regulation of LIP and MNP production in P. chrysosporium is independent of C and Mn(II) regulation.Abbreviations LIP lignin peroxidase - MNP manganese-dependent peroxidase - WT wild-type - der8-5 nitrogen-deregulated mutant