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We report here the hierarchical construction of a molecular Co(II)-salicylaldimine catalyst and an in situ derived In2S3 semiconductor in a MOF@In2S3 heterojunction through sequentially controllable in situ etching and post-synthetic modification for photocatalytic hydrogen production from formic acid. The enhanced catalyst stability and facilitated charge carrier mobility between the In2S3 photosensitizers and Co catalyst realize a superior H2 production rate of 18 746 µmol g-1 h-1 (selectivity > 99.9%) with a turnover number (TON) of up to 6146 in 24 h (apparent quantum efficiency of 3.8% at 420 nm), indicating a 165-fold enhancement over that of the pristine MOF. This work highlights a powerful strategy for synergistic Earth-abundant metal-based MOF photocatalysis in promoting H2 production from FA.
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METHODS: Diabetic Apoe-/- mice induced by streptozotocin were treated with vehicle, the Pin1 inhibitor juglone, or the BRD4 inhibitor JQ1 for 3 weeks. VSMCs were pretreated with juglone, JQ1, or vehicle for 45 min, and then exposed to high glucose for 48 h. Hematoxylin-eosin staining was performed to assess atherosclerotic plaques of the thoracic aorta. Western blotting was used to detect expression levels of Pin1, BRD4, cyclin D1, and matrix metalloproteinase-9 (MMP-9) in the thoracic aorta and VSMCs. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assay were used to measure proliferation and migration of VSMCs. RESULTS: Juglone and JQ1 significantly improved atherosclerosis of diabetic Apoe-/- mice and reduced high glucose-induced VSMC proliferation and migration. Cyclin D1 and MMP-9 levels in the thoracic aorta were lower in diabetic Apoe-/- mice treated with juglone and JQ1 compared with vehicle-treated diabetic Apoe-/- mice. Additionally, BRD4 protein expression in high glucose-induced VSMCs was inhibited by juglone and JQ1. Upregulation of Pin1 expression by transduction of the Pin1 plasmid vector promoted BRD4 expression induced by high glucose, and stimulated proliferation and migration of VSMCs. CONCLUSIONS: Inhibition of Pin1/BRD4 pathway may improve diabetic atherosclerosis by inhibiting proliferation and migration of VSMCs.
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Aterosclerosis/terapia , Glucosa/metabolismo , Músculo Liso Vascular/fisiopatología , Animales , Proliferación Celular , Humanos , Masculino , Ratones , Proteínas Nucleares , Factores de TranscripciónRESUMEN
Objectives: Apelin-APJ system has been implicated in the regulation of metabolic homeostasis. This study aimed to explore the genetic predisposition of the apelin-APJ system to metabolic syndrome. Materials And Methods: 1005 subjects were enrolled, including 448 metabolic syndrome patients and 557 controls. Seven single nucleotide polymorphisms, including rs909656, rs5975126, and rs3115757 of the apelin gene and rs7119375, rs10501367, rs9943582 and rs11544374 of the APJ gene, were genotyped. Results: For males, apelin-36 were higher in metabolic syndrome subjects compared with controls (p < 0.05). Apelin-36 were significantly lower in those with TT genotype of rs10501367 than those with CC and CT genotypes (p < 0.05), and fasting plasma glucose were higher in T allele carriers of rs10501367 and A allele carriers of rs7119375 compared with non-carriers (both p < 0.05). A significant difference in genotype distribution between diabetes mellitus patients and controls existed for both rs10501367 and rs7119375 (both p < 0.05). However, the association between apelin-APJ system genetic polymorphisms and metabolic syndrome was nonsignificant. For females, apelin-36 were higher in metabolic syndrome subjects compared with controls (p < 0.05). The association between apelin-APJ system genetic polymorphisms and apelin-36, fasting plasma glucose and diabetes mellitus was nonsignificant. However, carrying A allele in rs7119375 was associated with lower metabolic syndrome risk compared with non-carriers of A allele (odds ratio: 0.646, 95% confidence interval: 0.420-0.994, p = 0.043). Conclusions: The current findings revealed a gender-specific association of apelin-APJ system genetic polymorphisms with metabolic syndrome and glucose homeostasis disorders in a Han Chinese population.
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Background and Objectives: Growing evidence indicates that metabolic syndrome confers a differential risk for the development and progression of many types of cancer, especially in the digestive tract system. We here synthesized the results of published cohort studies to test whether baseline metabolic syndrome and its components can predict survival in patients with esophageal, gastric, or colorectal cancer. Methods: Literature retrieval, publication selection and data extraction were performed independently by two authors. Analyses were done using STATA software (version 14.1). Results: A total of 15 publications involving 54,656 patients were meta-analyzed. In overall analyses, the presence of metabolic syndrome was associated with a non-significant 19% increased mortality risk for digestive tract cancer (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.45 to 2.520.95 to 1.49, P = 0.130; I 2: 94.8%). In stratified analyses, the association between metabolic syndrome and digestive tract cancer survival was statistically significant in prospective studies (HR: 1.64, 95% CI: 1.18 to 2.28), in studies involving postsurgical patients (HR: 1.42, 95% CI: 1.06 to 1.92), and in studies assessing cancer-specific survival (HR: 1.91, 95% CI: 1.45 to 2.52). Further meta-regression analyses indicated that age and smoking were potential sources of between-study heterogeneity (both P < 0.001). The shape of the Begg's funnel plot seemed symmetrical (Begg's test P = 0.945 and Egger's test P = 0.305). Conclusions: Our findings indicate that metabolic syndrome is associated with an increased risk of postsurgical digestive tract cancer-specific mortality. Continued investigations are needed to uncover the precise molecule mechanism linking metabolic syndrome and digestive tract cancer.
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BACKGROUND AND AIM: Upregulation of prolyl isomerase-1 (Pin1) protein expression and activity was associated with the pathogenesis of diabetic vasculopathy through induction of endothelial oxidative stress and inflammation. Moreover, VDR agonist protects against high glucose-induced endothelial apoptosis through the inhibition of oxidative stress. We aimed to explore the effects of the VDR agonist on diabetes-associated endothelial dysfunction and the role of Pin1 in this process. METHODS: Streptozocin-induced diabetic mice were randomly treated with vehicle, VDR agonist (10 µg/kg/d, i.g., twice a week), or Pin1 inhibitor, Juglone (1 mg/kg/d, i.p., every other day), for eight weeks. In parallel, human umbilical vein endothelial cells (HUVECs) exposed to high-glucose condition were treated with 1,25-dihydroxyvitamin D3 and Juglone or vehicle for 72 hours. Organ chamber experiments were performed to assess endothelium-dependent relaxation to acetylcholine. Circulatory levels of Pin1, SOD, MDA, IL-1ß, IL-6, and NO in diabetic mice, Pin1 protein expression and activity, subcellular distribution of p66Shc, and NF-κB p65 in high glucose-cultured HUVECs were determined. RESULTS: Both VDR agonist and Juglone significantly improved diabetes-associated endothelial dysfunction and reduced high glucose-induced endothelial apoptosis. Mechanistically, the circulatory levels of SOD and NO were increased compared with those of vehicle-treated diabetic mice. Additionally, Pin1 protein expression and activity, p66Shc mitochondrial translocation, and NF-κB p65 in high glucose-cultured HUVECs were also inhibited by VDR agonist and Juglone. Knockdown of VDR abolished the inhibitory effects of VDR agonist on high glucose-induced upregulation of Pin1 protein expression and activity. CONCLUSIONS: VDR agonist prevents diabetic endothelial dysfunction through inhibition of Pin1-mediated mitochondrial oxidative stress and inflammation.
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Endotelio Vascular/patología , Inflamación/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Isomerasa de Peptidilprolil/antagonistas & inhibidores , Receptores de Calcitriol/uso terapéutico , Animales , Diabetes Mellitus Experimental/patología , Modelos Animales de Enfermedad , Humanos , Inflamación/patología , Masculino , Ratones , TransfecciónRESUMEN
BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity is a well-established pathological feature of major depression, accompanied by the persistent increase of glucocorticoid level and the dysfunction of hypothalamic-pituitary-gonadal (HPG) axis. Ginsenoside Rg1 (Rg1) is one of the most active ingredients of Panax ginseng, which has various biological activity. OBJECTIVE: This study aimed to investigate the antidepressive effects of Rg1 and elucidate its impact on neuroendocrine system. METHODS: The antidepressive effects of Rg1 were first analysed in mice, and was further identified in the chronic-unpredictable-mild-stress (CUMS) model and the gonadectomized (GDX) model. The effects of Rg1 on depression-like behaviour were analysed by the forced swimming test (FST), tail suspension test (TST), sucrose preference test, and measurement of pentobarbital-induced sleep. The serum corticosterone and testosterone levels were detected by ELISA. The protein levels of glucocorticoid receptor (GR) and androgen receptor (AR) were analysed by western blot and immunohistochemistry analysis. RESULTS: Rg1 significantly decreased the immobility time of mice in FST and TST. Furthermore, Rg1 alleviated anhedonia and hopelessness, decreased serum corticosterone level, and increased serum testosterone level, and the GR protein level in the PFC and hippocampus of the CUMS-treated rats. Moreover, Rg1 improved sleep disruption, down-regulated the serum corticosterone level, and increased AR protein level in the PFC of the GDX-treated mice. CONCLUSION: Together, these studies suggest that Rg1 displayed antidepressant activity through the modulation of the HPA and the HPG axis. These findings provide new mechanism involved in the antidepressive effects of Rg1 and propose theoretical clues for clinical therapies.
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Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Depresión/prevención & control , Ginsenósidos/farmacología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Testículo/efectos de los fármacos , Afecto/efectos de los fármacos , Animales , Corticosterona/sangre , Depresión/metabolismo , Depresión/fisiopatología , Depresión/psicología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Preferencias Alimentarias/efectos de los fármacos , Suspensión Trasera , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Orquiectomía , Ratas Sprague-Dawley , Receptores Androgénicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Sueño/efectos de los fármacos , Estrés Psicológico/complicaciones , Estrés Psicológico/psicología , Natación , Testículo/metabolismo , Testículo/fisiopatología , Testosterona/sangre , Factores de TiempoRESUMEN
IMM-H004, a 3-piperazinylcoumarin compound derived from coumarin, has been proved effective against CA1 cell loss and spatial learning impairments resulting from transient global ischemia/reperfusion (TGCI/R), while the mechanism is still largely unknown. Here, we confirmed that treatment of rats with IMM-H004 immediately after TGCI/R ameliorated delayed neuronal death (DND) in the CA1 of hippocampus and cortex. Further study suggested that IMM-H004 contributed to the expression of antiapoptotic protein survivin through the activation of PI3K-dependent protein kinase B (PKB/Akt), which led to the phosphorylation of forkhead box O1 (FoxO1), then relieved the inhibiting effect on survivin promoter. Additionally, IMM-H004 also enhanced the expression of hepatitis B X-interacting protein (HBXIP), which formed a complex with survivin to prevent the activation of caspase death cascade, thereby halting apoptotic cell death. Finally, we injected a HBXIP siRNA into hippocampus and performed microelectroporation before ischemia/reperfusion, which abolished the protective effect of IMM-H004. Further study revealed that HBXIP maintained the high expression of Akt and survivin. Collectively, our findings demonstrated that DND after TGCI/R was alleviated by IMM-H004 through promoting the formation of survivin-HBXIP complex, which further emphasized the importance of endogenous protein involved in self-repair after stroke.
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Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Cumarinas/administración & dosificación , Ataque Isquémico Transitorio/metabolismo , Ataque Isquémico Transitorio/prevención & control , Proteínas Asociadas a Microtúbulos/biosíntesis , Fármacos Neuroprotectores/administración & dosificación , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Expresión Génica , Ataque Isquémico Transitorio/genética , Masculino , Proteínas Asociadas a Microtúbulos/genética , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Survivin , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
Oxidative stress is mainly caused by reactive oxygen species (ROS). The damage causes a net stress on normal organs, leading to a gradual loss of vital physiological function. ROS, such as free radicals, represent a class of molecules which are derived from the metabolism of oxygen and exist inherently. However, excessive produced ROS can damage all aerobic organisms. Ginseng is one of the most commonly used alternative herbal medicines, also as a traditional Chinese medicine. The aim of this study is to investigate the antioxidant potential function of ginsenoside Rg1 against cisplatin-caused hepatic damage. Male mice were treated with cisplatin to induce oxidative stress to mimic the side effect of anti-cancer drug cisplatin. Ginsenoside Rg1 effectively prevented against cisplatin-induced hepatotoxicity, alleviating histological lesions. Antioxidant functions of Rg1 were restrained by the activation of p62-Keap1-Nrf2 signaling pathway, simultaneously accompanied with expression of protein products. Accumulative p62 and increased activation of JNK in hepatocytes promoted the activation of Nrf2. For the other, degradation of Nrf2 was guided by tyrosine phosphorylation, ubiquitin, and Keap1. In summary, Rg1 prevents hepatotoxicity mainly by inhibiting the binding of Keap1 and Nrf2, partly by p62 accumulation, and more importantly by increasing the production of antioxidative proteins associated to Nrf2. Pharmacological activation of Nrf2 is an effective way in combating against liver injury.
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Antineoplásicos/toxicidad , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cisplatino/toxicidad , Ginsenósidos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Antioxidantes/uso terapéutico , Evaluación Preclínica de Medicamentos , Ginsenósidos/uso terapéutico , Hígado/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , Estrés Oxidativo/efectos de los fármacos , Proteolisis , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Activación Transcripcional/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is the dried root of Panax ginseng C.A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Pharmacological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rg1 is the most pharmacological active one. AIM OF THE STUDY: Based on prior experimental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rg1 is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the underlying possible mechanisms. MATERIALS AND METHODS: C57BL/6 mice were given oral consumption of 6g/kg alcohol 1h after treated with Rg1 (10, 20 and 40mg/kg) or dexamethasone (1mg/kg) for 9 consecutive days. Biochemical analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. RESULTS: According to our data, Rg1 treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but restored in Rg1-treated groups. Overproductive inflammatory cytokines were also suppressed by Rg1 in alcohol-intoxicated mouse livers. In addition, changes of GR related NF-κB pathway, including phospho-IκB-α, were also modulated to normal levels. CONCLUSION: This study demonstrates that Rg1 might promote GR mediating the repression of NF-κB and inhibit the inflammatory reactions in alcoholic hepatitis.
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Antiinflamatorios/farmacología , Ginsenósidos/farmacología , Hepatitis Alcohólica/metabolismo , FN-kappa B/antagonistas & inhibidores , Sustancias Protectoras/farmacología , Alanina Transaminasa/sangre , Animales , Antiinflamatorios/uso terapéutico , Aspartato Aminotransferasas/sangre , Colesterol/sangre , Citocinas/metabolismo , Ginsenósidos/uso terapéutico , Hepatitis Alcohólica/sangre , Hepatitis Alcohólica/tratamiento farmacológico , Hepatitis Alcohólica/patología , L-Lactato Deshidrogenasa/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Panax , Raíces de Plantas , Sustancias Protectoras/uso terapéutico , Receptores de Glucocorticoides/metabolismo , Triglicéridos/sangreRESUMEN
Seven new 4-hydroxybenzyl-substituted glutathione derivatives (2-8), together with a known analogue (1), were isolated from the aqueous extract of Gastrodia elata Blume rhizomes. Their structures were determined by using spectroscopic and chemical methods. The absolute configurations of 1-8 were assigned by using Marfey's method, combined with comparing the NMR and CD spectroscopic data of sulfoxide moieties in 3-6 with those of S-(4-hydroxybenzyl)cysteine sulfoxide stereoisomers (9-12) synthesized as authentic samples. The configurations of 9-12 were confirmed by electronic CD calculations based on the quantum-mechanical time-dependent density functional theory. Furthermore, the structures of 1, 3, 5, 7, and 8 were verified by synthesis. Compound 3 was active against serum deprivation-induced PC12 cell damage and synthetic 9-14 exhibited activity against Fe(2+)-cysteine induced rat liver microsomal lipid peroxidation.
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Gastrodia/química , Glutatión , Animales , Glutatión/análogos & derivados , Glutatión/química , Glutatión/aislamiento & purificación , Glutatión/farmacología , Peroxidación de Lípido , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Células PC12 , Ratas , Rizoma/químicaRESUMEN
A gas chromatography/mass spectrometry (GC/MS) method was developed for the determination of multi-residues of steroid anabolic hormones epitestosterone (ETS), testosterone 17-propionate (PTS), nandrolone (17beta-NT), 17alpha-methyltestosterone (MTS), 17beta-estradiol (17beta-ES), estriol ( EST), 17alpha-ethinylestradiol (EES), estrone (ESN) and 17beta-estradiol 3-benzoate (BES) in the muscle tissues of various animal species. Homogenized tissue samples were enzymatically digested in acetate buffer (pH 5.0). Consequently, methanol was added and the mixtures were extracted under ultrasonication incubation. Clean-up was carried out for at least two times with methyl tert-butyl ether (MTBE) liquid-liquid partitioning followed by a reversed-phase solid phase extraction (SPE) cartridge purification. The eluate with methanol was evaporated to dryness by N2 at 40 degrees C and derivatization was achieved with N-methyl-N-( trimethylsilyl) trifluoroacetamide/iodotrimethylsilane/dithioerythritol (MSTFA-TMIS-DTE) at 60 degrees C for 45 min. The reaction mixture was injected into a gas chromatograph with a DB-1 capillary column coupled with a mass spectrometer. The samples were tested by different selected ion monitoring modes with electron impact (EI) source for the androgens and estrogens. The limits of quantitation (LOQ) for the above 9 hormones were in the range of 1.0 - 2.0 microg/kg. At the 2.0 microg/kg LOQ spiked level, the mean recoveries were within 62.5% - 80.5%, and the relative standard deviations were within 12.5% - 26.8%. The real sample tests showed this method can be used for the sensitive and accurate determination of multi-steroid anabolic hormones residues in biological muscle samples.
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Estradiol/análogos & derivados , Estradiol/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Metabolismo , Éteres Metílicos/química , Compuestos de Trimetilsililo/análisis , Acetamidas , Fluoroacetatos , Hormonas/análisis , Límite de Detección , Metiltestosterona/análisis , Esteroides/análisis , Ácido Trifluoroacético/análisis , Compuestos de Trimetilsililo/químicaRESUMEN
The presence of sulfonamide (SA) residues in foods is largely due to the raising of animals with sulfonamide antibiotics added or polluted feedstuff. Because of interference from the matrices, the commonly used immunoassay or chromatographic method is not suitable for the analysis of multi-SAs in feedstuff. A high performance liquid chromatographic-electrospray tandem mass spectrometric (HPLC/ESI-MS-MS) method has been established for the simultaneous determination of multi-SAs including sulfadiazine (SD), sulfapyridine (SPD), sulfamerazine (SM1), sulfameter (SM), sulfamethazine (SM2), sulfamethoxypyridazine (SMP), sulfamethoxazole (SMZ), sulfamonomethoxine (SMM), sulfadimethoxine (SDM) and sulfaquinoxaline (SQX). After solvent extraction, solid phase extraction, dilution and reversed-phase HPLC separation, SAs were detected by ESI-MS-MS under multi-reaction monitoring mode. The qualification analysis was done by using retention time and distribution of diagnostic ion pairs, and the quantification was based on the peak intensity of common fragment ion m/z 156. The limits of quantification for 10 SAs were 0.5 - 2.0 microg/kg (S/N = 10). The correlation coefficient of linear calibration curve was over 0.9995 within the SAs concentration range 2.0 - 200 microg/L except for SDM and SQX. At the spiked level of 1.0 mg/kg, the average recoveries for the 10 SAs were between 70% and 92%, the relative standard deviations were under 10% for intra-day and under 15% for inter-day. Routine tests showed the method was fast, sensitive, specific, and practical for the SAs determination in feedstuff.
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Alimentación Animal/análisis , Cromatografía Líquida de Alta Presión/métodos , Sulfonamidas/análisis , Sulfonamidas/química , Espectrometría de Masas en Tándem/métodos , Animales , Espectrometría de Masa por Ionización de Electrospray , Sulfadimetoxina/análisis , Sulfadimetoxina/química , Sulfameter/análisis , Sulfameter/química , Sulfametazina/análisis , Sulfametazina/química , Sulfametoxazol/análisis , Sulfametoxazol/química , Sulfametoxipiridazina/análisis , Sulfametoxipiridazina/química , Sulfamonometoxina/análisis , Sulfamonometoxina/química , Sulfapiridina/análisis , Sulfapiridina/química , Sulfaquinoxalina/análisis , Sulfaquinoxalina/químicaRESUMEN
OBJECTIVE: To establish a biological method for determining the macrolide content in various matrices. METHODS Human serum, urine and tissue homogenate samples were diluted or extracted with MSU buffer, and the specimens of grain and premixed feed extracted with methanol-H(3)PO(4) buffer, before microbial receptor competitive binding assay was carried out on these various specimens, with the elimination of interference from methanol with the M8 buffer. RESULTS: The method was sensitive, class-specific and precise, and the recommended screening concentrations for specimens of the serum, urine, tissue and grains were 200, 200, 100 and 1 200 ng/g (ng/ml), respectively, with a relative standard deviation less than 8%. CONCLUSION: Microbial receptor competitive binding assay is accurate and rapid for efficient qualitative and quantitative assay of the total macrolide content in various matrices.