Acerca de la muerte de Hernando de Magallanes: efectos de una flecha envenenada

Ferdinand Magellan's maritime expedition that resulted in the circumnavigation of the Earth and the discovery of the strait that bears his name is among the greatest feats in history. The trip, which took more than three years, was not completed by Magellan, who died on the island of Mactan, Philippines in a scuffle with the locals. As reported in Magellan's voyage journal written by Pigafetta, Magellan died after receiving a poisoned arrow in his right leg. This study reviews the main compounds used by indigenous from the Philippines and Southeast Asian to poison their arrows, their agents, and effects. These poisons are mainly derived from Aconitum and other species, such as Strychnos, Lophopetalum, Beaumontia, and Strophanthus. They contain cardiac alkaloids and glycosides, which can produce neurological and cardiac effects in just a few minutes. We argue that these toxic effects hindered the withdrawal of Magellan from the beach, facilitating his death in hands of the locals.

Intoxicación por adelfa, un caso poco frecuente / Oleander poisoning, a rare case

Introducción: Las intoxicaciones por plantas son infrecuentes, de complicada orientación diagnóstica, que en general, se dificulta la identificación de la planta, su potencial tóxico y el tratamiento específico. Entre ellas la adelfa, capaz de producir cuadros de intoxicación grave, como un caso consultado a la guardia del Centro Nacional de Toxicología. Objetivos: Presentar un caso clínico de intoxicación grave por adelfa. Caso clínico: Paciente adulto, con intranquilidad, vómitos, dolores abdominales, tensión arterial 150/90 mmHg, frecuencia cardiaca y respiratoria normales, refirió que había consumido vía oral y rectal una poción elaborada con una planta, como tratamiento antiparasitario. El médico de guardia decidió comunicarse con el Centro Nacional de Toxicología. Se identificó la planta como adelfa. A pesar de la aplicación de reposición de volumen, lavado gástrico y la administración de carbón activado; presentó bloqueo auriculoventricular, extrasístoles aisladas y bradicardia. Se suministró atropina endovenosa, luego se trasladó hacia la unidad de cuidados intensivos y posteriormente egresó. Conclusiones: El caso presentó una intoxicación aguda grave por adelfa, con un correcto diagnóstico y tratamiento, que requirió de la labor conjunta de los médicos del cuerpo de guardia del hospital, la terapia intensiva y del Centro Nacional de Toxicología(AU)

Introduction: Poisoning by plants is infrequent, with a complicated diagnostic orientation, which in general makes it difficult to identify the plant, its toxic potential and specific treatment. Among them the oleander, capable of producing serious intoxication, as a case consulted to the National Toxicology Center. Objectives: To present a clinical case of severe oleander poisoning. Clinical case: Adult patient with restlessness, vomiting, abdominal pain, blood pressure 150/90 mmHg, normal heart and respiratory rates, and reported that he had consumed orally and rectally a potion made with a plant, as an antiparasitic treatment. The doctor who assisted him decided to communicate with the National Toxicology Center. The plant was identified as oleander. Despite the application of volume replacement, gastric lavage and the administration of activated charcoal; the patient presented atrioventricular block, isolated extrasystoles and bradycardia, intravenous atropine was administered, and subsequent transfer to the intensive care unit, and later he was discharged. Conclusions: The case presented a severe acute oleander poisoning, there was correct diagnosis and treatment, which required the joint work of the doctors from hospital emergency, the intensive care unit and the National Toxicology Center(AU)

Research progress on chemical composition and pharmacological effects of Periplocae Cortex and predictive analysis on Q-marker / 中国中药杂志

Periplocae Cortex is a traditional Chinese medicine in China, which is mainly produced in northeast China, north China, northwest China, southwest China. In recent years, the increasing in-depth research resulted in the discovery of anti-tumor and cardiac pharmacological activities of Periplocae Cortex, which has broad application prospects. On the basis of summarizing chemical components and pharmacological effects, combined with the theoretical system of Q-marker, the quality control components of Periplocae Cortex were predicted from the aspects of the correlation between chemical composition and traditional medicinal properties, traditional efficacy, and new clinical use, plasma composition, measurable composition, storage time by analyzing literature. Among the components, periplocoside, periplocin, periplogenin, 4-methoxy salicylaldehyde showed significant activity, which provides a scientific basis for quality evaluation of Periplocae Cortex.

Advances in research on antitumor preparations of cardiac glycoside / 药学学报

Cardiac glycoside is a class of steroidal glycosides with significant physiological activities to the heart. Several drugs had been approved for the treatment of heart failure and atrial fibrillation. In recent studies, the researchers have found that cardiac glycoside can selectively inhibit the proliferation of human tumor cells and has potent antitumor efficacy. Unfortunately, the poor solubility and severe adverse effects of cardiac glycoside hindered further clinical application in the field of anticancer. It is an effective strategy to solve the "drug-like" problem of cardiac glycoside by changing the pharmacokinetics and distribution in vivo and reducing the dosage and side effects by virtue of modern preparations technology and treatment scheme. In this review, a brief introduction of the developmental course and mechanism of cardiac glycosides in anticancer field was made, and recent research progress of cardiac glycosides preparations were summarized and discussed. Finally, the further research direction was prospected.

Cardiac glycosides from Cascabela thevetioides by HPLC-MS analysis

Abstract The present work investigates the chemical composition of seeds of Cascabela thevetioides (Kunth) Lippold, an ornamental shrub of México. Six thevetia cardiac glycosides or thevetosides (thevetin A, B, and C, acetylthevetin A, B and C) were identified from the methanol extract of seeds of C. thevetioides by High-Performance Liquid Chromatography-Mass Spectrometry and by comparison of mass spectral fragmentation patterns. Enzymatic hydrolysis of a sample of thevetosides from methanol extract of seeds and subsequent High-Performance Liquid Chromatography-Mass Spectrometry analysis yielded the monoglycosides neriifolin, acetylneriifolin and acetylperuvoside, previously reported for this plant. For the fisrt time thevetin A, B and C, and acetylthevetin A, B and C are reported as components of seeds of C. thevetioides.

Analysis of chemical constituents of Jiashen Tablet extract by UPLC-Q-TOF-MS / 中草药

Objective To establish a method for the major content identification of Jiashen Tablet extract by using UPLC-Q-TOF-MS. Methods The chromatographic separation was executed on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with methanol-0.1% formic acid in water by gradient elution. Electrospray ionization (ESI) source was applied and operated in both positive and negative ion mode. Results A total of 72 compounds were found and 68 compounds among them were identified by the methods of comparing reference substance, matching Database and referencing related literature, including 13 phenolic acids, 6 tanshinones, 11 flavonoids and their glycosides, 4 cardiac glycosides, 15 triterpenoid saponins, 7 C21 steroids, and 13 other components. Conclusion This study introduces a comprehensive analysis method of chemical constituents in Jiashen Table extract. The results afford a significant guidance for the study of active constituents and quality control research for Jiashen Tablet.

Identification and screening of cardiac glycosides in Streptocaulon griffithii using an integrated data mining strategy based on high resolution mass spectrometry / 中国天然药物

The present study was designed to develop a practical strategy to tackle the problem of lacking standard compounds and limited references for identifying structure-related compounds in Streptocaulon griffithii Hook. f., especially those in trace concentrations, with a focus on antitumor activity. The cardiac glycosides (CGs)-enriched part was determined using in vitro bioactive assays in three cancer cell lines and then isolated using macroporous resins. The MS and MS/MS data were acquired using a high performance liquid chromatography coupled with hybrid quadrupole-time of flight (HPLC-Q-TOF-MS) system. To acquire data of trace compound in the extract, a multiple segment program was applied to modify the HPLC-Q-TOF-MS method. A mass defect filter (MDF) approach was employed to make a primary MS data filtration. Utilizing a MATLAB program, the redundant peaks obtained by imprecise MDF template calculated with limited references were excluded by fragment ion classification, which was based on the ion occurrence number in the MDF-filtered total ion chromatograms (TIC). Additionally, the complete cleavage pathways of CG aglycones were proposed to assist the structural identification of 29 common fragment ions (CFIs, ion occurrence number ≥ 5) and diagnostic fragment ions (DFIs, ion occurrence number < 5). As a result, 30 CGs were filtered out from the MDF results, among which 23 were identified. This newly developed strategy may provide a rapid and effective tool for identifying structure-related compounds in herbal medicines.

Identification and screening of cardiac glycosides in Streptocaulon griffithii using an integrated data mining strategy based on high resolution mass spectrometry / 中国天然药物

The present study was designed to develop a practical strategy to tackle the problem of lacking standard compounds and limited references for identifying structure-related compounds in Streptocaulon griffithii Hook. f., especially those in trace concentrations, with a focus on antitumor activity. The cardiac glycosides (CGs)-enriched part was determined using in vitro bioactive assays in three cancer cell lines and then isolated using macroporous resins. The MS and MS/MS data were acquired using a high performance liquid chromatography coupled with hybrid quadrupole-time of flight (HPLC-Q-TOF-MS) system. To acquire data of trace compound in the extract, a multiple segment program was applied to modify the HPLC-Q-TOF-MS method. A mass defect filter (MDF) approach was employed to make a primary MS data filtration. Utilizing a MATLAB program, the redundant peaks obtained by imprecise MDF template calculated with limited references were excluded by fragment ion classification, which was based on the ion occurrence number in the MDF-filtered total ion chromatograms (TIC). Additionally, the complete cleavage pathways of CG aglycones were proposed to assist the structural identification of 29 common fragment ions (CFIs, ion occurrence number ≥ 5) and diagnostic fragment ions (DFIs, ion occurrence number < 5). As a result, 30 CGs were filtered out from the MDF results, among which 23 were identified. This newly developed strategy may provide a rapid and effective tool for identifying structure-related compounds in herbal medicines.

Dogs poisoned with Nerium oleander fresh leaves: clinical and electrocardiographic findings / Cães intoxicados com folhas frescas de Nerium oleander: achados clínicos e eletrocardiográficos

ABSTRACT: Nerium oleander is distributed worldwide, mainly in tropical and subtropical regions. These shrubs are frequently used as ornamental plants. However, they contain more than 30 cardiac glycosides that can cause serious toxic effects in dogs. The objective of this study was to report the clinical and electrocardiographic alterations in dogs experimentally poisoned with N. oleander. Ten adult, healthy, mixed-breed dogs weighing 10-25kg and aged 3-6 years were selected for the study. We orally administered 0.25g kg-1 of fresh ground leaves of N. oleander to the dogs. No dog died after the ingestion, but all exhibited signs of poisoning such as vomiting, sialorrhea, nausea, apathy, conjunctiva congestion, dehydration, abdominal pain, tremors, diarrhea, loss of appetite, and tenesmus. Electrocardiogram revealed occurrence of several types of arrhythmias: sinus bradycardia, second-degree atrioventricular block, paroxysmal ventricular tachycardia, and ventricular premature complexes. Systolic blood pressure, as well as heart rate, decreased in the first 24 hours. The present study concluded that a single dose of 0.25g kg-1 of N. oleander green leaves is sufficient to cause a moderate intoxication in dogs, with nonspecific clinical changes mainly related to the digestive system and heart rate, thus demonstrating the importance of this type of intoxication in the list of differential diagnoses of small animals routine.

RESUMO: O Nerium oleander é uma planta com ampla distribuição mundial, principalmente em regiões tropicais e subtropicais. Esses arbustos são frequentemente usados como plantas ornamentais e possuem mais de 30 glicosídeos cardíacos causadores do quadro clínico de intoxicação em caninos. Sabendo-se disso, este artigo teve por objetivo a avaliar as alterações clínicas e eletrocardiográficas, nos animais intoxicados experimentalmente com N. oleander. Foram utilizados 10 cães adultos, hígidos, sem raça definida, com 10 a 25kg de peso, de 3 a 6 anos de idade. Os animais receberam uma única dose de 0,25g kg-1 de peso, de folhas frescas de N. oleander. Nenhum dos animais do experimento veio a óbito. Os sinais clínicos observados foram vômito, sialorréia, náuseas, apatia, conjuntiva ocular congesta, desidratação, dor abdominal, tremores, diarreia, inapetência e tenesmo. Pela análise do eletrocardiograma encontraram-se arritmias como: bradicardia sinusal, bloqueios atrioventriculares de segundo grau, taquicardia ventricular paroxística e complexo ventricular prematuro. A pressão arterial sistólica diminui nas primeiras 24 horas, assim como a frequência cardíaca. Concluiu-se com o presente estudo que uma única dose de 0,25g kg-1 de folhas verdes de N. oleander é suficiente para causar um quadro moderado de intoxicação em cães, com alterações clínicas inespecíficas principalmente relacionadas ao sistema digestório e no ritmo cardíaco, mostrando a importância deste tipo de intoxicação na lista de diagnósticos diferenciais da rotina de pequenos animais.

Exploration of the Micro-lecture Design of Pharmacology Based on the Sample of Positive Inotropic Effect and Mechanism of Cardiac Glycosides / 中国药房

OBJECTIVE:To provide reference for the application of micro-lecture in pharmacology teaching. METHODS:Based on a correct view of micro-lecture and the sample of positive inotropic effect and mechanism of cardiac glycosides,mi-cro-lecture design of pharmacology was explored from aspects of design objects,contents,technical support and application mode. RESULTS:As the main carrier of micro-lecture,video took the advantages of topic prominence,resource diversity,short and pithy and easy to use;the objects were five-year undergraduate medical students of the Jiangxi Univesity of Traditional Chinese Medicane;and the key and difficult points in pharmacology courses were selected for the complete teaching of these points in a short time as much as possible;record screen-based software model was conduced for video making and the course was uploaded to Kingsoft disk sharing. CONCLUSIONS:As a new teaching mode,course design is the basis and it is essential for the smooth de-velopment. A good micro-lecture design has positive improvement effect on improving the teaching efficacy of Pharmacolgy tradi-tional class.

Concentrações de oleandrina nas folhas de Nerium oleander de diferentes cores da floração / Oleandrin concentrations in leaves of Nerium oleander of different colors of flowering

Nerium oleander é uma planta ornamental responsável por intoxicações em animais e humanos. Todas as partes da planta contém glicosídeos cardiotóxicos, principalmente a oleandrina. Alguns autores apontam que a toxicidade da planta apresentaria variação em função da cor da flor. O objetivo deste trabalho foi determinar se existe variação na concentração de oleandrina nas folhas de N. oleander de exemplares da planta com diferentes cores de inflorescências. Foram coletadas 10 amostras de folhas para cada tipo de flor (branca, rosea e vermelha). Os níveis de oleandrina foram determinados por meio de HPLC-UV após extração com metanol, precipitação com acetato de chumbo e separação em cartucho de C18. A média da concentração obtida em todas as folhas analisadas foi de 4,89mg g-1, sendo 6,20±4,08mg g-1 na variedade de flores brancas, 4,16±3,44mg g-1 na de flores roseas e 4,31±1,99mg g-1 na de flores vermelhas. As concentrações de oleandrina não apresentaram diferença estatisticamente significante entre as variedades de flores.

Nerium oleander is an ornamental plant responsible for poisoning in animals and humans. All parts of the plant contain cardiotoxic glycosides, mainly oleandrin. Some authors suggest that the toxicity of the plant would present a dependence on flower color. The objective of this study was to determine whether there is variation in the concentration of oleandrin in the leaves of N. oleander specimens of different colors of flowers. Ten samples of leaves from each variety of flower (white, pink and red) were collected. Oleandrin levels were determined by HPLC-UV after extraction with methanol, precipitation with lead acetate and separation with C18 cartridge. The average concentration obtained in all analyzed leaves was 4.89mg g-1, being 6.20±4.08mg g-1 in variety of white flowers, 4.16±3.44mg g-1 in pink flowers, and 4.31±1.99mg g-1 in red flowers. The concentrations of oleandrin did not show statistically significant difference between the varieties of flowers.

Genus Kalanchoe (Crassulaceae): A Review of Its Ethnomedicinal, Botanical, Chemical and Pharmacological Properties.

Genus Kalanchoe comprises hundred species. Different extracts of these Kalanchoe species have been widely used in traditional medicine. Recently it has been reported that Kalanchoe extracts possess various biological activities viz. antiviral, sedative, antiulcer, immunomodulatory, antileishmanial, CNS depressant, anti-inflammatory, thyroid peroxidase inhibitor, cytotoxic, hepatoprotective, antioxidant, analgesic, anticonvulsant, antimicrobial, inhibition of B cell development, cardiovascular, antihyperglycemic, acetylcholinesterase inhibition, insecticidal and larvicidal activities. Earlier studies on different Kalanchoe species have reported the isolation of polysaccharides, flavonoids, sterols, ascorbic acid, trace elements, organic acids, hydrocarbons, triterpenoids, phenolic components and bufadenolides. This review presents the botany, chemistry, traditional uses and pharmacological data of genus Kalanchoe.

Research progress on pharmacokinetics of cardiac glycosides / 中草药

Cardiac glycosides are proven to be effective in the clinical treatment for chronic heart failure and certain types of arrhythmia, especially for antitumor treatment. This paper focused on the research progress on pharmacokinetics of cardiac glycosides in recent years, elucidated the behaviors of absorption, distribution, metabolism, and excretion in vivo and in vitro, and summarized the metabolism of this kind of drug, aiming to provide an evidence for new drug research as well as a reference for the clinical safe use of these drugs.

Non-fatal oleander poisoning: A case report.

In rural India, traditional methods are often employed for treatment of ailments and also for getting rid of unwanted pregnancy. Nerium oleander (common oleander) is one such plant, the leaves and roots of which are used in Indian traditional medicine and the root is often used by rural folk as abortifacient. In this paper, the case of a 20-year old girl who had developed signs and symptoms of oleander poisoning as a result of consumption of a drink prepared by boiling the root of oleander is presented. Even though oleander poisoning has been reported to be a common occurrence in many parts of India, it is a rare occurrence in the State of Manipur.

Digitálicos: os resultados do DIG no século XXI / Digoxin: the results of the DIG study in the XXI century / Digitálicos: los resultados del DIG en el siglo XXI

Depois da divulgação de que não houve significância estatística na mortalidade geral do estudo DIG, a indicação dos digitálicos nos esquemas de tratamento da insuficiência cardíaca congestiva (ICC) reduziu drasticamente. Estudos post hoc, que reavaliaram os dados do DIG, indicaram que um aspecto não considerado neste ensaio multicêntrico exerce influência decisiva no prognóstico dos pacientes: a concentração sérica da digoxina. Em relação àqueles que receberam placebo, a mortalidade geral e a hospitalização foram reduzidas em pacientes com concentração de digoxina inferior a 0,9 ng/ml. No primeiro trabalho que avaliou a influência dos digitálicos em modelo experimental de ICC, verificamos em nosso laboratório que ratas com síndrome congestiva secundária a infarto do miocárdio têm a sobrevida prolongada sob tratamento com digitoxina. As informações atuais recomendam que os méritos dos digitálicos continuem a ser analisados para estabelecer adequadamente sua importância no tratamento da ICC.

After the report that there was no statistical significance in the general mortality of the DIG study, the indication of digoxin in the treatment regimens for congestive heart failure (CHF) drastically decreased. Post hoc studies that reassessed the DIG study data, indicated that an aspect that was not considered in this multicenter study has a critical influence on the prognosis of patients: the serum levels of digoxin. Regarding those that received a placebo, the general mortality and hospitalization were decreased in patients with a digoxin level < 0.9 ng/ml. At the first study that assessed the influence of digitalis in an experimental model of CHF, we verified in our lab that female rats with congestive syndrome secondary to myocardial infarction have a prolonged survival when undergoing treatment with digitoxin. The current information recommends that the merits of digoxin continue to be analyzed in order to adequately establish its importance in the treatment of CHF.

Después de la divulgación de que no hubo significancia estadística en la mortalidad general del estudio DIG, la indicación de los digitálicos en los esquemas de tratamiento de la insuficiencia cardíaca congestiva (ICC) se redujo drásticamente. Estudios post hoc, que reevaluaron los datos del DIG, indicaron que un aspecto no considerado en este ensayo multicéntrico ejerce influencia decisiva en el pronóstico de los pacientes: la concentración sérica de la digoxina. En relación a aquellos que recibieron placebo, la mortalidad general y la hospitalización fueron reducidas en pacientes con concentración de digoxina inferior a 0,9 ng/ml. En el primer trabajo que evaluó la influencia de los digitálicos en modelo experimental de ICC, verificamos en nuestro laboratorio que ratas con síndrome congestivo secundario a infarto de miocardio tienen la sobrevida prolongada bajo tratamiento con digitoxina. Las informaciones actuales recomiendan que los méritos de los digitálicos continúen a ser analizados para establecer adecuadamente su importancia en el tratamiento de la ICC.

Effects of GHSC-73 on proliferation and cell cycle of human hepatocellular carcinoma HepG2 cells / 第二军医大学学报

Objective: To investigate the effects of β-D-glucosyl-(1-4)-α-L- thevetosides of 17β-digitoxigenin (GHSC-73), an isolate from the seeds of Cerbera manghas L., on cell growth and cell cycle regulation of human hepatocellular carcinoma cell line HepG2, and to discuss the related mechanism. Methods: HepG2 cells were treated with different concentrations (0-80 μmol/L) of GHSC-73. Cell viability was determined using MTT assay at 24, 48, and 72 h after treatment. Cell cycle distribution was assessed by flow cytometry after propidium iodide (PI) staining. Expression of the S phase associated genes GADD153, cyclin D1, cyclin A2, DHFR, TYMS, and p21 was determined by real-time RT-PCR before and after GHSC-73 treatment. Results: GHSC-73 inhibited the cell proliferation of HepG2 cells in a dose- and time-dependent manner. The values of IC50 were (5.18±0.21), (0.37±0.08), and (1.66±0.16) μmol/L at 24, 48, and 72 h, respectively. Compared with control group, the proportion of cells in S phase increased in the treatment group with the prolongation of treatment, the cells in G0/G 1 phase gradually decreased (P<0.05), and cells in G2/M phase remained unchanged, indicating that GHSC-73 blocked HepG2 cell in S phase. Real-time RT-PCR showed that cyclin A2, DHFR, and TYMS were down-regulated, and p21, GADD153, and cyclin D1 were up-regulated, which might be associated with the GHSC-73-induced S phase arrest in HepG2 cells. Conclusion: GHSC-73 can inhibit growth of HepG2 cells by inducing S phase arrest) down-regulation of cyclin A2, DHFR, and TYMS genes and upregulation of p21, GADD153, and cyclin D1 genes might participate in the induction of arrest.

Na+ ,K+ -ATPase and cerebral ischemia / 国际脑血管病杂志

The basic functions of the Na+/K+ -ATPase is to maintain the balance of the Na+/K+ electrochemical gradient. The latter is indispensable for maintaining cell osmotic pressure,regulating cell volume,and maintaining excitable membrane resting potential. The maintenance of the Na+/K+ -ATPase activity plays the important roles in neurotransmitter uptake in neurons and Ca2+ effiux. The decreased Na+/K+ -ATPase activity and dysfunction participate in the process of ischemic brain injury after cerebral ischemia. Ischemic precondi-tioning induces ischemic tolerance by maintaining the Na+/K+ -ATPase activity after ischemia.Cardiotonic steroids and citicoline may play a neuroprotective effect on cerebral ischemia by improving the Na +/K+ -ATPase activity.

Ultrastructural changes of myocardium in cardiacglycosides toxicosis and the protective effect of mannitol / 中国病理生理杂志

ⅳ Hydroxyl scavenger, mannitol, in the dosage of 1.1mol/L 2g/kg and 3g/kg could increase LD_(100) of ouabain on guineapigs from 298.54?33.30 ?g/kg to 367.44?44.58 ?g/kg (P

EFFECTS OF ERYSIUM CHEIRANTHOIDES L TOTAL CARDIAC GLYCOSIDES ON PHYSIOLOGICAL PROPERTIES OF GUINEA PIG LEFT ATRIA / 中国药理学通报

Total cardiac glycosides isolated from dry fruit of Erysium chei- ranthoides L ( ETCG ) possesed positive inotropic effect. Its effects on the physiological properties of guinea pig left atria were studied. in this paper. The effects of ETCG on dose-response curve were investigated. The results showed that ETCG increased contractility of left atria significantly and dose-dependently .The pD2 value was 7.94. ETCG ( 0.17mg/L)increased significantly excitability and automaticity induced by epinephrine. ETCG(0.01mg/L ,0 .043mg/L ,0 .17mg/L)prolonged functional refractory period obviously.

Monoclonal Antibodies Against Digoxin:The Development of Specific Antibody Secreting Hybridoma Cell Lines and Antibody Characterization / 中国免疫学杂志

In order to help the clinical use and pharmacological study of cardiac glycosides, we developed eight hybridoma cell lines which could secrete specific monoclonal ant- ibodies against digoxin.Digoxin was coulped to ovalbumin(Dig-OVA)or bovine serum albumin(Dig-BSA)by the periodate oxidation method.BALB/c mice were immunized with the mixture of Dig-OVA and complete Freund's adjuvant i.p.fourteen days bef- ore fusion.From the five to two days before fusion,the mice were boosted i.p.and i.v.daily.Spleen cells from the immunized mouse were fused with SP2/0 mouse myelo- ma line.Screened by indirect ELISA using Dig-BSA as the immobilized antigen and subcloned three or four times,eight hybridoma cell lines secreting specific monoclonal antibodies against digoxin were established.Those hybridomas could also produce mo- use antibody-enriched ascites in vivo.In contrast to the immunized animale sera,all the eight monoclonal antibodies had no reaction to the carrier proteins.Results show- ed those monoclonal antibodies with different immunoglobulin H chain isotypes,five IgGl,two IgG2b and one IgM,had variant affinity to digoxin.Fine specificity determ- ination showed the seven IgG antibodies had different binding styles to ten different steroid structures,which suggested their affinity to different portion on the haptens tested.Experiment with rabbit red blood cells showed one of the high affinity mono- clonal antibodies(FD8,IgGl)could antagonize the inhibition of Na~+-K~+ ATPase activity by digoxin in vitro and in vivo.Antibody FD8 could further reverse lethal digoxin toxicity completely in Guinea pigs.It is suggested that those monoclonal antibodies could be used to develop highly sensitive immunological detection for mo- nitoring blood digitalis concentration,to study the pharmacological mechanism of ca- rdiac glycosides,as well as to rescue severe digitalis toxicity.