Pharmacokinetics of two recombinant humanized monoclonal antibodies against ricin in rhesus monkeys / 药学学报

Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between Cmax and AUC0-5d in the two groups. The liquid preparation was the reference preparation, with Cmax ratio of 101.6% and AUC0-5d ratio of 101.9%, the 90% confidence interval of Cmax was 79.42%-129.92%, and the 90% confidence interval of AUC0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

Novel small molecule retrograde transport blocker confers post-exposure protection against ricin intoxication

Ricin is a highly toxic type 2 ribosome-inactivating protein (RIP) which is extracted from the seeds of castor beans. Ricin is considered a potential bioterror agent and no effective antidote for ricin exists so far. In this study, by structural modification of a retrograde transport blocker Retro-2, a series of novel compounds were obtained. The primary screen revealed that compound has an improved anti-ricin activity compare to positive control. pre-exposure evaluation in Madin-Darby Canine Kidney (MDCK) cells demonstrated that is a powerful anti-ricin compound with an EC of 41.05 nmol/L against one LC (lethal concentration, 5.56 ng/mL) of ricin. Further studies surprisingly indicated that confers post-exposure activity against ricin intoxication. An study showed that 1 h post-exposure administration of can improve the survival rate as well as delay the death of ricin-intoxicated mice. A drug combination of with monoclonal antibody mAb4C13 rescued mice from one LD (lethal dose) ricin challenge and the survival rate of tested animals is 100%. These results represent, for the first time, indication that small molecule retrograde transport blocker confers both and post-exposure protection against ricin and therefore provides a promising candidate for the development of anti-ricin medicines.

Terrorismo químico: proposta de modelagem de risco envolvendo ricina em eventos de grande visibilidade no Brasil / Chemical terrorism: risk modeling proposal for attacks involving ricin in mass gatherings in Brazil

RESUMO Grandes eventos estão no centro de estratégias terroristas e vem-se repetindo com frequência no âmbito internacional. Durante os últimos anos, o Brasil é palco de megaeventos esportivos; e este ano sediará a Copa do Mundo Fifa Sub-17. Assume-se que a maior exposição, nesses contextos, aumenta a vulnerabilidade ante as ameaças não convencionais, assim, é necessário que o planejamento da segurança brasileira seja apoiado em estudos sobre gestão de risco. Considera-se que um maior conhecimento sobre o tema é o primeiro passo para um sistema de defesa eficiente. A literatura apresenta relatos de episódios de emprego da ricina como arma química. Assim, este estudo objetivou avaliar a probabilidade de risco de um ataque terrorista com ricina, em um modelo matemático. Para isso, foi utilizada a teoria dos jogos e a equação de probabilidade de Major para análise de risco de terrorismo. A escolha da ricina justifica-se pelo fato de se tratar de uma biotoxina de extração relativamente simples, proveniente da mamona, que é uma planta endêmica no território brasileiro. Os parâmetros analisados foram os recursos de ataque, defesa e valor do alvo. A equação de probabilidade foi otimizada para defesa.

ABSTRACT Mass gatherings are at the center of terrorist strategies and are being repeated more frequently at international level. During the last years, Brazil has been the stage of mass gatherings, and it is supposed to host the Fifa Sub-17 World Cup this year. It is assumed that large exposure in these contexts increases vulnerability to threats, therefore it is necessary that safety planning be supported in risk management studies. It is considered that a greater knowledge of the topic is the first step towards an efficient defense system. This study aims to evaluate the probability of a ricin terrorist attack on a mathematical model. Existing literature shows reports of episodes of use of ricin as a chemical weapon. The choice of ricin is justified because it's a relatively easy biotoxin extraction from castor bean, which is an endemic plant in the Brazilian territory. For such study, we used game theory and the Major probability equation for terrorism risk analysis. The parameters analyzed were the resources of attack, defense, and value of the target. The probability equation has been optimized for defense.

Avaliação de diferentes processos de destoxificação sobre o valor nutricional e energético da torta de mamona para suínos / Evaluation of different detoxification procedures on nutritional and energy value of castor bean cake for pigs

O objetivo do presente estudo foi avaliar o valor nutricional e energético da torta de mamona destoxificada por diferentes métodos para suínos em crescimento. Foram utilizados 24 suínos machos, castrados, distribuídos em seis tratamentos, sendo uma ração referência e cinco rações testes (75% da dieta referência e 25% das tortas de mamona) contendo a torta de mamona destoxificada pelos métodos do hidróxido de cálcio, da autoclavagem, do hidróxido de cálcio+ensilagem, da autoclavagem+ensilagem e da extrusão. As tortas de mamona submetidas aos processos de destoxificação com hidróxido de cálcio e autoclavagem resultaram em maior teor de proteína digestível. Para o valor de energia metabolizável, os processos de destoxificação com hidróxido de cálcio, autoclavagem, hidróxido de cálcio+ensilagem e extrusão não diferiram entre si. Considerando-se a valoração nutricional e energética da torta de mamona por meio dos processos de destoxificação, os métodos com uso de hidróxido de cálcio e autoclavagem são os mais eficientes.(AU)

The aim of this study was to evaluate the nutritional and energy value of castor bean cake detoxified by different methods for growing pigs. A total of 24 barrows was distributed in six treatments, being in a reference diet and 5 test diets (75% of the reference diet and 25% of castor beam cake) containing castor bean cake detoxified by the method of calcium hydroxide, autoclaving, calcium hydroxide + silage, autoclaving + silage and extrusion. Castor bean cake subjected to detoxification processes with calcium hydroxide and autoclaving resulted in higher content of digestible protein. For the metabolizable energy value, the process of detoxification with calcium hydroxide, autoclaving, calcium hydroxide+silage, and extrusion did not differ. Considering the nutritional and energy valuation of castor bean cake detoxified by different procedures, the methods using calcium hydroxide and autoclaving were the most efficient.

Ricin and its antidote agents:research advances / 国际药学研究杂志

Ricin is a highly toxic plant protein produced by the seeds of the castor plant. It belongs to the ribosome inactivat-ing proteins(RIP)family and causes cell death by inhibiting the protein synthesis activity of ribosome. Ricin takes a unique pathway calledretrograde trafficking pathwayto enter the cytosol,where it interacts with ribosome and then exerts its inhibitory activity. No effective antidote agents have been developed for the treatment of ricin poisoning. In this paper,the structure,cell trafficking process, toxicological mechanism and the research progress in ricin antitoxin agents are reviewed.

Ricin and its antidote agents: Research advances / 国际药学研究杂志

Ricin is a highly toxic plant protein produced by the seeds of the castor plant. It belongs to the ribosome inactivating proteins (RIP) family and causes cell death by inhibiting the protein synthesis activity of ribosome. Ricin takes a unique pathway called "retrograde trafficking pathway" to enter the cytosol, where it interacts with ribosome and then exerts its inhibitory activity. No effective antidote agents have been developed for the treatment of ricin poisoning. In this paper, the structure, cell trafficking process, toxicological mechanism and the research progress in ricin antitoxin agents are reviewed.

Study on immune mechanism of a recombinant ricin B chain protein against ricin intoxication in BALB/c mice / 中国免疫学杂志

Objective:To explore the immunity provided to BALB/c mice by immunization with the recombinant ricin B chain protein (rRTB). Methods:Female BALB/c mice were randomly selected into rRTB-vaccinated group and PBS group. Mice were subcu-taneously (s. c. ) injected four times with 14 days immunization time interval. Changes of antibodies (IgG,IgG1and IgG2a) in serum were detected by ELISA. Meanwhile,the expression of IL-4 and IFN-γ were detected by flow cytometry. Results:The mean IgG titers reached 106 after the fourth immunization and a strong secondary response was induced in vaccinated mice when challenged with toxin. There was significant difference between rRTB-vaccinated group and PBS group ( P<0. 05 ) . The same result was shown in IgG1. However,no changed was detected in IgG2a. Meanwhile,there was significant difference for IL-4 between two groups (P<0. 05), while no significant difference for IFN-γwas observed. Conclusion:rRTB can produce higher levels of antigen-specific antibodies ( IgG and IgG1),and cytokine (IL-4) of splenocytes,which means the recombinant protein can induce the Th2-type immune response and trigger a good immune response. rRTB may be a potentially valuable vaccine candidate against human exposure to AT.

Toxicity and treament of ricin poisoning:a review / 中国药理学与毒理学杂志

Ricin is a plant toxin isolated from the seed of the castor plant(Ricinus communis). As a typical II ribosome inactivating protein,ricin consists of two polypeptide chains named ricin toxin A chain(RTA)and ricin toxin B chain(RTB),linked via a disulfide bridge. RTB binds to both glycopro?tein and glycolipid at the surface of the target cell and mediates ricin to be endocytosed and transported retro?gradely to the endoplasmic reticulum. After being reduced and retrotranslocated to the cytosol,RTA mediates its toxicity due to its activity of a RNA N- glycosidases. Aside from its main toxic effect of protein synthesis inhibition,ricin also displays other properties that contribute to its toxicity such as inducing apoptosis,cytokine secreting and peroxidation. Ricin is stable and can be easily isolated. It has many routes of intoxication with no specific antidotes. Due to its natural abundance,remarkable toxicity,and the potential to be used in biological warfare as well as terrorist attacks,ricin has been classified as a Category B biothreat agent. Here we reviewed its history as a biothreat agent,constitu?tion,intoxication mechanism,detection methods and the development of specific antitodes.

Preparation of monoclonal antibodies against ricin toxin and development of up-converting phosphor technology-based lateral flow assay for its quantitative detection / 军事医学

Objective To develop an up-converting phosphor technology based lateral flow assay ( UPT-LF) to detect ricin toxin ( RT) quickly, accurately and quantitatively.Methods Ricin-monoclonal antibodies were prepared and their affinity was evaluated before four types of monoclonal antibodies with the highest titer were applied to couple with the up-converting phosphor nano-particles ( UCP-NPs) as the bio-conjugate and disperse on the analysis membrane as the test line, respectively.Following systematic optimization to establish the RT-UPT-LF strip, the sensitivity, precision, quantita-tive ability and specificity of RT-UPT-LF were evaluated.Results The detection could be accomplished within 15 min and the detection limit of the RT-UPT-LF assay could reach 0.5 ng/ml within the quantitative detection range of 0.5-1000 ng/ml.Other non-specific toxins at a concentration of 1000 ng/ml did not cause any non-specific reactions.Conclusion The developed RT-UPT-LF strip provides a new means for on-site quantitative detection of ricin toxin.

Torta de mamona destoxificada para alimentação de poedeiras comerciais / Detoxified castor cake feed for laying hens

Objetivou-se com este experimento avaliar o efeito da inclusão de torta de mamona destoxificada (TMD) na ração de poedeiras comerciais sobre o desempenho e a qualidade interna e externa dos ovos. Foram utilizadas 200 poedeiras comerciais de 40 a 50 semanas de idade, da linhagem Hy-Line W-36®, com 1543±34g de peso corporal, que foram distribuídas em um delineamento inteiramente casualizado com cinco tratamentos (0, 5, 10, 15 e 20% de torta de mamona destoxificada na ração) com cinco repetições de oito aves cada. Foram avaliados o consumo de ração, a produção, o peso e a massa de ovos e a conversão alimentar. A qualidade interna foi avaliada por meio da unidade de Haugh, percentual de albúmen e de gema. A qualidade da casca foi medida pela espessura, densidade específica e percentual de casca. As variáveis de desempenho foram afetadas pela inclusão da TMD com resposta linear negativa para o consumo de ração e quadrática para produção de ovos, peso do ovo, massa do ovo e conversão alimentar, com os melhores níveis de 10,5, 5,7, 9,2 e 10,3% respectivamente. Não houve efeito significativo da inclusão da TMD para as variáveis de qualidade interna e externa dos ovos. Concluiu-se que a TMD pode ser incluída na ração de poedeiras em até 5,7% para otimizar o desempenho e não alterar a qualidade interna e externa dos ovos.

This experiment aimed to evaluate the use of detoxified castor cake (DCC) in the diet of laying hens on performance and internal and external quality of eggs. A total of 200 laying hens with 40-50 weeks of age, of Hy-Line W-36® line, with 1543±34g body weight, were distributed in a completely randomized design with five treatments (0, 5, 10, 15 and 20% of DCC in diet) with five replicates of eight birds each. The feed intake, egg production, egg weight, egg mass and feed conversion were evaluated. The egg internal quality was evaluated by Haugh unit, percentage of albumen and yolk. The shell quality was evaluated by the thickness, density and specific percentage of eggshell. The performance variables were affected by the inclusion of DCC with a negative linear response to food intake and quadratic for egg production, egg weight, egg mass and feed conversion, with the best levels of 10.5, 5.7, 9.2 and 10.3% respectively. There was no significant effect of DCC inclusion for the variables of egg quality. It is conclude that the DCC can be included in hens diets up to 5.7% to optimize performance and do not alter the internal and external quality of the eggs.

Cloning and chloroplast-targeted expression studies of insect-resistant gene with ricin fusion-gene under chloroplast transit peptide in cotton

Background: Transgenic plants inhabiting single Bt gene are prone to develop insect resistance and this resistance has been reported in case of some important yield-devastating insect larvae of commercial crops, such as cotton and rice. Therefore, it has become essential to adapt new strategies to overcome the problem of insect resistance and these new strategies should be sophisticated enough to target such resistant larvae in broad spectrum. Among these, plants may be transformed with Bt gene tagged with some fusion-protein gene that possesses lectin-binding capability to boost the binding sites for crystal protein gene within insect mid-gut in order to overcome any chances of insect tolerance against Bt toxin. Enhanced chloroplast-targeted Bt gene expression can also help in the reduction of insect resistance. Results: In the present investigation, a combined effect of both these strategies was successfully used in cotton (G. hirsutum). For this purpose, plant expression vector pKian-1 was created, after a series of cloning steps, carrying Cry1Ac gene ligated with chloroplast transit peptide towards N-terminal and Ricin B-Chain towards C-terminal, generating TP-Cry1Ac-RB construct. Conclusions: Efficacy of pKian-1 plasmid vector was confirmed by in-planta Agrobacterium-mediated leaf GUS assay in tobacco. Cotton (G. hirsutum) local variety MNH-786 was transformed with pKian-1 and the stable integration of TP-Cry1Ac-RB construct in putative transgenic plants was confirmed by PCR; while fusion-protein expression in cytosol as well as chloroplast was substantiated by Western blot analysis. Whereas, confocal microscopy of leaf-sections of transgenic plants exposed that hybrid-Bt protein was expressing inside chloroplasts.

Determination of MIL50, a humanized antibody, in different tissues of rats by a sandwich enzyme-linked immunosorbent assay / 军事医学

Objective To develop a sandwich enzyme-linked immunosorbent assay ( ELISA) for the determination of a humanized antibody MIL50.Methods RiVax, a mutant of RTA (a chain of ricin) expressed in E.coli, was used as the coating protein.Horseradish peroxidase (HRP) labeled IgG of goats against humans was used to determine MIL 50 captured by RiVax coated on the plate.Results Compared with ricin, RiVax could bind well with MIL50,indicating it could be used as a coating protein to determine MIL50 instead of holotoxin.Using this method, the detective limit of MIL50 in PBST (PBS containing 0.1%Tween 20) could be as low as 0.030 mg/L.The absorbance value of ELISA for MIL50 in the ser-um and homogenate of the liver , spleen, lung, kidney, muscle of rats was lower than that in PBST .Conclusion The sandwich ELISA is a sensitive method for the analysis of distribution of MIL 50 in rat tissues.

Location and expression of galactose β-1,4-glycosidic bonds in keloid tissue / 中华皮肤科杂志

Objective To observe the expression and location of galactose β-1,4-glycosidic bonds (Gal β-1,4-GlcNAc) in keloid tissue,and to investigate the role of glycoprotein galactosylation in the formation of keloid.Methods This study included 10 keloid tissue specimens,7 hyperplastic scar tissue specimens,and 6 normal skin specimens.Lectin blot analysis was performed to measure the glycosylation level of glycoproteins,saturated picric acid-Sirius red staining followed by polarization microscopy to observe the type,expression and distribution of collagens in these specimens.The type Ⅰ/type Ⅲ collagen ratio was calculated.Immunofluorescence-based histochemistry was carried out by using Ricinus communis agglutinin I to analyze the expression and location of Gal β-1,4-GlcNAc in these skin samples,and double immunofluorescent staining to observe the colocalization of Gal β-1,4-GlcNAc and type Ⅰ procollagen α1.Results Compared with the normal skin tissue,the keloid tissue showed a significant increase in the expression of Gal β-1,4-GlcNAc in glycoproteins with a relative molecular mass of 30 000 to 40 000.Polarization microscopy revealed that there was a considerable expression of type Ⅰ collagen fibers,which amounted to (71.53 ± 4.03)％ in all the collagen fibers.The type Ⅰ/type Ⅲ collagen ratio was significantly higher in keloid tissue specimens than in normal tissue specimens (2.56 ± 0.53 vs.0.91 ± 0.11,P ＜0.05).Fluorescence microscopy showed that Gal β-1,4-GlcNAc was uniformly distributed in the membrane and cytoplasm of fibroblasts in keloid tissue,and the expression intensity of Gal β-1,4-GlcNAc in keloid tissue was notably stronger than that in normal skin tissue.There was a colocalization between Gal β-1,4-GlcNAc and type Ⅰ procollagen α1 in keloid tissue.Conclusions The expression of Gal β-1,4-GlcNAc,which is mainly observed in fibroblasts,is upregulated in keloid tissue,suggesting that Gal β-1,4-GlcNAc may be involved in the modulation of factors responsible for excessive fibre formation during the repair process of keloid.

Prediction, cloning, expression and identification of the functional motif of the recombinant Ricin B / 中华微生物学和免疫学杂志

Objective To determine the functional motif of the recombinant Ricin B(rRicin B) in Vibrio vulnificus cytolysin (VVC) and understand its molecule pathogenic mechanism.Methods The motif of VVC was predicted through bioinformatics analysis and cloned into a procaryotic expression vector pET28a-rRicin B.The recombinant plasmid was transformed into E.coli BL21 (DE3) and induced by IPTG to express rRicin B.The expressed protein was further analyzed by SDS-PAGE and purified by Ni2+-NTA agarose.Renaturation of the rRicin B were also carried out for further analysis.ELISA assay and confocal microscope was applied to identify the activity of the rRicin B on human Hela cells.Results Ricin B motif located in the 336-465 amino acids of Vibrio vulnificus cytolysin with a relative molecular weight of 20×103.The result of ELISA showed that the antigenicity of rRicin B was 28.71 U/L after renaturation.FITC labeled rRicin B could bind to the cell membrane and enter the cytoplasm of human Hela cells.Conclusion The Ricin B motif in Vibrio vulnificus cytolysin bearing the similar ability with the natural Ricin B can bind to the cell membrane and enter the cytoplasm.This feature may play an important role in the activity of pore-forming and the cytotoxicity of Vibrio vulnificus cytolysin.

Simultaneous allergen inactivation and detoxification of castor bean cake by treatment with calcium compounds

Ricinus communis L. is of great economic importance due to the oil extracted from its seeds. Castor oil has been used for pharmaceutical and industrial applications, as a lubricant or coating agent, as a component of plastic products, as a fungicide or in the synthesis of biodiesel fuels. After oil extraction, a castor cake with a large amount of protein is obtained. However, this by-product cannot be used as animal feed due to the presence of toxic (ricin) and allergenic (2S albumin) proteins. Here, we propose two processes for detoxification and allergen inactivation of the castor cake. In addition, we establish a biological test to detect ricin and validate these detoxification processes. In this test, Vero cells were treated with ricin, and cell death was assessed by cell counting and measurement of lactate dehydrogenase activity. The limit of detection of the Vero cell assay was 10 ng/mL using a concentration of 1.6 x 10(5) cells/well. Solid-state fermentation (SSF) and treatment with calcium compounds were used as cake detoxification processes. For SSF, Aspergillus niger was grown using a castor cake as a substrate, and this cake was analyzed after 24, 48, 72, and 96 h of SSF. Ricin was eliminated after 24 h of SSF treatment. The cake was treated with 4 or 8% Ca(OH)2 or CaO, and both the toxicity and the allergenic properties were entirely abolished. A by-product free of toxicity and allergens was obtained.

Valor nutritivo de dietas contendo torta de mamona submetida a métodos alternativos de destoxificação para ovinos / Nutritive value of feeds containing castor bean cake subjected to alternative methods of detoxification for sheep

Avaliaram-se o consumo e a digestibilidade de nutrientes por ovinos alimentados com rações contendo torta de mamona sem tratamento (NT), tratadas com calcário calcítico (CC), ureia (UR), fosfato monobicálcico (FOS) e por autoclave (ACL). Foram utilizados 20 ovinos em delineamento em blocos ao acaso, sendo 10 machos inteiros e 10 fêmeas, mestiços de raça Morada Nova. As dietas foram isoproteicas e isoenergéticas. A ricina foi parcialmente desnaturada pelos tratamentos de destoxificação da torta de mamona. Não houve efeito dos tratamentos de destoxificação da torta de mamona sobre o consumo de nutrientes. A digestibilidade da fibra em detergente neutro no tratamento NT foi de 57,5 por cento, maior que no tratamento CC, de 52,4 por cento. A digestibilidade do extrato etéreo foi mais alta no tratamento CC, média de 71,3 por cento, em relação ao tratamento FOS, de 68,2 por cento. Houve maior consumo de fibra em detergente neutro e fibra em detergente ácido dos machos em relação às fêmeas quando o consumo foi expresso em g/dia. A torta de mamona NT pode ser utilizada em dietas de ovinos como alimento proteico alternativo, participando em até 8 por cento da dieta total, sem ocasionar redução expressiva no consumo e na digestibilidade.

Feed intake and digestibility were evaluate in sheep fed diets containing castor bean cake with no treatment (NT), treated with calcium carbonate (CC), urea (UR), phosphate monodicalcium (FOS) and autoclave (ACL). We used 20 sheep in a randomized block design, being 10 males and 10 females, crossbred Morada Nova. The diets were isonitrogenous and isocaloric. Ricin was partially denatured through the treatments of detoxification of the castor bean cake. There was no treatment effect of detoxification of the castor bean cake on the intake of nutrients. The digestibility of neutral detergent fiber in the NT treatment had a 57.52 percent average, higher than the CC treatment which had an average of 52.42 percent. The digestibility of ether extract was higher in CC treatment, which had an average of 71.29 percent compared to the FOS treatment that had an average of 68.22 percent. Regarding the effect of sex, there was a higher intake of neutral detergent fiber and acid detergent fiber in males compared to females when intake was expressed as g/day. The castor bean cake NT can be used in rations for sheep as an alternative protein source participating in up to 8 percent of the total ration, without causing significant reductions in intake and digestibility.

Inhibitory effect of pterin acid against ricin and recombinant ricin A chain / 军事医学科学院院刊

Objective To study the inhibitory effect of pterin acid (PTA) against ricin and recombinant ricin A chain protein. Methods Luciferase protein synthesis inhibition assay in a cell-free system and in vitro cytotoxicity experiments were performed to assess the biological activity of ricin and rRTA treated with PTA.Results The result showed that PTA could significantly inhibit the activity of ricin and rRTA in a dose-dependent manner.Conclusion PTA might be used as a small molecular probe to develop an evaluating system for ricin/RTA small molecular inhibitor in vitro. The cell-free system adopted in the current study could also serve as a necessary basis for screening some novel small molecular compounds against ricin and RTA in the future.

Toxic effect of oral ricin on the mouse intestinal tract and immune organs / 中国兽医学报

The experiment aimed to study the toxic effect of oral ricin on gastrointestinal tract and immune organs of mice with the dose of 1/5 LD50.In early days of intoxication,there was an obviously decrease in daffy weight and relative weight of thymus and spleen,fllowing the excretion of toxin,they had a trend of recovering to the normal state.Also,results of pathological section,scanning electron microscope and transmission electron microscope showed that ricin would induce a series of pathological reaction in intestines,meanwhile,the splenocytes displayed significant symptom of apoptosis and necrosis.

Trends in detection methods of ricin / 军事医学科学院院刊

Ricin is a plant-derived ribosome-inhibitor which can be easily purified in large quantities from castor beans. It is a potent irreversible inhibitor of protein synthesis. The mode of intoxication could be inhalation, ingestion, intravenous injection.Ricin has been classified as a schedule 1 threat agent by the Chemical Weapons Convention.A fast and sensitive method for the detection of this threat agent is an important tool for preventing or dealing with the consequences of intoxication. An ideal method should be highly sensitve, highly selective, and well capable of identifying ricin in a short assay time. Several methods have been established for ricin detection. This review summaries the development of detection methods for ricin in recent years.

Percutaneous intratumoral injection of ricin-loaded thermosensitive hydrogel in treatment of hepatic carcinoma xenograft / 中华超声影像学杂志

Objective To evaluate the effectiveness and feasibility of riein-loaded thermosenaitive hydrogel in percutaneous intratumoral injection for treatment of hepatic carcinoma. Methods BALB/c-nu mice were inoculated subcutaneously in the right flank with human liver cancer cell line HepG2. A total of 32 male mice bearing subcutaneous hepatic carcinoma (7-10mm in diameter) were randomized into 4 groups. Each group of mice were administered percutaneous intratumoral injection of different agents as follows: salin, thermosensitive hydrogel,ricin, ricin-loaded thermosensitive hydrogel. The tumor volume was totally measured 3 times by high frequency ultrasound once a week. One mouse of each group was sacrificed to perform tumor histopathological examination on 7th day, 14th day, respectively, and survival time of the remaining mice was recorded. Results After intratumoral therapy,tumor volume in ricin group was smaller than that of saline group on 7th day, 14th day and 21st day( P<0.01 ),and mice got a life-prolonging rate of 36.8%. In ricin-loaded thermosensitive hydrogel group,obvious necrosis occurred in tumors treated since 5th day, and the tumor almost regressed on 21st day. Histopathological assay showed serious necrosis with a large number of leucocyte infiltration in tumor. All the remaining mice treated with riein-loaded thermosensitive hydrogel survived at the end of experiment sans tumor recurrence. Conclusions Percutaneous intratutnoral injection of ricin-loaded thermosensitive hydrogel could completely ablate hepatic carcinoma,which may provide an effective and feasible method for tumor ablation therapy.