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1.
G Jann-Para  I Schwob  M Feuillade 《Toxicon》2004,43(3):279-285
Cyanobacteria including genus Oscillatoria are known to release toxins into waterbodies. To study the occurrence of toxic blooms in Lake Nantua, the Planktothrix rubescens species (Oscillatoria rubescens) was considered. At the same time, some physicochemical parameters were analysed to estimate their impact on toxin production. The investigations were conducted during summertime and the highest toxin concentration analysed by HPLC was detected in August (10.8 microg/l of lake water). The results of this work suggested that the toxin production increased when the light intensity, temperature, alkaline pH and phosphorus contents were at low levels. Moreover, the toxin production was positively related with NT/PT ratio. TLC analysis of the purified fractions revealed the occurrence of 4-7 polypeptide or protein bands. Two of them were shown to be toxic using Artemia bioassays and the most toxic one was identified as MCYST-RR.  相似文献   

2.
A monitoring program, carried out in 1996 and 1997, has confirmed that toxic compounds, other than the most frequently detected toxins okadaic acid (OA) and dinophysistoxin-1 (DTX-1), are involved in DSP phenomena in the Adriatic Sea. Toxicity was assessed by the mouse bioassay; the content and the nature of the toxic components were established through fluorometric HPLC analysis combined with mass spectrometry. A rare pectenotoxin-2 (PTX-2) derivative, 7-epi-pectenotoxin-2 seco acid (7-epi-PTX-2SA), was the exclusive contaminant of samples collected from the central Adriatic in 1996. Contrary to its marked oral toxicity, intraperitoneally 7-epi-PTX-2SA displayed no toxic effects, hampering its detection by the mouse bioassay. In 1997, its concentration and frequency of appearance were lower than in 1996, with concomitant occurrence of OA, DTX-2, and a new unidentified component related to the DSP toxic group of compounds. This is the first report on the occurrence of DTX-2 in Adriatic mussels. A survey of the phytoplankton community in the surrounding seawater has established the presence of Prorocentrum micans and several potentially toxic species from the Dinophysis genus. A case of unexplained toxicity, associated with the occurrence of Gonyaulax polyedra, suggested possible shellfish contamination with yessotoxin (YTX).  相似文献   

3.
张文学  王莉  于莉  丁体龙  马勇 《中国基层医药》2011,18(20):2762-2763
探讨乙型肝炎患者血浆D.二聚体(D-D)含量与肝功能储备状态的关系。方法、根据肝功能储备状态,将77例乙型肝炎患者分成肝功能代偿组44例,肝功能失代偿组33例,两组测定血浆D.二聚体、凝血酶原时间(PT)和肝功能指标。结果肝功能失代偿组患者血浆D.二聚体含量(299.0±498.5)μg/L显著高于肝功能代偿组(27.9±34.0)彬L(t=3.1,P〈0.01);D.二聚体与血清白蛋白(ALB)和凝血酶原活动度(PA)呈显著负相关(r=-0.6、-0.6,均P〈0.01);而与TBIL和P,r呈显著正相关(r=0.4、0.6,均P〈0.01)。结论乙型肝炎患者血浆D一二聚体水平与肝功能储备状态相关,检测D.二聚体有助于肝功能储备的评估和预后的判断。  相似文献   

4.
Toxicokinetic modeling and its applications in chemical risk assessment   总被引:7,自引:0,他引:7  
In recent years physiologically based pharmacokinetic (PBPK) modeling has found frequent application in risk assessments where PBPK models serve as important adjuncts to studies on modes of action of xenobiotics. In this regard, studies on mode of action provide insight into both the sites/mechanisms of action and the form of the xenobiotic associated with toxic responses. Validated PBPK models permit calculation of tissue doses of xenobiotics and metabolites for a variety of conditions, i.e. at low-doses, in different animal species, and in different members of a human population. In this manner, these PBPK models support the low-dose and interspecies extrapolations that are important components of current risk assessment methodologies. PBPK models are sometimes referred to as physiological toxicokinetic (PT) models to emphasize their application with compounds causing toxic responses. Pharmacokinetic (PK) modeling in general has a rich history. Data-based PK compartmental models were developed in the 1930's when only primitive tools were available for solving sets of differential equations. These models were expanded in the 1960's and 1970's to accommodate new observations on dose-dependent elimination and flow-limited metabolism. The application of clearance concepts brought many new insights about the disposition of drugs in the body. In the 1970's PBPK/PT models were developed to evaluate metabolism of volatile compounds of occupational importance, and, for the first time, dose-dependent processes in toxicology were included in PBPK models in order to assess the conditions under which saturation of metabolic and elimination processes lead to non-linear dose response relationships. In the 1980's insights from chemical engineers and occupational toxicology were combined to develop PBPK/PT models to support risk assessment with methylene chloride and other solvents. The 1990's witnessed explosive growth in risk assessment applications of PBPK/PT models and in applying sensitivity and variability methods to evaluate model performance. Some of the compounds examined in detail include butadiene, styrene, glycol ethers, dioxins and organic esters/aids. This paper outlines the history of PBPK/PT modeling, emphasizes more recent applications of PBPK/TK models in health risk assessment, and discusses the risk assessment perspective provided by modern uses of these modeling approaches.  相似文献   

5.
6.
The effectiveness and safety of cefmenoxime (CMX) in the treatment of respiratory tract infections were evaluated, mainly in relation to the appearance of hemorrhagic tendency. Out of 80 patients treated in this study, 57 were treated with CMX alone, and an effective rate was determined to be 75.4%. As for a tendency toward hemorrhage, none of the patients clinically exhibited a hemorrhagic tendency, while the prolongation of prothrombin time (PT) and/or activated partial thromboplastin time (APTT) was seen in 3 patients (3.8%), who were all at ages over 63. The prolongation of APTT was clearly related to CMX in 1 patient. Although the causal relation between CMX and the prolongation of PT or APTT was unclear in the remaining 2 patients because they had severe primary diseases (lung cancer and respiratory failure due to chronic obstructive lung disease in addition to severe hepatic disorder and received combination treatment with anticancer agents or other antibiotics), CMX might have a role in causing these phenomena. Even though none of the patients showed a hemorrhagic tendency clinically arousing problems, we should be careful in using CMX in the treatment of the aged and patients in poor general conditions because PT and/or APTT was observed to prolong with the use of CMX in some patients.  相似文献   

7.
Crude ethanol extracts (CEE) of dried leaves (CEE1), fresh leaves (CEE2), dried petioles (CEE3) and stem bark (CEE4) of Gliricidia sepium were investigated for their toxic properties on the late third instar larvae of Anopheles stephansi, Aedes aegypti and Culex quinquefasciatus. The results indicate that all the CEEs are toxic to the larvae of the three species, causing 100% mortality at or below a dosage of 16,000 ppm. Although the mortality rate is dose-dependent, the larvae of different species exhibit genetic variability with respect to their tolerance at lower doses of CEE. It is likely that the toxicity, at least in some cases, could be due to more than one toxic principle. The findings also suggest that toxic principles vary quantitatively and/or qualitatively in different organs of the plant. Overall, CEE2 shows a higher toxicity and CEE3 shows a weaker toxicity compared to CEEs from fresh leaves and bark.  相似文献   

8.
Cancers continue to be the second leading cause of death worldwide. Despite the development and improvement of surgery, chemotherapy, and radiotherapy in cancer management, effective tumor ablation strategies are still in need due to high cancer patient mortality. Hence, we have established a new approach to achieve treatment-actuated modifications in a tumor microenvironment by using synergistic activity between two potential anticancer drugs. Dual drug delivery of gemcitabine (GEM) and cisplatin (PT) exhibits a great anticancer potential, as GEM enhances the effect of PT treatment of human cells by providing stability of the microenvironment. However, encapsulation of GEM and PT fanatical by methoxypoly(ethylene glycol)-block-poly(D, L-lactic acid) (PEG-PLA in termed as NPs) is incompetent owing to unsuitability between the binary Free GEM and PT core and the macromolecular system. Now, we display that PT can be prepared by hydrophobic coating of the dual drug centers with dioleoylphosphatidic acid (DOPA). The DOPA-covered PT can be co-encapsulated in PLGA NPs alongside GEM to stimulate excellent anticancer property. The occurrence of the PT suggestively enhanced the encapsulations of GEM into PLGA NPs (GEM-PT NPs). Further, the morphology of GEM NPs, PT NPs, and GEM-PT NPs and nanoparticle size was examined by transmission microscopy (TEM), respectively. Furthermore GEM-PT NPs induced significant apoptosis in human nasopharyngeal carcinoma CNE2 and SUNE1 cancer cells by in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assays (AO-EB, nuclear staining, and annexin V-FITC). In a xenograft model of nasopharyngeal cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose. Our results suggest that a macromolecular hydrophobic and highly toxic drug can be rationally converted into a pharmacologically efficient and self-deliverable of nanotherapy.  相似文献   

9.
唐纯海  吴全理 《天津医药》2012,40(2):178-179
【摘要】 目的:探讨术前急性等容血液稀释联合术中自体血回收在颅脑择期手术中对患者凝血功能的影响以纠正贫血的作用。方法:选择16例神经外科择期手术患者,分别比较患者术前、血液等容稀释后、止血基本完成时、回输机采自体血以及术前采集自体血后的APTT、PT、PLT、HB、HCT;结果:等容稀释后和术前相比患者凝血功能无明显变化,HB、HCT明显下降;止血基本完成时和术前相比患者APTT、PT延长,PLT、HB、HCT明显下降,输机采血后和止血基本完成时相比患者的PLT下降,APTT、PT延长,同时HCT及HB明显升高;输术前采集自体动脉血后和输机采血后相比患者的APTT及PT明显缩短,PLT、 HCT、HB明显升高。结论:在出血量较大的神经外科手术中使用术前急性等容血液稀联合术中自体血回收对改善纠正患者贫血,保证患者术后正常凝血功能,增加手术安全性方面是非常有益的。  相似文献   

10.
Patrizia Pagliara 《Toxicon》2012,60(6):1203-1214
In many coastal areas the abundant proliferation of microalgae producing biotoxins determines the occurrence of Harmful Algal Blooms (HABs). Their presence in temperate waters is well documented and often associated with marine toxin-derived disease. The occurrence and toxicity of three harmful microalgae (Amphidinium carterae, Coolia cfr. monotis and Ostreopsis cfr. ovata) from the northern Ionian Sea (Mediterranean Sea) is hereby reported. The three dinoflagellates were sampled both on macroalgae and water and their morphology and occurrence were compared to those of other Mediterranean sites. The toxicity of the three cultured strains was tested by Artemia salina and hemolysis tests and their effects on the first stages of the sea urchin development was also evaluated. The contemporary presence of the three species inhibited the in vitro sea urchin embryonic development. But this action could be ascribed to the sole Ostreopsis as the addition of the single species to the sea urchins embryos evidenced no effects in presence of Amphidinium or Coolia cells, and an irregular segmentation in presence of Ostreopsis. In particular, this latter species exerted a cytotoxic effect in a dose-dependent manner, with a production of deformed embryos even at very low cell concentration (42 cells mL−1). Nevertheless, when algal cell lysate was added, some effects on the sea urchin development was detected for each dinoflagellate, and also in this case Ostreopsis has proved to be the most toxic species. However, the lysate of Amphidinium and Ostreopsis strongly affects the A. salina nauplii vitality, while the hemolytic activity was very low for Amphidinium and Coolia lysate and very strong for Ostreopsis.Our results highlight the importance to monitoring the presence of these dinoflagellates whose effects may also be reflected on the early life stages of marine organisms, especially those species that are important from both an ecological and economic point of view, as the sea urchins are.  相似文献   

11.
The blooms of toxic cyanobacteria (blue-green algae) are causing problems in many countries. During a screening of toxic freshwater cyanobacteria in Brazil, three strains isolated from the State of Sao Paulo were found toxic by the mouse bioassay. They all were identified as Cylindrospermopsis raciborskii by a close morphological examination. Extracts of cultured cells caused acute death to mice when injected intraperitoneally after developing neurotoxic symptoms which resembled to those caused by paralytic shellfish toxins. The analysis of the sample by HPLC-FLD postcolumn derivatization method for paralytic shellfish toxins resulted in the detection of several saxitoxin analogs. To avoid being misled by false peaks, the sample was reanalyzed after purification and also under the different postcolumn derivatizing conditions. Finally, the newly developed LC-MS method for paralytic shellfish toxins was applied to unambiguously identify the toxins. One isolate produced neosaxitoxin predominantly with saxitoxin as a minor component. The other two showed identical toxin profiles containing saxitoxin and gonyautoxins 2/3 isomers in the ratio of 1:9. This is the first evidence of paralytic shellfish toxins in this species and also the occurrence of the toxin producing cyanobacterium in South American countries.  相似文献   

12.
Idiosyncratic hepatotoxicity is a well-known complication associated with aromatic antiepileptic drugs (AAED), and it has been suggested to occur due to the accumulation of toxic arene oxide metabolites. Although there is clear evidence of the participation of an immune process, a direct toxic effect involving mitochondria dysfunction is also possible. The effects of AAED on mitochondrial function have not been studied yet. Therefore, we investigated, in vitro, the cytotoxic mechanism of carbamazepine (CB), phenytoin (PT) and phenobarbital (PB), unaltered and bioactivated, in the hepatic mitochondrial function. The murine hepatic microsomal system was used to produce the anticonvulsant metabolites. All the bioactivated drugs (CB-B, PB-B, PT-B) affected mitochondrial function causing decrease in state three respiration, RCR, ATP synthesis and membrane potential, increase in state four respiration as well as impairment of Ca2+ uptake/release and inhibition of calcium-induced swelling. As an unaltered drug, only PB, was able to affect mitochondrial respiration (except state four respiration) ATP synthesis and membrane potential; however, Ca2+ uptake/release as well as swelling induction were not affected. The potential to induce mitochondrial dysfunction was PT-B>PB-B>CB-B>PB. Results suggest the involvement of mitochondrial toxicity in the pathogenesis of AAED-induced hepatotoxicity.  相似文献   

13.
Protein toxins produced by pathogenic vibrios.   总被引:5,自引:0,他引:5  
Genus Vibrio includes some pathogenic species which are classified into two groups: a gastrointestinal infection group and an extraintestinal infection group. The vibrios produce various toxic proteins. Cholera toxin (CT) produced by V. cholerae O1 and O139 is a factor causing diarrhea with severe dehydration by ADP-ribosylation of the alpha subunit of the GTP-binding protein which stimulates adenylate cyclase activity. CT-like toxins are found in some strains of V. cholerae non-O1 or V. mimicus, but not in V. parahaemolyticus, another major diarrheagenic vibrio species. A thermostable direct hemolysin (TDH) is thought to be the pathogenic factor causing diarrhea in the vibrio. Hemolysin is the most widely distributed toxin in the pathogenic vibrios and plays various roles in the infection process. Protease activity is also common in the vibrios. Many of the proteases produced by the vibrios are a metalloprotease having a zinc atom immunologically cross reactive to each other. The proteases act not only for processing and activation of protein toxins but also direct toxic factors causing edematous or hemorrhagic skin lesions or disturbance of host defense system.  相似文献   

14.
We briefly report here the occurrence of toxic blooms in the eutrophic reservoir Billings, S?o Paulo city, Brazil. Water samples were collected in May 2004, during a cyanobacterial bloom. The presence of toxic species was confirmed by using PCR amplifications of a fragment region of genes encoding microcystin synthetase-mcyB. The determination of toxins was performed by liquid chromatography coupled with mass spectrometry (LC-MS). LC-MS analyses of the toxins from the bloom revealed variants of microcystins (MC), such as MC-LR, MC-RR and MC-YR. HPLC-FLD was used to determine the paralytic shellfish poisoning (PSP) saxitoxin (STX), neosaxitoxin (NEO), gonyautoxins 2 (GTX2) and 3 (GTX3). GTX2, GTX3 and NEO were detected for the first time in a natural sample from Billings reservoir. These results are a contribution to the knowledge of the biogeography of toxic cyanobacteria and their toxins, specifically in S?o Paulo.  相似文献   

15.
3-Butene-1,2-diol (BDD), a major metabolite of 1,3-butadiene (BD), can readily be oxidized to hydroxymethylvinyl ketone (HMVK), a Michael acceptor. In previous studies, 4-(N-acetyl-l-cystein-S-yl)-1,2-dihydroxybutane (DHB), a urinary metabolite of BD that was used to assess human BD exposure, was suggested to be a metabolite of HMVK, but DHB formation from BDD and the formation of the DHB precursor 4-(N-acetyl-l-cystein-S-yl)-1-hydroxy-2-butanone (HB) have not been previously investigated. In the current study, four HMVK-derived mercapturic acids [DHB, HB, 3-(N-acetyl-l-cystein-S-yl)propan-1-ol (POH), and 3-(N-acetyl-l-cystein-S-yl)propanoic acid (PA)] were identified in the urine of mice and rats given BDD (284-2272 micromol/kg, i.p.) based on GC/MS analyses and comparisons with synthetic standards after esterification and silylation of the carboxyl and hydroxyl groups, respectively. The combined amounts of the mercapturic acids excreted after BDD exposure were dose-dependent and were mostly similar between mice and rats given equivalent doses of BDD. The mercapturic acids accounted for a greater fraction of the administered BDD dose as the dose was lowered, suggesting that HMVK formation represents a prominent route for BDD metabolism in both mice and rats. The major mercapturic acid excreted by mice was DHB, whereas rats excreted equivalent amounts of DHB and HB. The levels of POH or PA were significantly lower in both species relative to DHB or HB. The observed species differences in the excretion of DHB and HB were thought to be due to differences in the capacity of mice and rats to reduce HB to DHB.  相似文献   

16.
《Toxin reviews》2013,32(3):169-191
Abstract

Pyrularia thionin (PT) is a unique thionin which occupies a position between the viscotoxins and Gramineae thionins. Like the viscotoxins, PT comes from a dicotyledonous plant, Pyrularia pubera, and PT has a higher degree of amino acid homology with the viscotoxins than it does with the cereal grain thionins (1). However, PT has 4 disulfide bonds, as do the cereal grain thionins, and the viscotoxins have only 3. PT is distinct from both in that it is monomorphic. All thionins interact with and increase the permeability of cell membranes and are cytotoxic to some degree. PT and cardiotoxins also depolarize cell membranes, and PT opens a Ca2+ channel. PT as well as the other thoinins are amphipathic. This is apparent in the reported three dimensional structure of α-1 purothionin, which clearly shows distinct hydrophilic and hydrophobic domains on the surface of the protein, which contains two helical and one anti-parallel β-pleated sheet region. Examination of the physical properties show that PT combines with acidic phospholipids in synthetic membranes, and shows some specificity for phosphatidylserine. Our thesis is that PT combines with a specific phospholipid domain on the cellular membrane, most likely contining phosphatidylserine, causing early changes in membrane properties, including an increase in order parameter of the phospholipids, an increase in membrane permeability, depolarization of the membrane and opening of a Ca2+ channel. Later membrane responses include blebbing of the membrane bilayer and activation of an endogenous phospholipase A2. The activation of this enzyme results in membrane degradation and is the major cause of the long term cellular responses attributed to the basic peptide, including killing of cells in culture and neurotoxicity to animals. The cause of PT-induced hemolytic activity is not immediately apparent. In its binding properties, physical responses of the membrane and biological responses of cells, cardiotoxin from cobra venom behaves in a very similar manner to PT, indicating a similar mechanism of action for both toxic peptides.  相似文献   

17.
Hospital effluents cause environmental problems since they are 5–15 more toxic than urban effluents and they are not subjected to any pre-treatment before being discharged into urban sewage networks. The hypothesis used to explain this toxicity is the presence of disinfectants and detergents. This study is aimed at highlighting the ecotoxicity of a peracetic acid-based disinfectant to Daphnia magna, as well as the combined effects of this disinfectant in binary mixtures with three types of detergent. The detergents used here are: cetyltrimethylammonium bromide (CTAB, cationic), sodium dodecylsulfate (SDS, anionic) and Triton X-100 (TX, non-ionic). The toxicity of the mixtures is studied as a function of five predefined ratios. At the end of the study, we conclude that peracetic acid seems to be slightly toxic to Daphnia magna. Indeed, the efficient concentration inhibiting the mobility of 50% of the population of Daphnia at 24 h (EC50) is 116.6 mg/l. Globally, additive effects are observed for all the binary peracetic acid-detergent mixtures. However, for the peracetic acid–TX mixture, its effects have antagonistic tendencies whereas the peracetic acid–CTAB mixture has slight synergic tendencies. The mixture containing peracetic acid and SDS is slightly antagonistic for ratios containing more than 50% peracetic acid.  相似文献   

18.
IntroductionPlant identification applications for use on smartphones have been increasing in availability, accuracy, and utilization. We aimed to perform an introductory study to determine if a plant identification application (ID app) used on a smartphone could identify toxic plants, and to compare apps to determine which is most reliable.MethodsWe compared three popular iPhone plant ID apps, PictureThis (PT), PlantSnap (PS), and Pl@ntNet (PN), used to identify 17 commonly encountered toxic plants. Apps were used to photograph the entire plant, leaves, and flowers of ≥ 10 different plants for each species. Two toxicologists performed plant identification with confirmation of identification performed by a botanist, and inter-researcher agreement was confirmed. For each plant species, scores for accuracy of app identification of leaves, flowers, and whole plant were combined to create an overall composite score used to compare accuracy of each app (95% C.I.).ResultsPictureThis had the best performance with 10/17 (59% [36 to 78]) plant species identified 100% correctly, as opposed to 8/17 (47% [26 to 69]) for Pl@ntNet and 1/17 for PlantSnap (5.8% [1.1 to 27]).ConclusionA plant identification app may be a useful tool to assist healthcare providers and the public in identifying toxic plants.  相似文献   

19.
Phenolphthalein (PT), used in over-the-counter laxatives, has recently been identified as a multisite carcinogen in rodents, but the molecular species responsible for the carcinogenicity is not known. A catechol metabolite of PT, hydroxyphenolphthalein (PT-CAT), was recently identified and may be the molecular species responsible for at least part of the toxicity/carcinogenicity of PT. We hypothesize that PT-CAT inhibits the enzyme catechol-O-methyltransferase (COMT) and therefore potentiates genotoxicity by either PT-CAT itself or the endogenous catechol estrogens (CEs) in susceptible tissues. The present studies were conducted to determine the effects of PT treatment and PT-CAT itself on the COMT-mediated metabolism of 4- and 2-hydroxyestradiol both in vitro and in vivo. Female mice were treated with PT (50 mg/kg/d) for 21 days and then euthanized. PT-CAT concentration in urine reached plateau levels by 7 days of exposure. An O-methylated metabolite of PT-CAT was detected in feces. In vitro experiments demonstrated that PT treatment resulted in an increase in free CEs, which are normally cleared by COMT and a concurrent decrease in the capacity of hepatic catechol clearance by COMT. In vitro, PT-CAT was a substrate of COMT, with kinetic properties within the range measured with endogenous substrates. PT-CAT was an extremely potent mixed-type inhibitor of the O-methylation of the catechol estrogens, with 90-300 nM IC50s. The above data, when taken together, suggest that chronic administration of PT may enhance metabolic redox cycling of both PT-CAT and the catechol estrogens and this, in turn, may contribute to PT-induced tumorigenesis.  相似文献   

20.
The increasing use of carbon nanotubes (CNTs) in biomedical applications underlines the importance of its potential toxic effects to human health. In the present study, we first exposed PC12 cells, a commonly used in vitro model for neurotoxicity study, to two kinds of commercially available single-walled carbon nanotubes (SWCNTs), to investigate the effect of SWCNTs on nervous system in vitro. The decrease of PC12 cells viability was time and dose-dependent with exposure to SWCNTs demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release and morphological observation. Flow cytometry analysis showed that the PC12 cells’ cycle was arrested in the G2/M phase, and their apoptotic rate induced by SWCNTs was dose-dependent. Further studies revealed SWCNTs decreased mitochondrial membrane potential (MMP), induced the formation of reactive oxygen species (ROS) and increased the level of lipid peroxide and decreased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and the content of glutathione (GSH) in a time and dose-dependent manner. These findings reveal that SWCNTs may induce oxidative stress to nervous system in vivo, causing the occurrence of diseases related to cellular injuries of neuronal cells, such as neurodegenerative disorders, and demonstrating the necessity of further research in vivo.  相似文献   

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