Potency evaluation of antivenoms in Brazil: The national control laboratory experience between 2000 and 2006

Araújo, Humberto Pinheiro de; Bourguignon, Saulo Cabral; Boller, M. A. A.; Dias, André Alves; Lucas, Elizabeth Porto Reis; Santos, Ingrid Cardoso dos; Delgado, Isabella Fernandes

doi:10.1016/j.toxicon.2007.11.002

Cited by 62 publications

(23 citation statements)

References 9 publications

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“…Deaths occurring within a specified time interval are recorded and neutralization is expressed as Median Effective Dose (ED 50 ), i.e., the volume of antivenom or the venom/antivenom ratio at which 50% of injected mice survived. Some quality control laboratories express the neutralizing efficacy in terms of “potency” [35]. …”

Section: Neutralization Of Lethality: the Gold Standard In The Prementioning

confidence: 99%

“…route in the estimation of LD 50 and ED 50 [32], although others, especially in Latin America, use the intraperitoneal (i.p.) route [35,40]. Different pathophysiological mechanisms, and hence different toxins, may predominate in the overall toxicity depending on the route of injection (see below).…”

Section: Neutralization Of Lethality: the Gold Standard In The Prementioning

confidence: 99%

“…This has to include, at least, a basic understanding on antivenom manufacture and preclinical efficacy and, ideally, the establishment of national or regional quality control laboratories that assess the neutralization of venom lethality by antivenoms. The case of Brazil is noteworthy, whereby a national quality control laboratory, the Instituto Nacional de Controle de Qualidade em Saúde (INCQS), evaluates all antivenom batches produced by the various manufacturing laboratories on the country [35]. The improvement of the capacities of national regulatory agencies could be achieved through international workshops organized by the WHO and its regional offices, with the collaboration of international experts.…”

Section: The Need Of International Partnerships To Evaluate Antivmentioning

confidence: 99%

See 2 more Smart Citations

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Gutiérrez

Solano

Plá

et al. 2017

Toxins

132

100

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Animal-derived antivenoms constitute the mainstay in the therapy of snakebite envenoming. The efficacy of antivenoms to neutralize toxicity of medically-relevant snake venoms has to be demonstrated through meticulous preclinical testing before their introduction into the clinical setting. The gold standard in the preclinical assessment and quality control of antivenoms is the neutralization of venom-induced lethality. In addition, depending on the pathophysiological profile of snake venoms, the neutralization of other toxic activities has to be evaluated, such as hemorrhagic, myotoxic, edema-forming, dermonecrotic, in vitro coagulant, and defibrinogenating effects. There is a need to develop laboratory assays to evaluate neutralization of other relevant venom activities. The concept of the 3Rs (Replacement, Reduction, and Refinement) in Toxinology is of utmost importance, and some advances have been performed in their implementation. A significant leap forward in the study of the immunological reactivity of antivenoms against venoms has been the development of “antivenomics”, which brings the analytical power of mass spectrometry to the evaluation of antivenoms. International partnerships are required to assess the preclinical efficacy of antivenoms against snake venoms in different regions of the world in order to have a detailed knowledge on the neutralizing profile of these immunotherapeutics.

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Section: Neutralization Of Lethality: the Gold Standard In The Prementioning

confidence: 99%

Section: Neutralization Of Lethality: the Gold Standard In The Prementioning

confidence: 99%

Section: The Need Of International Partnerships To Evaluate Antivmentioning

confidence: 99%

See 1 more Smart Citation

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Gutiérrez

Solano

Plá

et al. 2017

Toxins

132

100

View full text Add to dashboard Cite

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“…Although there are differences in the toxic content of the venom of L. obliqua and L. achelous [4,30] , they may lead to hemorrhagic syndrome by consumption coagulopathy, resembling a disseminated intravascular coagulation in combination with a hyperfibrinolytic state [10,40,41] . Some toxins act in the initial stage of envenoming and other components are directly responsible for the hemostatic dysfunctions observed in humans and in experimental animals.…”

Section: Lonomia Obliqua Venom and The Hemorrhagic Syndromementioning

confidence: 99%

New Insight into the Mechanism of <i>Lonomia obliqua</i> Envenoming: Toxin Involvement and Molecular Approach

Alvarez-Flores

Zannin²,

Chudzinski-Tavassi³

2010

Pathophysiol Haemos Thromb

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Despite the nearly worldwide distribution of Lepidoptera, there are few species with clear documentation of adverse reactions in humans. Most syndromes caused by Lepidoptera are consequences of direct contact with the hairs or setae of caterpillars. In most instances, the adverse effects caused by moth and caterpillars are self-limited and the treatment is based on the removal of hairs, application of topical antipruritics and, in some cases, the use of oral antihistamines. However, in the case of envenoming by South American Lonomiaobliqua caterpillars, the antilonomic serum produced at Instituto Butantan in Brazil is the only effective treatment to re-establish the physiological coagulation parameters in poisoned patients and to abolish the complications seen in severe cases (e.g. consumptive coagulopathy, intracerebral hemorrhage, and acute renal failure). Many studies have been carried out to understand the pathophysiological mechanism of envenoming by L. obliqua. Several toxic principles were found in bristle extract and the hemolymph, probably related to the envenoming. An interesting fact is that some toxins from the venom usually have more than one function. With the advent of molecular biology techniques it has become possible to analyze these processes at a molecular level, thus giving rise to hypotheses on the molecular basis of envenomation. This review contributes to enhance our understanding of the dramatic alterations that hemorrhagic syndrome causes in patients, current treatment, and the diversity of the molecules involved in this pathology.

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“…So, to show the behavior of ER 50 under these conditions, we have carried out simulated assays where when the potency is fixed at 1 LD 50 /mL; the venom dose challenge, n, changes between 2 and 20 and the ED 50 and ER 50 are estimated from equations [1] and [2], respectively. The results of the assays are presented in Table 1 in increasing values of n. Notice that for low values of n (2 or 3), as frequently used in the literature, ER 50 can differ from P by as much as 100%.…”

mentioning

confidence: 99%

Antivenoms: potency or median effective dose, which to use?

Morais

Ifrán

Berasain

et al. 2010

J. Venom. Anim. Toxins incl. Trop. Dis

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Dear Editor:In the field of envenomations by poisonous animals, the ability of antivenoms to neutralize the lethal effects of venoms is estimated by a biological assay in which mice are inoculated with a range of venom/antivenom concentrations and the survival/death ratio is recorded. A statistical technique (e.g., Probit) is employed to estimate the amount of antivenom that protects 50% of the animals. This quantity is called median effective dose or effective dose 50 (ED 50 ) and is normally expressed in volume units (i.e., mL or μL). The ED 50 is used in an expression for the assessment of the potency (P) of the antivenom, as follows (1, 2): P = (n -1)LD 50 / ED 50 [1]where "LD 50 " is the median lethal dose (mass of venom that kills 50% of mice), and "n" is the number of LD 50 s used in the assay. "P" is the amount of venom, expressed in mass units or number of median lethal doses, that is completely neutralized per unit volume of antivenom (the expression "(n -1) LD 50 " is used instead of the total amount of venom, nLD 50 , because at the endpoint of the neutralization assay, one LD 50 remains unneutralized and causes the death of 50% of mice). However, in the literature, it is very frequent to find that the same term, ED 50 , is utilized to represent

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Potency evaluation of antivenoms in Brazil: The national control laboratory experience between 2000 and 2006

Cited by 62 publications

References 9 publications

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

New Insight into the Mechanism of <i>Lonomia obliqua</i> Envenoming: Toxin Involvement and Molecular Approach

Antivenoms: potency or median effective dose, which to use?

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