An in vivo but insensate model for the evaluation of antivenoms (ED 50 ) using fertile hens' eggs

Sells, Paula G.; Laing, G.D.; Theakston, R.D.G.

doi:10.1016/s0041-0101(00)00191-4

Cited by 22 publications

(14 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the aim of eliminating the unpleasant effects of the antivenom treatment, it is necessary to achieve antivenom immunoglobulins in a reasonable purification state. Investigators 24,25,30 have proposed that birds are a suitable and economical supply of IgY immunoglobulins. Chicken egg yolks have IgY, which is a species-specific immunoglobulin with a molecular weight of 190kDa 26 .…”

Section: Discussionmentioning

confidence: 99%

CORAL SNAKE ANTIVENOM PRODUCED IN CHICKENS (Gallus domesticus)

Aguilar

Sánchez

Girón

et al. 2014

Rev. Inst. Med. trop. S. Paulo

View full text Add to dashboard Cite

The production of anti-snake venom from large mammal's blood has been found to be low-yielding and arduous, consequently, antivenom immunoglobulins for treatment are achieved regularly as polyvalent serum. We have standardized an undemanding technique for making purified immunoglobulin IgY antivenom consisting of polyclonal antibodies against coral snake venom in the egg yolk of immunized hens. We have adapted a reported process of antibody purification from egg yolks, and achieved 90% antibody purity. The customized technique consisted of the removal of lipids from distilled water-diluted egg yolks by a freeze–thaw sequence. The specific immunoglobulins were present in the egg yolk for up to 180 days postimmunization. Therefore, by means of small venom quantities, a significant amount of immunoglobulins were found in an adequately purified state (The obtained material contained about 90% pure IgY). The antigen binding of the immunoglobulins was detected by a double immunodiffusion test. Titers of antibodies in the yolk were estimated with a serum protection assay (Median effective dose = ED50) (ED50= 477 mg/kg). Given that breeding hens is economically feasible, egg gathering is noninvasive and the purification of IgY antibodies is quick and easy, chicken immunization is an excellent alternative for the production of polyclonal antibodies. To the best of our knowledge, this is the first coral snake antivenom prepared in birds.

show abstract

Section: Discussionmentioning

confidence: 99%

CORAL SNAKE ANTIVENOM PRODUCED IN CHICKENS (Gallus domesticus)

Aguilar

Sánchez

Girón

et al. 2014

Rev. Inst. Med. trop. S. Paulo

View full text Add to dashboard Cite

show abstract

“…Finally, in terms of animal welfare, it has long been regarded as acceptable to expose neurologically immature chick embryos to what would be potentially noxious procedures if applied to aware chicks after hatching (see Sells et al 1998Sells et al , 2001. In addition to invasive aspects of direct developmental or functional studies like many of those referred to above, such procedures have included testing tissue (chorioallantoic membrane) and/or embryonic responses to a range of pharmaceutical, toxic, mutagenic and other substances (see Castelli et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Birth and hatching: Key events in the onset of awareness in the lamb and chick

Mellor¹,

Diesch²

2007

New Zealand Veterinary Journal

View full text Add to dashboard Cite

The neuroanatomical and neurophysiological development of the embryo and fetus and unique features of the physiological environment of the fetal brain, features which are lost at birth, support recent conclusions that under normal circumstances awareness (or consciousness) is probably not exhibited by the ovine embryo-fetus before birth and that it appears for the first time only after birth. However, there has apparently been no evaluation of whether or not similar mechanisms modulate awareness-related functions in domestic chicks before and after hatching. This comparative review, in seeking to rectify this, arrived at the following conclusions. First, the neural apparatus of both lambs and chicks appears to be too immature to support any states resembling awareness during at least the first half of pregnancy or incubation. Second, electroencephalographic (EEG) activity, which evolves subsequently, shows that states of sleep-like unconsciousness are likely to be continuously present in lambs until after birth, and that such states at least predominate in chicks until after hatching. Third, as in fetal lambs, epochs of so-called 'wakefulness' previously reported in chick embryos do not seem likely to represent short periods of awareness in ovo. Fourth, several neurosuppressive mechanisms, with some unique features, also operate or have the potential to operate in chicks before hatching, but a dearth of published information currently hinders a full comparison with those demonstrated to operate in fetal lambs. Fifth, contradicting the intuitive perception that vocalisation pre-hatching by the chick indicates the presence of awareness, published evidence suggests that vocalisation before and during hatching occurs mostly during EEG states indicating sleep-like unconsciousness. Sixth, as seems to be the case for newborn lambs after birth, it is possible that demonstrable awareness may appear for the first time only after hatching in chicks, presumably through waning neurosuppression and burgeoning neuroactivation, but such awareness seems to take longer to manifest itself. However, additional research in chicks is recommended to further assess this suggestion. Particular attention should be given to the status of vocal interactions between hen and chick which begin several days before hatching, and to the operation of neurosuppressive and neuroactivating mechanisms throughout the last 40% of incubation and during and after hatching.

show abstract

“…Current preclinical testing involves the median effective dose (ED 50 ) test in mice. This involves calculating the amount of antivenom that, when injected intravenously together with a defined lethal quantity of venom, results in the survival of 50% of animals over a 24 h period 65 . However, this test requires large numbers of animals.…”

Section: Antivenoms and In Vitro Testingmentioning

confidence: 99%

“…One method that has been proposed involves the use of chicken eggs. Hatching eggs are used on the 6th day after fertilization, at which stage the embryo is alive but is insensate 65–67 . However, while this methodology appears promising for the examination of haemorrhagic venoms (e.g.…”

Section: Antivenoms and In Vitro Testingmentioning

confidence: 99%

In vitro neuromuscular activity of snake venoms

Hodgson

Wickramaratna

2002

Clin Exp Pharma Physio

115

View full text Add to dashboard Cite

1. Snake venoms consist of a multitude of pharmacologically active components used for the capture of prey. Neurotoxins are particularly important in this regard, producing paralysis of skeletal muscles. These neurotoxins can be classified according to their site of action (i.e. pre- or post-synaptic). 2. Presynaptic neurotoxins, which display varying phospholipase A2 activities, have been identified in the venoms of the four major families of venomous snakes (i.e. Crotalidae, Elapidae, Hydrophiidae and Viperidae). The blockade of transmission produced by these toxins is usually characterized by a triphasic effect on acetylcholine release. Considerable work has been directed at identifying the binding site(s) on the presynaptic nerve terminal for these toxins, although their mechanism of action remains unclear. 3. Post-synaptic neurotoxins are antagonists of the nicotinic receptor on the skeletal muscle. Depending on their sequence, post-synaptic toxins are subdivided into short- and long-chain toxins. These toxins display different binding kinetics and different affinity for subtypes of nicotinic receptors. Post-synaptic neurotoxins have only been identified in venoms from the families Elapidae and Hydrophiidae. 4. Due to the high cost of developing new antivenoms and the reluctance of many companies to engage in this area of research, new methodologies are required to test the efficacy of existing antivenoms to ensure their optimal use. While chicken eggs have proven useful for the examination of haemorrhagic venoms, this procedure is not suited to venoms that primarily display neurotoxic activity. The chick biventer cervicis muscle has proven useful for this procedure, enabling the rapid screening of antivenoms against a range of venoms. 5. Historically, the lethality of snake venoms has been based on murine LD50 studies. Due to ethical reasons, these studies are being superseded by in vitro studies. Instead, the time taken to produce 90% inhibition of nerve-mediated twitches (i.e. t90) in skeletal muscle preparations can be determined. However, these two procedures result in different rank orders because they are measuring two different parameters. While murine LD50 determinations are based on "quantity", t90 values are based on how "quick" a venom acts. Therefore, knowledge of both parameters is still desirable. 6. In vitro neuromuscular preparations have proven to be invaluable tools in the examination of snake venoms and isolated neurotoxins. They will continue to play a role in further elucidating the mechanism of action of these highly potent toxins. Further study of these toxins may provide more highly specific research tools or lead compounds for pharmaceutical agents.

show abstract

An in vivo but insensate model for the evaluation of antivenoms (ED 50 ) using fertile hens' eggs

Cited by 22 publications

References 11 publications

CORAL SNAKE ANTIVENOM PRODUCED IN CHICKENS (Gallus domesticus)

CORAL SNAKE ANTIVENOM PRODUCED IN CHICKENS (Gallus domesticus)

Birth and hatching: Key events in the onset of awareness in the lamb and chick

In vitro neuromuscular activity of snake venoms

Contact Info

Product

Resources

About