Susceptibility to toxins

In addition to nonhuman primates, most other animal species that show some sensitivity to botulinum intoxication are in fact susceptible to toxin serotypes Cl and D. Several rodent species are susceptible to oral intoxication with most botulinum toxins, including types Cl and D (Matveev, 1959 ... 

Children differ from adults in a number of ways that can increase their susceptibility to toxins in the home. For example ... 

Allergenic plants causing skin eruption by contact include poison ivy (Rhus radicans L.), poison oak (Rhus toxicodendron L.), poison sumac (Rhus vernix L.), and stinging nettle (Urtica dioica L.). In the United States, poison ivy and poison oak cause nearly 2 million cases of skin poisoning and skin irritation annually, for a loss of 333,000 working days. In addition, these weeds cause 3.7 million days of restricted activity among those people who are susceptible to the toxins (1). 

Transfers of materials across tissue surfaces exposed to the atmosphere are critical to life processes for humans, other animals, and plants. Thus, living things are particularly susceptible to harm by airborne irritants or toxins. The risk of such harm has been a major motivation for the development of techniques for the analysis of atmospheric dispersion. 

The anthrax bioterrorist attacks that followed the events of September 11th 2001 resulted in a renewed interest BadUus anthracis, the causative agent of this disease. Research has focused on the development of better vaccines than the one currently available. It has been estimated that the aerosolized release of 100 kg of anthrax spores upwind of Washington DC would cause mortalities of 130,000-3,000,000 [63]. Nonetheless, wild-type Bacillus anthracis is susceptible to conventional antibiotics, including penicillin, oxyfloxacin and ciprofloxacin. The problem lies not with the bacterial infection itself, but with three proteins released by the bacteria - protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa) and edema factor (EF, 89 kDa) -known as anthrax toxins [63]. 

Diphtheria causes a demyelinative neuropathy. Coryne-bacterium diphtheriae colonizes the pharynx or open wounds, and secretes a protein exotoxin. The B subunit of this exotoxin binds to plasma membranes and facilitates entry into cytosol of the A subunit, which catalyzes ADP-ribosylation, and inactivation of an elongation factor required for protein synthesis. Cardiac muscle and Schwann cells are particularly susceptible to this toxin, and hence patients with diphtheria develop cardiomyopathy and demyelinative polyneuropathy [20]. While diphtheria is now uncommon because of childhood immunization against C. diphtheriae, the disruption in preventative medicine programs caused by disintegration of the Soviet Union was followed by a substantial incidence of diphtheritic polyneuropathy in Russia. 

Compared to people in a noncontaminated area, plasma IgG levels were also significantly decreased in proportion to increasing plasma levels of TCDD in a cohort exposed in an industrial accident in Seveso, Italy.118 There was no effect on IgM or IgA levels, or on complement levels IgE was not measured. In separate studies, in vitro exposure to TCDD enhanced the spontaneous production of IgE by B cells isolated from atopic but not non-atopic individuals, but did not affect the levels of other isotypes.119 Other recent studies have reported small changes in immune cells from individuals exposed occupationally to PHAH.120121 For example, compared to unexposed controls, a cohort of men exposed occupationally to TCDD had diminished IFNy production in a recall response to tetanus toxin, while IFNy production following polyclonal activation was unaffected.120 This observation is consistent with mouse studies, in which antigen-specific responses are highly suppressed by TCDD, but mitogen-driven T cell responses are less susceptible to impairment.83 88122123... 

Treatment — There is no specific treatment for C. perfringens toxins, even though the organism is susceptible to penicillin, which is the drug of choice for a naturally acquired infection. Recent laboratory data indicate that clindamycin and rifampin may suppress toxin formation. Available polyvalent antitoxins contain antibodies to several toxins that have been used in treatment, but not enough data exist to prove efficacy.3... 

Phytosterol dealkylation can be harnessed in insects to release a fluoroacetate equivalent from a 29-fluorinated sterol. Moreover, the fluorocitrate which then results from the "lethal synthesis" can be isolated and chemically characterized. hope that the range of insects susceptible to the 29-fluorophytosterols and more commercially viable analogs will be further explored. Furthermore, we urge wider scrutiny of insect biochemical pathways in search of possible targets for suicide substrates or latent toxin release. 

Other cyclic tetrapeptides have also been isolated by Japanese workers and AM toxins I, II, and III, isolated from Alternaria mail., are extremely toxic to certain plant species (9.10). These are constructed of L- i-hydroxyisovaleric acid, L-alanine, c-amino-acrylic acid and, in AM toxin I, L-6(-amino- -( .-methoxyphenyl)-valeric acid. The phenyl residue in AM toxin II is L-t(-amino-S-phenylvaleric acid, while in AM toxin III, it is L-ol-amino-( .-hydroxyphenyl)valeric acid (Figure 2), All the AM toxins produce leaf spot, or necrosis, in apple but as might he expected slight change in substitution (R-group) on the phenyl ring radically alters the specific activity of the molecule. Both AM toxin I and III induce interveinal necrosis in the "Indo" apple cultivar, which is also highly susceptible to A. mail. at concentrations as low as 0.1 pph within 18 h after treatment. In contrast, the resistant apple cultivar "Jonathan" is only affected by 1 ppm of AM toxin I and 10 ppm of AM toxin III. 

Children, because of their small size, are often the most susceptible to many of the naturally occurring toxins, just as they are to other toxicants. The caffeine from a can of cola will have a much bigger effect on a small child than it will on an adult. 

---