Toxins exposure time

Apoptotic cells in any system can die and disappear relatively quickly. The time from initiation of apoptosis to completion can occur as quickly as 2-3 hr. Therefore a false negative can occur if the assay is done too early or too late. Moreover, apoptosis can occur at low frequency or in specific sites within organs, tissues, and cultures. In such cases, the ability to rapidly survey large areas could be useful. In general, if detailed information on the mechanism of cell death is desired, the duration of toxin exposure, the concentration of the test compound, and the choice of assay endpoint become critical. 

In vivo toxicity tests involve the direct exposure (via appropriate exposure routes) of hving animals to variable doses of toxins over time, followed by measurement of toxic effects or exposure indicators. Inhalation tests either expose the subject animals to known concentrations of particles in an airstream, or utihze direct intratracheal implantation of the particles in the subject animals (e.g., studies summarized in Johnson and... 

Since toxin induced chronic renal failure is theorized to occur after years of low-level toxin exposure, it stands to reason that the incidence would be clustered in elderly patients. The study of Chester et al. [172] provides indirect support that elderly patients may be at greater risk. Of the 79 patients with chronic renal failure who met age criteria of 70 year or more, 29% were classified as having chronic interstitial nephritis, a clinical diagnosis quite compatible with toxin induced renal failure and an incidence substantially higher than the 10.4% in accumulated series in which patients 50 year and older were included [173]. Furthermore, in the 2006 USRDS survey of causes of ESRD, the average age for patients with a diagnosis of interstitial nephropathy was 56 year compared to 58 years for the entire population reported [119]. In the recent analysis of the PICARD database, advanced age was associated with increased mortahty in AKI patients both at time of consultation and after initiation of dialysis treatment [38]. 

Internalization affords the next opportunity to ameliorate the toxic actions of BoNT. A number of pharmacological agents have been examined for inhibition of this process with various degrees of success. Simpson (1983) demonstrated that pretreatment of phrenic nerve-hemidiaphragm preparations with the lysosomotropic agents ammonium chloride or methylamine hydrochloride delayed the time-to-block of nerve-evoked muscle contractions after exposure to BoNT serotypes A, B, Cl, and TeNT. Incubation of nerve-muscle preparations with ammonium chloride and methylamine hydrochloride was effective if applied before, concurrently, or up to 20 min after toxin exposure. The efficacy of the lysosomotropic agents was reduced rapidly with further delays, such that no effect was observed if they were administered 30-35 min after toxin exposure. At optimal concentrations, these compounds produced a twofold delay in the time-to-block (Simpson, 1983). 

In the case of T-2 toxin the toxicity increased with the temperature from 10 to 15°Cand then decreased to show a stimulation of the light emission at 25° C. This effect was found to be independent of the exposure time. HT-2 toxin and DAS, however, showed the opposite pattern with decreasing toxicity from 10 to 15°C and increasing toxicity at higher temperature. For DON, the toxicity i ncreased with temperature at all exposure times. An overview of the observed toxicity temperature dependencies is given in FIGURE 4. 

Increasing the test temperature increased the toxicity of DON. For HT-2 toxin and DAS a stimuiation of luminescence was observed with increasing temperatures up to 15° C and an increase in toxicity was observed afterwards. Temperature had the opposite effect on the behaviour of the T-2 toxin, where the luminescence was inhibited at 10 and 15°C and increased at greater temperature. Consequently, the effects of the trichothecenes tested on the bioluminescent bacteria are highly dependent on the test temperature and exposure time. 

The diagnosis of aflatoxicosis will be difficult to make without a clear history of exposure as the features may mimic other causes of acute hepatitis. Blood testing may demonstrate raised liver function tests and prolongation of prothrombin time, although these are not specific to toxin exposure. Detection of the toxin by serum assay will require specialised laboratory services. 

Casualties I personnel Do not attempt to brush the agent off the individual or their clothing as this can aerosolize the agent. Remove all clothing immediately. To avoid further exposure of the head, neck, and face to the agent, cut off potentially contaminated clothing that must be pulled over the head. Wash the skin surface and hair at least three times with copious amounts of soap and water. Do not delay decontamination to find warm or hot water if it is not readily available. Rinse with copious amounts of water. If there is a potential that the eyes have been exposed to toxins, irrigate with water or 0.9% saline solution for a minimum of 15 minutes. 

Medical Management Victims may have a feverish respiratory syndrome without chest x-ray abnormalities, and diagnosis is usually clinical. Medical and emergency medical services personnel should be aware of and should report any number of victims showing up within a limited amount of time presenting typical symptoms and instances of SEB pulmonary exposure as being indicative of being an intentional attack with SEB toxin. 

When this interview took place she and Ron had recently moved to a rural location to minimize her exposures to toxins in the city. She spends most of her time alone or with Ron, because exposure to other people can cause her to be incapacitated for days. One of the places she longs to go is to a theater to see the movie Life Is Beautiful. 

---