Toxicology
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There exist in animals a large number of enzymes that primarily metabolize xenobiotics including drugs, toxins and carcinogens. While these enzymes are known to activate or inactivate toxins and carcinogens in vitro, it had not been demonstrated until recently whether they are responsible for the biological effects of these chemicals in intact animal models. ⋯ However, in many cases, mice lacking certain xenobiotic-metabolizing enzymes confer resistance to acute toxicities and chemical carcinogenesis thus demonstrating that these enzymes mediate the deleterious effects of chemicals. The use of xenobiotic metabolism null animal models to study the mechanisms of actions of toxins and carcinogens will be reviewed.
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Polychlorinated biphenyls (PCBs) cross the placenta and expose the fetus to the body burden of the mother. Additionally, the breastfed baby is postnatally exposed to PCBs in maternal milk. Among the broad spectrum of biological effects interaction with endocrine systems and developmental neurotoxicity are prominent features of these chemical mixtures. ⋯ The underlying mechanisms of this action is still unknown. However, interaction with endocrine systems, namely the estrogen/androgen and, particularly, the thyroid hormone systems are discussed as a possible explanation for PCB-induced neurodevelopmental adversity. Some evidence in this respect is being reviewed.
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A significant portion of the world's geography lies above 10,000 feet elevation, an arbitrary designation that separates moderate and high altitude. Although the number of indigenous people living at these elevations is relatively small, many people travel to high altitude for work or recreation, exposing themselves to chronic or intermittent hypoxia and the associated risk of acute mountain sickness (AMS) and less frequently, high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The symptoms of AMS (headache, nausea, anorexia, fatigue, lassitude) occur in those who travel too high, too fast. ⋯ Oxidative stress can be observed at altitude without strenuous physical exertion; however, environmental factors other than hypoxia, such as exercise, UV light exposure and cold exposure, can also contribute to the burden. Providing antioxidant nutrients via the diet or supplements to the diet can reduce oxidative stress secondary to altitude exposure. In summary, the significant unanswered question concerning altitude exposure and antioxidant supplementation is when does oxidative stress become potentially damaging enough to merit antioxidant therapy and conversely, what degree of oxidative stress is necessary to foster the adaptive response of altitude exposure?
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Carbon monoxide (CO) may be the cause of more than one-half of the fatal poisonings reported in many countries; fatal cases also are grossly under-reported or misdiagnosed by medical professionals. Therefore, the precise number of individuals who have suffered from CO intoxication is not known. The health effects associated with exposure to CO range from the more subtle cardiovascular and neurobehavioral effects at low concentrations to unconsciousness and death after acute or chronic exposure to higher concentrations of CO. ⋯ Carbon monoxide poisoning during pregnancy results in high risk for the mother by increasing the short-term complication rate and for the fetus by causing fetal death, developmental disorders, and chronic cerebral lesions. In conclusion, CO poisoning occurs frequently; has severe consequences, including immediate death; involves complications and late sequelae; and often is overlooked. Efforts in prevention and in public and medical education should be encouraged.
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Primary blast injury occurs in civilian and military detonations and from the firing of weapon systems. The pathology of primary blast injury has been reported for the last 70 years and has primarily been limited to descriptions of gross pathology and histology. ⋯ Organ systems other than the ear and the lung are playing a greater role in injury definition and research importance. This paper is an overview and update of the current understanding of the pathology of primary blast injury.