Toxicology
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Burn trauma produces significant fluid shifts that, in turn, reduce cardiac output and tissue perfusion. Treatment approaches to major burn injury include administration of crystalloid solutions to correct hypovolemia and to restore peripheral perfusion. While this aggressive postburn volume replacement increases oxygen delivery to previously ischemic tissue, this restoration of oxygen delivery is thought to initiate a series of deleterious events that exacerbate ischemia-related tissue injury. ⋯ Antioxidant therapy in burn therapy (ascorbic acid, glutathione, N-acetyl-L-cysteine, or vitamins A, E, and C alone or in combination) have been shown to reduce burn and burn/sepsis mediated mortality, to attenuate changes in cellular energetics, to protect microvascular circulation, reduce tissue lipid peroxidation, improve cardiac output, and to reduce the volume of required fluid resuscitation. Antioxidant vitamin therapy with fluid resuscitation has also been shown to prevent burn related cardiac NF-kappaB nuclear migration, to inhibit cardiomyocyte secretion of TNF-alpha, IL-1beta, and IL-6, and to improve cardiac contractile function. These data collectively support the hypothesis that cellular oxidative stress is a critical step in burn-mediated injury, and suggest that antioxidant strategies designed to either inhibit free radical formation or to scavage free radicals may provide organ protection in patients with burn injury.
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Complementary medicines, including herbal medicines in Australia are regulated under therapeutics goods legislation. Based on risk, Australia has developed a two tiered approach to the regulation of therapeutic goods. Listed medicines are considered to be of lower risk than Registered medicines. ⋯ They may only be formulated from ingredients that have undergone pre-market evaluation for safety and quality and are considered low risk. Listed complementary medicines may only carry indications and claims for the symptomatic relief of non-serious conditions, health maintenance, health enhancement and risk reduction. An important feature of risk management in Australia is that early market access for low risk complementary medicines is supported by appropriate post-market regulatory activity.
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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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The Australian adverse drug reaction reporting system is acknowledged as one of the best in the world. Despite its small population of less than 20 million people, Australia's current ADR reporting rate of over 12,000 reports per year places it in the top few nations in terms of reports per capita. The ADRAC program has been in operation for over 30 years. ⋯ Of particular importance are flucloxacillin-induced hepatitis, amoxycillin/clavulanate-induced hepatitis, and the association of cystitis with tiaprofenic acid. The number and quality of the reports has allowed an understanding of the characteristics of the reactions and, using ADRAC reporters as a major source of cases, case-control studies have been completed which have identified risk factors. ADRAC's review of Australian reports has highlighted many important associations that have been disseminated through the Australian Adverse Drug Reactions Bulletin.