Toxicology
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Aminoglycosides are bactericidal aminoglycosidic aminocyclitols. They are cost effective and therefore widely used, however ototoxicity is a prominent dose-limiting side effect. Aminoglycoside induced ototoxicity leads to permanent bilaterally severe, high-frequency sensorineural hearing loss and temporary vestibular hypofunction. ⋯ The development of aminoglycoside otoprotective strategies is a primary goal in ototoxicity research. Animal experiments have provided encouraging evidence for the protection of cochlear hair cells and neurons from aminoglycoside toxicity. However, the extent to which such protection, generalize to human ototoxicity remains unresolved.
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Acute kidney injury (AKI) is a common condition with significant associated morbidity and mortality. Epidemiologic data suggest that a significant proportion of AKI cases is at least partially attributable to nephrotoxin exposure. This is not surprising given intrinsic renal susceptibility to toxicant-induced injury, a consequence of the unique physiologic and biochemical properties of the normally functioning kidney. ⋯ Unfortunately, standard metrics used to diagnose and monitor kidney injury, such as blood urea nitrogen and serum creatinine, are insensitive and nonspecific, resulting in delayed diagnosis and intervention. Considerable effort has been made to identify biomarkers that will allow the earlier diagnosis of AKI. Further characterization of these candidate biomarkers will clarify their utility in the setting of acute nephrotoxicity, define new diagnostic and prognostic paradigms for kidney injury, facilitate clinical trials, and lead to novel effective therapies.
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Sulphur mustard is one of the major chemical warfare agents developed and used during World War I. Large stockpiles are still present in several countries. It is relatively easy to produce and might be used as a terroristic weapon. ⋯ In the latter conflict, sulphur mustard was heavily used and until now about 30,000 victims still suffer from late effects of the agent like chronic obstructive lung disease, lung fibrosis, recurrent corneal ulcer disease, chronic conjunctivitis, abnormal pigmentation of the skin, and several forms of cancer. Despite enormous research efforts during the last 90 years, no specific sulphur mustard antidote has been found. The prospering knowledge and developments of modern medicine created nowadays new chances to minimize sulphur mustard-induced organ damage and late effects.
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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.