Pharmacology & therapeutics
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Alzheimer's disease (AD) is the most common cause of progressive decline of cognitive function in aged humans, and is characterized by the presence of numerous senile plaques and neurofibrillary tangles accompanied by neuronal loss. Some, but not all, of the neuropathological alterations and cognitive impairment in AD can be reproduced genetically and pharmacologically in animals. It should be possible to discover novel drugs that slow the progress or alleviate the clinical symptoms of AD by using these animal models. We review the recent progress in the development of animal models of AD and discuss how to use these model animals to evaluate novel anti-dementia drugs.
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Complex paracrine interactions exist between endothelial cells and cardiac myocytes in the heart. Cardiac endothelial cells release (or metabolize) several diffusible agents (e.g., nitric oxide [NO], endothelin-1, angiotensin II, adenylpurines) that exert direct effects on myocyte function, independent of changes in coronary flow. Some of these mediators are also generated by cardiac myocytes, often under pathological conditions. ⋯ Beneficial effects of NO can result from endothelial-type nitric oxide synthase-derived NO or from spatially and temporally restricted expression of the inducible isoform, inducible-type nitric oxide synthase. Deleterious effects may result from (1) deficiency of NO or (2) excessive production, often inducible-type nitric oxide synthase-derived and usually with concurrent reactive oxygen species production and peroxynitrite formation. The balance between beneficial and deleterious effects of NO is of key importance with respect to its pathophysiological role.
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The three anesthetic drugs introduced most recently to the market are sevoflurane, desflurane, and ropivacaine. Sevoflurane and desflurane are both inhalational anesthetic agents and ropivacaine is a local anesthetic agent. Sevoflurane provides a rapid onset and offset of action; it is well tolerated with little airway irritation. ⋯ While desflurane also provides rapid onset and recovery from anesthesia, it is not as hemodynamically stable as sevoflurane, and also causes airway irritation. Ropivacaine is a unique local anesthetic in that it is supplied as the pure S-enantiomer. It is at least as effective as bupivacaine, with lower toxicity and less motor block for the same degree of sensory block.
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Laboratory data, economic pressures, and the wish for humane treatment have been some of the driving forces behind improvements in paediatric pain management. Within the space of 10 years, there have been dramatic changes in the quality of treatment received by children undergoing surgical operations. Moreover, those receiving medical treatment, for example, sickle cell disease, have also benefited from increased experience in pain management. ⋯ Improved care, with close attention to pain relief, is not only humane, but improves the patient turnaround by enhancing rapid discharge. Further education is required to spread these benefits to children being managed outside highly specialised centres. Not only education, but investment, is needed also to ensure that all children receive a standard of care second to none.
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The medical treatment and some currently known aspects of the aetiology of five neurogenic pain states are discussed. Neurogenic pain can be described as pain resulting from noninflammatory dysfunction of the peripheral or central nervous system without nociceptor stimulation or trauma. The enormity of the field has limited this review to post-herpetic neuralgia, complex regional pain syndromes, phantom pain, trigeminal neuralgia and diabetic neuralgia. ⋯ This may be due in part to a lack of understanding of the aetiology of these conditions and to the lack of high quality studies evaluating existing treatments. A compact review of the literature is presented with some treatment options and possible future directions. Where appropriate surgical management and physical therapy have been discussed; however, a thorough appraisal of nondrug treatments was not the main priority of this review.