Pharmacological reviews
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The study of pain in awake animals raises ethical, philosophical, and technical problems. We review the ethical standards for studying pain in animals and emphasize that there are scientific as well as moral reasons for keeping to them. Philosophically, there is the problem that pain cannot be monitored directly in animals but can only be estimated by examining their responses to nociceptive stimuli; however, such responses do not necessarily mean that there is a concomitant sensation. ⋯ The main tests are critically reviewed in terms of their sensitivity, specificity, and predictiveness. Weaknesses are highlighted, including 1) that in most tests responses are monitored around a nociceptive threshold, whereas clinical pain is almost always more severe; 2) differences in the fashion whereby responses are evoked from healthy and inflamed tissues; and 3) problems in assessing threshold responses to stimuli, which continue to increase in intensity. It is concluded that although the neural basis of the most used tests is poorly understood, their use will be more profitable if pain is considered within, rather than apart from, the body's homeostatic mechanisms.
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Pharmacological reviews · Mar 2001
ReviewThe complex effects of heparins on cancer progression and metastasis in experimental studies.
Patients with cancer are frequently treated with anticoagulants, including heparins, to treat or to prevent thrombosis. Recent randomized trials that compared low molecular weight heparin to unfractionated heparin for the treatment of deep vein thrombosis have indicated that heparins affect survival of patients with cancer. Experimental studies support the hypothesis that cancer progression can be influenced by heparins, but results of these studies are not conclusive. ⋯ It is shown that heparins can affect proliferation, migration, and invasion of cancer cells in various ways and that heparins can interfere with adherence of cancer cells to vascular endothelium. Moreover, heparins can affect the immune system and have both inhibitory and stimulatory effects on angiogenesis. Because of the wide variety of activities of heparins, it is concluded that the ultimate effect of heparin treatment on cancer progression is uncertain.
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Pharmacological reviews · Dec 2000
ReviewThe sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system.
The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system "talk to each other" and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). ⋯ Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages. The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth. Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.
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Pharmacological reviews · Mar 2000
ReviewC1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema.
C1-esterase inhibitor (C1-Inh) therapy was introduced in clinical medicine about 25 years ago as a replacement therapy for patients with hereditary angioedema caused by a deficiency of C1-Inh. There is now accumulating evidence, obtained from studies in animals and observations in patients, that administration of C1-Inh may have a beneficial effect as well in other clinical conditions such as sepsis, cytokine-induced vascular leak syndrome, acute myocardial infarction, or other diseases. Activation of the complement system, the contact activation system, and the coagulation system has been observed in these diseases. ⋯ Here we will give an overview on the biochemistry and biology of C1-Inh. We will discuss studies addressing therapeutic administration of C1-Inh in experimental and clinical conditions. Finally, we will provide an explanation for the therapeutic benefit of C1-Inh in so many different diseases.