Current pharmaceutical design
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Characteristic symptoms of fibromyalgia syndrome (FM) include widespread pain, fatigue, sleep abnormalities, and distress. FM patients show psychophysical evidence for mechanical, thermal, and electrical hyperalgesia. To fulfill FM criteria, the mechanical hyperalgesia needs to be widespread and present in at least 11 out of 18 well-defined body areas (tender points). ⋯ It frequently comprises multiple areas of deep tissue pain (trigger points) with adjacent much larger areas of referred pain. Analgesia of areas of extensive nociceptive input has been found to provide often long lasting local as well as general pain relief. Thus interventions aimed at reducing local FM pain seem to be effective but need to focus less on tender points but more on trigger points (TrP) and other body areas of heightened pain and inflammation.
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This article describes the studies that have been performed evaluating complementary or alternative medical (CAM) therapies for efficacy and some adverse events fibromyalgia (FM). There is no permanent cure for FM; therefore, adequate symptom control should be goal of treatment. Clinicians can choose from a variety of pharmacologic and nonpharmacologic modalities. ⋯ Another CAM therapy such as chiropractic care has neither well-designed studies nor positive results and is not currently recommended for FM treatment. Once CAM therapies have been better evaluated for safety and long-term efficacy in randomised, placebo-controlled trials, they may prove to be beneficial in treatments for FM. It would then be important to assess studies assessing cost-benefit analyses comparing conventional therapies and CAM.
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Population studies have identified diabetes mellitus as a risk factor for cardiac and vascular events, with a common association with hypertension. Observational studies have consistently demonstrated blood glucose as a continuous cardiovascular risk factor. ⋯ However, an unconvincing temporal relationship (raised blood glucose preceding cardiovascular events) and the limited impact of glucose reduction in patients with diabetes on cardiovascular events do not support blood glucose as a major cause of cardiovascular disease. In this review, we discuss the relationship between hyperglycaemia and a hypercoagulable state in diabetes and the implications of this relationship for the treatment of patients with diabetes, who also commonly have hypertension.
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The intention of this review is to give a brief overview of the continuously expanding field of sepsis therapy based on recent studies with animal models and clinical trials. Over the past few years, it has become apparent that the mechanisms controlling this disease are more complex than was previously thought, with factors such as free radicals, nuclear factors, and enzyme co-factors all contributing in the control of the pathogenesis of sepsis as well and improvements in the morbidity. Recent advances at the molecular biology level have facilitated the development of a whole new field of research. ⋯ Further elucidation of the signals that influence the production and actions of free radicals will, without doubt, further our understanding of the numerous pathophysiological processes involved in sepsis. For these reasons, there is considerable interest in alternative treatment modalities which focus on recent animal studies. These recent experimental approaches to the therapy of sepsis are discussed in light of each step in the complex inflammatory cascade involved and compared to traditional approaches to the prevention and therapy of sepsis and septic shock.
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Human ether-a-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current, IKr, which is crucial for repolarization of cardiac action potentials. Moderate hERG blockade may produce a beneficial class III antiarrhythmic effect. In contrast, a reduction in hERG currents due to either genetic defects or adverse drug effects can lead to hereditary or acquired long QT syndromes characterized by action potential prolongation, lengthening of the QT interval on the surface ECG, and an increased risk for "torsade de pointes" arrhythmias and sudden death. ⋯ Recently, mutations in hERG have been shown to cause current increase and hereditary short QT syndrome with a high risk for life-threatening arrhythmias. Finally, the discovery of adrenergic mechanisms of hERG channel regulation as well as the development of strategies to enhance hERG currents and to modify intracellular hERG protein processing may provide novel antiarrhythmic options in repolarization disorders. In conclusion, the increasing understanding of hERG channel function and molecular mechanisms of hERG current regulation could improve prevention and treatment of hERG-associated cardiac repolarization disorders.