Current pharmaceutical design
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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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Fibromyalgia syndrome is a nonarticular rheumatic disorder characterised by diffuse musculoskeletal pain, stiffness, fatigue, disturbed sleep and tender points. The pathophysiology is not well understood and treatment remains a challenge. Although pharmacological therapy is still the primary treatment choice, a long-term effective intervention has not been demonstrated yet. ⋯ Although, there is a great number of exercise studies, the large diversity of outcome measures and measurement instruments that have been used in studies, varying intensity and types of exercises, small sample sizes, high attrition rates, large variability in baseline function, symptom severity and psychosocial status limit to come to a conclusion about the efficacy of exercise in the treatment of fibromyalgia syndrome. There are also inconclusive results about the efficacy of cognitive-behavioural treatment because of limited number of studies with small sample sizes of patients with fibromyalgia syndrome. However, the results of the trials overall demonstrate the beneficial effects of both different types of exercise and cognitive-behavioural treatment, on the other hand, there is still a need for larger, more systematic and randomised controlled trials to evaluate the effectiveness.
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Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary or secondary role in various diseases, with essentially too little or too much apoptosis leading to proliferative or degenerative diseases, respectively. The machinery responsible for killing and degradation of the cell via apoptosis is expressed constitutively and become activated through various stimuli. ⋯ These defects might appear at the initiation and/or execution stages of apoptosis and result in the insufficient elimination of tumor cells, which might lead either to acquired resistance to treatment, or to uncontrolled migration of cancer cells and metastasis. Hence, identification and targeting of the disabled pathway, which is most efficiently inactivated in a particular type of tumor might be the most successful approach in the future. Here we review current knowledge concerning function of apoptotic machinery in cancer cells, and how this information can be used to increase the efficiency of tumor treatment.
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The aim of virtual high throughput screening is the identification of biologically relevant molecules amongst either tangible or virtual (large) collections of compounds. Amongst the various virtual screening approaches, those that are ligand based are becoming very popular due to the possibility to screen millions of molecules in a timely way. Descriptors and methods are briefly introduced and reviewed with more emphasis for those approaches that are based on fingerprint descriptors and that seems to be more utilized during the drug discovery process.
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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.