Current pharmaceutical design
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Cytokines are centrally involved in the regulation of normal hematopoiesis, the production of mature blood cells by bone marrow stem cells. Cytokines influence stem survival, proliferation, and differentiation commitment, as well as controlling the orderly maturation of progenitor cells into functional leucocytes, erythrocytes, and platelets. Acute leukemias result from malignant transformation of bone marrow stem cells. ⋯ Conversely, the concept of using either of these two cytokines to induce acute myeloid leukemia cells into active DNA synthesis, thus potentially sensitising them to the effects of S-phase-specific drugs, has not been shown to be clinically beneficial. Both G-CSF and GM-CSF have been demonstrated to accelerate the recovery of normal granulopoiesis after intensive initial cytotoxic chemotherapy for acute leukemia, significantly shortening the duration of severe treatment-induced neutropenia, and resulting in a number of tangible benefits including reduction in infection, use of intravenous antibiotics, and duration of hospital stay. However, the final role for these agents in the treatment of acute leukemia remains controversial and still to be fully defined.
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Review Comparative Study
Comparative analgesia, cardiovascular and renal effects of celecoxib, rofecoxib and acetaminophen (paracetamol).
Comparisons are made between the specific COX-2 inhibitors, celecoxib and rofecoxib, and acetaminophen. The specific COX-2 inhibitors are a significant advance in therapy because their anti-inflammatory, analgesic and antipyretic activities are associated with a high degree of gastrointestinal safety. Acetaminophen is often not considered to be a potent inhibitor of COX-2 but it is a potent inhibitor of prostaglandin synthesis in intact cells after stimulation by cytokines. ⋯ Acetaminophen also may decrease the excretion of sodium and the reason for its greater renal safety at therapeutic doses is unclear. Myocardial infarction has also been attributed to the specific COX-2 inhibitors from meta-analysis of large scale clinical trials and examination of reports of adverse drug reactions although this is still a topic of considerable discussion. No such associations have been made with acetaminophen, possibly because it is a weak inhibitor of COX-1 in platelets.
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The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide / lanreotide analogs as tumor tracers in nuclear medicine. Other (nontumoral) potential indications for SSTR scintigraphy are based on an increased lymphocyte binding at sites of inflammatory or immunologic diseases such as thyroid-associated ophthalmology. The vast majority of human tumors seem to over-express the one or the other of five distinct hSSTR subtype receptors. ⋯ However, an optimal radiopeptide formulatioents. However, an optimal radiopeptide formulation does not yet exist for receptor-targeted radionuclide therapy. Ongoing developments may result in peptides more suitable for this kind of receptor-targeted radionuclide therapy.
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The recent literature on the antinociceptive action of ionotropic glutamate receptor antagonists is reviewed with special emphasis on their clinical potential. Actually the glutamatergic pathways descending from the brain stem into the spinal cord may generate analgesia. However, physiologically more important is that glutamate and aspartate are apparently the main neurotransmitters along the ascending nociceptive pathways in the spinal cord. ⋯ Not being registered there are no clinical data on the AMPA antagonists. There are, however, some investigational new drugs and some novel compounds in the stage of preclinical development which antagonise the AMPA receptors in competitive fashion or allosterically. Of the latter molecules 2,3-benzodiazepines are particularly promising.
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In the complex pathogenesis of airway inflammation seen in asthma, several cytokines are recognized to play a crucial role. Modulation of the effect of these cytokines can provide alternative and more specific treatment approach to currently widely-used systemic immunosuppression by glucocorticoids. ⋯ Also, some cytokines are known to possess anti-inflammatory effects in allergic inflammation, being thus themselves potentially used as a therapeutic agent. The current review discusses the present knowledge on the involvement of cytokines in the pathogenesis of allergic asthma and the experience on modulation of the effect of these cytokines in clinical situations.