Showing papers in "Current Opinion in Pharmacology in 2003"

TL;DR: Emerging results suggest that inhibition of mTOR signaling can be exploited as a potential tumour-selective therapeutic strategy.

TL;DR: Only five major lineages of hospital methicillin-resistant Staphylococcus aureus exist, but these are globally distributed and evolving resistance to even the newest antibiotics.

TL;DR: Cannabinoid receptor agonists significantly diminish pain responses in animal models; however, they exhibit only modest analgesic effects in humans, and show promise for the treatment of acute and chronic pain without psychoactive effects.

TL;DR: The induction of apoptosis of macrophages, synovial fibroblasts or lymphocytes, either through suppression of signaling pathways or inhibition of the expression of anti-apoptotic molecules, could be therapeutically beneficial in RA.

TL;DR: Research to date is promising and confirms the need for continuing work to forge the way for new drug discovery in trace amines.

TL;DR: There is now cautious optimism that isoform-selective PI3K inhibitors will provide new avenues for therapeutic applications in a range of diseases.

TL;DR: It appears that endocannabinoids might modulate cell-cell signalling via effects on neurotransmitter re-uptake and postsynaptic actions mediating cross talk between multiple receptor types, whereas CB(1) receptor agonists could have value in reducing levodopa-induced dyskinesia.

TL;DR: The cloning of the P2Y(12) receptor and its subsequent knockout in mice promises further understanding of its downstream signaling events.

TL;DR: The common signalling pathways used by all members of the TLR superfamily are being targeted, with drugs that block nuclear factor-kappaB and p38 mitogen-activated protein kinase in clinical development for diseases such as rheumatoid arthritis and psoriasis.

TL;DR: This data indicates that activated JNK could be critical in causing diabetes, insulin resistance and obesity, and if JNK is considered as a stress-activated protein kinase, there appear to be multiple mechanisms through which it might promote diabetes.

TL;DR: Interest in CDK inhibitors as antineoplastic agents will continue for the foreseeable future, as efforts are underway to uncover inhibitors that selectively target specific CDKs and to develop these as a new generation of antitumour drugs.

TL;DR: Recent findings shed new light on mechanisms of cell death in the central nervous system, especially with respect to in vivo apoptosis, and views that are contrary to prevailing interpretations are expressed.

TL;DR: Antibody-targeted chemotherapy with immunoconjugates of calicheamicin, exemplified by gemtuzumab ozogamicin (Mylotarg), is a clinically validated therapeutic strategy for the treatment of human cancer.

TL;DR: Synthetic glucocorticoids are potent modulators of the immune system, and are clinically invaluable in the treatment of a wide variety of conditions, but their use can be limited by harmful side effects, and their mechanisms of action remain poorly understood and controversial.

TL;DR: The severity of gastrointestinal effects caused by drugs that inhibit SERT, such as tricyclic antidepressants, selective serotonin reuptake inhibitors and cocaine, does not usually prevent their therapeutic or recreational use because backup transporters and alterations in receptor gene expression allow the gut to adapt, albeit imperfectly, to their toxicity.

TL;DR: Repeat administration of ghrelin improves cardiac structure and function, and attenuates the development of cardiac cachexia in rats with heart failure, suggesting that gh Relin has therapeutic potential in the treatment of severe chronic heart failure.

TL;DR: High-quality monoclonal antibodies with specificity for relevant disease molecules can now be produced in abundance and there is preliminary evidence for the clinical efficacy of both keliximab and rituximab, a chimeric mAb against the B cell antigen CD20 and CTLA4-Ig.

TL;DR: Observations identify the LXR pathway as an attractive target for intervention in cardiovascular disease because of its links to the pathogenesis of atherosclerosis.

TL;DR: Small-molecule CFTR inhibitors reduce enterotoxin-induced intestinal fluid secretion in animal models and might also reduce intestinal fluid losses in cholera and possibly in other infectious and non-infectious diarrheas.

TL;DR: Can the identification of a fish peptide as a ligand for an 'orphan' mammalian G-protein-coupled receptor really tell us something about human physiology?

TL;DR: Many of the pro-inflammatory cytokines that are released in response to immune/inflammatory insults exert marked stimulatory influences on the hypothalamo-pituitary-adrenocortical axis, and provoke the release of glucocorticoid release, and thereby complete a homeostatic neuroendocrine loop.

TL;DR: In this paper, a systematic approach for target selection could significantly increase the rate of successful new drug development, thereby enhancing industry productivity, and it has been shown that mouse knockout phenotypes for the targets of the 100 best-selling pharmaceutical drugs correlate well with known drug efficacy.

TL;DR: The current challenge for modulator-based GPCR drug discovery is the optimization of both binding and functional assays to better detect and validate allosteric ligands.

TL;DR: Recent data demonstrate that neuronal excitation modulates both the pial and meningeal circulation through a critical interaction with the trigeminal nerve, supporting the concept that the integration of neuronal and vascular information in the trigeminovascular network represents a key event in the aetiology of migraine.

TL;DR: GnRH is a decapeptide that stimulates pituitary synthesis and secretion of gonadotropins and, therefore, gonadal hormones as mentioned in this paper, inducing a pharmacological hypophysectomy Peptide derivations of GnRH and non-peptide compounds are both in clinical trials or approved for assisted reproduction.

TL;DR: GABA(A) (gamma-n-aminobutyric acid) receptor dysfunction has long been implicated in the development of epilepsy and status epilepticus and genetic mutations found in GABA( A) receptor subunits strongly implicate the GABA(A), receptor in idiopathic generalised epilepsies.

TL;DR: These acid sensors, which are expressed by afferent neurons, are most relevant to the regulation of acid secretion, foregut motility and mucosal protection, as well as to gastrointestinal disturbances associated with inflammation, ischaemia and stasis.

TL;DR: The first antibody derived from phage display technology has been approved in the US by the Food and Drug Administration, indicating the versatility of antibodies as therapeutic and diagnostic agents.

TL;DR: Future advances in the pharmacological treatment of traumatic brain injury are likely to include the evaluation of sequentially timed therapies combining multiple and targeted agents, and manipulation of the newly discovered neurogenic potential of the adult brain together with the refinement of traditional interventions to block specific cytotoxic cascades.

TL;DR: It will only be a matter of time before the authors know whether compounds that modulate the function of PPARgamma and beta/delta are also efficacious at combating atherosclerosis.