MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Current Drug Targets' source. Sun, 21 Mar 2010 14:57:33 +0100 http://www.medworm.com/index.php?rid=3338721&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199388%26dopt%3DAbstract Authors: Blom AB, van Lent PL, van der Kraan PM, van den Berg WB Recent evidence from animal experiments and clinical samples points at a role for Wnt-signaling in osteoarthritis (OA) pathology. These pathways are key inducers and regulators of joint development, and are involved in formation of bone, cartilage and also synovium. Disregulation of members from this pathways have been described in OA. This makes the Wnt-family of proteins and signaling pathways an attractive target for therapy. Although knowledge is increasing rapidly it is still a challenge to decide on the best approach in targeting Wnt signaling. Activation of the canonical signaling pathway, which features intra-cellular accumulation of beta-catenin, is most often implicated in recent studies in OA pathology, in expe... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338721 Thu, 04 Mar 2010 00:00:00 +0100 3338721 http://www.medworm.com/index.php?rid=3338720&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199389%26dopt%3DAbstract Authors: Flannery CR Therapeutic alleviation of the pathophysiology of osteoarthritis (OA) is a great and unmet medical challenge. At the basic science level, significant progress has facilitated the identification of distinct pathways and targets which appear to be central to the OA-associated deterioration of articular cartilage. For example, the dysregulated activities of aggrecanases such as ADAMTS-4 and ADAMTS-5, and collagenases such as MMP-13, point to strategies for the development of selective protease inhibitors to curtail OA disease progression. Likewise, blockade of disease-associated "pro-catabolic" cytokines may offer promising opportunities in this regard. Other novel biotherapeutic approaches are also emerging, including the use of recombinant lubricin molecules for int... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338720 Thu, 04 Mar 2010 00:00:00 +0100 3338720 http://www.medworm.com/index.php?rid=3338719&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199390%26dopt%3DAbstract Authors: Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB In the context of OA disease, NF-kappa;B transcription factors can be triggered by a host of stress-related stimuli including pro-inflammatory cytokines, excessive mechanical stress and ECM degradation products. Activated NF-kappa;B regulates the expression of many cytokines and chemokines, adhesion molecules, inflammatory mediators, and several matrix degrading enzymes. NF-kappa;B also influences the regulated accumulation and remodeling of ECM proteins and has indirect positive effects on downstream regulators of terminal chondrocyte differentiation (including beta-catenin and Runx2). Although driven partly by pro-inflammatory and stress-related factors, OA pathogenesis also involves a "loss of maturational arrest" that in... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338719 Thu, 04 Mar 2010 00:00:00 +0100 3338719 http://www.medworm.com/index.php?rid=3338718&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199391%26dopt%3DAbstract Authors: Iannone F, Lapadula G Obesity is one of the main risk factors for osteoarthritis (OA). For many years the association of obesity and OA has been simply attributed to the effects of overload on weight-bearing joints, and epidemiological surveys have shown a strict correlation between an increased body mass index and the severity of knee or hip OA, as well as some relief of pain and disability following weight loss. Instead, there is now a growing body of evidence that obesity is a complex syndrome in which an abnormal activation of neuroendocrine and pro-inflammatory pathways leads to an altered control of food intake, fat expansion and metabolic changes. Activated white adipose tissue increases the synthesis of pro-inflammatory cytokines, such as IL-6, IL-1, IL-8, TNFalpha, IL... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338718 Thu, 04 Mar 2010 00:00:00 +0100 3338718 http://www.medworm.com/index.php?rid=3338717&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199392%26dopt%3DAbstract Authors: Bondeson J The great success of targeted biologic therapy against rheumatoid arthritis (RA) in recent years has meant that much research has been devoted to investigating the pathophysiology of osteoarthritis (OA) in the hope of defining novel therapeutic targets. In contrast to RA, with its pannus and erosions, OA has long been thought of as a degenerative disease of cartilage, with secondary bony damage and osteophytes. But in recent years, the importance of the synovium, and in particular the synovial macrophages, in OA, has been highlighted in both in vitro and in vivo studies. This review will discuss the potential of synovial macrophages and their mediators, in particular the proinflammatory cytokines tumour necrosis factor alpha and interleukin-1, as potential therapeut... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338717 Thu, 04 Mar 2010 00:00:00 +0100 3338717 http://www.medworm.com/index.php?rid=3338716&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199393%26dopt%3DAbstract Authors: Little CB, Fosang AJ Progressive cartilage degradation is considered a hallmark of osteoarthritis (OA), and as such methods to inhibit this process have been extensively investigated as potential disease-modifying therapies. However, all tissues of the joint are affected by disease in OA, and it is likely that the pain and disability which are the major clinical symptoms of OA, arrise predominantly from pathology in these extra-cartilaginous structures. It is unclear therefore, whether specifically targeting inhibition of cartilage matrix breakdown will ameliorate global joint pathology and thereby affect the clinically-relevant OA-related disability. We have investigated this question by reviewing the literature and data available from studies of genetically-modified (GM) mic... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338716 Thu, 04 Mar 2010 00:00:00 +0100 3338716 http://www.medworm.com/index.php?rid=3338715&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199394%26dopt%3DAbstract Authors: Chevalier X To date, no targeted treatments for osteoarthritis have been developed. Therefore the challenge for the next years is to find a treatment that may slow down the progression of the disease. Osteoarthritis of the weight-bearing joints, such as knee OA, is more a local mechanical driven disease than a generalized one. To reach a non-vascularised tissue such as the cartilage, local intra-articular administration of drugs should be considered. The purpose of this review is to evaluate the advantages of local intra-articular drug administration compared with a systemic one in patients with osteoarthritis of weight-bearing joints. New perspectives of such strategy are reviewed, including anti-cytokine therapy, gene therapy, delivery of growth factors, stem cells therapy a... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338715 Thu, 04 Mar 2010 00:00:00 +0100 3338715 http://www.medworm.com/index.php?rid=3338714&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199395%26dopt%3DAbstract Authors: Hunter DJ, Losina E, Guermazi A, Burstein D, Lassere MN, Kraus V This narrative review outlines the work done in other fields with regards biomarker validation and qualification and the lessons that we may learn from this experience. Defining a universally agreed upon path for biomarker validation and qualification is urgently needed to circumvent many of the hurdles faced in OA therapeutic development irrespective of whether we are discussing biochemical markers, imaging markers or other measures. This review proposes a path that may be suitable for osteoarthritis and poses some logical next steps that will take us in this direction. PMID: 20199395 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338714 Thu, 04 Mar 2010 00:00:00 +0100 3338714 http://www.medworm.com/index.php?rid=3338713&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199396%26dopt%3DAbstract Authors: Le Graverand-Gastineau MP Osteoarthritis (OA) is a slowly, progressive, ultimately degenerative disorder of movable joints, mainly characterized by joint pain and functional limitation and affecting all joint structures not just articular cartilage, but also the subchondral bone, ligaments, capsule, synovial membrane, and menisci. OA occurs when the equilibrium between breakdown and repair of the joint tissues becomes unbalanced. There are currently no pharmacological interventions available to patients for modifying the underlying disease (DMOADs) in relation to major drug development challenges. The current regulatory draft guidances for clinical development programs for DMOAD agents suggest radiographic joint space narrowing (JSN) as a primary endpoint. However, research ef... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338713 Thu, 04 Mar 2010 00:00:00 +0100 3338713 http://www.medworm.com/index.php?rid=3338712&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199397%26dopt%3DAbstract Authors: Schmitz N, Kraus VB, Aigner T Osteoarthritis, the degeneration of the joints, is the leading source of physical disability with severely impaired quality of life due to pain and loss of joint functioning in industrialized nations. Clinically, degeneration affects mostly the large weight bearing joints of the legs like the hip or the knees, but in principle it can affect any joint of the body. Osteoarthritis represents a disease group with disease subsets that have different underlying pathophysiological mechanisms. Therefore primary osteoarthritis has to be distinguished from secondary forms of the disease, which are due to traumatic events, endocrine or metabolic disorders etc. The enormous frequency of this disease makes osteoarthritis one of the most expensive conditions in... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338712 Thu, 04 Mar 2010 00:00:00 +0100 3338712 http://www.medworm.com/index.php?rid=3338711&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199398%26dopt%3DAbstract Authors: Kraus VB PMID: 20199398 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338711 Thu, 04 Mar 2010 00:00:00 +0100 3338711 http://www.medworm.com/index.php?rid=3331967&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196742%26dopt%3DAbstract Authors: López-Moreno JA, López-Jiménez A, Gorriti MA, de Fonseca FR Although the first studies regarding the endogenous opioid system and addiction were published during the 1940s, addiction and cannabinoids were not addressed until the 1970s. Currently, the number of opioid addiction studies indexed in PubMed-Medline is 16 times greater than the number of cannabinoid addiction reports. More recently, functional interactions have been demonstrated between the endogenous cannabinoid and opioid systems. For example, the cannabinoid brain receptor type 1 (CB1) and mu opioid receptor type 1 (MOR1) co-localize in the same presynaptic nerve terminals and signal through a common receptor-mediated G-protein pathway. Here, we review this variety of behavioral models of drug addi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3331967 Fri, 19 Feb 2010 00:00:00 +0100 3331967 http://www.medworm.com/index.php?rid=3331966&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196743%26dopt%3DAbstract Authors: Tucci S PMID: 20196743 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3331966 Fri, 19 Feb 2010 00:00:00 +0100 3331966 http://www.medworm.com/index.php?rid=3105923&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20017722%26dopt%3DAbstract Authors: Ten Cate B, de Bruyn M, Wei Y, Bremer E, Helfrich W Despite recent advances, treatment of leukemia is often not curative. New insights indicate that this may be attributable to a small population of therapy-resistant malignant cells with self-renewal capacity and the ability to generate large numbers of more differentiated leukemia cells. These leukemia-initiating cells are commonly referred to as Leukemia Stem Cells (LSCs). LSCs are regarded as the root of leukemia origin and leukemia recurrence after seemingly successful therapy. Not surprisingly therefore, contemporary leukemia research has focused on ways to specifically eliminate LSCs, leading to the identification of several promising anti-LSC strategies. Firstly, LSCs may be eliminated by antibody- or ligand-based cell ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3105923 Sun, 20 Dec 2009 13:42:16 +0100 3105923 http://www.medworm.com/index.php?rid=3105922&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20017723%26dopt%3DAbstract This article reviews the physiological roles of CoQ10, as well as the rationale and the role in clinical practice of CoQ10 supplementation in different neurological and muscular diseases, from primary CoQ10 deficiency to neurodegenerative disorders. We also briefly report a case of the myopathic form of CoQ10 deficiency. PMID: 20017723 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3105922 Sun, 20 Dec 2009 13:42:12 +0100 3105922 http://www.medworm.com/index.php?rid=3105921&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20017724%26dopt%3DAbstract Authors: Wang D PMID: 20017724 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3105921 Sun, 20 Dec 2009 13:42:09 +0100 3105921 http://www.medworm.com/index.php?rid=3105920&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20017725%26dopt%3DAbstract Authors: Athyros VG, Tziomalos K, Karagiannis A, Anagnostis P, Mikhailidis DP White adipose tissue (WAT) is an important endocrine organ that secretes approximately 30 biologically active peptides and proteins, collectively termed "adipokines". These are either produced exclusively by WAT (mainly adiponectin, leptin and resistin) or also by other tissues [e.g. tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, plasminogen activator inhibitor (PAI)-1, angiotensinogen]. Adipokines play a central role in body homeostasis including the regulation of food intake and energy balance, insulin action, lipid and glucose metabolism, angiogenesis and vascular remodelling, regulation of blood pressure and coagulation. Excess WAT, especially visceral obesity, is linked to obesity-related health... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3105920 Sun, 20 Dec 2009 13:42:06 +0100 3105920 http://www.medworm.com/index.php?rid=3101107&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20015012%26dopt%3DAbstract Authors: Gallo D, Ferlini C, Scambia G Epithelial ovarian cancer is the leading cause of death for gynecological cancer in most of the Western world; lethality ensues from the occurrence of occult metastasis within the peritoneal cavity, a process requiring the acquisition of capacity for migration and invasiveness by ovarian tumor cells (metastatic phenotype), and characterized by a complex series of interrelated cellular events. Unlike most carcinomas that dedifferentiate during neoplastic progression with loss of epithelial E-cadherin (epithelial to mesenchymal transition, EMT), ovarian carcinomas undergo transition to a more epithelial phenotype, early in tumor progression, with increased E-cadherin expression. Subsequent reacquisition of mesenchymal features is observed in late-st... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3101107 Wed, 16 Dec 2009 00:00:00 +0100 3101107 http://www.medworm.com/index.php?rid=3101111&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20014999%26dopt%3DAbstract Authors: Sarra M, Pallone F, Macdonald TT, Monteleone G Interleukin (IL)-21, a cytokine mostly produced by activated CD4+ T cells, has been reported to play an important role in the tissue-damaging immune response in various organs. This pathogenic effect is strictly linked to the ability of IL-21 to control the functional activities of multiple immune and non-immune cells. For instance, IL-21 regulates the differentiation and function of effector CD4+ T helper cells; controls activation, proliferation, and survival of B cells; enhances the cytotoxic activity of CD8+ T cells and NK cells; inhibits the differentiation of inducible regulatory T cells (Tregs) and makes effector CD4+ T cells resistant to the Tregs-mediated immunesuppression; stimulates epithelial cells and fibroblasts to m... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3101111 Tue, 08 Dec 2009 00:00:00 +0100 3101111 http://www.medworm.com/index.php?rid=3101110&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20015000%26dopt%3DAbstract Authors: Ashihara E, Kawata E, Maekawa T RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing in mammalian cells and its discovery has lead to its wide application as a powerful tool in post-genomic research. Recently, short interfering RNA (siRNA), which induces RNAi, has been experimentally introduced as a cancer therapy and is expected to be developed as a nucleic acid-based medicine. Selection of appropriate gene targets is an important parameter in the potential success of siRNA cancer therapies. Candidate targets include genes associated with cell proliferation, metastasis, angiogenesis, and drug resistance. Importantly, silencing of such genes must not affect the functions of normal cells. Development of suitable drug delivery systems (DDSs) is also an imp... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3101110 Tue, 08 Dec 2009 00:00:00 +0100 3101110 http://www.medworm.com/index.php?rid=3101109&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20015001%26dopt%3DAbstract Authors: Giossi A, Pezzini A, Del Zotto E, Volonghi I, Costa P, Ferrari D, Padovani A Thrombus formation at a site of arterial injury (eg, rupture of an atherosclerotic plaque in a carotid artery), a crucial step in the pathogenesis of cerebral ischemia, is initiated by the adhesion of platelets to the arterial wall. In vivo, activated platelets release adenosine diphosphate (ADP), whose binding to the platelet P2Y12 receptor elicits progressive and sustained platelet aggregation. As a result, this receptor has been a target for the development of clinically effective antiplatelet agents, such as the thienopyridines ticlopidine and, more recently, clopidogrel, the only two currently FDA-approved P2Y12 antagonists. Clopidogrel has a well-established role as an antithrombotic agent in th... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3101109 Tue, 08 Dec 2009 00:00:00 +0100 3101109 http://www.medworm.com/index.php?rid=3101108&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20015011%26dopt%3DAbstract Authors: Guardia-Laguarta C, Pera M, Lleó A gamma-secretase is an intramembranous multi-protein complex that cleaves many type-I proteins with critical roles in neuronal function. In Alzheimer's disease (AD) interest in gamma-secretase comes, in part, from the fact that this complex is responsible for the last cleavage step of the amyloid precursor protein (APP) that generates the amyloid-beta peptide (Abeta). Abeta represents the primary component of the amyloid plaque, one of the main pathological hallmarks of AD. Over the last years, considerable efforts have been made to develop drugs to reduce Abeta production with the aim to slow AD progression. Many inhibitors of this protease have been identified, although the clinical use has been limited by concerns about the possible to... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3101108 Tue, 08 Dec 2009 00:00:00 +0100 3101108 http://www.medworm.com/index.php?rid=3017253&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925452%26dopt%3DAbstract Authors: Rosner MH PMID: 19925452 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3017253 Sun, 22 Nov 2009 18:28:05 +0100 3017253 http://www.medworm.com/index.php?rid=3004621&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19909232%26dopt%3DAbstract Authors: Passalacqua G, Compalati E, Canonica GW After several decades of controversies, allergen specific immunotherapy (SIT) was recognized as an effective treatment for respiratory and hymenoptera allergy by the World Health Organization in 1998. SIT involves the administration (usually subcutaneous) of increasing doses of allergen in order to achieve a hyposensitization. Moreover, SIT is the only allergen-specific treatment capable of modifying the natural history of the disease. During the last 25 years, there was an impressive development of basic and clinical research in the field of SIT, with the goal of improving the safety, the efficacy and ameliorating the knowledge on the mechanisms of action. In this regard, the sublingual route (SLIT) was extensively studied and, recently... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3004621 Thu, 19 Nov 2009 01:38:11 +0100 3004621 http://www.medworm.com/index.php?rid=3004620&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19909233%26dopt%3DAbstract Authors: Clutterbuck AL, Asplin KE, Harris P, Allaway D, Mobasheri A The matrix metalloproteinases (MMPs) and their endogenous regulators, the tissue inhibitors of MMPs (TIMPs) are responsible for the physiological remodelling of the extracellular matrix (ECM) in healthy connective tissues. MMPs are also involved in the regulation of cell behaviour via the release of growth factors and cytokines from the substrates they cleave, increasing the magnitude of their effects. Excess MMP activity is associated with ECM destruction in various inflammatory conditions, such as osteoarthritis (OA), while MMP under-activity potentially impairs healing by promoting fibrosis and preventing the effective removal of scar tissue. Both direct (TIMPs, small molecule MMP inhibitor drugs, blocking antibodi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3004620 Thu, 19 Nov 2009 01:38:09 +0100 3004620 http://www.medworm.com/index.php?rid=3004619&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19909234%26dopt%3DAbstract Authors: Pasello G, Favaretto A Malignant mesothelioma is an aggressive tumour of the serosal surfaces with poor prognosis and increasing incidence due to widespread previous asbestos exposure. Relative chemotherapeutic and radiotherapeutic resistance makes malignant pleural mesothelioma (MPM) difficult to manage, even though encouraging results were achieved with multimodality treatment. Better knowledge of angiogenesis and molecular pathways involved in MPM seems to be the right way to define new targets for systemic treatment. Neoangiogenesis may be considered as a critical step in the development of mesothelioma. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are autocrine growth factors in MPM and epidermal growth factor receptor (EGFR) appears... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=3004619 Thu, 19 Nov 2009 01:38:05 +0100 3004619 http://www.medworm.com/index.php?rid=2752945&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715534%26dopt%3DAbstract Authors: Midwood KS, Piccinini AM, Sacre S In the past few years there has been an increasing appreciation of the importance of Toll-like receptors (TLRs), not just in immunity, but also in autoimmune diseases. TLRs were first identified as sensors of viral and bacterial pathogens that form an integral part of the innate immune response. It was later discovered that these receptors can also respond to endogenous ligands that are produced as a result of tissue damage. This lead to the hypothesis that TLRs may be key contributors to the pathogenesis of chronic inflammatory conditions. A large body of data supporting the role of TLRs in autoimmunity has emerged from animal models and more data is increasingly being generated from human studies as further tools to examine these receptors h... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752945 Wed, 02 Sep 2009 10:18:25 +0100 2752945 http://www.medworm.com/index.php?rid=2752944&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715535%26dopt%3DAbstract Authors: Song JH, Humes HD Acute kidney injury (AKI) continues to have an exceedingly high mortality rate, despite advances in dialysis technology. Current dialysis therapies replace only the filtration function of the kidney, not the critical transport, metabolic, and endocrine functions of renal tubule cells. Replacement of these additional functions would provide more complete AKI therapy and thereby change the natural history of this disease process. A renal tubule assist device (RAD) containing living renal proximal tubule cells has been successfully engineered and has demonstrated differentiated absorptive, metabolic, and endocrine functions of normal kidney in vitro and ex vivo in animal experiments. The addition of the RAD containing human cells to conventional continuous renal... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752944 Wed, 02 Sep 2009 10:18:23 +0100 2752944 http://www.medworm.com/index.php?rid=2752943&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715536%26dopt%3DAbstract Authors: Pelte CH, Chawla LS Sepsis associated Acute Kidney Injury (SA-AKI) is the leading cause of AKI in the hospital setting and its incidence is increasing. Although the exact pathophysiology and phenotype of SA-AKI are not known, it is widely accepted that SA-AKI has a multi-injury pathway. This form of AKI has components of ischemia-reperfusion injury, direct inflammatory injury, coagulation and endothelial cell dysfunction, and apoptosis. As such, multiple agents have been shown in pre-clinical studies to ameliorate SA-AKI, but there are no interventions currently available for the treatment of SA-AKI. Promising agents that are in development include toll-like receptor inhibition, IL-10 augmentation, modulators of the protein C pathway, and mesenchymal stem cell mediated therape... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752943 Wed, 02 Sep 2009 10:18:21 +0100 2752943 http://www.medworm.com/index.php?rid=2752942&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715537%26dopt%3DAbstract Authors: Gupta A, Williams MD, Macias WL, Molitoris BA, Grinnell BW Protein C is a plasma serine protease that when activated plays a central role in modulating the function of the vascular endothelium and its interface with the innate immune system. Activated protein C (APC) has a dual mechanism of action via the feedback inhibition of thrombin generation, and as an agonist of protease activated receptor-1 (PAR-1). Through different cofactor interactions, this dual mechanism of antithrombotic and cytoprotective activity results in the ability of APC to modulate endothelial dysfunction by blocking cytokine signaling, functional cell adhesion expression, vascular permeability, apoptosis, and modulating leukocyte migration and adhesion. Deficiency in protein C, which occurs during system... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752942 Wed, 02 Sep 2009 10:18:18 +0100 2752942 http://www.medworm.com/index.php?rid=2752941&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715538%26dopt%3DAbstract Authors: Bajwa A, Kinsey GR, Okusa MD Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and both innate and adaptive immunity contribute to the pathogenesis. Kidney resident cells promote inflammation after IRI by increasing endothelial cell adhesion molecule expression and vascular permeability. Kidney epithelial cells bind complement and express toll-like receptors and resident and infiltrating cells produce cytokines/chemokines. Early activation of kidney dendritic cells (DCs) initiates a cascade of events leading to accumulation of interferon-gamma-producing neutrophils, infiltrating macrophages, CD4(+) T cells, B cells and invariant natural killer T (NKT) cells. Recent studies from our laboratory now implicate the IL23/IL17 pathway in kidney IRI. Foll... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752941 Wed, 02 Sep 2009 10:18:16 +0100 2752941 http://www.medworm.com/index.php?rid=2752940&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715539%26dopt%3DAbstract Authors: Liu KD, Glidden DV Acute kidney injury is associated with significant morbidity and mortality in hospitalized patients. Clinical trials for acute kidney injury have been hampered not only by a paucity of appropriate potential therapeutic agents, but also by several clinical trial design challenges. First, for novel therapies to have the best chance at efficacy, early patient identification is critical. Second, for certain novel therapies with a mechanism of action directed at the underlying disease state (e.g., sepsis) or a specific pathogenic process, careful disease phenotyping may be required. Third, even among patients with AKI, risk stratification may be required to select a higher-risk subset for clinical trials. Finally, clinical endpoints for clinical trials must be co... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752940 Wed, 02 Sep 2009 10:18:14 +0100 2752940 http://www.medworm.com/index.php?rid=2752939&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715540%26dopt%3DAbstract Authors: Kalantarinia K Imaging of the kidneys can provide valuable information in the work up and management of acute kidney injury. Several different imaging modalities are used to gather information on anatomy of the kidney, to rule out obstruction, differentiate acute kidney injury (AKI) and chronic kidney disease and to obtain information on renal blood flow and GFR. Ultrasound is the most widely used imaging modality used in the initial work up of AKI. The utility of contrast enhanced computerized tomography and magnetic resonance imaging is limited because of toxicities associated with contrast agents used. In this review the basics of ultrasonography are reviewed with an emphasis on findings in AKI. The new developments in different imaging modality and their potential uses in ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752939 Wed, 02 Sep 2009 10:18:11 +0100 2752939 http://www.medworm.com/index.php?rid=2752938&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715541%26dopt%3DAbstract Authors: Ricci Z, Ronco C Septic acute kidney injury (AKI) occurs between 15% and 20% of all intensive care unit admissions and its mortality ranges from 20% to 60%. The incidence and mortality of septic AKI has remained high throughout the last 10 years, whereas our understanding of septic AKI pathogenesis has remained limited. Current evidence about the pathophysiology of septic AKI will be reviewed and areas that require further investigation will be discussed. Improvement of knowledge about this condition seems to be most important in order to find valid diagnostic exams to exactly identify septic AKI and effective therapies to treat it: both of them are currently lacking. Finally, new preventive strategies might be experimented in order to protect critically ill patients from sept... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752938 Wed, 02 Sep 2009 10:18:09 +0100 2752938 http://www.medworm.com/index.php?rid=2752937&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715542%26dopt%3DAbstract Authors: Parmar A, Langenberg C, Wan L, May CN, Bellomo R, Bagshaw SM The incidence of sepsis and acute kidney injury (AKI) are increasing in critically ill patients and both portend a higher risk of morbidity and death. Sepsis has consistently been shown to be a key contributing factor for the development of AKI. Numerous observational studies have found septic AKI to be highly common among the critically ill. Septic AKI patients are characterized by important differences in baseline demographics, acuity of illness and treatment intensity when compared with non-septic AKI. In particular, these patients are often older, have a higher prevalence of co-morbid illnesses, and are admitted for medical or emergency surgical indications. These patients show greater aberrancy in vital signs, l... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752937 Wed, 02 Sep 2009 10:18:07 +0100 2752937 http://www.medworm.com/index.php?rid=2752936&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19715543%26dopt%3DAbstract Authors: Rosner MH Acute kidney injury (AKI) associated with sepsis remains an all too common occurrence with an associated high mortality rate. However, recent developments bring hope that this scenario may be changing. This change is being brought about by a multi-pronged approach that highlights several different but inter-related aspects of AKI. These include: (1) defining a standard definition for AKI; (2) understanding the importance of early recognition of AKI; (3) improving imaging techniques for the diagnosis of AKI; (4) improved understanding of the complex pathogenesis of AKI, especially in sepsis; (5) the development of targeted strategies to prevent and treat AKI and (6) an improved understanding of the design and implementation of clinical trials in AKI. Through advances ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2752936 Wed, 02 Sep 2009 10:18:05 +0100 2752936 http://www.medworm.com/index.php?rid=2738395&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702551%26dopt%3DAbstract Authors: Ruf BM, Bhagwagar Z The serotonergic (5-HT) system has been widely implicated in the pathophysiology of Major Depressive Disorder (MDD). Although the 5-HT system is a popular target for drug therapy in MDD the role that serotonin plays in MDD is not clearly understood. An abundance of research suggests that several 5-HT receptor subtypes may be dysfunctional in patients with MDD including the 5-HT(1B) receptor. Evidence implicating 5-HT(1B) receptors in the pathophysiology of depression comes from a number of converging lines of research. Two common genetic polymorphisms of 5-HT(1B) receptors, G861C and C129T, have been implicated in affective disorders. Rats predisposed to learned helplessness have exhibited downregulation of 5-HT(1B) receptor messenger ribonucleic acid (mRNA... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738395 Thu, 27 Aug 2009 22:06:18 +0100 2738395 http://www.medworm.com/index.php?rid=2738394&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702552%26dopt%3DAbstract Authors: Mnie-Filali O, Lambas-Señas L, Scarna H, Haddjeri N Serotonin (5-HT) exerts its diverse physiological and pharmacological effects through the activation of multiple receptor subtypes. One of the newest members of this family is the 5-HT(7) receptor. Increasing investigations on this receptor are currently undertaken to highlight its physiological and physiopathological significance. With the development of selective 5-HT(7) receptor ligands, preclinical studies have started to elucidate the functions of this receptor subtype in more details. Hence, growing body of evidence suggests that the 5-HT(7) receptor is involved in biological processes such as circadian rhythm and thermoregulation, in addition to disorders in which disturbances of the latter are considered to be an... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738394 Thu, 27 Aug 2009 22:06:16 +0100 2738394 http://www.medworm.com/index.php?rid=2738393&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702553%26dopt%3DAbstract Authors: Merenlender-Wagner A, Dikshtein Y, Yadid G Long known for its anti-nociceptive effects, the opioid beta-endorphin is also reported to have rewarding and reinforcing properties and to be involved in stress response. In this manuscript we summarize the present neurobiological and behavioral evidence regarding the role of beta-endorphin in stress-related psychiatric disorders, depression and PTSD. There is existing data that support the importance of beta-endorphin neurotransmission in mediating depression. As for PTSD, however, the data is thus far circumstantial. The studies described herein used diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and behavioral monitoring, in two animal models of depression and PTSD. We suggest that th... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738393 Thu, 27 Aug 2009 22:06:14 +0100 2738393 http://www.medworm.com/index.php?rid=2738392&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702554%26dopt%3DAbstract Authors: Lucas G Serotonin(4) (5-HT(4)) receptors have been shown to be involved in several peripheral and central functions, including control of the gastro-intestinal tract, modulation of memory and food intake, as well as positive regulation of the release of various neurotransmitters. Recently, we have proposed that the study of these receptors may also bring a new hope for treating depression, their agonists possibly acting as fast-acting antidepressants. This hypothesis was based on several studies showing that 5-HT(4) receptors play an important role in the modulation of central 5-HT neurotransmission, both at pre- and postsynaptic levels. The possible physiological meaning of this control is discussed, together with the different research perspectives opened by its discovery. ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738392 Thu, 27 Aug 2009 22:06:12 +0100 2738392 http://www.medworm.com/index.php?rid=2738391&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702555%26dopt%3DAbstract Authors: Guiard BP, El Mansari M, Blier P Biogenic amine transporters for serotonin and norepinephrine (5-HT and NE respectively), are major targets for currently available antidepressant drugs, particularly those inhibiting the reuptake of 5-HT and/or NE. Compelling evidence suggest that dopamine (DA) is also involved in the pathophysiology and treatment of depression, leading to the development of a new class of antidepressants: the triple reuptake inhibitors that simultaneously inhibit 5-HT, NE and DA reuptake thereby prolonging their duration of action at postsynaptic levels. Although preclinical studies strongly suggest that triple reuptake inhibitors display antidepressant-like activity in various behavioural paradigms, including the forced swimming and the tail suspension tests,... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738391 Thu, 27 Aug 2009 22:06:09 +0100 2738391 http://www.medworm.com/index.php?rid=2738390&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702556%26dopt%3DAbstract Authors: Dremencov E, El Mansari M, Blier P There are numerous lines of evidence pointing to norepinephrine being of crucial importance in pathophysiology of anxiety and mood disorders. First, norepinephrine projections innervate the limbic system, suggesting the involvement of norepinephrine in the regulation of emotions and cognition. Second, norepinephrine closely interacts with serotonin and dopamine systems, which also play very important roles in the regulation of mood. Third, it has been shown that various agents which increase norepinephrine availability, such as norepinephrine reuptake inhibitors, are also effective antidepressant drugs. And fourth, the depletion of norepinephrine causes a resurgence of depressive symptoms after successful treatment with antidepressant drugs. ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738390 Thu, 27 Aug 2009 22:06:07 +0100 2738390 http://www.medworm.com/index.php?rid=2738389&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702557%26dopt%3DAbstract Authors: Bourin M, Chenu F, Hascoët M Antidepressant drugs modify in different ways the activity of neurons, by increasing monoamines levels and by modulating ion channels. Sodium channels are molecular targets for antiepileptic drugs, which can also be mood stabilizers (i.e. lamotrigine, topiramate, phenytoin, carbamazepine, valproic acid). After a short overview on the sodium channels and the interaction with antidepressants and mood stabilizers, a comparison of the activity of both antidepressants and mood stabilizers with the addition of veratrine (sodium channel opener) on the forced swimming test (FST) in mice was presented. By comparing the antidepressant-like effect of the antidepressants (paroxetine, imipramine and desipramine) with the one of anticonvulsants (lamotrigine... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738389 Thu, 27 Aug 2009 22:06:05 +0100 2738389 http://www.medworm.com/index.php?rid=2532042&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538174%26dopt%3DAbstract CONCLUSIONS: Volatile agents and levosimendan consistently reduce perioperative myocardial infarction and mortality in cardiac surgery but they have not been properly studied in non-cardiac surgery. Minor (epidural analgesia, statins, calcium antagonists and alfa agonists) or doubtful (beta-blockers) results were found in non-cardiac surgery. PMID: 19538174 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532042 Sat, 27 Jun 2009 15:46:07 +0100 2532042 http://www.medworm.com/index.php?rid=2532041&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19548862%26dopt%3DAbstract Authors: Testa U The ubiquitin-proteasome pathway is involved in intracellular protein turnover and plays an essential function in many cellular processes, thus contributing to cellular homeostasis. The observation that proteasome inhibitors are able to induce apoptosis preferentially in tumor cells opened the way to their use as potential drugs. One of these drugs, bortezomib, was introduced in cancer therapy and its use was approved for the treatment of multiple myeloma and mantle cell lymphoma. The investigation of the mechanisms through which bortezomib causes cell death of cancer cells showed that this drug affects many cellular pathways and many of its effects cannot be related to proteasome inhibition. These observations, as well as the occurrence of bortezomib resistance observ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532041 Sat, 27 Jun 2009 15:46:05 +0100 2532041 http://www.medworm.com/index.php?rid=2532054&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519349%26dopt%3DAbstract Authors: Bretthauer RK Glycosylation of proteins on asparagine amino acids (N-linked) in proteins of eukaryotic cells is initiated by the biosynthesis of dolichol-pyrophosphate-N-acetylglucosamine from dolichol-phosphate and UDP-N-acetylglucosamine. The enzyme catalyzing this reaction, UDP-GlcNAc:Dolichol Phosphate GlcNAc-1-Phosphate Transferase (DPAGT1), has been further characterized in several cell types with respect to its gene, gene products, membrane topology, functional sites, lipid dependence, and metabolic regulation. This review summarizes these properties as an update from an earlier detailed and critical review by Lehrman (Lehrman, M. A. (1991) Glycobiology, 1, 553-562). PMID: 19519349 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532054 Sun, 31 May 2009 23:00:00 +0100 2532054 http://www.medworm.com/index.php?rid=2532053&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519350%26dopt%3DAbstract Authors: Datta AK The sialyltransferase family represents a group of enzymes that transfers sialic acid from its common nucleotide sugar donor, CMP-NeuAc, to the terminal carbohydrates group of various glycoproteins and glycolipids. Cloning of these enzymes from mammalian sources indicated these are all type II membrane proteins with topological features common to other glycosyltransferases. To date, 20 cloned enzymes with distinct substrate specificity have been obtained for mammalian sialyltransferases. These account for four subfamilies according to the carbohydrate linkages synthesized, namely, ST3Gal, ST6Gal, ST6GalNAc, and ST8Sia. Comparative peptide sequence analysis of these cloned enzymes showed the presence of four conserve sialylmotifs, namely 'L'- (for long), 'S'- (for shor... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532053 Sun, 31 May 2009 23:00:00 +0100 2532053 http://www.medworm.com/index.php?rid=2532052&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519351%26dopt%3DAbstract Authors: Albacker T, Lachapelle K In the current era, more complex cardiac surgical procedures are being performed on elderly patients with variety of co-morbid conditions, which increases the demand to further improve the outcome of cardiac surgery. The role of insulin therapy in improving cardiac surgical outcomes has long been studied. However, the more recent evidence suggests that the entire potential of the insulin therapy has not yet been fully disclosed. The aim of this paper is to review different aspects of insulin therapy including different protocols used, timing of therapy and the objective glycemic target levels with its effect on improving cardiac surgical outcomes. PMID: 19519351 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532052 Sun, 31 May 2009 23:00:00 +0100 2532052 http://www.medworm.com/index.php?rid=2532051&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519352%26dopt%3DAbstract Authors: Balsano C, Alisi A, Nobili V PURPOSE OF REVIEW: This review summarizes the current state of knowledge on non-alcoholic fatty liver disease (NAFLD) and the hepatitis C virus (HCV)-associated liver fibrosis, and provides insight into the role of dysmetabolism in hepatic fibrogenesis. Clinical relevance of drugs correcting these metabolic disturbances in the reversion of liver fibrosis will also be discussed. RECENT FINDINGS: Liver fibrosis affects more than ten millions of people worldwide and may lead to cirrhosis, liver failure, and death. Recent epidemiological data indicate that the incidence of liver fibrosis is expected to triple during the next 10 to 15 years as a result of the HCV infection and NAFLD escalation. In accordance with the modern view of liver fibrogenesis, t... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532051 Sun, 31 May 2009 23:00:00 +0100 2532051 http://www.medworm.com/index.php?rid=2532050&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519353%26dopt%3DAbstract Authors: Balogh S, Kiss I, Csaszar A Myocardial infarction and stroke are exaggerated by rupture of atherosclerotic lesions. Rupture-sensitive plaques have a specific composition which renders them vulnerable, but additional factors (acute infection, higher sympathetic activity, excessive increase of blood pressure or exposure to a variety of drugs) are needed to set off the event. Toll-like receptors are important components of the innate and adaptive immune system and seem to be a potential link between inflammation, infectious disease and atherosclerosis. In addition to classical bacterial and viral antigens, several endogenous ligands (HSP, ox-LDL, apoptotic cells) have also been proposed to react to TLRs. There is accumulating evidence substantiating the contribution of the TLR-si... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532050 Sun, 31 May 2009 23:00:00 +0100 2532050 http://www.medworm.com/index.php?rid=2532049&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519354%26dopt%3DAbstract This article reviews the current data on coronary stents, in-stent restenosis and stent thrombosis and role of antiplatelet medication post percutaneous coronary intervention (PCI) to provide a concise and clear algorithm for managing perioperative antiplatelet therapy in patients having undergone recent PCI. The algorithm encourages a multidisciplinary approach and is based on the surgical bleeding risk, operative risk of adverse cardiac events and stent thrombosis risk to guide safe practice. Challenging areas including aspirin and clopidogrel hypersensitivity, clopidogrel resistance and concomitant vitamin K antagonist therapy are also addressed. PMID: 19519354 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532049 Sun, 31 May 2009 23:00:00 +0100 2532049 http://www.medworm.com/index.php?rid=2532048&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519355%26dopt%3DAbstract Authors: Breccia M, Alimena G Imatinib mesylate is currently the standard therapy for chronic myeloid leukemia (CML) patients. Despite the remarkable results achieved with imatinib, the emergence of resistance to this drug has become a significant problem. Several strategies have been developed to overcome imatinib resistance, including dose escalation of the drug, combination treatments or novel targeted agents. Nilotinib is a second-generation tyrosine kinase inhibitor 30-50 fold more potent than imatinib with high affinity and selectivity on BCR/ABL, active against a wide range of mutant clones, except T315I mutation. Phase II trials of nilotinib showed high activity in imatinib-resistant or intolerant CML patients; front-line treatment of chronic phase Ph+ CML demonstrated rapid an... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532048 Sun, 31 May 2009 23:00:00 +0100 2532048 http://www.medworm.com/index.php?rid=2532047&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519356%26dopt%3DAbstract Authors: Al-Dasooqi N, Gibson R, Bowen J, Keefe D HER2 (v-erb-b2 erythroblastic leukemia viral oncogene) is a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. Since the discovery of a role for HER2 and other EGF receptors in the development and progression of cancer, they have become targets for a number of targeted anti-cancer drugs. These drugs have proven to be effective in treating and managing a range of cancers, however, recent observations in the clinic have suggested that their administration causes many toxicities, including gastrointestinal toxicity. Drugs with HER2 inhibitory activity fall into two categories; the monoclonal antibodies and small molecule tyrosine kinase inhibitors. Both of these drug classes have been shown to induce ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532047 Sun, 31 May 2009 23:00:00 +0100 2532047 http://www.medworm.com/index.php?rid=2532046&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519357%26dopt%3DAbstract Authors: Ruiz-Romero C, Blanco FJ Osteoarthritis (OA) is the most common rheumatic pathology. It is related to aging, and is characterized mainly by cartilage degradation. Despite its high prevalence, currently available therapy is limited and focused on treating pain, which is the principal symptom of OA. Therefore, new treatments for OA that slow the progression of the disease are urgently needed. Because the progression of OA involves different tissues and complex biological processes, ongoing research is attempting to increase our knowledge of OA pathogenesis. New approaches for the characterization of molecules that play a role in OA have recently emerged. These include genomic, proteomic and metabolomic technologies. These techniques, coupled with sophisticated statistical method... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532046 Sun, 31 May 2009 23:00:00 +0100 2532046 http://www.medworm.com/index.php?rid=2532045&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519358%26dopt%3DAbstract This article will review currently used immunosuppressants in liver transplantation, novel therapies in development and the impact of these medications of the recurrence of hepatitis C after liver transplantation. PMID: 19519358 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532045 Sun, 31 May 2009 23:00:00 +0100 2532045 http://www.medworm.com/index.php?rid=2532044&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519359%26dopt%3DAbstract Authors: Ocana A, Serrano R, Calero R, Pandiella A PMID: 19519359 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532044 Sun, 31 May 2009 23:00:00 +0100 2532044 http://www.medworm.com/index.php?rid=2532043&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19526638%26dopt%3DAbstract Authors: Rodriguez-Nunez A, Martínez V, Lopez-Herce J PMID: 19526638 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532043 Sun, 31 May 2009 23:00:00 +0100 2532043 http://www.medworm.com/index.php?rid=2532063&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442110%26dopt%3DAbstract Authors: Kutateladze TG PMID: 19442110 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532063 Thu, 30 Apr 2009 23:00:00 +0100 2532063 http://www.medworm.com/index.php?rid=2532062&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442111%26dopt%3DAbstract Authors: Shah S, Riabowol K Members of the ING family of type II tumor suppressors reside in different chromatin regulatory complexes and are stoichiometeric members of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes. It has been frequently observed that expressing ING proteins promotes apoptosis in both normal and transformed cells of different species. They have also been reported to either rely upon p53, or to add to its ability to promote programmed cell death (apoptosis) although whether ING proteins require p53 to induce apoptosis is now questionable based upon observations using knockout cell lines and animal models. Genetic studies in model organisms, and particularly in Caenorhabditis elegans, have identified different pathways involved in apoptosis du... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532062 Thu, 30 Apr 2009 23:00:00 +0100 2532062 http://www.medworm.com/index.php?rid=2532061&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442112%26dopt%3DAbstract Authors: Maher SK, Helbing CC The inhibitor of growth (ING) gene family proteins regulate many critical cellular processes such as cell proliferation and growth, apoptosis, DNA repair, senescence, angiogenesis, and drug resistance. Their transcripts and proteins are differentially expressed in health and disease and there is evidence for developmental regulation. The vast majority of studies have characterized ING levels in the context of cancer. However, relatively little attention has been paid to the expression of ING family members in other contexts. This review summarizes the findings from human and animal model systems that provide insight into the factors influencing the expression of these important proteins. We examine the influence of cell cycle and aging as well as genotoxic... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532061 Thu, 30 Apr 2009 23:00:00 +0100 2532061 http://www.medworm.com/index.php?rid=2532060&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442113%26dopt%3DAbstract Authors: Menéndez C, Abad M, Gómez-Cabello D, Moreno A, Palmero I Cellular senescence is an effective anti-tumor barrier that acts by restraining the uncontrolled proliferation of cells carrying potentially oncogenic alterations. ING proteins are putative tumor suppressor proteins functionally linked to the p53 pathway and to chromatin regulation. ING proteins exert their tumor-protective action through different types of responses. Here, we review the evidence on the participation of ING proteins, mainly ING1 and ING2, in the implementation of the senescent response. The currently available data support an important role of ING proteins as regulators of senescence, in connection with the p53 pathway and chromatin organization. PMID: 19442113 [PubMed - in process] (Source... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532060 Thu, 30 Apr 2009 23:00:00 +0100 2532060 http://www.medworm.com/index.php?rid=2532059&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442114%26dopt%3DAbstract Authors: Bua DJ, Binda O Since their discovery, the members of the ING (inhibitor of growth) family of tumor suppressors have emerged as essential and core components of chromatin modifying complexes. Recent work has identified the ING family as histone mark sensors that orchestrate cellular responses to genotoxic insults and regulate chromatin homeostasis. Dysregulation of chromatin homeostasis is implicated in tumorigenesis through mechanisms such as silencing of tumor suppressor genes, inappropriate activation of oncogenes, and genomic instability due to failure to repair DNA damage. This review will concentrate on the chromatin signaling aspects of the ING proteins, focusing on how recognition of histone H3 trimethylated at lysine 4 (H3K4me3) by the PHD (plant homeodomain) finger o... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532059 Thu, 30 Apr 2009 23:00:00 +0100 2532059 http://www.medworm.com/index.php?rid=2532058&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442115%26dopt%3DAbstract Authors: Champagne KS, Kutateladze TG The Inhibitor of Growth (ING) tumor suppressors are implicated in oncogenesis, control of DNA damage repair, cellular senescence and apoptosis. All members of the ING family contain unique amino-terminal regions and a carboxy-terminal plant homeodomain (PHD) finger. While the amino-terminal domains associate with a number of protein effectors including distinct components of histone deacetylase (HDAC) and histone acetyltransferase (HAT) complexes, the PHD finger binds strongly and specifically to histone H3 trimethylated at lysine 4 (H3K4me3). In this review we describe the molecular mechanism of H3K4me3 recognition by the ING1-5 PHD fingers, analyze the determinants of the histone specificity and compare the biological activities and structures wi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532058 Thu, 30 Apr 2009 23:00:00 +0100 2532058 http://www.medworm.com/index.php?rid=2532057&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442116%26dopt%3DAbstract Authors: Unoki M, Kumamoto K, Harris CC Recent emerging evidence suggests that ING family proteins play roles in carcinogenesis both as oncogenes and tumor suppressor genes depending on the family members and on cell status. Previous results from non-physiologic overexpression experiments showed that all five family members induce apoptosis or cell cycle arrest, thus it had been thought until very recently that all of the family members function as tumor suppressor genes. Therefore restoration of ING family proteins in cancer cells has been proposed as a treatment for cancers. However, ING2 knockdown experiments showed unexpected results: ING2 knockdown led to senescence in normal human fibroblast cells and suppressed cancer cell growth. ING2 is also overexpressed in colorectal cancer,... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532057 Thu, 30 Apr 2009 23:00:00 +0100 2532057 http://www.medworm.com/index.php?rid=2532056&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442117%26dopt%3DAbstract Authors: Li J, Wang Y, Wong RP, Li G The INhibitor of Growth (ING) genes were discovered during the past decade and identified as type II tumor suppressor genes. Previous studies demonstrated that ING family members participate in various cellular stress responses and thus play important roles in the pathogenesis of various types of cancers, including melanoma. Epidemiological studies showed that UV radiation is the primary etiological factor in melanoma development. Here we review the studies on the role of ING proteins in cellular responses to UV irradiation, melanoma cell motility, and melanoma progression. PMID: 19442117 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532056 Thu, 30 Apr 2009 23:00:00 +0100 2532056 http://www.medworm.com/index.php?rid=2532055&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19442118%26dopt%3DAbstract Authors: Gunduz M, Demircan K, Gunduz E, Katase N, Tamamura R, Nagatsuka H The Inhibitor of Growth (ING) gene family is an emerging putative type II tumor suppressor gene (TSG). Proteins of INGs (ING1-5), critical modulator of the histone code via PHD fingers, are able to suppress cell growth and proliferation, induce apoptosis, and modulate cell cycle progression. ING proteins are involved in transcriptional regulation of genes, such as the p53-inducible gene p21. ING proteins also serve as shuttling proteins between nucleus and cytoplasm, and dysregulation of this nucleocytoplasmic traffic has been shown in some cancer cells. In cancer cells, ING mRNA levels are often lost or suppressed but the genes are rarely mutated. Recently the potential roles of ING proteins as prognostic bioma... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532055 Thu, 30 Apr 2009 23:00:00 +0100 2532055 http://www.medworm.com/index.php?rid=2532074&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355854%26dopt%3DAbstract Authors: Anagnostopoulou K, Kolovou G, Mikhailidis DP PMID: 19355854 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532074 Tue, 31 Mar 2009 23:00:00 +0100 2532074 http://www.medworm.com/index.php?rid=2532072&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355855%26dopt%3DAbstract Authors: Karantonis HC, Nomikos T, Demopoulos CA Apart from being the main energy reserves of the human body, triacylglycerols take part in metabolic processes that determine the rate of fatty acid oxidation, the plasma levels of free fatty acids, the biosynthesis of other lipid molecules and the metabolic fate of lipoproteins. Allosteric, hormonal, nutritional and transcriptional signals activate short-term and long-term regulatory mechanisms that assure the storage of triacylglycerols (TAGs) under states of excess energy and their mobilization under conditions of metabolic stress. New enzymes and novel regulatory mechanisms, involved in triacylglycerol metabolism, have been recently discovered and new details on the fine tuning of their metabolic reactions are coming to light. This k... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532072 Tue, 31 Mar 2009 23:00:00 +0100 2532072 http://www.medworm.com/index.php?rid=2532070&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355856%26dopt%3DAbstract Authors: Tziomalos K, Athyros VG, Karagiannis A, Kolovou GD, Mikhailidis DP The role of elevated triglyceride (TG) levels in the pathogenesis of atherosclerosis is controversial. Some studies suggest that TG might play a direct role in the development of vascular disease. Elevated TG levels are also associated with other vascular risk factors and may therefore represent an indirect marker of a high risk state. Another issue is that laboratory measurements of TG levels frequently show a substantial variability. Accumulating epidemiological data show that there is an independent association of TG levels with vascular risk. Some interventional studies also suggested that lowering TG levels might prevent vascular events. It appears that TG might be more important as therapeutic targets aga... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532070 Tue, 31 Mar 2009 23:00:00 +0100 2532070 http://www.medworm.com/index.php?rid=2532069&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355857%26dopt%3DAbstract Authors: Nordestgaard BG, Langsted A, Freiberg JJ Most humans are in the nonfasting or postprandial state in the majority of a 24 hour cycle; however, lipids, lipoproteins, and apolipoproteins are usually measured in the fasting state. Recent studies demonstrate that these values at most change minimally in response to normal food intake, changes that are clinically unimportant. Also, elevated levels of nonfasting triglycerides as a marker of elevated remnant lipoprotein cholesterol associate strongly with increased risk of myocardial infarction, ischemic stroke, and early death. The mechanism behind these findings likely involves entrance of remnant lipoproteins into the arterial intima with subsequent retention leading to atherogenesis, while low HDL cholesterol levels may be an inno... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532069 Tue, 31 Mar 2009 23:00:00 +0100 2532069 http://www.medworm.com/index.php?rid=2532068&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355858%26dopt%3DAbstract Authors: Kolovou GD, Anagnostopoulou KK, Kostakou PM, Bilianou H, Mikhailidis DP Familial hypertriglyceridaemia is inherited in an autosomal dominant manner. The responsible genetic abnormality is unknown but recently, a novel gene encoding apolipoprotein AV has been linked to familial hypertriglyceridaemia. All patients develop the same phenotype with elevated levels of very low density lipoproteins (VLDL) in plasma. The main disorder of this dyslipidaemia is decreased intestinal absorption of biliary acids, leading to a compensatory increase of VLDL production. In familial hypertriglyceridaemia, a marked increase in plasma triglyceride (TG) levels can cause acute pancreatitis. Moreover, patients with other genetic factors, like familial chylomicronaemia, familial combined hyperlipida... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532068 Tue, 31 Mar 2009 23:00:00 +0100 2532068 http://www.medworm.com/index.php?rid=2532067&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355859%26dopt%3DAbstract Authors: Manfredini F, D'Addato S, Laghi L, Malagoni AM, Mandini S, Boari B, Borghi C, Manfredini R Hypertriglyceridaemia is a common dyslipidaemia encountered in clinical practice. People with hypertriglyceridaemia are frequently obese, insulin-resistant, hypertensive or diabetic, all of which are risk factors for cardiovascular diseases. Hypertriglyceridaemia also contributes to metabolic syndrome, in which an atherogenic diet, sedentary lifestyle, overweight/obesity and genetic factors interact. A multi-factorial intervention for all risk factors is necessary, including weight reduction, dietary modification and increased physical exercise. This review focuses on the influence of diet, sedentary lifestyle and negative habits (such as excessive alcohol intake, smoking and drug addict... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532067 Tue, 31 Mar 2009 23:00:00 +0100 2532067 http://www.medworm.com/index.php?rid=2532066&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355860%26dopt%3DAbstract Authors: Viljoen A, Wierzbicki AS Hypertriglyceridaemia is associated with insulin resistance, hypertension, obesity and diabetes. The management of hypertriglyceridaemia and atherogenic dyslipidaemias increasingly involves the use of several drugs for different aspects of the metabolic syndrome. This review highlights the agents for treatment of blood pressure, weight and blood pressure that reduce triglycerides as a number of drugs used to treat these co-morbidities also lower triglycerides as additional effects beyond their primary actions. Lipid-lowering drugs particularly fibrates and niacin and to a lesser degree statins and omega-3 fatty acids reduce plasma triglyceride levels. Additional reductions can be gained from the appropriate choice of therapies for co-morbid condition a... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532066 Tue, 31 Mar 2009 23:00:00 +0100 2532066 http://www.medworm.com/index.php?rid=2532065&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355861%26dopt%3DAbstract Authors: Boumendjel A, Ronot X, Boutonnat J Chalcones (1,3-diphenylpropen-1-ones) are naturally occurring compounds belonging to the flavonoid family and are largely investigated in various therapeutic area and especially as antitumor drugs. In the latter field, the literature survey indicates that effect on the cell cycle is one of the most important targets domains of chalcones. In this review, we will shed light on: a) the structural criteria responsible for the cell cycle perturbations, b) the activity of chalcones on cell cycle molecular players or regulators c) the correlation between the chalcone-structure and proteins involved directly or not in cell cycle regulation and apoptosis by enhancement of proapoptotic molecules expression. We will discuss some perspectives related on ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532065 Tue, 31 Mar 2009 23:00:00 +0100 2532065 http://www.medworm.com/index.php?rid=2532064&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355862%26dopt%3DAbstract Authors: Bhuiyan MS, Fukunaga K Deregulation of apoptosis has been shown to contribute to the development of many diseases, including ischemia/reperfusion injury of organs, different types of cancer formation, as well as neurodegenerative and autoimmune disorders. Recently, the mitochondrial serine protease High temperature requirement A2 (HtrA2)/Omi has drawn attention as it played pivotal role in different pathological conditions. We critically discussed the rationale for therapeutically targeting HtrA2 signaling in pathological conditions and explore the molecular mechanisms of HtrA2 inhibition as a novel therapeutic strategy. The precise mode of action and importance of HtrA2 in mitochondrial quality control as well as in apoptosis in mammalian cells has been recently studied throu... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532064 Tue, 31 Mar 2009 23:00:00 +0100 2532064 http://www.medworm.com/index.php?rid=2263599&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275554%26dopt%3DAbstract Authors: Soares MB PMID: 19275554 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263599 Sun, 01 Mar 2009 05:00:00 +0100 2263599 http://www.medworm.com/index.php?rid=2263592&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275555%26dopt%3DAbstract This article reviews the agents currently in use for treatment of these diseases, their known mechanisms of action and weaknesses. We present an overview of the main strategies for drug discovery and the relevance of these parasites genomics/proteomics data for a rational search of molecular targets and matching leads. In this direction, we emphasize the importance of the highly integrated partnerships and networks between scientists in academic institutions and industry involving several countries that promise to increase the chances of success and enhance cost-effectiveness in drug discovery against these parasitic diseases. In addition, we approach the available assays for testing lead compounds in large scale and their limitations for they represent one of the bottlenecks in the pipeli... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263592 Sun, 01 Mar 2009 05:00:00 +0100 2263592 http://www.medworm.com/index.php?rid=2263587&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275556%26dopt%3DAbstract Authors: de Azevedo WF, Soares MB Sequencing of parasite genomes opened the possibility to identify potential protein targets for drug development. Several protein targets have been found in the genome of Plasmodium falciparum, Trypanosoma cruzi, Trypanosoma brucei and Leishmania major. Bioinformatics analysis is an important tool for the identification of protein targets for drug development against parasitic diseases. In this review we comment about three protein targets, identified in parasite genomes, and discuss the main features that may guide future efforts for virtual screening initiatives. PMID: 19275556 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263587 Sun, 01 Mar 2009 05:00:00 +0100 2263587 http://www.medworm.com/index.php?rid=2263582&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275557%26dopt%3DAbstract Authors: Queiroz EF, Wolfender JL, Hostettmann K Higher plants represent a rich source of new molecules with pharmacological properties, which are lead compounds for the development of new drugs. During the last decades, the renewed interest in investigating natural products has led to the introduction of several important drugs, such as the anticancer drugs vinblastine and taxol, or the antimalarial agent artemisinin. Success in natural products research is conditioned by careful plant selection, based on various criteria such as chemotaxonomic data, information from traditional medicine, field observation, or even random collection. One main strategy in the isolation of new lead compounds consists of so-called bioactivity-guided isolation, in which pharmacological or biological assay... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263582 Sun, 01 Mar 2009 05:00:00 +0100 2263582 http://www.medworm.com/index.php?rid=2263578&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275558%26dopt%3DAbstract Authors: Moreira DR, Leite AC, dos Santos RR, Soares MB The recent highlights on the biochemical pathways of Trypanosoma cruzi have allowed a significant improvement in the development of new strategies for drug design and also in the understanding of the mechanisms of action of new trypanocidal agents. Several biochemical pathways of fundamental importance and validated targets (e.g. cysteine protease cruzain, trypanothione reductase, trans-sialidase) of T. cruzi have proved usefulness for drug development in many examples of new candidates to anti-T. cruzi drugs. This review will focus on some approaches used for the design of new potential trypanocidal agents, exploring modern concepts of medicinal chemistry such as bioisosterism, molecular hybridization, bioinspired design in lead ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263578 Sun, 01 Mar 2009 05:00:00 +0100 2263578 http://www.medworm.com/index.php?rid=2263574&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275559%26dopt%3DAbstract Authors: de Azevedo WF, Dias R, Timmers LF, Pauli I, Caceres RA, Soares MB Drug development has become the Holy Grail of many structural bioinformatics groups. The explosion of information about protein structures, ligand-binding affinity, parasite genome projects, and biological activity of millions of molecules opened the possibility to correlate this scattered information in order to generate reliable computational models to predict the likelihood of being able to modulate a target with a small-molecule drug. Computational methods have shown their potential in drug discovery and development allied with in vitro and in vivo methodologies. The present review discusses the main bioinformatics tools available for drug discovery and development. PMID: 19275559 [PubMed - in process] (... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263574 Sun, 01 Mar 2009 05:00:00 +0100 2263574 http://www.medworm.com/index.php?rid=2263569&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275560%26dopt%3DAbstract Authors: Timmers LF, Pauli I, Barcellos GB, Rocha KB, Caceres RA, de Azevedo WF, Soares MB The development of databases devoted to biological information opened the possibility to integrate, query and analyze biological data obtained from several sources that otherwise would be scattered through the web. Several issues arise in the handling of biological information, mainly due to the diversity of biological subject matter and the complexity of biological approaches towards phenomena of the living world. The integration of genomic data, three-dimensional structures of proteins, biological activity, and drugs availability allows a system approach to the study of the biology. Here we review the current status of these research efforts to develop genomic databases for protozoan parasites,... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263569 Sun, 01 Mar 2009 05:00:00 +0100 2263569 http://www.medworm.com/index.php?rid=2263565&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275561%26dopt%3DAbstract Authors: Vannier-Santos MA, De Castro SL Electron microscopy may be useful in chemotherapy studies at distinct levels, such as the identification of subcellular targets in the parasites and the elucidation of the ultimate drug mechanism of action, inferred by the alterations induced by antiparasitic compounds. In this review we present data obtained by electron microscopy approaches of different parasitic protozoa, such as Trypanosoma cruzi, Leishmania spp., Giardia lamblia and trichomonads, under the action of drugs, demonstrating that the cell architecture organization is only determined in detail at the ultrastructural level. The transmission electron microscopy may shed light (i.e. electrons) not only on the affected compartment, but also on the manner it is altered, which may indi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263565 Sun, 01 Mar 2009 05:00:00 +0100 2263565 http://www.medworm.com/index.php?rid=2263561&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275562%26dopt%3DAbstract Authors: Krettli AU, Adebayo JO, Krettli LG The search for new antimalarials, which in the past relied on animal models, is now usually performed with cultures of Plasmodium falciparum (PF) blood parasites by evaluation of parasite growth inhibition. Field isolates of PF human malaria parasite, parasite strains and clones, well characterized for their susceptibility to chloroquine and other standard antimalarials are available for the in vitro tests. The simplest method to evaluate parasite growth is the determination of parasitemias in Giemsa stained blood smears through light microscopy. Other methodologies have proven to be more precise and allow mass screening of new compounds against PF blood stages, such as: (i) measuring the incorporation of radioactive hypoxanthine by the paras... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263561 Sun, 01 Mar 2009 05:00:00 +0100 2263561 http://www.medworm.com/index.php?rid=2263556&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275563%26dopt%3DAbstract Authors: de Azevedo WF, Caceres RA, Pauli I, Timmers LF, Barcellos GB, Rocha KB, Soares MB The study of protein-drug interaction is of pivotal importance to understand the structural features essential for ligand affinity. The explosion of information about protein structures has paved the way to develop structure-based virtual screening approaches. Parasitic protein kinases have been pointed out as potential targets for antiparasitic development. The identification of protein kinases in the Plasmodium falciparum genome has opened the possibility to test new families of inhibitors as potential antimalarial drugs. In addition, other key enzymes which play roles in biosynthetic pathways, such as enoyl reductase and chorismate synthase, can be valuable targets for drug development. This r... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263556 Sun, 01 Mar 2009 05:00:00 +0100 2263556 http://www.medworm.com/index.php?rid=2263551&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275564%26dopt%3DAbstract This article provides an overview of the latest developments in terms of cell and molecular biology that will improve the knowledge related to drug-resistant malaria and to new molecular targets. PMID: 19275564 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263551 Sun, 01 Mar 2009 05:00:00 +0100 2263551 http://www.medworm.com/index.php?rid=2263546&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275565%26dopt%3DAbstract Authors: Nogueira RC, Oliveira-Costa JF, de Sá MS, dos Santos RR, Soares MB Despite many advances made in disease mechanisms knowledge and drug discovery and development processes, the election of promising lead compounds continues to be a challenge. Efficient techniques are required for lead selection of hit compounds selected through in vitro pharmacological studies, in order to generate precise low cost throughput data with minimal amount of compound to support the right decision making. In this context, the selection of lead compounds with physicochemical parameters that will benefit orally bioavailable drugs are crucial for patients compliance and cost effectiveness, as well as for successful pharmacology. A concept based in Lipinski's rules point out the importance of analyz... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263546 Sun, 01 Mar 2009 05:00:00 +0100 2263546 http://www.medworm.com/index.php?rid=2174159&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199902%26dopt%3DAbstract Authors: Bachran C, Fuchs H PMID: 19199902 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174159 Sun, 01 Feb 2009 05:00:00 +0100 2174159 http://www.medworm.com/index.php?rid=2174158&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199903%26dopt%3DAbstract Authors: Fuchs H, Bachran C Conventional tumor therapy is usually based on surgery, radiation and chemotherapy. Treatment with chemotherapeutics is often impeded by dose-limiting toxicities. Therefore, medical scientists sought for tools to improve chemotherapy by directly coupling targeting molecules to cytotoxic substances. This review provides a general overview on the development of targeted drugs designed for tumor therapy. Further carrier-based delivery systems of anti-tumorigenic drugs will not be described here. The targeting moiety is usually an antibody or a fragment thereof. Growth factors, cytokines and ligands are also used as targeting moiety. The targeting moiety is coupled to the toxic moiety either chemically or both components were combined as fusion proteins. In addi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174158 Sun, 01 Feb 2009 05:00:00 +0100 2174158 http://www.medworm.com/index.php?rid=2174157&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199904%26dopt%3DAbstract Authors: Bremer E, de Bruyn M, Wajant H, Helfric W Antibody-based therapeutic approaches are yielding more and more of the promise they have held since the conception of the 'magic bullet' theory by Paul Ehrlich. The beneficial effect of antibody-based therapies is directly related to antibody-dependent functions, such as neutralization and antibody-dependent cellular cytotoxicity, but in many cases also relies on the delivery of toxic compounds to cancerous cells. However, the clinical utility of toxic antibody conjugates can be significantly hampered by side effects. Ideal effector compounds are inactive 'en route', but gain full activity once the antibody conjugate has bound to cancerous cells. Of significant potential in this respect are the pro-apoptotic ligands Tumor Necrosis Fac... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174157 Sun, 01 Feb 2009 05:00:00 +0100 2174157 http://www.medworm.com/index.php?rid=2174156&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199905%26dopt%3DAbstract Authors: Frankel AE, Zuckero SL, Mankin AA, Grable M, Mitchell K, Lee YJ, Neville DM, Woo JH The recombinant CD3 immunotoxin, A-dmDT(390)-bisFv(UCHT1), composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain Fv fragments of an anti-CD3epsilon monoclonal antibody was administered to five patients with cutaneous T cell lymphoma (CTCL) by eight 15 min intravenous infusions over four days. Side effects were fever, chills, nausea, hypoalbuminemia, transaminasemia and reactivation of EBV and CMV. Half-life of drug was 40 min. Anti-immunotoxin antibodies developed in all patients after two weeks. Two patients had partial remissions lasting 1 and 6+ months. The agent is undergoing further dose escalation and shows promising results in this disease. ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174156 Sun, 01 Feb 2009 05:00:00 +0100 2174156 http://www.medworm.com/index.php?rid=2174155&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199906%26dopt%3DAbstract In this report, we give a short overview of CD30-targeting approaches in humans. Furthermore, we introduce two novel anti-CD30 fusion proteins consisting of the single chain variable fragment of the CD30 monoclonal antibody Ber-H2 and human interleukin-2, evaluate their biological activity in a human CD30-positive syngeneic murine model, and demonstrate the immunological mechanisms leading to tumor rejection by these reagents. The data indicate that there are several promising approaches in CD30-targeted immunotherapy. The findings of the anti-CD30 IL-2 constructs suggest that these fusion proteins are particularly useful to remove small, residual tumors. PMID: 19199906 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174155 Sun, 01 Feb 2009 05:00:00 +0100 2174155 http://www.medworm.com/index.php?rid=2174154&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199907%26dopt%3DAbstract Authors: Elsässer-Beile U, Bühler P, Wolf P Prostate cancer is the most common cancer in men from Western industrialized countries and a significant proportion of patients progress to advanced metastatic disease, for which currently no curative treatment exists. Therefore, new therapeutic approaches need to be considered. Prostate specific membrane antigen (PSMA) is an integral, non-shed type 2 membrane protein that is highly and specifically expressed on prostate epithelial cells and strongly upregulated in prostate cancer. PSMA is also present in the neovasculature of other solid tumors. These findings have spurred the development of PSMA-targeted therapies and first-generation products have entered clinical testing. The proposed strategies range from targeted toxins and ra... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174154 Sun, 01 Feb 2009 05:00:00 +0100 2174154 http://www.medworm.com/index.php?rid=2174153&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199908%26dopt%3DAbstract Authors: Hall WA Because primary brain tumors treated with surgery, radiation therapy, and chemotherapy have a poor prognosis, this has led investigators to develop new innovative therapies such as targeted toxins. These large molecules do not cross the blood brain barrier and must be delivered into the brain by a technique known as convection-enhanced delivery (CED). When administering these agents, there are a number of pharmacokinetic considerations that must be considered that will directly affect the volume of distribution of the drug being administered and ultimately the therapeutic effect of the agent. A number of different catheter types have been used to perform CED with a hollow fiber design offering several advantages over other variations. Specific parameters have been deve... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174153 Sun, 01 Feb 2009 05:00:00 +0100 2174153 http://www.medworm.com/index.php?rid=2174152&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199909%26dopt%3DAbstract Authors: Onda M Protein therapeutics, such as antibodies, enzymes and toxins, are very promising reagents for the treatment of human disease. However, many therapeutic proteins are known to elicit immune responses when administered to humans. Certain antibodies work by neutralization; others reduce drug efficacy. It is clear that helper T cells are an important factor in the development of class-switched and affinity-maturated anti-therapeutic protein antibodies. Elimination of the T cell epitope seems reasonable, but it is probably impossible to remove all T cell epitopes from protein drugs because T cell epitopes are closely related to the major histocompatibility complex (MHC) molecules, which are known to be highly polymorphic. Accordingly, a possible practical approach for reducin... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174152 Sun, 01 Feb 2009 05:00:00 +0100 2174152 http://www.medworm.com/index.php?rid=2174151&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199910%26dopt%3DAbstract Authors: Fuchs H, Bachran D, Panjideh H, Schellmann N, Weng A, Melzig MF, Sutherland M, Bachran C Saponins are plant glycosides that consist of a steroid, steroid alkaloid or triterpenoid aglycone and one or more sugar chains that are covalently linked by glycosidic binding to the aglycone. Glucose, galactose, glucuronic acid, xylose and rhamnose are commonly bound monosaccharides. Saponins are found in all organs of a variety of higher plants. Due to the great variability of their structures, diverse functions have been described for distinct saponins; including foaming and pore forming properties as well as selective removal of protozoa from the rumen. The most interesting properties are, however, favorable anti-tumorigenic effects. Several saponins inhibit tumor cell growth by cell ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174151 Sun, 01 Feb 2009 05:00:00 +0100 2174151 http://www.medworm.com/index.php?rid=2174150&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199911%26dopt%3DAbstract Authors: Bagshawe KD Antibody-directed enzyme prodrug therapy aims to restrict the action of a cytotoxic drug to cancer sites. An enzyme that has no human analogue is delivered to cancer sites by attachment to an antibody directed at a tumour associated antigen. In a second step an antibody or other agent inactivates and clears enzyme from blood. The third step is administration of a low toxicity prodrug that is a substrate for the enzyme thus generating a potent cytotoxic agent at cancer sites. Encouraging results were obtained with this system in small scale clinical trials using unrefined agents. During the past 10 years attempts have been made to reduce the system to two components. Although these have met with some success it is now accepted that future progress requires all three... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174150 Sun, 01 Feb 2009 05:00:00 +0100 2174150 http://www.medworm.com/index.php?rid=2174149&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199912%26dopt%3DAbstract Authors: Deckert PM Almost ever since their invention, monoclonal antibodies have held the promise of cancer-specific drug targeting - Paul Ehrlich's "magic bullet" - but only during the past decade have a modest number of anti-cancer antibodies received approval for clinical use. These, however, have proven largely successful, with very different kinds of conventional or recombinant, murine, humanized, recombinant fully human and fusion constructs, and mechanisms of action as diverse as complement or antibody dependent cytotoxicity, anti-angiogenesis, and growth factor inhibition. In these latter two mechanisms of action, antibodies compete with novel small-molecule drugs. This review tries to elucidate current trends in those antibody-based therapeutics that are currently in clinical... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2174149 Sun, 01 Feb 2009 05:00:00 +0100 2174149 http://www.medworm.com/index.php?rid=2116871&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149530%26dopt%3DAbstract This article will deal with different aspects of MBC including biomarkers, pathways, drug targets, and common dietary phytochemicals as effective alternatives of conventional chemotherapeutic drugs for targeted therapy without any side effect. PMID: 19149530 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116871 Thu, 01 Jan 2009 05:00:00 +0100 2116871 http://www.medworm.com/index.php?rid=2116870&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149531%26dopt%3DAbstract Authors: Sousa DM, Herzog H, Lamghari M Neuropeptide (NPY) is a neurotransmitter widely distributed in central and peripheral nervous system that has been implicated in several physiological processes through activation of five different Y receptors: Y1, Y2, Y4, Y5, and y6. NPY system has been extensively studied for the last decades due to its implications in a wide variety of physiological processes. For this purpose a diversity of sophisticated animal models and receptors agonists and antagonists has been developed to better understand its actions throughout body homeostasis. Consequently, NPY and its receptors have recently emerged as a potential regulator of bone homeostasis. This is supported by the demonstration of an increase of bone mass in mice lacking Y1 or Y2 receptor genes... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116870 Thu, 01 Jan 2009 05:00:00 +0100 2116870 http://www.medworm.com/index.php?rid=2116869&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149532%26dopt%3DAbstract Authors: Novo S, Lunetta M, Evola S, Novo G Hypertension has a worldwide high incidence in the general population and undoubtedly it is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries. In this Review we investigated the role of angiotensin II receptor antagonists (ARBs) therapy in the treatment of essential hypertension. We selected in the PubMed and in a list of selected sources the most significant clinical trials and meta-analysis carried out from 1999 to now, to assess, in adult patients populations, ARBs' efficacy, safety and tolerability profile, in comparison with the efficacy of the other common antihypertensive drugs, with particular regard to both the prevention of disabling consequences of hypertension (like cerebrovascu... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116869 Thu, 01 Jan 2009 05:00:00 +0100 2116869 http://www.medworm.com/index.php?rid=2116868&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149533%26dopt%3DAbstract Authors: Robak E, Robak T Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell hyperactivity and defective T-cell function, with production of high titer autoantibodies. In the recent years, conceptual advances and the introduction of new therapies are yielding improvements in the management of this disease. In recent years, clinical studies have been undertaken with selected monoclonal antibodies (mAbs) in the treatment of SLE. The important role of B cells in the pathogenesis of autoimmune disorders has provided a strong rationale to target B cells in SLE. Selective therapeutic depletion of B-cells became possible with the availability of the anti-CD20 antibody rituximab and anti-CD22 antibody epratuzumab. Several clinical studies confirm high activity ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116868 Thu, 01 Jan 2009 05:00:00 +0100 2116868 http://www.medworm.com/index.php?rid=2116867&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149534%26dopt%3DAbstract Authors: Wang Z, Kong D, Li Y, Sarkar FH Platelet-derived growth factor-D (PDGF-D) is a newly recognized growth factor that can regulate many cellular processes, including cell proliferation, transformation, invasion, and angiogenesis by specifically binding to and activating its cognate receptor PDGFR-beta. The functions of PDGF-D in human cancer progression are largely unknown. We discuss here the role of PDGF-D signaling pathway in cancer and how its deregulation is involved in tumor development and progression to metastatic disease. PMID: 19149534 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116867 Thu, 01 Jan 2009 05:00:00 +0100 2116867 http://www.medworm.com/index.php?rid=2116866&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149535%26dopt%3DAbstract Authors: Sourris KC, Forbes JM Diabetes, is a metabolic disorder characterised by chronic hyperglycaemia, hypertension, dyslipidaemia, microalbuminuria and inflammation. Moreover, there are a number of complications associated with this condition including retinopathy, neuropathy and nephropathy. Diabetic nephropathy, is the major cause of end-stage renal disease in Western societies affecting a substantial proportion (25-40%) of patients with diabetes. Advanced glycation end products (AGEs) have been identified as important modulators of the development and progression of diabetic nephropathy, through both receptor dependant and independent interactions. AGEs elicit their receptor mediated effects via their engagement with numerous receptors and binding proteins which are broadly thou... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116866 Thu, 01 Jan 2009 05:00:00 +0100 2116866 http://www.medworm.com/index.php?rid=2116865&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149536%26dopt%3DAbstract This article is intended to review: (i) composition/structure and conditions for the formation of lipid rafts in plasma membranes, (ii) interaction of HIV-1 with lipid rafts and (iii) to introduce a novel concept that dietary and plant-derived compounds, which can target lipid rafts, could have potential preventive/therapeutic values against the progression of AIDS. More emphasis has been given to the roles of omega-3 fatty acids and plant-derived various triterpenes, especially euphane-types of triterpenes extracted from Neem tree, targeting lipid rafts and its major component cholesterol. PMID: 19149536 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116865 Thu, 01 Jan 2009 05:00:00 +0100 2116865 http://www.medworm.com/index.php?rid=2116864&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149537%26dopt%3DAbstract Authors: De Gaudio AR, Rinaldi S, Chelazzi C, Borracci T The aging world population will increase the incidence and mortality of severe sepsis. The aim of the present article is to review the pathophysiological differences in sepsis and its clinical impact on the elderly. The impact of immunosenescence on innate and acquired immunity is associated with relative immunologic depression that may favor the spreading of inflammation. Elderly patients also have enhanced apoptotic pathways that may contribute to the incidence of mortality due to sepsis. The inflammation-coagulation network is activated by age, explaining the success of some specific therapies. The initial clinical picture of sepsis in the elderly may be ambiguous but the specific pathopysiological changes of aging increase th... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116864 Thu, 01 Jan 2009 05:00:00 +0100 2116864 http://www.medworm.com/index.php?rid=2116863&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19149538%26dopt%3DAbstract Authors: Gupta R, Walunj SS, Tokala RK, Parsa KV, Singh SK, Pal M Dipeptidyl peptidase IV (DPP IV) is a key regulator of insulin-stimulating hormones, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thus it is a promising target for the treatment of Type 2 Diabetes mellitus (T2DM). Inhibition of plasma DPP IV enzyme leads to enhanced endogenous GLP-1 and GIP activity, which ultimately results in the potentiation of insulin secretion by pancreatic beta-cells and subsequent lowering of blood glucose levels, HbA[1(c)], glucagon secretion and liver glucose production. Various classes of structurally different DPP IV inhibitors are currently being explored and few of them such as Sitagliptin and Vildagliptin were successfully launched. These drugs have ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2116863 Thu, 01 Jan 2009 05:00:00 +0100 2116863 http://www.medworm.com/index.php?rid=2093377&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128211%26dopt%3DAbstract Authors: de Azevedo WF PMID: 19128211 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093377 Mon, 01 Dec 2008 05:00:00 +0100 2093377 http://www.medworm.com/index.php?rid=2093376&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128212%26dopt%3DAbstract Authors: de Azevedo WF, Dias R Precise computational methods to determine ligand-binding affinity are needed to accelerate the discovery of new drugs. Assessing protein-ligand interaction is of great importance for virtual screening initiatives. The affinity may be computational evaluated using scoring functions involving terms for intermolecular hydrogen bonds, contact surface, hydrophobic contacts, electrostatic interactions and others. Empirical scoring functions have been developed to evaluate ligand-binding affinity very rapidly. In addition to predict affinity, these scoring functions have been employed to identify the best results obtained from docking simulations. This review describes several computational methods, employed to estimate ligand-binding affinity and discuss their... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093376 Mon, 01 Dec 2008 05:00:00 +0100 2093376 http://www.medworm.com/index.php?rid=2093375&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128213%26dopt%3DAbstract Authors: Dias R, de Azevedo WF By means of virtual screening of small molecules databases it is possible to identify new potential inhibitors against a target of interest. Molecular docking is a computer simulation procedure to predict the conformation of a receptor-ligand complex. Each docking program makes use of one or more specific search algorithms, which are the methods used to predict the possible conformations of a binary complex. In the present review we describe several molecular-docking search algorithms, and the programs which apply such methodologies. We also discuss how virtual screening can be optimized, describing methods that may increase accuracy of the simulation process, with relatively fast docking algorithms. PMID: 19128213 [PubMed - in process] (Source: Curre... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093375 Mon, 01 Dec 2008 05:00:00 +0100 2093375 http://www.medworm.com/index.php?rid=2093374&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128214%26dopt%3DAbstract Authors: Canduri F, de Azevedo WF Protein crystallography is the main technique used to obtain three-dimensional information for binary complexes involving protein and drugs. Once a protein target has its three-dimensional structure elucidated, the next natural step is the solving of the structure complexed either with its natural substrate, or any ligand or even an inhibitor. Such information is of pivotal importance to understand the structural basis for inhibition of an enzyme. The relevant features, for application of protein crystallography to drug discovery, are discussed in this review. PMID: 19128214 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093374 Mon, 01 Dec 2008 05:00:00 +0100 2093374 http://www.medworm.com/index.php?rid=2093373&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128215%26dopt%3DAbstract Authors: Pauli I, Timmers LF, Caceres RA, Soares MB, de Azevedo WF Drug development is a high cost and laborious process, requiring a number of tests until a drug is made available in the market. Therefore, the use of methods to screen large number of molecules with less cost is crucial for faster identification of hits and leads. One strategy to identify drug-like molecules is the search for molecules able to interfere with a protein function, since protein interactions control most biological processes. Ideally the use of in silico screenings would make drug development faster and less expensive. Currently, however, the confirmation of biological activity is still needed. Due to the complexity of the task of drug discovery, an integrated and multi-disciplinary approach is ultimately ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093373 Mon, 01 Dec 2008 05:00:00 +0100 2093373 http://www.medworm.com/index.php?rid=2093372&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128216%26dopt%3DAbstract Authors: Dias R, Timmers LF, Caceres RA, de Azevedo WF Molecular docking simulations are of pivotal importance for analysis of protein-ligand interactions and also an essential resource for virtual-screening initiatives. In molecular docking simulations several possible docked structures are generated, which create an ensemble of structures representing binary complexes. Therefore, it is crucial to find the best solution for the simulation. One approach to this problem is to employ empirical scoring function to identify the best docked structure. It is expected that scoring functions show a descriptive funnel-shaped energy surface without many false minima to impair the efficiency of conformational sampling. We employed this methodology against a test set with 300 docked structures. Do... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093372 Mon, 01 Dec 2008 05:00:00 +0100 2093372 http://www.medworm.com/index.php?rid=2093371&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128217%26dopt%3DAbstract Authors: de Azevedo WF, Dias R Precise experimental methods to determine ligand-binding affinity are needed to accelerate the discovery of new drugs. Assessing protein-ligand interaction is of great importance for drug development. One of the techniques that may be used to evaluate ligand-binding affinitty is isothermal titration calorimetry (ITC). This experimental methodology may be used to measure the heat of binding of a ligand to a protein. Furthermore, the development of new empirical scoring functions to assess evaluation protein-ligand interaction lack abundance of experimental information to be used to generate reliable scores. ITC technique may be used to fill this gap. Here we describe the application of this technique to ligand-binding affinity determination, and discuss th... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093371 Mon, 01 Dec 2008 05:00:00 +0100 2093371 http://www.medworm.com/index.php?rid=2093370&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128218%26dopt%3DAbstract Authors: Caceres RA, Pauli I, Timmers LF, de Azevedo WF Molecular recognition process describes the interaction involving two molecules. In the case of biomolecules, these pairs of molecules could be protein-protein, protein-ligand or protein-nucleic acid. The first model to capture the essential features, behind the molecular recognition problem, was the lock-and-key paradigm. The overall analysis protein-protein, protein-nucleic acid and protein-ligand interaction based on the three-dimensional structures and physicochemical parameters, such as binding affinity, opened the possibility to provide further insights in this basic phenomenon. The main ideas behind the molecular recognition are discussed in the present review. PMID: 19128218 [PubMed - in process] (Source: Current Drug ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093370 Mon, 01 Dec 2008 05:00:00 +0100 2093370 http://www.medworm.com/index.php?rid=2093369&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128219%26dopt%3DAbstract Authors: Barcellos GB, Pauli I, Caceres RA, Timmers LF, Dias R, de Azevedo WF With the progression of structural genomics projects, comparative modeling remains an increasingly important method of choice to obtain 3D structure of proteins. It helps to bridge the gap between the available sequence and structure information by providing reliable and accurate protein models. Comparative modeling based on more than 30% sequence identity is now approaching its natural template-based limits and further improvements require the development of effective refinement techniques capable of driving models toward native structure. For difficult targets, for which the most significant progress in recent years has been observed, optimal template selection and alignment accuracy are still the major pro... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093369 Mon, 01 Dec 2008 05:00:00 +0100 2093369 http://www.medworm.com/index.php?rid=2093368&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128220%26dopt%3DAbstract Authors: Timmers LF, Pauli I, Caceres RA, de Azevedo WF Recent developments in computer power and chemoinformatics methodology make possible that a huge amount of data become available through internet. These databases are devoted to a wide spectrum of scientific fields. Here we are concerned with databases related to protein-drug interactions. More specifically, databases where potential new molecules could be accessed to be used in virtual screening initiatives. In the past decade several databases have been developed where molecules to be used in the virtual screening could be easily identified, downloaded and even purchased. This review describes and summarizes the recent advances in the development of these databases, and also the main applications related to virtual screening pro... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093368 Mon, 01 Dec 2008 05:00:00 +0100 2093368 http://www.medworm.com/index.php?rid=2093367&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128221%26dopt%3DAbstract Authors: de Amorim HL, Caceres RA, Netz PA Currently, in order to accelerate the process of drug development and also reduce costs, many of the experimental assays related to lead discovery and lead optimization processes are being replaced by computational, in silico, methods. In this context, the LIE (linear interaction energy) method has been used to calculate binding free energies for widely different compounds by averaging interaction energies obtained from molecular dynamics (MD) or Monte Carlo (MC) simulations. In particular, the combination of docking and affinity predictions with the LIE method can thus save valuable resources in lead discovery and optimization projects. This review presents a description of LIE methodology and some recent studies that illustrate the importanc... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093367 Mon, 01 Dec 2008 05:00:00 +0100 2093367 http://www.medworm.com/index.php?rid=1953008&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991603%26dopt%3DAbstract Authors: Tekwani BL PMID: 18991603 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953008 Sat, 01 Nov 2008 04:00:00 +0100 1953008 http://www.medworm.com/index.php?rid=1953007&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991604%26dopt%3DAbstract Authors: Gobert GN, Jones MK Microarrays are a platform resource that allow the analysis of the entire transcriptome profile of an organism. New advances in the design and production phases make microarrays the perfect tool for parasitology. The mode of action of many drugs employed to treat parasitic diseases are not understood and coupled with rising concerns of drug resistance, all emphasises the importance of research into the interactions drugs have on their target transcriptomes. One particular disease schistosomiasis, relies on a limited number of chemotherapies for treatment and is a prime example of the need for detailed gene expression information while under drug pressure. Recent microarray studies investigating the basic biology of the major species of Schistosoma and their... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953007 Sat, 01 Nov 2008 04:00:00 +0100 1953007 http://www.medworm.com/index.php?rid=1953006&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991605%26dopt%3DAbstract Authors: Ehrenkaufer GM, Singh U Expression profiling with microarray technology has revolutionized exploration of transcriptional regulatory networks on a genome-wide scale. This approach has been successfully applied to the study of Entamoeba histolytica, which causes dysentery and liver abscesses and is a leading parasitic cause of death globally. A variety of microarray platforms have been developed for this system including those generated from genomic DNA, long oligonucleotides, and short oligonucleotides. Using these tools researchers have identified parasite genes whose transcript abundance is differentially regulated during stress, host invasion, and stage conversion. Additionally, novel virulence factors have been identified by identifying genes that are highly expressed in v... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953006 Sat, 01 Nov 2008 04:00:00 +0100 1953006 http://www.medworm.com/index.php?rid=1953005&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991606%26dopt%3DAbstract Authors: Kumari S, Kumar A, Samant M, Singh N, Dube A Among the three clinical forms (cutaneous, mucosal and visceral) of leishmaniasis visceral (VL) one is the most devastating type caused by the invasion of the reticuloendothelial system of human by Leishmania donovani, L. infantum and L. chagasi. India and Sudan account for about half the world's burden of VL. Current control strategy is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. An understanding of resistance mechanism(s) operating in clinical isolates might provide additional leads for the development of new drugs. Further, due to the lack of fully effective treatment the search for novel immune targets is also needed. So far, no vaccine exis... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953005 Sat, 01 Nov 2008 04:00:00 +0100 1953005 http://www.medworm.com/index.php?rid=1953004&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991607%26dopt%3DAbstract Authors: Fleige T, Soldati-Favre D Apicomplexans are obligate intracellular parasites causing devastating disease in both humans and livestock. Nearly all apicomplexans, with the exception of Cryptosporidium, contain two endosymbiontic organelles carrying their own DNA; the mitochondrion and the plastid-like organelle called the apicoplast. The apicoplast is an attractive drug target as it harbors not only metabolic pathways not found in the host cell, but it is also dependent on its ancient transcriptional and translational machinery. These parasites rely on the plastid, and inhibition of its function or loss of this organelle leads to immediate or delayed death. Replication of plastidic DNA shows differences between the members of this phylum. In Plasmodium parasites, two forms of re... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953004 Sat, 01 Nov 2008 04:00:00 +0100 1953004 http://www.medworm.com/index.php?rid=1953003&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991608%26dopt%3DAbstract Authors: Chauhan SC, Padmanabhan PK, Madhubala R Trypanosomatids are pathogenic protozoa of the order Kinetoplastida. A unique feature of these parasitic protozoa is the presence of a unique dithiol trypanothione (N(1), N(8) -bis(glutathionyl)spermidine) and the flavoenzyme trypanothione reductase. This is in contrast to human and other eukaryotes, which contain ubiquitous glutathione/glutathione reductase system. An important function of thiols is to protect cells from toxic metabolic by-products such as methylglyoxal, a reactive 2-oxoaldehyde. Methylglyoxal is a mutagenic and a cytotoxic compound. The glyoxalase system is involved in the detoxification of methylglyoxal. The exceptionality of the glyoxalase enzyme in the parasitic protozoa is the dependence on the dithiol -trypanothio... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953003 Sat, 01 Nov 2008 04:00:00 +0100 1953003 http://www.medworm.com/index.php?rid=1953002&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991609%26dopt%3DAbstract Authors: Reguera RM, Díaz-González R, Pérez-Pertejo Y, Balaña-Fouce R African and South American trypanosomes and leishmanias are unicellular protozoan parasites, forming part of the order Kinetoplastida. These ancient eukaryotes are causative agents of some of the most devastating neglected Tropical Diseases called trypanosomiasis and leishmaniasis. Despite the efforts to develop effective vaccines, immunoprophylaxis is not even a method of prevention of these diseases at present. Current antiprotozoal chemotherapy is often expensive, has side or toxic effects and it does not provide economic profits to the Pharmaceuticals, which have scant enthusiasm in R + D investments in this field. The surprising finding of unusual bi-subunit type IB DNA-topoisomerase in kinet... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953002 Sat, 01 Nov 2008 04:00:00 +0100 1953002 http://www.medworm.com/index.php?rid=1953001&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991610%26dopt%3DAbstract Authors: Vanhamme L Trypanosomes and Leishmaniae are the agents of several important parasitic diseases threatening hundreds of million human beings worldwide. As they diverged early in evolution, they display original molecular characteristics. These peculiarities are each defining putative specific targets for anti-parasitic drugs. Transcription displays its lot of unique characteristics in trypanosomes and will be taken as an example to uncover these targets. Unique features of transcription in trypanosomes include constitutive and poly-cistronic transcription by RNA polymerase II as well as transcription of protein-coding genes by RNA polymerase I. It is becoming clear that these unique mechanisms are performed by dedicated molecular players. The first of them have been recently ch... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953001 Sat, 01 Nov 2008 04:00:00 +0100 1953001 http://www.medworm.com/index.php?rid=1953000&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991611%26dopt%3DAbstract Authors: Bajsa J, Duke SO, Tekwani BL Availability of complete genome sequence for Plasmodium falciparum has been useful in drawing a comprehensive metabolic map of the parasite. Distinct and unique metabolic characteristics of the parasite may be exploited as potential targets for new antimalarial drug discovery research. Reversible phosphorylation of proteins is a ubiquitous process and an indispensable part of cell signaling cascades, which regulate different cellular functions. Not so long ago the role of protein phosphatases in the cell life was underestimated but now these enzymes strongly focus attention of many researches. Based on primary structure and functional characteristics protein phosphatases have been divided into number of families and subfamilies. The amino acid sequ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1953000 Sat, 01 Nov 2008 04:00:00 +0100 1953000 http://www.medworm.com/index.php?rid=1952999&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991612%26dopt%3DAbstract Authors: Takigawa Y, Brown AM Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide. As in many other types of cancer, aberrant activation of the canonical Wnt/beta-catenin signaling pathway is an important contributor to tumorigenesis. In HCC this frequently occurs through mutations in the N-terminal region of beta-catenin that stabilize the protein and permit an elevated level of constitutive transcriptional activation by beta-catenin/TCF complexes. In this article we review the abundant evidence that Wnt/beta-catenin signaling contributes to liver carcinogenesis. We also discuss what is known about the roles of Wnt signaling in liver development, regeneration, and stem cell behavior, in an effort to understand the mechanisms by which activation of the canonical W... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952999 Sat, 01 Nov 2008 04:00:00 +0100 1952999 http://www.medworm.com/index.php?rid=1952998&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991613%26dopt%3DAbstract This article summarizes the pathophysiological role of PEDF for vascular complication in diabetes and its potential therapeutic implication in this devastating disorder. PMID: 18991613 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952998 Sat, 01 Nov 2008 04:00:00 +0100 1952998 http://www.medworm.com/index.php?rid=1884084&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855622%26dopt%3DAbstract Authors: Liu HC, Chen GG, Vlantis AC, Tong MC, van Hasselt CA Laryngeal cancer is a common head and neck cancer. Despite advances in treatment, improvement in survival and quality of life of patients still remains a challenge. Chemotherapy has become more and more important since this treatment is able to preserve laryngeal function. There is increasing evidence showing that many chemotherapeutic agents kill laryngeal tumor cells via apoptotic mechanisms. The balance between anti-apoptotic molecules and pro-apoptotic ones plays a critical role in determining the sensitivity of the tumor cells to chemotherapy. The commonly used chemotherapeutic agents for laryngeal cancer include cisplatin, 5-fluorouracil and paclitaxel. These three agents may target common apoptotic molecules, but more... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1884084 Wed, 01 Oct 2008 04:00:00 +0100 1884084 http://www.medworm.com/index.php?rid=1880817&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855615%26dopt%3DAbstract Authors: Lawler J, Pagès JM PMID: 18855615 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880817 Wed, 01 Oct 2008 04:00:00 +0100 1880817 http://www.medworm.com/index.php?rid=1880816&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855616%26dopt%3DAbstract Authors: Bonnefoy A, Hoylaerts MF Thrombospondin-1 (TSP1), expressed in many cells and tissues is abundantly present in platelet alpha-granules, from where it is released upon platelet activation. Murine Tsp1(-/-) platelet studies have revealed that TSP1 is redundant for platelet aggregation, but that it reinforces platelet aggregate stabilization, especially in a shear field. von Willebrand factor (VWF), synthesized by megakaryocytes and endothelial cells is stored both in platelet alpha-granules and in endothelial Weibel-Palade bodies as ultralarge multimers. When released from endothelial cells, these multimers are temporarily retained on the endothelium, to be cleaved by the plasma protease ADAMTS13 into smaller and hemostatically less reactive multimers, released in plasma. This p... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880816 Wed, 01 Oct 2008 04:00:00 +0100 1880816 http://www.medworm.com/index.php?rid=1880815&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855617%26dopt%3DAbstract Authors: Isenberg JS, Frazier WA, Krishna MC, Wink DA, Roberts DD Activation of soluble guanylate cyclase by nitric oxide (NO) controls signaling pathways that play critical roles in normal vascular physiology and in the pathogenesis of cardiovascular disease. We have identified the secreted protein thrombospondin-1 as a key regulator of NO signaling. Thrombospondin-1 limits the angiogenic activity of NO in endothelial cells, its vasodilator activity in vascular smooth muscle, and its antithrombotic activity in platelets. Loss of either thrombospondin-1 or its receptor CD47 in transgenic mice results in hyperdynamic responses to NO and reveals the importance of this pathway in normal physiology. Thrombospondin-1 and CD47 null mice show improved abilities to respond to ischemic stress, ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880815 Wed, 01 Oct 2008 04:00:00 +0100 1880815 http://www.medworm.com/index.php?rid=1880814&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855618%26dopt%3DAbstract Authors: Sarfati M, Fortin G, Raymond M, Susin S The past decades have been marked by spectacular progress towards understanding how dendritic cells (DCs) interact with T cells to elicit protective immune responses to fight infectious diseases and cancer. DCs that are lying at the interface between innate and adaptive immunity, are educated in peripheral tissues prior to their journey to the secondary lymphoid organs (SLO) whereby they dictate different classes of T cell responses. Uncontrolled or unwanted inflammatory responses are the price to pay to eliminate pathogens. However, if not self-limited, they may induce collateral damages that result in chronic inflammation often associated with autoimmune disorders. CD47 and its two ligands, i.e. thrombospondin 1 (TSP-1) and SIRP-alpha,... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880814 Wed, 01 Oct 2008 04:00:00 +0100 1880814 http://www.medworm.com/index.php?rid=1880813&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855619%26dopt%3DAbstract Authors: Mirochnik Y, Kwiatek A, Volpert OV Thrombospondin-1 is the first and most studied naturally occurring protein inhibitor of angiogenesis. Its characteristic multi-domain structure determines thrombospondin-1 divergent functions, which include but are not limited to the regulation of angiogenesis. Below we overview the structural determinants and receptors expressed on the endothelial and other cell types, that are at the root of thrombospondin-1 striking ability to block neovascularization. We specifically emphasize thrombospondin-1 direct apoptotic action on the remodeling vascular endothelium and summarize current knowledge of its pro-apoptotic signaling and transcriptional networks. Further, we provide comprehensive survey of the thrombospondin-based anti-angiogenic strategi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880813 Wed, 01 Oct 2008 04:00:00 +0100 1880813 http://www.medworm.com/index.php?rid=1880812&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855620%26dopt%3DAbstract Authors: Iruela-Arispe ML The contribution of proteases to developmental, physiological and pathological processes has been well accepted. Cleavage of matrix proteins is a key requirement for cell migration and remodeling of the extracellular environment. The constant process of matrix turnover is dependent on the delicate balance between degradation and synthesis. In addition, regulated proteolysis also allows for the release and activation of growth factors and cytokines. Similarly to other extracellular matrix proteins, thrombospondins are also targets of proteolysis. While in some cases enzymatic activity is associated with degradation of the protein; in other situations, targeted and selective cleavage offers the means to release polypeptides with either alternative or enhanced fu... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880812 Wed, 01 Oct 2008 04:00:00 +0100 1880812 http://www.medworm.com/index.php?rid=1880811&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855621%26dopt%3DAbstract Authors: Posey KL, Hecht JT Cartilage oligomeric matrix protein is a non-collagenous extracellular matrix protein expressed primarily in cartilage, ligament, and tendon. Cartilage oligomeric matrix protein has been studied extensively because mutations in the gene cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. Pseudoachondroplasia is a disproportionate dwarfing condition associated with joint abnormalities, while multiple epiphyseal dysplasia is less severe. Both of these skeletal dysplasias have a characteristic chondrocyte pathology that consists of intracellular retention of cartilage oligomeric matrix protein and other extracellular matrix proteins in an enlarged rough endoplasmic reticulum. This toxic intracellular retention of extracellular... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880811 Wed, 01 Oct 2008 04:00:00 +0100 1880811 http://www.medworm.com/index.php?rid=1880810&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855622%26dopt%3DAbstract Authors: Liu HC, Chen GG, Vlantis AC, Tong MC, van Hasselt CA Laryngeal cancer is a common head and neck cancer. Despite advances in treatment, improvement in survival and quality of life of patients still remains a challenge. Chemotherapy has become more and more important since this treatment is able to preserve laryngeal function. There is increasing evidence showing that many chemotherapeutic agents kill laryngeal tumor cells via apoptotic mechanisms. The balance between anti-apoptotic molecules and pro-apoptotic ones plays a critical role in determining the sensitivity of the tumor cells to chemotherapy. The commonly used chemotherapeutic agents for laryngeal cancer include cisplatin, 5-fluorouracil and paclitaxel. These three agents may target common apoptotic molecules, but more... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880810 Wed, 01 Oct 2008 04:00:00 +0100 1880810 http://www.medworm.com/index.php?rid=1880809&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855623%26dopt%3DAbstract This article reviews the mechanisms by which EIs act and elucidates the pathways involved. PMID: 18855623 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880809 Wed, 01 Oct 2008 04:00:00 +0100 1880809 http://www.medworm.com/index.php?rid=1880808&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855624%26dopt%3DAbstract Authors: Agarwal A, Tripathi PK, Tripathi S, Jain NK In the context of drug delivery it is crucial to gain knowledge of nature of the cell's internal barriers, as well as one needs to be aware of requirements for the study of spatial and temporal interactions of drug delivery vehicles with the cell. Fluorescent imaging technology can be a great innovation in the field of science as far as study of live cell imaging and dynamic events are concerned. The technique has also demonstrated the ability to integrate the anatomic, functional, and statistical data. The current review article discusses various fluorescent techniques and also elaborates the scope of fluorescent imaging in the field of drug delivery. PMID: 18855624 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880808 Wed, 01 Oct 2008 04:00:00 +0100 1880808 http://www.medworm.com/index.php?rid=1880807&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855625%26dopt%3DAbstract Authors: Telvekar VN, Kundaikar HS Type-2 diabetes is strongly linked to visceral obesity and elevated levels of circulating free fatty acids. For years this correlation of obesity to diabetes has intrigued the minds of researchers and research in this direction has led to a possible solution to this question. Human Genome project has identified nearly 150 orphan GPCRs. The reverse pharmacology approaches have identified free fatty acids as ligands for the GPR40 family of orphan receptors. This review mainly emphasizes on the role of GPR40 carboxylic acid receptor family in the development of diabetes alongwith detailed coverage of each receptor of the family. GPR40 family has provided an insight into regulation of carbohydrate and lipid metabolism in vertebrates and has further provid... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880807 Wed, 01 Oct 2008 04:00:00 +0100 1880807 http://www.medworm.com/index.php?rid=1880806&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855626%26dopt%3DAbstract Authors: Vaidya HB, Goyal RK Diabetes mellitus (DM) has been recognized as a growing world-wide epidemic by many health advocacy groups including the World Health Organization (WHO). DM affects about 6% of the North American population. A recent report estimated that 8.2% of adult population worldwide has impaired glucose tolerance. Current treatment approaches include diet, exercise, and a variety of pharmacological agents including insulin, biguanides, sulfonylureas and thiazolidinediones. New therapies are still needed to control metabolic abnormalities, and also to preserve beta-cell mass and to prevent loss of beta-cell function. In many cases monotherapy gradually fails to improve blood glucose control and combination therapy is employed. The long-term success of these treatments... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1880806 Wed, 01 Oct 2008 04:00:00 +0100 1880806 http://www.medworm.com/index.php?rid=1795199&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781918%26dopt%3DAbstract Authors: Amaral L, Pagès JM PMID: 18781918 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1795199 Mon, 01 Sep 2008 04:00:00 +0100 1795199 http://www.medworm.com/index.php?rid=1795198&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781926%26dopt%3DAbstract Authors: Walsh C, Fanning S The widespread use of antibiotics in food animal production systems has resulted in the emergence of antibiotic resistant zoonotic bacteria that can be transmitted to humans through the food chain. Infection with antibiotic resistant bacteria negatively impacts on public health, due to an increased incidence of treatment failure and severity of disease. Development of resistant bacteria in food animals can result from chromosomal mutations but is more commonly associated with the horizontal transfer of resistance determinants borne on mobile genetic elements. Food may represent a dynamic environment for the continuing transfer of antibiotic resistance determinants between bacteria. Current food preservation systems that use a combination of environmental str... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1795198 Mon, 01 Sep 2008 04:00:00 +0100 1795198 http://www.medworm.com/index.php?rid=1783441&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781918%26dopt%3DAbstract Authors: Amaral L, Pagès JM PMID: 18781918 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1783441 Mon, 01 Sep 2008 04:00:00 +0100 1783441 http://www.medworm.com/index.php?rid=1783440&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781919%26dopt%3DAbstract We describe recent structural and functional studies on the individual pump components and discuss models that explain how they associate in the dynamic, active assembly. Based on the available data, we suggest that the assembly of these multi-drug efflux pumps is accompanied by induced fit of the outer membrane component driven mainly by accommodation of the periplasmic component. PMID: 18781919 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1783440 Mon, 01 Sep 2008 04:00:00 +0100 1783440 http://www.medworm.com/index.php?rid=1783439&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781920%26dopt%3DAbstract Authors: Seeger MA, Diederichs K, Eicher T, Brandstätter L, Schiefner A, Verrey F, Pos KM Antimicrobial resistance of human pathogenic bacteria is an emerging problem for global public health. This resistance is often associated with the overproduction of membrane transport proteins that are capable to pump chemotherapeutics, antibiotics, detergents, dyes and organic solvents out of the cell. In Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, tripartite multidrug efflux systems extrude a large variety of cytotoxic substances from the cell membrane directly into the medium bypassing the periplasm and the outer membrane. In E. coli, the tripartite efflux system AcrA/AcrB/TolC is the pump in charge of the efflux of multiple antibiotics, dyes, bile salts an... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1783439 Mon, 01 Sep 2008 04:00:00 +0100 1783439 http://www.medworm.com/index.php?rid=1783438&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781921%26dopt%3DAbstract Authors: Davin-Regli A, Bolla JM, James CE, Lavigne JP, Chevalier J, Garnotel E, Molitor A, Pagès JM In Enterobacteriaceae, membrane permeability is a key in the level of susceptibility to antibiotics. Modification of the bacterial envelope by decreasing the porin production or increasing the expression of efflux pump systems has been reported. These phenomena are frequently associated with other resistance mechanisms such as alteration of antibiotics or modification of the drug targets, in various clinical isolates showing a MultiDrugResistant phenotype (MDR). In Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae and Salmonella enterica several genes and external factors are involved in the emergence of MDR isolates. These bacterial isolates exhibit a noticeable redu... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1783438 Mon, 01 Sep 2008 04:00:00 +0100 1783438 http://www.medworm.com/index.php?rid=1783437&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781922%26dopt%3DAbstract Authors: Viveiros M, Martins M, Couto I, Rodrigues L, Spengler G, Martins A, Kristiansen JE, Molnar J, Amaral L We have developed a number of methods that identify efflux pump mediated multi-drug resistant bacteria, characterize efflux systems and screen for inhibitors of efflux pumps. These approaches were complemented by the quantification of the expression of genes that regulate and code for constituents of efflux pumps. The methods described are easy to use, reproducible and for the most part, require instrumentation normally present in a clinical bacteriology laboratory. Because each method provides good reproducibility, they lend themselves for inter-laboratory use. PMID: 18781922 [PubMed - in process] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1783437 Mon, 01 Sep 2008 04:00:00 +0100 1783437 http://www.medworm.com/index.php?rid=1783436&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781923%26dopt%3DAbstract Authors: Ceccarelli M, Ruggerone P Bacteria can resist antibiotics simply by hindering physical access to the interior, where in general antibiotic targets are located. Gram-negative bacteria, protected by the outer membrane, possess in the latter several porins that act as a gate for the exchange of small hydrophilic molecules. These porins are water-filled membrane-protein channels that are considered to be the main pathway for different class of antibiotics, such as beta-lactams and fluoroquinolones. Bacterial strains resistant to antibiotics can either decrease the density of porins expressed in the outer membrane or decrease the porin internal size by mutating a few amino acids. In both cases, understanding how antibiotics diffuse through bacterial porins can help the design of ne... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=1783436 Mon, 01 Sep 2008 04:00:00 +0100 1783436