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 'Drug Development Research' source. Wed, 08 Feb 2012 14:04:11 +0100 http://www.medworm.com/index.php?rid=5648134&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.21002 AbstractStrategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IVHeliopsis longipes is a popular medicinal plant in Mexico. One of the main constituents that can be extracted from H. longipes is affinin (N‐isobutylamide). However, available information regarding this compound is scarce, and there is only a single report related to the effect of affinin on the central nervous system. Affinin extracted from H. longipes was evaluated for its psychopharmacological activity in several models and for its safety. H. longipes extract and affinin demonstrated antinociceptive effect... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5648134 Wed, 01 Feb 2012 05:00:00 +0100 5648134 http://www.medworm.com/index.php?rid=5552467&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20491 AbstractStrategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IVThe inability to cure many diseases, such as cancer and arthritis, has stimulated the need for the development of new drugs from natural sources. Of all natural sources, the marine environment is clearly the last great frontier for pharmaceutical and medical research. As part of our search for new anti‐inflammatory or anticancer potential drugs, organic fractions (chloroform, ethyl acetate and methanol) from the Mediterranean brown seaweed, Cystoseira compressa were evaluated for in vivo anti‐inflammatory activit... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5552467 Thu, 29 Dec 2011 05:00:00 +0100 5552467 http://www.medworm.com/index.php?rid=5552466&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20492 AbstractStrategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IVWhile business predictions suggest that 19 companies will have new or improved targeted drug delivery products on the market by 2018, no effective drug‐targeting systems have as yet been developed for use as human therapeutics despite a steadily increasing number of publications on the topic of drug targeting. This critical review argued that efforts in this field have failed so far largely because the basic requirements of targeted drug delivery are not been taken into consideration by researchers. The review outl... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5552466 Thu, 29 Dec 2011 05:00:00 +0100 5552466 http://www.medworm.com/index.php?rid=5552465&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20493 AbstractStrategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IVTreatment of refractory gout remains a challenge on drug development. While pegloticase, a recombinant mammalian uricase modified with monomethoxyl poly(ethylene glycol) (mPEG) is effective in treating refractory gout, after continued treatment for 3 months biweekly at a therapeutic dose of 0.14 mg/kg body weight, it elicits an immune response against mPEG in nearly 20% of patients. For continued treatment of refractory gout, PEGylated uricases at monthly therapeutic doses below 4 μg/kg body weight have promis... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5552465 Thu, 29 Dec 2011 05:00:00 +0100 5552465 http://www.medworm.com/index.php?rid=5648133&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.21001 AbstractStrategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IVRhodiola rosea is a popular medicinal plant that is commonly used as an adaptogen in folklore medicine in Europe and Asia due to its ability to increase an organism's resistance to physical, chemical and biological stress. The aim of this study was to determine the central nervous system activity and toxicity parameters of R. rosea. An ethanol extract from the roots of R. rosea was orally (p.o.) administered to mice (10–316 mg/kg); exploratory activity, anti‐anxiety, behavior, sodium pentobarbital‐induced... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5648133 Thu, 01 Dec 2011 05:00:00 +0100 5648133 http://www.medworm.com/index.php?rid=5628865&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.21003 AbstractStrategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IV3,5‐Di‐t‐butylcatechol (DTCAT) stimulates the rat skeletal muscle sarcoplasmic reticulum ryanodine receptor (RyR). In the present study, its effects on the contractile response of diaphragm preparation were characterized using electrically stimulated phrenic nerve–diaphragm preparations and diaphragm strips. DTCAT reduced, concentration‐dependently, twitch contraction of the phrenic nerve–diaphragm preparation evoked by both direct and indirect stimulation and increased spontaneous tone. Twitch amplitude ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5628865 Thu, 01 Dec 2011 05:00:00 +0100 5628865 http://www.medworm.com/index.php?rid=5552464&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.21000 AbstractStrategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IVNebulized corticosteroid drugs have several shortcomings due to their poor water solubility and nonoptimal deposition pattern. The aims of this study were to investigate the in vitro and in vivo characteristics of beclomethasone dipropionate (BDP)‐loaded sterically stabilized phospholipid nanomicelles (SSMs) of a polyethylene glycol–phosphatidylethanolamine conjugate as a pulmonary delivery system. The particle size distribution and zeta potential measurements were 14.60 ± 1.11 nm and −46.94 ± 3.27�... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5552464 Thu, 01 Dec 2011 05:00:00 +0100 5552464 http://www.medworm.com/index.php?rid=5505085&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20490 AbstractRheumatoid arthritis (RA) is an autoimmune disease with a significant morbidity defined by marked destruction and deformity of joints. It is characterized by autoantibody production, synovial inflammation, and erosion of the cartilage and bone. The current first‐line treatment for RA is methotrexate (MTX), an orally active disease‐modifying anti‐rheumatic drug (DMARD). Biologic DMARDs that target tumor necrosis factor (TNF) or other molecules have emerged as potent alternative therapies for patients with inadequate response to MTX therapy. Despite the huge success of MTX and/or biologics, there is still a significant unmet medical need in RA. Approximately one‐third of RA patients are nonresponsive to currently available therapies. With their critical roles in mediating mul... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505085 Thu, 01 Dec 2011 05:00:00 +0100 5505085 http://www.medworm.com/index.php?rid=5505084&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20488 AbstractThe incidence of autoimmune diabetes mellitus is growing worldwide; currently the only treatment is injection of insulin formulations to maintain glycemic control. Islet transplantation has been examined as a potential cure for diabetes. However, it has several limitations, including side effects of immunosuppressive agents required to prevent graft rejection. Other approaches have been to examine immune modulation to halt or prevent the autoimmune attack, with the hope that by preventing tissue damage, it will eventually regenerate and permit patients to be free from insulin injections. The focus of the current review is the three major antigen‐based vaccines, insulin, glutamic acid decarboxylase 65 (GAD65; Diamyd), and heat shock protein 60 (Hsp60; DiaPep277), with respect to t... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505084 Thu, 01 Dec 2011 05:00:00 +0100 5505084 http://www.medworm.com/index.php?rid=5505083&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20487 AbstractB‐cell targeted therapies have enjoyed recent success in the treatment of systemic autoimmune diseases. Among these, Belimumab, which blocks the B‐cell survival cytokine BLyS, was recently approved for the treatment of systemic lupus erythematosus. It is therefore important to consider the roles BLyS plays in B‐cell tolerance. Herein, we review how BLyS contributes to the negative selection of autoreactive B‐cell clones from the preimmune repertoire as well as its role in regulating both germinal center and extrafollicular peripheral B‐cell responses. We further examine the complex role of Toll‐like receptors (TLRs) in humoral autoimmunity, pointing out potential crosstalk between BLyS and TLR pathways. Drug Dev Res 72:779–787, 2011. © 2011 Wiley Periodicals, Inc. (S... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505083 Thu, 01 Dec 2011 05:00:00 +0100 5505083 http://www.medworm.com/index.php?rid=5505082&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20486 AbstractPhosphodiesterases (PDEs) and their substrates, cAMP and cGMP, are ubiquitously expressed in the immune system. Inhibiting PDEs may represent a novel approach for regulating immune functions and have a therapeutic potential in the management of autoimmune diseases. Phosphodiesterase inhibitors (PDEi) have proved effective in clinical trials in the management of pulmonary artery hypertension and Raynaud's phenomenon. Data from animal models suggest that the immunomodulatory effect of PDEi may have a therapeutic potential in the management of diseases such as multiple sclerosis and rheumatoid arthritis. The antifibrotic potential of PDEi, as suggested by animal experiments, if proven in further studies will be a major step in the treatment of fibrosing diseases such as scleroderma an... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505082 Thu, 01 Dec 2011 05:00:00 +0100 5505082 http://www.medworm.com/index.php?rid=5505081&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20485 AbstractThe development of high‐resolution musculoskeletal ultrasound (US) has improved our ability to evaluate the structural and inflammatory pathology involving the articular cartilage and cortical bony surface of joints affected by osteoarthriris (OA). US has also allowed us to “visualize” the surrounding soft tissues ranging from synovium, joint capsule and retinacular supporting tissue to tendons, ligaments and nerves, and this, in turn, has given us a much more complete picture of the extent of damage caused by OA, the most common of all types of arthritis. As a result, it appears that inflammation of the synovium is a relevant feature in patients with OA. Early osteophytic bone changes at the interface of the joint capsule with the bony articular margin, degeneration of the a... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505081 Thu, 01 Dec 2011 05:00:00 +0100 5505081 http://www.medworm.com/index.php?rid=5505080&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20484 AbstractMedication adherence is a significant problem in patients with rheumatoid arthritis (RA), a prevalent autoimmune disease. Because of the equivocal results reported in the research, consistent predictors of medication adherence in patients with RA are undetermined. A cross‐sectional descriptive, predictive study of 108 patients with RA was used to: (1) describe self‐reported medication adherence to disease‐modifying anti‐rheumatic drugs (DMARDs); (2) compare demographic (age, residence, marital status, employment status, years of education, and ethnicity) and clinical (duration of disease and number of medications) factors of adherent and nonadherent individuals; and (3) determine the predictive power of demographic and clinical factors for DMARD adherence using various cut�... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505080 Thu, 01 Dec 2011 05:00:00 +0100 5505080 http://www.medworm.com/index.php?rid=5505079&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20483 We describe the efficacy and safety of bosentan, an orally active dual ET‐receptor antagonist, in patients with digital ulcers. Bosentan increases exercise capacity and improves hemodynamics in patients with pulmonary hypertension, suggesting that ET has an important role in pulmonary hypertension but in our experience also for refractory skin ulcers. Drug Dev Res 72:750–755, 2011. © 2011 Wiley Periodicals, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505079 Thu, 01 Dec 2011 05:00:00 +0100 5505079 http://www.medworm.com/index.php?rid=5505078&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20482 AbstractRheumatoid arthritis (RA) is a systemic inflammatory disorder that affects not only joints but also the cardiovascular (CV) system. Premature endothelial dysfunction and accelerated atherosclerosis are pertinent findings in patients with RA, resulting in increased CV morbidity and mortality. Thus, detection of subclinical atherosclerosis is important in RA management. A range of promising imaging modalities is currently available to visualize early vascular disease and monitor changes in atherosclerotic plaque burden, serving as important tools in CV risk stratifications and as surrogate markers for CV endpoints in intervention trials. This review summarizes various noninvasive imaging modalities, implemented in widespread clinical use, such as vascular ultrasonography and cardiac ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505078 Thu, 01 Dec 2011 05:00:00 +0100 5505078 http://www.medworm.com/index.php?rid=5505077&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20481 AbstractUlcerative colitis (UC) is a lifelong, immune‐mediated inflammatory condition of the colonic mucosa characterized by a relapsing and remitting course. The mainstay of treatment used to be the 5‐aminosalicylates (5‐ASA) and corticosteroids. Nevertheless, some patients are unable to discontinue or reduce the steroid dosage and are exposed to a number of side effects. The efficacy of thiopurines is well proven in inflammatory bowel disease (IBD); azathioprine (AZA) is considered the first‐line immunosuppressant with a steroid‐sparing effect in UC patients with steroid dependence or resistance. Success rates of 70% occur in induction therapy with AZA and 6‐mercaptopurine (MP) in UC with a number‐needed‐to‐treat (NNT) to avoid recurrence (with AZA/MP, as compared with ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505077 Thu, 01 Dec 2011 05:00:00 +0100 5505077 http://www.medworm.com/index.php?rid=5505076&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20480 AbstractThe cytokine interleukin (IL)‐6 has a wide range of biological activities. It contributes to host defense against pathogens by inducing immune responses, hematopoiesis, and acute‐phase reactions. However, dysregulation of IL‐6 production plays a significant pathological role in various autoimmune and chronic inflammatory disorders. Because IL‐6 blockade was anticipated to provide a novel strategy for the treatment of such diseases, tocilizumab, a humanized anti‐IL‐6 receptor antibody, was developed. Clinical trials have demonstrated the efficacy of tocilizumab for patients with moderate to severe rheumatoid arthritis, resulting in approval in more than 90 countries worldwide of this innovative biologic for the treatment of rheumatoid arthritis. Tocilizumab was also appr... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505076 Thu, 01 Dec 2011 05:00:00 +0100 5505076 http://www.medworm.com/index.php?rid=5505075&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20479 AbstractAutoimmune diseases result from a dysfunctional immune system in which the body attacks its own organs, tissues, cells, and macromolecules. This group of diseases consists of more than 80 chronic diseases that often lead to disabilities. Targeting therapy for autoimmune diseases faces two major challenges: (1) identification of autoreactive cells that can be targeted for suppression; and (2) penetration through target tissues to specifically deliver drugs to the desired cells and thus to achieve sufficient therapeutic efficacy. Regarding the latter, multiple drug delivery approaches have been developed. In the present work, the current nanomedicine development strategies for the improved treatment of several common autoimmune diseases are reviewed. Drug Dev Res 72:703–716, 2011. ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505075 Thu, 01 Dec 2011 05:00:00 +0100 5505075 http://www.medworm.com/index.php?rid=5505074&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20478 AbstractThe present work reviews the available data on rheumatoid arthritis (RA) during pregnancy and the postpartum period. The data generally support some improvement in RA during pregnancy, but these data are not consistent, and a subgroup of patients may have significant disability and flares. The literature supports a tendency toward postpartum flares. Babies born to mothers with RA are found to have lower birth weight, intrauterine growth restriction, and an increased risk of delivery by cesarean section. Limited safety information is available for medications used for treatment during pregnancy and lactation. There are many options for treatment during the first trimester and throughout pregnancy, but each decision must be made on an individual basis. Whereas methotrexate and leflun... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505074 Thu, 01 Dec 2011 05:00:00 +0100 5505074 http://www.medworm.com/index.php?rid=5505073&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20477 AbstractThe rational development of disease‐modifying therapies for multiple sclerosis (MS) requires a detailed knowledge of disease pathogenesis, but this remains incomplete. Dynamic computer‐assisted modeling of MS is currently hindered by uncertainties about the connectivity, compartmentalization, and dynamic sequencing of the components of the disease process. The present work presents a simple but versatile model of the mammalian immune system, incorporating both innate and adaptive immunity and innate and adaptive tolerance. The model is applied to MS and its animal model, experimental autoimmune encephalomyelitis (EAE), to interrogate the concept of initiation of MS lesions through activation of the peripheral innate immune system, triggering auto‐reactive T cells against myel... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505073 Thu, 01 Dec 2011 05:00:00 +0100 5505073 http://www.medworm.com/index.php?rid=5505072&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20476 AbstractMultiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Current therapies are mainly biological agents (β‐interferons, a 4‐amino acid peptide, and a monoclonal antibody to a cell adhesion molecule on the blood CNS barrier) that either attenuate the inflammatory response or block the movement of immune cells into the CNS. The market landscape for MS drugs is set to change substantially in the near future with the market leaders coming off patent, which gives permission for the emergence of biosimilars. In addition, new small‐molecule immunomodulatory drugs are beginning to enter the market (Gilenya is the first to gain widespread approval), alo... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505072 Thu, 01 Dec 2011 05:00:00 +0100 5505072 http://www.medworm.com/index.php?rid=5505071&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20475 AbstractRheumatoid arthritis (RA) is characterized by a symmetric polyarthritis of unknown etiology that, if untreated or unresponsive to therapy, typically leads to deformities and destruction of joints through the erosion of cartilage and bone. Currently available disease‐modifying antirheumatic drugs (DMARDs) can control synovitis and may slow, or even stop, radiographic progression, improve function and quality of life, and normalize mortality rates. This review gives a brief overview on commonly used conventional DMARDs and their role in the current management of RA. Methotrexate is still considered the gold standard among the DMARDs, and is widely accepted as first‐line treatment in the management of RA. Other DMARDs are less frequently used in monotherapy or as first‐line agen... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5505071 Thu, 01 Dec 2011 05:00:00 +0100 5505071 http://www.medworm.com/index.php?rid=5457952&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20489 This article presents the results of questionnaires administered dutring interviews with 60 senior people representing the industry. It narrates their expertise, knowledge management, and innovative behaviors. NZ's industry comprises highly qualified, very experienced, and motivated people. Their organizations have particular expertise in drug discovery, which has arisen from long‐term government support for biomedical research. There is also significant expertise in early‐stage clinical development and contract clinical research. Knowledge sharing was rated as better within organizations than externally. The participants gave the highest ratings of their organizations' innovative performance to solving problems that had caused others difficulty, teamwork and having new ideas; they pre... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5457952 Mon, 28 Nov 2011 05:00:00 +0100 5457952 http://www.medworm.com/index.php?rid=5457951&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20463 AbstractBOBA (4‐[3‐(3, 5‐di‐tert‐butyl‐4‐methoxyphenyl)‐3‐oxo‐propenyl]benzoic acid), a substituted chalcone derivative, exhibits an excellent inducing differentiation on neoplastic cellular differentiation. FUDR (5‐fluoro‐2′‐deoxyuridine, floxuridine) inhibits DNA biosynthesis and has been used extensively to treat various cancers. In our efforts to find a new dual‐action antitumor prodrug, 3′‐floxuridinyl 4‐[3‐(3, 5‐di‐t‐butyl‐4‐methoxyphenyl)‐3‐oxo‐propenyl] benzoate (3′‐O‐BOBA‐ FUDR) was synthesized, and its antiproliferative activity in vitro and antitumor efficacy in vivo were evaluated. Compared with FUDR, the antiproliferative activity of 3′‐O‐BOBA‐FUDR was improved by 3–7‐fold. In rat hepatocellular carcinom... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5457951 Tue, 01 Nov 2011 04:00:00 +0100 5457951 http://www.medworm.com/index.php?rid=5441220&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20474 AbstractBehçet's syndrome (BS), or Behçet's disease (BD), is a multisystem inflammatory disorder that mainly affects population clusters along the Old Silk Road; however, it has been reported worldwide. The disease is currently classified as a vasculitis, characterized by sporadic outbreaks. The hallmarks of BS are recurrent, painful oral ulcers. Skin, eyes, central nervous system (CNS), gastrointestinal tract (GI) tract, and other organs may also be involved. CNS, GI, and major vascular involvement can be life‐threatening, and uveitis may lead to blindness. Immunosuppressive and immunomodulatory treatment is the mainstay of therapy for this inflammatory disease. Whereas the most frequently used agents for the treatment of BS have been corticosteroids, colchicine, and azathioprine, the... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441220 Tue, 01 Nov 2011 04:00:00 +0100 5441220 http://www.medworm.com/index.php?rid=5441219&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20473 AbstractCyclosporine is one of the most effective agents available for the treatment of psoriasis. It is also widely used in atopic dermatitis and other dermatological disorders. Recent consensus guidelines for psoriasis recommend an initial dosage of 2.5–5 mg/kg/day (in one or two daily doses), with adjustments of 0.5–1 mg/kg/day every 1–2 weeks; the maximum daily dosage is 6 mg/kg/day. The most widely used cyclosporine schedule is intermittent short‐term therapy for 12–16 weeks; subsequently, when relapse occurs, treatment is restarted at the previously established, effective dosage. Short‐term cyclosporine therapy is also particularly useful as a “rescue” treatment for severe disease flares, and as a “bridging” treatment to other maintenance schedules. Hyperten... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441219 Tue, 01 Nov 2011 04:00:00 +0100 5441219 http://www.medworm.com/index.php?rid=5441218&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20472 AbstractB‐lymphocyte stimulator (BLyS) maintains the survival of B cells, and is elevated in serum or locally in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Belimumab (LymphoStat‐B) is a fully human IgG1λ monoclonal antibody that binds to soluble human BLyS and inhibits its biological activity. It has been developed for therapy for SLE and the potential treatment of other autoimmune diseases. Belimumab was well tolerated in the treatment of SLE for more than 5 years and of RA for more than 24 weeks. In the pooled analyses of two Phase III trials including 1,684 seropositive SLE patients, a statistically significant improvement was observed for the SLE responder index at week 52 for belimumab 1 mg/kg and 10 mg/kg as compared with placebo (46% vs ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441218 Tue, 01 Nov 2011 04:00:00 +0100 5441218 http://www.medworm.com/index.php?rid=5441217&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20471 AbstractAnti‐tumor necrosis factor‐α (TNF‐α) therapies, also called biologic therapies or immunotherapies, are being used increasingly in dermatology, rheumatology, and gastroenterology in the context of established and emerging indications. Anti‐TNF agents target TNF‐α and include infliximab (a chimeric IgG1 monoclonal antibody), adalimumab (a fully human recombinant IgG1 monoclonal antibody), and etanercept (a dimeric fusion protein of TNFR1 linked to the Fc portion of IgG1). Among skin diseases, only plaque psoriasis represents an approved indication for the use of anti‐TNF‐α agents; however, anti‐TNF therapies have been used as off‐label treatments in a plethora of immune‐mediated or inflammatory cutaneous disorders, such as hidradenitis suppurativa, alopecia ar... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441217 Tue, 01 Nov 2011 04:00:00 +0100 5441217 http://www.medworm.com/index.php?rid=5441216&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20470 AbstractFirst‐line treatment for moderate to severe rheumatoid arthritis (RA) has been the use of disease‐modifying anti‐rheumatic drugs (DMARDs), e.g., methotrexate. Because of the cases of failure reported to respond to available treatments, newer RA drugs including tumor necrosis factor (TNF‐α) blockers have emerged. Certolizumab pegol (CZP) is a unique polyethylene glycolated (PEG) humanized monoclonal antibody designed specifically to target TNF‐α pro‐inflammatory cytokine. Given that its properties closely reflect its PEG fragment, CZP has demonstrated a clear efficiency. Pharmacokinetics and pharmacodynamics of CZP are described together with Phase II and III CZP clinical studies focused on CZP efficiency and safety. We also discuss the future of CZP and new clinical s... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441216 Tue, 01 Nov 2011 04:00:00 +0100 5441216 http://www.medworm.com/index.php?rid=5441215&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20469 AbstractThe chemokine CXCR4 receptor is a G‐protein‐coupled receptor that has multiple functions in normal physiologies involving the hematopoietic and immune systems. Although the CXCR4 receptor was initially discovered as one of the co‐receptors involved in human immune deficiency virus (HIV) cell entry, it has also been linked to many central immune system functions through the direct regulation of cell trafficking and adhesion, and is present in many cell types within the body. The receptor ligand combination of CXCL12 (SDF‐1) and CXCR4 underlies pathologies such as HIV infection, cancer metastasis and drug resistance, leukemia progression, rheumatoid arthritis, and lupus. This alternative and widespread functionality has allowed researchers to discover new potential uses for s... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441215 Tue, 01 Nov 2011 04:00:00 +0100 5441215 http://www.medworm.com/index.php?rid=5441214&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20468 AbstractSignificant advances have been made during the past decade in the understanding of autoimmune diseases and in the development of therapeutics targeting various immune pathways. T‐cell‐mediated immune dysregulation occurs in a variety of autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. Inhibition of the T‐cell function using CTLA‐4Ig is currently approved for management of rheumatoid arthritis. Select therapies targeting adhesion molecules are used for the management of patients with psoriasis and multiple sclerosis. Therapeutics targeting tumor necrosis factor‐α (TNF‐α), a cytokine secreted by T cells, is widely used in patients with rheumatoid arthritis and inflammatory bowel disease. Furthermore, several ther... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441214 Tue, 01 Nov 2011 04:00:00 +0100 5441214 http://www.medworm.com/index.php?rid=5441213&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20467 AbstractThe voltage‐gated Kv1.3 and the calcium‐activated KCa3.1 potassium channel modulate many calcium‐dependent cellular processes in immune cells, including T‐cell activation and proliferation and have therefore been proposed as novel therapeutic targets for immunomodulation. Kv1.3 is highly expressed in CCR7− effector memory T cells and is emerging as a target for T‐cell‐mediated diseases like multiple sclerosis, rheumatoid arthritis, type‐1 diabetes mellitus, allergic contact dermatitis, and psoriasis. In contrast, KCa3.1 is expressed in CCR7+ naive and central memory T cells, as well as in mast cells, macrophages, dedifferentiated vascular smooth muscle cells, fibroblasts, vascular endothelium, and airway epithelium. Given this expression pattern, KCa3.1 is a potenti... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441213 Tue, 01 Nov 2011 04:00:00 +0100 5441213 http://www.medworm.com/index.php?rid=5441212&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20466 AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous presentation and clinical manifestations. These aspects represent a problem in the treatment of the disease. Nonspecific medications for SLE that include antimalarials, corticosteroids, and cytotoxic drugs improve the prognosis of SLE yet carry significant side effects. Therefore, new targeted therapies that block pathways involved in the pathogenesis of SLE have been developed as possible additions to the standard management of the disease. This work reviews the current therapies and novel approaches in the treatment of SLE. Drug Dev Res 72:561–572, 2011. ©2011 Wiley Periodicals, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441212 Tue, 01 Nov 2011 04:00:00 +0100 5441212 http://www.medworm.com/index.php?rid=5441211&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20465 AbstractThe cryopyrin‐associated periodic syndromes (CAPS) comprise three rare autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle–Wells syndrome, and neonatal‐onset multisystem inflammatory disorder. A mutation in the NLRP3 (CIAS1) gene, encoding cryopyrin, leads to inflammation and results in fever, chills, urticarial rash, arthralgias, conjunctivitis, and other difficult‐to‐control systemic features. Major advances in understanding interleukin‐1 (IL‐1) have led to better treatment options. This review focuses on a promising new medication, canakinumab, which is a recombinant, human anti‐human‐IL‐1β monoclonal antibody that has been effective in treating adult and pediatric CAPS. Drug Dev Res 72:553–560, 2011. © 2011 Wiley Periodicals, Inc.... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441211 Tue, 01 Nov 2011 04:00:00 +0100 5441211 http://www.medworm.com/index.php?rid=5441210&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20464 AbstractBiological drugs are gradually becoming the treatment of choice for chronic autoimmune diseases. However, their high costs are a key healthcare concern limiting their attractiveness for payers. This can, in part, be offset by implementing drug response biomarkers so that payers will only cover the drugs for patients who are most likely to benefit from them. Identifying such biomarkers in turn depends on the availability of well‐characterized clinical samples. Research collaboration between the pharmaceutical industry, clinicians, and academia is paramount for achieving this goal. Drug Dev Res 72:549–552, 2011. © 2011 Wiley Periodicals, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5441210 Tue, 01 Nov 2011 04:00:00 +0100 5441210 http://www.medworm.com/index.php?rid=5238015&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20459 AbstractSchistosoma mansoni infection is associated with a low prevalence of asthma and a less severe form of the disease. The mechanisms underlying this association may include the production of regulatory cells and cytokines. The aim of this study was to evaluate the immune response induced by the S. mansoni antigens, Sm22.6, PIII, and Sm29 and their ability to suppress allergen‐specific IL‐5 production by peripheral blood mononuclear cells (PBMC) from asthmatic individuals. PBMCs were stimulated in vitro with S. mansoni antigens in the presence or absence of antigen‐1 of the mite Dermatophagoides pteronyssinus (Der p1). Cytokines were measured in PBMC supernatants by enzyme‐linked immunosorbent assay (ELISA), and the phenotype of cells producing IL‐10 was assessed using flow c... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238015 Thu, 01 Sep 2011 04:00:00 +0100 5238015 http://www.medworm.com/index.php?rid=5238014&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20458 AbstractParacoccidioidomycosis (PCM) is the most important mycosis in Latin America. The etiological agent is the fungus, Paracoccidioides brasiliensis. Approximately 1 million people are infected with the fungus, 10% of whom will show symptoms of the disease. However, clinical and laboratorial studies addressing the diagnosis for this disease are both scarce and diverse in terms of definition. Nevertheless, two main advances were included in the portfolio of available diagnostic methods for paracoccidioidomycosis during the last decades: the detection of antibodies against P. brasiliensis antigens by serological methods, and the detection of the fungi DNA in peripheral blood and fragments of lesions using the polymerase chain reaction (PCR) assay and species‐specific primers. Normally, ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238014 Thu, 01 Sep 2011 04:00:00 +0100 5238014 http://www.medworm.com/index.php?rid=5238013&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20457 AbstractLeprosy is a chronic infection caused by Mycobacterium leprae. It affects the skin and peripheral nerves and can cause irreversible chronic disabilities. The worldwide registered number of cases in 2009 was 213,036. This review discusses clinical aspects of the disease, including leprosy reactions and neuronal damage, as well as immunological and immunogenetic aspects influencing disease susceptibility and outcome. The cardinal signs of leprosy are skin lesions with altered sensation, thickened peripheral nerves, and presence of alcohol acid‐resistant bacilli in skin biopsy or lymph. Confirmatory examinations include (1) bacteriological examination, which allows patients' classification into two operational groups, multibacillary (MB) and paucibacillary (PB); and (2) histopatholo... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238013 Thu, 01 Sep 2011 04:00:00 +0100 5238013 http://www.medworm.com/index.php?rid=5238012&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20456 AbstractTuberculosis (TB) remains an important health problem worldwide. The structure necessary for delivering TB treatment and implementing the directly observed treatment accounts for more than two‐thirds of its final cost. Furthermore, although with efficacy greater than 90%, the effectiveness of present treatment regimens ranges within 55–85%, depending on the setting, mainly because of poor adherence. Duration of treatment with the current first‐line anti‐TB drugs is a minimum of 6 months. Reducing the duration of treatment from 6 to 2 months or less could result in significant increase of adherence to treatment and cost reduction. The aim of this review is to highlight potential new agents or new drug combinations that could reduce the time of treatment of drug‐susceptible... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238012 Thu, 01 Sep 2011 04:00:00 +0100 5238012 http://www.medworm.com/index.php?rid=5238011&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20455 AbstractInfection by one of the four serotypes of the arthropod‐borne dengue virus produces a spectrum of disease manifestations, ranging from asymptomatic to life‐threatening Dengue hemorrhagic fever/Dengue shock syndrome (DHF/DSS). During the last several decades, dengue has spread its geographic distribution to become the most common arboviral infection of humans in the subtropical and tropical regions of the world. There is no specific treatment or vaccine approved for human use. This fact, associated with the large number of infected individuals and the lack of markers that indicate which patients will develop severe disease, place an enormous burden on health systems of affected countries. Many efforts have been made to elucidate several aspects of dengue disease, but the pathoge... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238011 Thu, 01 Sep 2011 04:00:00 +0100 5238011 http://www.medworm.com/index.php?rid=5238010&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20454 AbstractThe interaction between the protozoan parasite Trypanosoma cruzi and the human host dates back 9,000 years, as demonstrated by molecular analysis of material obtained from Andean mummies indicating the presence of the parasite's kinetoplast DNA in populations from Chile and Peru. This long‐established interaction, which persists today, demonstrates that T. cruzi has established a very well adapted relationship with the human host. From the point of view of a host–parasite relationship, this is desirable; however, such a high degree of adaptation is perhaps the foundation for many of the unknowns that surround this disease. Unveiling of the immunological mechanisms that underlie the establishment of pathology, identification of parasite‐associated factors that determine strain... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238010 Thu, 01 Sep 2011 04:00:00 +0100 5238010 http://www.medworm.com/index.php?rid=5238009&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20453 AbstractThe goal of this article is to provide an overview of market needs and opportunities regarding the development of new drugs against leishmaniasis, an emergent infection that is spreading throughout the world. We provide an analysis of the current pipeline and discuss how the new scenario in drug discovery and development for neglected diseases may favor the entry of smaller players in the market of new therapeutics. Drug Dev Res 72:463–470, 2011. © 2011 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238009 Thu, 01 Sep 2011 04:00:00 +0100 5238009 http://www.medworm.com/index.php?rid=5238008&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20452 AbstractVisceral leishmaniasis (VL) represents a major public health problem in many areas of the world. This review focuses on the impact of periurbanization on the epidemiology and treatment of VL, using Brazil as an example. VL continues to be primarily a disease of poverty with impact on families. However, the disease has expanded in Latin America, with foci reported as far south as Argentina. There is an increasing overlap of Leishmania infantum chagasi and human immune deficiency virus (HIV) infections and other immunosuppressive conditions, resulting in the emergence of VL as an opportunistic infection. This new setting poses new challenges for VL disease control and patient management. Drug Dev Res 72:451–462, 2011. © 2011 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238008 Thu, 01 Sep 2011 04:00:00 +0100 5238008 http://www.medworm.com/index.php?rid=5238007&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20451 AbstractThe major constraint in conducting visceral leishmaniasis (VL) population studies is the difficulty of diagnosing asymptomatic infection. The aims of the present study, conducted in an urban area in the southeast of Brazil, were to appraise the performance of serological techniques in identifying VL asymptomatic cases and to follow up a cohort of Leishmania infantum‐exposed individuals living in an active transmission area, in an effort to understand infection dynamics and disease natural history. After an initial population‐based survey, three evaluations were carried out, covering a 7‐year follow‐up period. In addition to diagnostic tests, with polymerase chain reaction (PCR)‐hybridization as the reference test, the study population was interviewed and clinically examin... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238007 Thu, 01 Sep 2011 04:00:00 +0100 5238007 http://www.medworm.com/index.php?rid=5238006&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20450 AbstractDisseminated leishmaniasis (DL) is a distinct, severe, and emerging form of American tegumentary leishmaniasis. DL has been characterized by more than 10 multiple and pleomorphic cutaneous lesions, distributed in more than two noncontiguous parts of the body. Mucosal involvement is detected in up to 44% of cases. The development of the DL involves a complex and poorly understood network involving parasite, host immune response, and the environment, where L. braziliensis polymorphism plays a major role. A decrease in the type 1 immune response in the peripheral blood of DL patients appears to be caused by the attraction of Leishmania‐activated T cells to the multiple cutaneous lesions. DL is a difficult to cure disease and failure to pentavalent antimony therapy is observed in at ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238006 Thu, 01 Sep 2011 04:00:00 +0100 5238006 http://www.medworm.com/index.php?rid=5238005&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20449 AbstractIndividuals infected with Leishmania braziliensis may develop the relatively benign localized cutaneous (CL) form or the mucosal (ML) form of the disease, which represents a more severe and mutilating variation. Interaction between parasite and host cells, as well as the genetic background of the host, are important determinants of the immune response, which is critical in determining disease outcome. Our studies over the years have been designed to determine the immunoregulatory and effector functions that culminate in the formation of lesions in CL and ML disease and how these host response factors may be better understood for design of novel therapies and prophylaxis. By studying the immune response from CL and ML patients in both the peripheral blood and in situ, we have learne... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238005 Thu, 01 Sep 2011 04:00:00 +0100 5238005 http://www.medworm.com/index.php?rid=5238004&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20448 (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5238004 Thu, 01 Sep 2011 04:00:00 +0100 5238004 http://www.medworm.com/index.php?rid=5162022&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20439 AbstractAn aim of the present study was to improve the dissolution of the inherently low water solubility hypolipidemic agent, Atorvastatin calcium (ATC), through the preparation and characterization of ATC with cyclodextrins (CDs) inclusion complexes employing different techniques. A second goal was to study the in vivo hypolipidemic efficacy of ATC‐complexes with enhanced dissolution characteristics. Inclusion complexation of ATC with β‐cyclodextrin (β‐CD) and hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) was evaluated in aqueous and solid states. ATC formed inclusion complexes with β‐CD and HP‐β‐CD depending to a great extent upon ATC ionization state. Evaporation and freeze‐drying were the most efficient techniques to achieve complexation. In contrast, kneading was... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5162022 Sun, 31 Jul 2011 23:00:00 +0100 5162022 http://www.medworm.com/index.php?rid=5070381&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20461 This study was designed to evaluate the antinociceptive interaction of the tramadol–meloxicam combination in different proportions (tramadol + meloxicam in 1:1, 1:3, and 3:1 ratios), as well as the role of nitric oxide, opioidergic, and serotonergic pathways in the antinociceptive effect of the combination. The effects of individual drugs and fixed‐ratio combinations were assayed using the 3% formalin test in mice. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Tramadol (3.16–10 mg/kg, i.m.), meloxicam (3.16–17.8 mg/kg, i.m.), and tramadol–meloxicam combinations produced a dose‐dependent antinociceptive effect. ED30 values were estimated for the individual drugs, and isobolograms were constructed. The tramadol + meloxicam 1:... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5070381 Tue, 26 Jul 2011 23:00:00 +0100 5070381 http://www.medworm.com/index.php?rid=5070380&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20447 AbstractWe investigated the effect of hetastarch, used for the treatment of acute ischemic stroke, on neuronal cell damage by oxidative stress, a main pathogenic mechanism in ischemic stroke. Neuronally differentiated PC12 cells (nPC12 cells) were treated with varying concentrations of hetastarch and hydrogen peroxide (H2O2), and their viability was measured with a 3,(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and trypan blue staining. The effect of hetastarch on free radical production by H2O2 was evaluated using the fluorescent probe 2′,′‐dichlorodihydrofluorescein diacetate (DCFH‐DA) and by quantifying the amount of 2,5‐ and 2,3‐dihydroxybenzoic acid (DHBA). Additionally, the expression levels of BAX, Bid, Bcl‐2, Bcl‐xL, cytosolic cyt... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5070380 Tue, 26 Jul 2011 23:00:00 +0100 5070380 http://www.medworm.com/index.php?rid=5132309&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20462 AbstractIn the event of another bioterrorism attack with a bacterial agent, antibiotics will be critical medical countermeasures to have in the US Strategic National Stockpile. Conventional antibiotics such as ciprofloxacin, doxycycline, and streptomycin are generally considered a first line of defense against organisms such as Bacillus anthracis and Yersinia pestis. However, antibiotic resistance is a growing public health threat, especially among potentially life‐threatening pathogens; it is possible that threat agent bacteria could naturally evolve, or be engineered to express, antibiotic resistance against commonly used antibiotics. At the same time that the need for novel or improved antibiotics is becoming urgent, the antibiotic development pipeline has slowed, with only two comple... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5132309 Tue, 31 May 2011 23:00:00 +0100 5132309 http://www.medworm.com/index.php?rid=5079689&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20446 This article challenges the sequential tradition, and instead proposes a parallel drug development paradigm, in which several candidate compounds are nominated at the same time, and are simultaneously evaluated through the development process. Evaluating several compounds as candidate drugs (CDs) simultaneously, and in particular in the same studies, will potentially bring huge productivity benefits. The average time to a successful launch, or time to the closure of research on a futile target (family of CDs), may be substantially reduced. Other benefits imply substantially reduced costs as a result of fewer studies, fewer patients receiving placebo, and fewer animals receiving vehicle. A further benefit of the parallel drug development approach is the potential for head‐to‐head compar... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5079689 Tue, 31 May 2011 23:00:00 +0100 5079689 http://www.medworm.com/index.php?rid=5070379&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20460 AbstractMany countries employ a range of policies to support their drug development industry. The support is primarily because of the perceived potential benefits from wealth creation, employment, and international trade related to a high‐technology industry. New Zealand (NZ) has a growing drug development industry; this article reports on the results of interviews with people representing the industry. The NZ industry reported that government policies that included funding of scientific, medical, and drug development research, a robust regulatory system, and strong patent laws have created a cluster of expertise for specialized drug development services. This is similar to those that have been reported to encourage the biotechnology industries of many countries. Threats to the industry ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=5070379 Tue, 31 May 2011 23:00:00 +0100 5070379 http://www.medworm.com/index.php?rid=4937263&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20443 AbstractNon‐thiazide loop diuretics such as bumetanide and furosemide are well‐established medicaments, with varying substituents that alter their chemical properties in ways that affect biological parameters, including biodistribution, efficacy, and safety. However, literature data supporting the assignment of pKa values and ionization sequence of bumetanide are limited. The present study summarizes available literature data and then characterizes nuclear magnetic resonance (NMR) and ultraviolet (UV) spectral changes over a range of pH values to delineate the apparent sequence of deprotonations. Three macroscopic pKa values, 1.44, 3.74, and 10.37, were determined in water via pH titration experiments monitored by 1H NMR. Both 1H and 13C analyses support assignment of the lowest pKa va... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4937263 Sat, 30 Apr 2011 23:00:00 +0100 4937263 http://www.medworm.com/index.php?rid=4885934&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20445 In conclusion, CHD‐FA is a safe compound with anti‐inflammatory and wound‐healing properties and merits further evaluation in the treatment of patients suffering from similar conditions. Drug Dev Res 2011.  © 2011 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4885934 Sat, 30 Apr 2011 23:00:00 +0100 4885934 http://www.medworm.com/index.php?rid=4748747&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20444 AbstractIt is widely recognized that glutamate (Glu)‐induced cytotoxicity, intracellular calcium overload and the excessive free radical production are key events in the development and progression of ischemic brain injury. dl‐3‐n‐butylphthalide (NBP), an anti‐ischemic agent, has therapeutic effects in animal models of vascular dementia. The aim of the present study was to investigate the protective effect of 3‐butyl‐6‐fluoro‐1(3H)‐isobenzofuranone (6‐F‐NBP), a derivative of NBP on Glu‐induced cytotoxicity in rat pheochromocytoma (PC12) cells, and to compare this action with NBP. The results showed that after 24‐h incubation with Glu (5 mM), cell viability and mitochondrial membrane potential (MMP) were decreased. In contrast, the content of reactive oxygen sp... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4748747 Tue, 01 Mar 2011 00:00:00 +0100 4748747 http://www.medworm.com/index.php?rid=4715723&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20442 AbstractNovel NO‐donor‐ferulic acid hybrids were designed and synthesized through a symbiotic approach using ferulic acid and three different NO‐donating groups, such as nitric ester, 4‐hydroxyl‐3‐phenylfuroxan, and 4‐hydroxymethyl‐3‐phenylsulfonylfuroxan. Antioxidant, nitric oxide release, and vasodilator properties studies showed that the target phenylsulfonylfuroxan 14, especially 14c, while keeping the antioxidant activity, showed more NO release activity and vasodilating activity than isosorbide dinitrate (ISDN). Thus, 14c may be considered a novel potent anti‐atherosclerosis drug candidate. Drug Dev Res 72, 2011. © 2011 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4715723 Tue, 01 Mar 2011 00:00:00 +0100 4715723 http://www.medworm.com/index.php?rid=4686598&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20441 This study was designed to evaluate the possible synergistic antinociceptive interactions between diclofenac, benfotiamine, and resveratrol on acetic acid‐induced nociception in mice. Isobolographic analyses were used to define the nature of the interactions between drugs. Diclofenac, benfotiamine, or resveratrol, as well as their combinations, produced a dose‐dependent antinociceptive effect. ED30 values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED30 values for the combinations estimated from the isobolograms were 170.9±23.4, 4.9±1.0, and 173.3±11.8 mg/kg for the diclofenac+benfotiamine, diclofenac+resveratrol, or benfotiamine+resveratrol combination, respectively. These values were significantly higher than the actually observed ED30 ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4686598 Tue, 01 Mar 2011 00:00:00 +0100 4686598 http://www.medworm.com/index.php?rid=4437123&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20439 AbstractAn aim of the present study was to improve the dissolution of the inherently low water solubility hypolipidimic agent, Atorvastatin calcium (ATC), through the preparation and characterization of ATC with cyclodextrins (CDs) inclusion complexes employing different techniques. A second goal was to study the in vivo hypolipidimic efficacy of ATC‐complexes with enhanced dissolution characteristics. Inclusion complexation of ATC with β‐cyclodextrin (β‐CD) and hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) was evaluated in aqueous and solid states. ATC formed inclusion complexes with β‐CD and HP‐β‐CD depending to a great extent upon ATC ionization state. Evaporation and freeze‐drying were the most efficient techniques to achieve complexation. In contrast, kneading was... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4437123 Fri, 04 Feb 2011 00:00:00 +0100 4437123 http://www.medworm.com/index.php?rid=4644771&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20440 AbstractDiclofenac and tramadol are drugs widely used for the treatment of pain. However, side effects may limit their use. As both drugs produce side effects that are dose‐dependent, it seems appropriate to combine them in order to reduce the requirements for efficacy and, consequently, side effects. The purpose of this study was to evaluate the possible synergistic effect of these drugs in three experimental models of nociception in the rat. Dose‐response curves for diclofenac and tramadol were constructed in three models, thermal hyperalgesia, formalin, and hot plate. From these curves, ED40 or ED30 (according to the model employed) values were obtained and isobolographic analyses were carried out based on 0.5:0.5 proportions. Synergistic interactions were observed in the thermal hy... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4644771 Tue, 01 Feb 2011 00:00:00 +0100 4644771 http://www.medworm.com/index.php?rid=4567147&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20434 AbstractThe present study evaluated the effects of thimerosal, a vaccine preservative, on cytosolic free Ca2+ concentrations ([Ca2+]i) in human prostate cancer cells (PC3). Thimerosal (10–200 µM) increased [Ca2+]i in a concentration‐dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Thimerosal‐induced Ca2+ influx was inhibited by econazole, SKF963656, the phospholipase A2 inhibitor aristolochic acid, and protein kinase C modulators [phorbol 12‐myristate 13‐acetate (PMA) and GF109203X]. In Ca2+‐free medium, a 200‐µM thimerosal‐induced [Ca2+]i rise was partly inhibited after pretreatment with 2,5‐di‐tert‐butylhydroquinone (BHQ) (an endoplasmic reticulum Ca2+ pump inhibitor). Thimerosal at 1–7 µM induced cell death in a concentr... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4567147 Tue, 01 Feb 2011 00:00:00 +0100 4567147 http://www.medworm.com/index.php?rid=4299129&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20432 AbstractCentella asiatica herb is a frequently prescribed drug in southeastern Asia and China that can simultaneously facilitate wound healing and prevent scar formation. The active constituents and underlying mechanisms responsible for these biphasic actions remain unknown. Previous studies in our laboratory demonstrated that madecassoside, the main active triterpene saponin in C. asiatica herbs, was able to treat trauma‐caused scars in rabbit ear and facilitate burn wound healing in mice. As the formation and progression of keloid scars is closely related to the excessive proliferation and insufficient apoptosis of dermal fibroblasts, the effects of madecassoside on the proliferation and apoptosis of keloid fibroblasts (KFs) were examined in the present study. Primary KFs, originating ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4299129 Thu, 30 Dec 2010 00:00:00 +0100 4299129 http://www.medworm.com/index.php?rid=4299128&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20436 AbstractA Unani herbal formulation known as Majoon‐e‐Dabeed‐ul‐ward (MD) was evaluated for hepatoprotective effect against acetaminophen (APAP; 2 g/kg p.o.)‐induced liver damage. The latter was evidenced by elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), serum alkaline transaminase (SALP), lactate dehydrogenase (LDH), bilirubin, albumin, urea, and creatinine in experimental animals. Increased levels of lipid peroxidation were associated with a concomitant decline in reduced glutathione levels, adenosine triphosphatase (ATPase), and glucose‐6‐phosphatase (G‐6‐Pase) caused by APAP treatment. Treatment with MD (250,500, and 1,000 mg/kg p.o.) reverse the altered levels of AST, ALT, SALP, LDH, bilirubin, albumin, urea, and creatinine in a dose�... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4299128 Thu, 30 Dec 2010 00:00:00 +0100 4299128 http://www.medworm.com/index.php?rid=4267650&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20396 AbstractRecent advances in computational power permit accurate in silico predictions of the interactions between small molecules and protein targets. Countless studies have been published about such interactions and about computational tools for predicting drug—target interactions. What is still missing, and would greatly facilitate drug design and development, is a comprehensive and open database allowing the extraction of information on the predicted interactions (interactome) between small molecules and the human proteome. Ideally, such a catalog should include the entire repertoires of published small natural and synthetic compounds and each member of the human proteome. This would be a huge undertaking requiring massive public support. The PubChem database at the National Center for... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267650 Thu, 16 Dec 2010 00:00:00 +0100 4267650 http://www.medworm.com/index.php?rid=4267649&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20398 AbstractPharmacophores are fundamental tools in the process of rational drug discovery. Pharmacophores are associated with binding sites of proteins and characterize the arrangement of chemical and physical features that govern the modes of interactions of different ligands within the binding sites. Methods designed to infer pharmacophores computationally have been successfully applied in drug discovery pipelines. Virtual high‐throughput screening (HTS), lead optimization, and de novo drug design are just a few areas in which pharmacophores are actively used. This review surveys different computational methods to elucidate pharmacophores and discuss their utilization in drug discovery applications. Drug Dev Res, 2010. © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267649 Thu, 16 Dec 2010 00:00:00 +0100 4267649 http://www.medworm.com/index.php?rid=4267648&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20403 This report will present top‐down Mechanistic Disease Modeling approaches in relation to bottom‐up Systems Biology with specific emphasis on CNS drug R&D. Both combine basic research data with human clinical outcome, but in contrast to System Biology that generically models intracellular pathways and protein‐protein networks, Mechanistic Disease Modeling models the emergent properties of neuronal cell firing activity in large interacting neuronal networks. Such an outcome is much closer to physiological and behavioral processes that drive actual clinical scales. Also illustrated here are some practical applications in the area of Alzheimer's disease and schizophrenia for CNS Research and Development, such as guiding multitarget drug discovery, evaluating both the harmful and bene... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267648 Thu, 16 Dec 2010 00:00:00 +0100 4267648 http://www.medworm.com/index.php?rid=4267647&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20399 AbstractProteins have inherent flexibility, and this plays a critical role in a vast array of biological functions, including ligand binding. Structure‐based drug design (SBDD) strategies incorporate biomolecular structures with computational methods to predict and optimize ligand–receptor complexes. However, these strategies largely involve using static protein snapshots derived by classical X‐ray crystallography, and thus critical and valuable information on flexibility is completely absent. With a historical perspective, we highlight relevant fundamental aspects of the character and importance of the tapestry of flexibility in molecular recognition events, especially when a ligand binds to a protein. Knowledge of methods that can provide details of the full spectrum of flexibility... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267647 Thu, 16 Dec 2010 00:00:00 +0100 4267647 http://www.medworm.com/index.php?rid=4267646&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20405 AbstractWith computational tools, it has become straightforward to obtain three‐dimensional (3D) conformers for drug‐like molecules, even for large numbers of compounds. This underpins many downstream molecular modeling activities. We summarize the principles behind the methods, explain why considering multiple conformers per compound is necessary, and discuss the tests used to assess the computed conformers. It leads us to suggest that conformational sampling per se is essentially a solved problem for small drug‐like compounds, and that efforts should focus on improving the energy models. Drug Dev Res 2010. © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267646 Thu, 16 Dec 2010 00:00:00 +0100 4267646 http://www.medworm.com/index.php?rid=4267645&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20404 AbstractCombinatorial synthesis and high‐throughput screening (HTS) are playing increasingly important roles in chemoinformatics. This review gives an overview of the strategies available for library design and compound selection. Although the traditional approach of diversity‐oriented library design continues to be an important criterion in lead generation, nevertheless, pharmacokinetic properties are also widely recognized in compound selection for generating lead libraries. We summarize all the current molecular similarity and diversity methods employed in chemoinformatics to design lead libraries for in silico drug discovery. We have also included a section on popular molecular descriptors and similarity/diversity coefficients. Recent developments, include multi‐optimization desi... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267645 Thu, 16 Dec 2010 00:00:00 +0100 4267645 http://www.medworm.com/index.php?rid=4267644&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20400 AbstractThe ability to predict, through computer simulation, the free energy of binding between drug‐like ligands and their biological target(s) is one of the most difficult yet rewarding tasks in computer‐aided drug design (CADD) efforts. Successful and consistent predictions are likely to have a profound effect on the efficiency of hit discovery and lead optimization campaigns. However, the route to achieving this goal is paved with challenges resulting from the complexity of the binding process and from the ability to simulate it, given contemporary computational tools. In this review we present the challenges faced by binding free energy simulations within the context of lead optimization, survey the main tools currently in use for performing such calculations, and discuss their ap... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267644 Thu, 16 Dec 2010 00:00:00 +0100 4267644 http://www.medworm.com/index.php?rid=4267643&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20402 This report reviews some of the more popular applications. Drug Dev Res 72, 2010.© 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267643 Thu, 16 Dec 2010 00:00:00 +0100 4267643 http://www.medworm.com/index.php?rid=4267642&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20401 AbstractMultiscale modeling is being recognized increasingly as a promising research area in computational cancer systems biology. In the present review, exemplified by two pioneering studies, we attempt to explain why and how such a multiscale approach paired with an innovative cross‐scale analytical technique can be useful in identifying high‐value molecular therapeutic targets. This novel, integrated approach has the potential to offer a more effective in silico framework for target discovery and represents an important technical step toward systems medicine. Drug Dev Res 2010. © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267642 Thu, 16 Dec 2010 00:00:00 +0100 4267642 http://www.medworm.com/index.php?rid=4267641&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20397 AbstractPharmaceutical researchers must evaluate vast numbers of protein sequences and formulate innovative strategies to identify valid targets and discover leads against them in order to accelerate drug discovery. The ever‐increasing number and diversity of novel protein sequences identified by genomic sequencing projects and the success of worldwide structural genomics initiatives have spurred great interest and impetus in the development of methods for accurate, computationally empowered protein function prediction and active site identification. Previously, in the absence of direct experimental evidence, homology‐based protein function annotation remained the gold standard for in silico analysis and prediction of protein function. However, with the continued exponential expansion ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267641 Thu, 16 Dec 2010 00:00:00 +0100 4267641 http://www.medworm.com/index.php?rid=4267640&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20410 AbstractIn this article, we review the recent development for in silico Structure‐Activity‐Relationship (SAR) models using machine‐learning techniques. The review focuses on the following topics: machine‐learning algorithms for computational SAR models, single‐target‐oriented SAR methodologies, Chemogenomics, and future trends. We try to provide the state‐of‐the‐art SAR methods as well as the most up‐to‐date advancement, in order for the researchers to have a general overview at this area. Drug Dev Res, 2010. © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267640 Thu, 16 Dec 2010 00:00:00 +0100 4267640 http://www.medworm.com/index.php?rid=4267639&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20411 AbstractThe set of genes common to a group of organisms is known as the “core” set and the set of genes common to one or more of a group of organisms, but not to all of them is known as the “dispensable” set. Collectively, these two sets comprise the “pan‐genome” of a set of organisms. While there are many software tools available for ortholog detection and clustering, there are far fewer tools to determine the core set of genes as well as the dispensable set. Continued development of these computational and data mining tools is essential to further our understanding of the pan‐genomes of organisms and to make use of them. Drug Dev Res © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267639 Thu, 16 Dec 2010 00:00:00 +0100 4267639 http://www.medworm.com/index.php?rid=4267638&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20414 AbstractComputational approaches are becoming increasingly popular for the discovery of drug candidates against a target of interest. Proteins have historically been the primary targets of many virtual screening efforts. Although in silico screens targeting proteins have proved successful, other classes of targets, in particular DNA, remain largely unexplored using virtual screening methods. With the realization of the functional importance of many noncanonical DNA structures such as G‐quadruplexes, increased efforts are under way to discover new small molecules that can bind selectively to DNA structures. In the present work, we describe efforts to build an integrated in silico and in vitro platform for discovering compounds that may bind to a chosen DNA target. Millions of compounds ar... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267638 Thu, 16 Dec 2010 00:00:00 +0100 4267638 http://www.medworm.com/index.php?rid=4267637&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20412 We present a vision of how the biological wet‐lab side of the R&D process might function when these models and methods are fully implemented within a common computational framework. Accumulated mechanistic knowledge is easily measured and visualized in action; thus, it can be easily challenged. Components within analogues that have been validated for many compounds can use programmed “intelligence” to automatically parameterize for, and respond to, a new, not previously seen compound based on its physicochemical properties. Each analogue can be tuned to reflect differences in experimental conditions and individuals, making translational research more concrete, while moving closer to personalized medicine. Drug Dev Res 72, 2011. © 2010 Wiley‐Liss, Inc. (Source: Drug Development... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267637 Thu, 16 Dec 2010 00:00:00 +0100 4267637 http://www.medworm.com/index.php?rid=4267636&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20417 AbstractComputer‐assisted simulations are important for present‐day chemical investigations, producing large amount of structural data. In molecular design, we calculate molecular descriptors for factual or virtual structures in chemical space attempting to predict their chemical properties and evaluate potential biological effects. In the current study, we investigated the application of the MoStBiodat software platform for the extensive screening of spatial arrangement and conformational analysis locating intramolecular hydrogen‐bonded motifs in catechols. We compared the experimentally determined structural data to those that are simulated using virtual structural data. The relevant topological incoherence among structural and molecular data coming from different sources is thus r... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267636 Thu, 16 Dec 2010 00:00:00 +0100 4267636 http://www.medworm.com/index.php?rid=4267635&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20408 AbstractMycobacterium tuberculosis is the deadly pathogen responsible for causing tuberculosis in humans, continuing to infect and kill millions of people globally. Despite the availability of a number of anti‐tuberculosis drugs and advances in high‐throughput drug discovery technology there is an urgent need for designing novel anti‐tubercular treatments due to growing parasite resistance and compromised immune systems in some patients. Therefore, it is highly necessary to develop systematic approaches that can facilitate the drug discovery by identification of drug targets in effective and efficient ways. In this sense, with the availability of whole genome sequence, application of genome‐scale modeling is becoming increasingly important for deriving rational drug target identifi... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267635 Thu, 16 Dec 2010 00:00:00 +0100 4267635 http://www.medworm.com/index.php?rid=4267634&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20406 This article reviews the use of different in silico structure‐based and ligand‐based virtual screening (VS) tools for the discovery of potential HIV entry inhibitors for the CXCR4 receptor. More specifically, it discusses homology modelling, de novo design, docking, QSAR analyses, pharmacophore modelling, and similarity searches. Results from retrospective VS of a library of known CXCR4 inhibitors taken from the literature and from prospective VS of a combinatorial virtual library are reviewed. The structures of active compounds found by these approaches, as well as CXCR4 inhibitors currently in development, are also discussed. Drug Dev Res, 2010. © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267634 Thu, 16 Dec 2010 00:00:00 +0100 4267634 http://www.medworm.com/index.php?rid=4267633&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20409 AbstractFragment‐based drug design (FBDD) has become an important and successful approach to drug discovery. In this review, we discuss two classes of simulation technologies that we routinely employ as part our of computational FBDD efforts. The first class centers on simulation methods in torsion space to develop high‐quality protein models suitable for FBDD. These algorithms allow for fast molecular dynamics and modal Monte Carlo simulations. The torsion space dynamics techniques have been applied to develop models for the bound conformations of a variety of proteins including the HIV‐1 protease, p38 MAP kinase, and the 5′‐AMP‐activated protein kinase. The second class of simulations is comprised of the Grand Canonical Monte Carlo and systematic sampling methods, which are u... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267633 Thu, 16 Dec 2010 00:00:00 +0100 4267633 http://www.medworm.com/index.php?rid=4267632&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20415 This article presents a translational systems biology approach to inflammation. This approach is based on the use of mechanistic computational modeling centered on inherent clinical applicability, namely that a unified suite of models can be applied to generate in silico clinical trials, individualized computational models as tools for personalized medicine, and rational drug and device design based on disease mechanism. Drug Dev Res 72, 2010.   © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267632 Thu, 16 Dec 2010 00:00:00 +0100 4267632 http://www.medworm.com/index.php?rid=4267631&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20413 AbstractTarget identification is the first step in the drug and vaccine discovery process; in silico subtractive genomics is widely used in this process. Using this approach, in recent years, a large number of targets have been identified for bacterial pathogens that are either drug resistant or for which no suitable vaccine is available; most such reports concern a specific pathogen. The in silico method reduces the time as well as the cost of target screening. Although a powerful technique that can be applied to a wide range of pathogens, there are many pitfalls in the analysis and interpretation of the data. We review this approach, including targets that have been identified with this technique and various other aspects, including advantages and disadvantages. We also discuss our own e... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267631 Thu, 16 Dec 2010 00:00:00 +0100 4267631 http://www.medworm.com/index.php?rid=4267630&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20407 AbstractIn‐silico tools and computational techniques have become an integral part of pharmaceutical research. These techniques are now used extensively at various phases during the drug development process. Such tools perform a wide range of functions from retrieving and analyzing data to sophisticated computational models for many biological and chemical processes in drug discovery. Among them, machine‐learning techniques are becoming especially popular because of their emphasis on obtaining accurate predictions. In this overview, we discuss the increasing role of Machine Learning in Drug Discovery. Since this field has close connections with the field of Statistics, we will first describe similarities and differences between these fields. We will then highlight various domains and pr... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267630 Thu, 16 Dec 2010 00:00:00 +0100 4267630 http://www.medworm.com/index.php?rid=4267629&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20416 AbstractObesity is currently an epidemic that affects almost 15% of the global adult population. The complex metabolic processes involved in energy homeostasis, which are regulated by signals from multiple sources, present a challenging problem for drug discovery. In the current analysis, we present bibliometric and data‐mining approaches based on categorizing literature according to medical subject headings (MeSH) to examine “hot” and “cold” trends, which indicate emerging areas of scientific research within obesity. This trend analysis corrects for increase in the overall size of obesity publications. A “hot” trend within obesity research is a concept on which publications are growing statistically faster than the background rise in obesity publications. In addition to grow... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267629 Thu, 16 Dec 2010 00:00:00 +0100 4267629 http://www.medworm.com/index.php?rid=4267628&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20428 This article briefly reviews the theoretical basis, calculation, and applications of mathematical chemodescriptors as well as biodescriptors derived using the techniques of discrete mathematics, in particular chemical graph theory and information theory. The utility of easily calculable mathematical chemodescriptors for the in silico screening of chemical databases in drug discovery and predictive toxicology is discussed. The use of multiple mathematical approaches derived from graph theory in the characterization of chirality is reviewed along with applications of chirality indices to molecules with multiple chiral centers. The utility of diverse sets of mathematical molecular descriptors in differential QSAR of ligands tested using targets from wild‐type and resistant organisms is show... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267628 Thu, 16 Dec 2010 00:00:00 +0100 4267628 http://www.medworm.com/index.php?rid=4267651&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20431 This study demonstrated that nicotine dose‐ dependently facilitated BSR, whereas varenicline did not. Similarly to mecamylamine, varenicline reversed nicotine facilitation of BSR, suggesting that nAChRs mediate the effects of nicotine on BSR. Thus, specifically targeting α4β2 nAChRs inhibits the ability of nicotine to facilitate BSR. The efficacy of varenicline as a treatment for smoking cessation may be related to its unique ability to reduce the rewarding effects of nicotine while not producing rewarding effects alone, a critical consideration in effective drug replacement therapies. Drug Dev Res, 2011. © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267651 Wed, 15 Dec 2010 00:00:00 +0100 4267651 http://www.medworm.com/index.php?rid=4242631&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20429 AbstractIn some countries, economic evaluations now have a prominent role and provide information to use in resource allocation decisions for health care technologies and interventions. This editorial describes the importance of understanding the degree and extent of uncertainty in a published economic evaluation. Some countries have diverted considerable resources toward health technology assessments (HTAs) and appraisals of health care interventions using deliberative decision‐making processes. However, given the scarcity of health care resources on a global scale, there is a growing need to support other countries that do not have the skill base or considerable resources needed to conduct their own HTAs and appraisal of the evidence. As a minimum, it is vital that individual countries... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242631 Wed, 08 Dec 2010 00:00:00 +0100 4242631 http://www.medworm.com/index.php?rid=4242630&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20423 AbstractNo country can afford all the health care interventions that might benefit patients. Demand will always outstrip available resources, so priorities have to be agreed upon. Such decisions are controversial, making it vital that they are underpinned by robust transparent processes and methods. In the United Kingdom, this is the responsibility of the National Institute for Health and Clinical Excellence (NICE). In 2009, in response to challenges that NICE was not giving sufficient value to innovation, an independent enquiry was undertaken by Sir Ian Kennedy. The enquiry raised important questions about whether NICE should only offer incentives for innovation when the benefits are actually seen by the National Health Service (NHS) as improved outcomes for patients, or whether future, b... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242630 Wed, 08 Dec 2010 00:00:00 +0100 4242630 http://www.medworm.com/index.php?rid=4242629&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20420 AbstractThe goal of health care policies is to maximize the health of the population within the limits of the available budget and taking into account equity considerations. For innovative drugs, this means that an increasing number are being assessed in terms of their value for money, which is the amount of additional health that can be achieved per additional euro, pound, dollar, or other currency invested. Ideally such assessments and resulting appraisals and decisions should be made in a transparent and efficient way. Transparent means consisting of clear procedures and criteria such as relative effectiveness, cost effectiveness, budget impact, social, and ethical consequences. Transparent also means that stakeholders (physicians, patients, industry, and others) are involved in the ass... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242629 Wed, 08 Dec 2010 00:00:00 +0100 4242629 http://www.medworm.com/index.php?rid=4242628&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20421 AbstractThe pharmaceutical industry has a well‐known and formally recognized process for drug development, consisting of four distinct phases of clinical assessment. Similar to this drug development process, there is a five‐stage iterative process for economic evaluation, beginning with early indicative studies and progressing toward more rigorous assessment as data become available. This overview outlines the four phases of drug development and the five‐stage iterative approach to economic evaluation. The commonalities of the two approaches are discussed, drawing parallels in support of the case for incorporating an iterative economic process into the drug development process. Both frameworks support a process of information gathering and reducing uncertainty in order to improve dec... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242628 Wed, 08 Dec 2010 00:00:00 +0100 4242628 http://www.medworm.com/index.php?rid=4242627&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20422 AbstractHealth Technology Assessment (HTA) has been formally used in the United Kingdom for more than 10 years to help determine evidence‐based decisions on the access to new drugs, based on evidence of clinical and cost‐effectiveness. Separate HTA systems have developed in England and Wales (NICE, AWMSG), and Scotland (SMC). The primary clinical evidence desired for technology appraisal by the HTA bodies is the comparative randomized controlled trial because of its good internal validity, but the role and value of observational study designs for providing data on real‐world effectiveness have been recognized in the methods guidance of these bodies. To date HTA has had a fairly limited impact on drug development and clinical trial design in the United Kingdom, coupled with limited us... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242627 Wed, 08 Dec 2010 00:00:00 +0100 4242627 http://www.medworm.com/index.php?rid=4242626&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20419 This article outlines the recent evidence from major empirical studies on the complex landscape of diagnostic DNA patents in the United States and Europe and discusses the traditional arguments in favor and against gene patenting in PGx and genetic testing. It also explores the extent to which concerns in clinical genetics might be relevant to PGx. We find that although recent evidence on genetic testing suggests that many of the issues might have been overestimated or overemphasized, no dedicated studies have been published on the intellectual property aspects of PGx. Drug Dev Res, 2010. © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242626 Wed, 08 Dec 2010 00:00:00 +0100 4242626 http://www.medworm.com/index.php?rid=4242625&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20424 AbstractPharmacogenetics and pharmacogenomics show great potential for developing individual treatment modalities to achieve optimal therapy effectiveness. Economic analyses are performed to determine whether pharmacogenetic screening strategies provide good value for money. The current review provides an update of published economic studies. Economic analyses of pharmacogenetic screening programs published between 2000 and July 2010 were included in the review. Information was extracted on research area, genetic information, type of economic analysis, key aspects of adherence to economic guidelines, costs and commercial availability of genetic tests, and the role of the funding party. A total of 42 economic studies on pharmacogenetic screening strategies were included. Over time, more cos... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242625 Wed, 08 Dec 2010 00:00:00 +0100 4242625 http://www.medworm.com/index.php?rid=4242624&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20427 AbstractPharmacogenetic tests are proposed as a means of targeting therapy to patients such that ineffective medicine prescription and adverse events are reduced and overall benefit in terms of improved health outcomes is maximized. However, the true impact of introducing pharmacogenetic tests into clinical practice remains to be confirmed. This commentary presents some of the key requirements in developing a pharmacogenetic clinical practice model in a hospital setting. The analysis considers the need to select carefully which pharmacogenetic tests are best offered, while balancing the cost to the institution given the potential benefits to the patient population base. Drawing on our experience in Taiwan, we recommend that developing a hospital task force for pharmacogenetic testing is a ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242624 Wed, 08 Dec 2010 00:00:00 +0100 4242624 http://www.medworm.com/index.php?rid=4437122&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20438 AbstractThe purpose of this study was to develop a cell‐based screening assay for identification of small molecules for the treatment of asthma. Eosinophils are leukocytes that contribute to the pathology of asthma. Lidocaine inhibits interleukin‐5 (IL‐5)‐mediated survival and activation of human eosinophils, and it is able to replace inhaled glucocorticoids for the treatment of asthma; however, lidocaine has many side effects, including anesthesia. Therefore, a collection of commercial and novel, synthesized lidocaine analogues were investigated for inhibitory activity of the IL‐5‐stimulated proliferation of TF‐1 cells, a CD34+, cytokine‐dependent, erythroleukemic cell line model for eosinophil growth. Among 74 investigated compounds, 10 were more potent inhibitors of cell... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4437122 Wed, 01 Dec 2010 00:00:00 +0100 4437122 http://www.medworm.com/index.php?rid=4362964&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20435 AbstractHydroxycamptothecin (HCPT)‐loaded PLA nanoparticles were prepared by a one‐step method using the direct dialysis technique, and were examined for particle characteristics, in vitro drug release, and cytotoxicity, as well as antitumor efficiency. Three main influential factors based on the results of a single‐factor test, i.e., PLA concentration, ratio of HCPT to PLA (wt/wt), and dialysis bags with different molecule weight cutoffs, were evaluated using an orthogonal design, giving nanoparticles an average diameter of ∼226.8 nm with smooth surface, modest drug entrapment efficiency (65.15%), and fine drug‐loading content (5.16%, w/w). HCPT was in a crystalline state within the particles. In vitro drug release studies exhibited a slow and prolonged release profile over a ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4362964 Wed, 01 Dec 2010 00:00:00 +0100 4362964 http://www.medworm.com/index.php?rid=4310458&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20427 AbstractPharmacogenetic tests are proposed as a means of targeting therapy to patients such that ineffective medicine prescription and adverse events are reduced and overall benefit in terms of improved health outcomes is maximized. However, the true impact of introducing pharmacogenetic tests into clinical practice remains to be confirmed. This commentary presents some of the key requirements in developing a pharmacogenetic clinical practice model in a hospital setting. The analysis considers the need to select carefully which pharmacogenetic tests are best offered, while balancing the cost to the institution given the potential benefits to the patient population base. Drawing on our experience in Taiwan, we recommend that developing a hospital task force for pharmacogenetic testing is a ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4310458 Wed, 01 Dec 2010 00:00:00 +0100 4310458 http://www.medworm.com/index.php?rid=4299127&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20437 AbstractCompetition for clinical trial projects outsourced by the global pharmaceutical industry is increasing with more countries bidding to provide these services. A comprehensive review of the clinical trial landscape in New Zealand was conducted by analysing clinical trial applications, and interviewing senior industry representatives on their expertise, capabilities, knowledge management, and innovative behaviours, as well as the policies and factors that had influenced the development of the industry. The number of clinical trial application approvals increased from 33 in 1989/1990 to 113 in 2008/2009 indicating continued confidence of the pharmaceutical industry in placing clinical research projects in New Zealand. Much of this growth has been due to an increasing number of phase I ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4299127 Mon, 01 Nov 2010 00:00:00 +0100 4299127 http://www.medworm.com/index.php?rid=4295996&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20433 AbstractThe current study explored whether capsazepine changed basal cytosolic free Ca2+ concentrations ([Ca2+]i) levels in suspended Madin Darby canine kidney (MDCK) cells cells by using fura‐2 as a Ca2+‐selective fluorescent dye. At concentrations of 10–200 µM, capsazepine increased [Ca2+]i in a concentration‐dependent manner. The Ca2+ signal was partially reduced by 40% by removing extracellular Ca2+. Capsazepine induced Mn2+ quench of fura‐2 fluorescence, indirectly implicating Ca2+ entry. Capsazepine‐induced Ca2+ influx was unchanged by L‐type Ca2+ entry inhibitors and protein kinase C modulators [phorbol 12‐myristate 13‐acetate (PMA) and GF109203X]. In Ca2+‐free medium, 100 µM capsazepine‐induced Ca2+ release was substantially suppressed by pretreatment wi... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4295996 Mon, 01 Nov 2010 00:00:00 +0100 4295996 http://www.medworm.com/index.php?rid=4282292&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20430 AbstractIn the effort to inhibit P‐glycoprotein (P‐gp) efflux function with greater activity and less side effect, the combined effect of pair CJZ3 and verapamil (Ver) was evaluated isobolographically in numerous fixed‐ratio combinations of 1:1, 1:2, 1:4, 1:8, 1:10 in doxorubicin‐resistant human myelogenous leukemia (K562/ DOX) cells and in rat brain microvessel endothelial cells (RBMEC). The results displayed that mixtures of both drugs at the fixed‐ratios of 1:2, 1:4, 1:8, 1:10 exerted synergistic interactions, indicating that when the two reversers that bind P‐gp on separated sites were combined, each can contribute to the overall interaction with P‐gp, leading to the greater effect than that given by either agent alone. Drug Dev Res 72, 2011.  © 2010 Wiley‐Liss, In... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4282292 Mon, 01 Nov 2010 00:00:00 +0100 4282292 http://www.medworm.com/index.php?rid=4267627&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20418 In this study, two different methods were first utilized to construct chemical and genomic spaces, respectively. Then two spaces were combined into a integrate space to discover the potential compound‐target pairs in the known drug‐target interaction data by an improved semi‐supervised learning method (FLapRLS). The results demonstrated that this prediction method is effective. Drug Dev Res, 2011.  © 2010 Wiley‐Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4267627 Mon, 01 Nov 2010 00:00:00 +0100 4267627 http://www.medworm.com/index.php?rid=4242623&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20425 AbstractThe information needs of drug payers at the provincial or national level are reasonably similar across the world. Until recently, the evidence generated to meet these needs has been largely intended to meet the information needs of regulatory agencies responsible for determining whether marketing approval should be authorized. This has meant that evidence for one purpose (determining whether a drug should be approved for marketing) usually has to be translated to meet another purpose (determining whether the drug should be paid for in a reimbursement or subsidy). As the context in each jurisdiction might be different, there is also a need to translate evidence developed for a global audience to address different local contexts. A common set of methods to translate evidence can help... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4242623 Mon, 01 Nov 2010 00:00:00 +0100 4242623 http://www.medworm.com/index.php?rid=4226481&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20426 AbstractWith the view of developing novel apoptosis‐inducing agents against malignant cells, nicotinamide derivatives containing substituted O‐benzoyl‐tyrosine, dopamine, and norepinephrine residues were synthesized. Antiproliferative activity measurements using leukemia U937 cells revealed that the benzoyl‐tyrosine derivative having two hydroxys at C‐2 and C‐3 on the benzoyl group, and the one having a hydroxy at C‐2 and a methoxy at C‐4 proved the most potent among the 9 nicotinamide derivatives. The IC50 values of these compounds were 0.87 and 3.15 µM, which indicates their noteworthy activity compared with epigallocatechin gallate, a catechin component in green tea known for its noticeable activity. The cell death process was confirmed to be the result of apoptosis b... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4226481 Mon, 01 Nov 2010 00:00:00 +0100 4226481 http://www.medworm.com/index.php?rid=4187416&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20385 AbstractThe wide interest in developing improved therapies for cancer has led to a dramatic increase in the number of highly potent active pharmaceutical ingredients (HAPIs) under development and in use today. The following is an overview of the “cradle‐to‐grave” health risk issues that must be addressed during drug development of a HAPI, as seen from a drug sponsor's perspective. Although much of the handling of the drug may be outsourced, this article points out the principal responsibilities of the drug sponsor and what they need to know about the responsibilities of the CMOs and CROs in handling HAPIs to ensure the most effective partnership. The major focus is on manufacturing activity, but upstream and downstream issues are also presented. Drug Dev Res 71:420–428, 2010. © ... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4187416 Mon, 01 Nov 2010 00:00:00 +0100 4187416 http://www.medworm.com/index.php?rid=4089834&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20392 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4089834 Tue, 31 Aug 2010 23:00:00 +0100 4089834 http://www.medworm.com/index.php?rid=4068641&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20395 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4068641 Tue, 31 Aug 2010 23:00:00 +0100 4068641 http://www.medworm.com/index.php?rid=4041669&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20393 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4041669 Tue, 31 Aug 2010 23:00:00 +0100 4041669 http://www.medworm.com/index.php?rid=4024069&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20383 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4024069 Tue, 31 Aug 2010 23:00:00 +0100 4024069 http://www.medworm.com/index.php?rid=4019484&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20390 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4019484 Tue, 31 Aug 2010 23:00:00 +0100 4019484 http://www.medworm.com/index.php?rid=3984483&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20384 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3984483 Tue, 31 Aug 2010 23:00:00 +0100 3984483 http://www.medworm.com/index.php?rid=3970428&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20386 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3970428 Sat, 31 Jul 2010 23:00:00 +0100 3970428 http://www.medworm.com/index.php?rid=3900800&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20382 (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3900800 Sat, 31 Jul 2010 23:00:00 +0100 3900800 http://www.medworm.com/index.php?rid=3892893&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20377 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3892893 Sat, 31 Jul 2010 23:00:00 +0100 3892893 http://www.medworm.com/index.php?rid=3796318&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20378 Clavulanic acid is a psychoactive compound with excellent blood-brain barrier permeability and safety profiles. Previous studies showed that clavulanic acid suppresses anxiety in rodents and in a primate model. In addition, clavulanic acid is thought to enhance sexual function in animal models via central nervous system (CNS) mechanisms. To further examine its potential as a CNS-modulating agent, we investigated the effects of clavulanic acid in neurotoxin-induced animal models that emulate neurodegenerative disease symptoms. Clavulanic acid was administered to rodents that were exposed to kainic acid or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Using histochemical staining of brain sections, we demonstrated that clavulanic acid protects hippocampal and dopaminergic neurons from... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3796318 Wed, 28 Jul 2010 23:00:00 +0100 3796318 http://www.medworm.com/index.php?rid=3738597&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20376 Four isatin-isoniazid derivatives with proven efficacy against resistant strains of Mycobacterium tuberculosis, that had greater lipophilicity than isoniazid were evaluated for effects on hepatic drug metabolizing and chemoprotective enzymes and compared to isoniazid. Following intragastric administration to mice (75 or 150 mg/kg×3 days), none of the four compounds exhibited hepatotoxicity, and only isoniazid was found to elevate CYP2E1 activity. All compounds slightly elevated Cyp1a1/2 mRNA levels, but these did not result in increased methoxyresorufin demethylase activity. With the exception of isoniazid, approximately twofold elevations in Ugt1a mRNAs (seen with isatin-isoniazid [Ugt1a1, Ugt1a6, Ugt1a9], 1-propynylisatin-isoniazid [Ugt1a1, Ugt1a9], and 1-propylisatin-isoniazid [Ugt1a1]... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3738597 Fri, 09 Jul 2010 23:00:00 +0100 3738597 http://www.medworm.com/index.php?rid=3711835&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20375 CPUY11018 has anti-atrial fibrillation (AF) effects in rats. The effects of CPUY11018 on the transient outward K+ current (Ito) and ultra-rapid delayed rectifier K+ current (IKur) were studied using whole-cell patch clamp techniques and an acetylcholine (ACh)-CaCl2 induced AF model. CPUY11018 inhibited Ito and IKur in a concentration-dependent manner with IC50 values of 18.5 and 1.7 µM, respectively. Inhibition was independent of the depolarizing voltage. In the AF ACh-CaCl2 model, AF duration was effectively shortened after treatment with 5 mg/kg CPUY11018 for 4 days. These results indicate that CPUY11018 is effective in treating AF partly by blocking Ito and IKur. Drug Dev Res 71, 2010. © 2010 Wiley-Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3711835 Wed, 30 Jun 2010 23:00:00 +0100 3711835 http://www.medworm.com/index.php?rid=3711837&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20373 In conclusion, the changes in the position of chloride at phenylpiperazine influenced the serotonergic receptor, adrenoceptor antagonistic activities, but not anti-aggregation and antioxidant activities. Drug Dev Res 71:1-9, 2010. © 2010 Wiley-Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3711837 Tue, 29 Jun 2010 23:00:00 +0100 3711837 http://www.medworm.com/index.php?rid=3711836&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20374 Lipophilic derivatives of the antitumor drug gemcitabine (GEM) with the potential for improving drug loading in lipid-based colloidal carriers, like liposomes or lipid nanoparticles, are described. GEM free base was conjugated to lipoamino acids bearing an alkyl side chain of different length, by either a carbodiimide-assisted or an ethylchloroformiate-assisted coupling reaction, to obtain N4-acyl GEM derivatives. These compounds retained the same in vitro cell growth inhibitory activity of the parent drug against two lines of human anaplastic thyroid cancer cells. Stability studies suggested that the observed activity was due mainly to intact derivatives and not to released GEM. Accordingly, these amphiphilic derivatives can be proposed in a further step for the encapsulation in liposomes... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3711836 Tue, 29 Jun 2010 23:00:00 +0100 3711836 http://www.medworm.com/index.php?rid=3653805&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20372 The vascular endothelium can be activated by multiple factors, including lipopolysaccharide (LPS) functioning as a key component of the inflammatory response. Activated endothelium promotes the recruitment of leukocytes mainly by releasing various adhesion molecules and amplifies inflammation via a feedback loop. Peoniflorin, the main active constituent of the roots of Paeonia lactiora Pall., possesses anti-inammatory, anti-infective, and anti-platelet aggregative properties. To elucidate the anti-inammatory mechanism of peoniflorin, the present study was conducted to address its effects on the adhesion of inflammatory endothelial cells to leukocytes. Peoniflorin substantially reduced adhesion of either human acute monocytic leukemia cells (THP-1) or human acute promyelocytic leukemia cell... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3653805 Fri, 11 Jun 2010 23:00:00 +0100 3653805 http://www.medworm.com/index.php?rid=3878307&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20381 (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3878307 Mon, 31 May 2010 23:00:00 +0100 3878307 http://www.medworm.com/index.php?rid=3850733&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20371 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850733 Mon, 31 May 2010 23:00:00 +0100 3850733 http://www.medworm.com/index.php?rid=3850732&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20370 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850732 Mon, 31 May 2010 23:00:00 +0100 3850732 http://www.medworm.com/index.php?rid=3850731&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20368 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850731 Mon, 31 May 2010 23:00:00 +0100 3850731 http://www.medworm.com/index.php?rid=3850730&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20367 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850730 Mon, 31 May 2010 23:00:00 +0100 3850730 http://www.medworm.com/index.php?rid=3850729&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20366 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850729 Mon, 31 May 2010 23:00:00 +0100 3850729 http://www.medworm.com/index.php?rid=3850728&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20365 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850728 Mon, 31 May 2010 23:00:00 +0100 3850728 http://www.medworm.com/index.php?rid=3587166&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20371 The effect of maprotiline on cytosolic free Ca2+ concentrations ([Ca2+]i) and cell viability was explored in human osteosarcoma cells (MG63), using the fluorescent dyes fura-2 and WST-1, respectively. Maprotiline at concentrations of [ge]20 µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The maprotiline-induced Ca2+ influx was sensitive to inhibition by aristolochic acid (a phospholipase A2 inhibitor). In Ca2+-free medium, after treatment with 1 µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 200 µM maprotiline failed to induce a [Ca2+]i rise. At concentrations of 50-100 µM maprotiline killed cells in a concentration-dependent manner. The cytotoxic effect of 60 µM maprotiline was slightly enha... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3587166 Fri, 21 May 2010 23:00:00 +0100 3587166 http://www.medworm.com/index.php?rid=3587167&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20370 Idazoxan is reference [alpha]2 adrenoceptor antagonist and has been extensively used preclinically to support the "[alpha]2/D2 receptor hypothesis" for atypical antipsychotic effects. However, previous studies have shown that the anticataleptic and discriminative stimulus properties of idazoxan may be mediated by 5-HT1A receptor agonism. The present study was conducted to further assess the role of [alpha]2 adrenoceptor antagonism and 5-HT1A receptor agonism in the discriminative stimulus properties of idazoxan using a 5.0-mg/kg training dose in rats. Idazoxan produced full-stimulus generalization to itself, the [alpha]2 adrenoceptor antagonist yohimbine, and the 5-HT1A receptor partial agonist, 8-OH-DPAT. Both the [alpha]2 adrenoceptor agonists clonidine and guanfacine, and the 5-HT1A rec... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3587167 Thu, 20 May 2010 23:00:00 +0100 3587167 http://www.medworm.com/index.php?rid=3430705&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20368 We report on the newly developed PARP-1 inhibitors, among which 12a showed good activity (IC50=7.8 nM in an enzyme-based assay and=0.73 µM in a cell-based assay) and pharmacokinetic profiles. Treatment of the middle cerebral artery (MCA) occluded rats with 3 mg/kg 12a reduced infarct volume suggesting that, may be a good candidate for the treatment of ischemic stroke. Drug Dev Res 71, 2010. © 2010 Wiley-Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3430705 Thu, 01 Apr 2010 23:00:00 +0100 3430705 http://www.medworm.com/index.php?rid=3391884&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20366 The effect of econazole on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability was explored in human oral cancer cells (OC2), using the fluorescent dyes fura-2 and WST-1, respectively. Econazole at concentrations of >1 µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The econazole-induced Ca2+ influx was sensitive to blockade of aristolochic acid (phospholipase A2 inhibitor) and GF109203X (PKC inhibitor). In Ca2+-free medium, after treatment with 1 µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 30 µM econazole failed to induce a [Ca2+]i rise. Inhibition of phospholipase C with 2 µM U73122 substantially suppressed econazole-induced [Ca2+]i rise. At concentrations of 5-70 µM econazole kil... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3391884 Tue, 23 Mar 2010 00:00:00 +0100 3391884 http://www.medworm.com/index.php?rid=3351807&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20365 The anti-leukemic drug, etoposide (ETO), has variable oral bioavailability ranging from 24-74% with a short terminal half-life of 1.5 h i.v. necessitating continuous infusion for 24-34 h for the treatment of leukemia. In the present study, etoposide-loaded PLGA-based surface-modified nanoparticles (NPs) with long circulation were designed as an alternative to continuous i.v. administration. PLGA-mPEG and PLGA-PLURONIC copolymers were synthesised and used to prepared ETO-loaded NPs by high-pressure homogenization. The mean particle size of ETO-loaded PLGA-MPEG nanoparticles was 94.02±3.4 nm, with an Entrapment Efficiency (EE) of 71.2% and zeta potential value of -6.9±1.3 mV. ETO-loaded PLGA-pluronic nanoparticles had a mean particle size of 148.0±2.1 nm, an EE of 73.12±2.7%, and zeta po... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3351807 Thu, 11 Mar 2010 00:00:00 +0100 3351807 http://www.medworm.com/index.php?rid=3351808&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20359 Syndrome X is a combination or co-occurrence of several known cardiovascular risk factors (including central obesity, dyslipidemias, fatty liver disease, hyperinsulinemia, insulin resistance, and hypertension) that affects at least one in five people in developed countries. Syndrome X shortens life and increases morbidity by contributing to the development of both diabetes and cardiovascular disease. Type 1 or 2 diabetes affects approximately 170 million people globally, and these numbers are rapidly rising. In patients with diabetes, vascular diseases develop early and progress at an accelerated rate. It has recently become evident that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose-phosphate pathway and its reaction products play key roles in regulating... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3351808 Wed, 10 Mar 2010 00:00:00 +0100 3351808 http://www.medworm.com/index.php?rid=3312952&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20364 This study identifies IK9 as a new potent inhibitor of angiogenesis and suggests its potential use as a therapeutic agent. Drug Dev Res 71, 2010. © 2010 Wiley-Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3312952 Sat, 27 Feb 2010 00:00:00 +0100 3312952 http://www.medworm.com/index.php?rid=3260512&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20361 Unintentionally omitted from the recently published Special Issue, "Current Considerations for Development of Cannabinoid Receptor 1 Antagonists", Volume 70, Issue 8 (December 2009), was the acknowledgement of Dr. Thomas's co-editors, Drs. Patrick M. Beardsley and Herbert H. Seltzman, and their co-authorship of the issue's opening editorial on pages 525-526 [DOI: 10.1002/ddr.20332].Drs. Beardsley and Seltzman should also have been listed as Guest Editors of this special issue, in addition to Dr. Thomas.Herein reprinted with all Guest Editors' names, is the now-revised title page that preceded the articles in the special issue:Current Considerations for Development of Cannabinoid Receptor 1 AntagonistsGuest EditorsBrian F. ThomasSenior Director - Analytical Chemistry and PharmaceuticsDiscov... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3260512 Thu, 11 Feb 2010 00:00:00 +0100 3260512 http://www.medworm.com/index.php?rid=3241165&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20363 Indirubin is an active constituent of traditional Chinese preparations used for the treatment of chronic myelocytic leukemia (CML). In the present study, the inhibitory activity of indirubin and its derivatives toward Fms-like tyrosine kinase 3 (FLT3) was examined. Indirubin-3[prime]-oxime (IO) and 6-bromoindirubin-3[prime]-oxime (BIO) had potent inhibitory activity against FLT3 (IC50=79 nM and 254 nM, respectively). We also tested the cytotoxicity of these compounds against acute myeloid leukemia cell lines: MV4;11 cells harboring a constitutively activated form of FLT3, and RS4;11 cells with wild-type FLT3. IO and BIO potently inhibited the growth of MV4;11 cells with IC50 values of 30 nM and 61 nM, respectively. Conversely, RS4;11 cells were far less sensitive to these compounds. IO arr... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3241165 Fri, 05 Feb 2010 00:00:00 +0100 3241165 http://www.medworm.com/index.php?rid=3199144&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20362 Protein kinases have become the second most important group of drug targets for the pharmaceutical industry next to G-protein-coupled receptors. Thus, over the past decade, a significant number of small molecules have been generated for protein kinase drug optimization programs. The vast majority of kinase inhibitors target the ATP binding site of the enzyme; however, the poor protein kinase selectivity of ATP-competitive protein kinase inhibitors (PKIs) limits their use for treating chronic diseases. In contrast, for inhibitors of bacterial signal transduction systems targeting bacterial kinase(s), there are no such selectivity requirements as long as the inhibitor does not act on any human kinases at the effective concentrations for killing bacteria in vivo. Protein phosphorylation in ba... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3199144 Sat, 23 Jan 2010 00:00:00 +0100 3199144 http://www.medworm.com/index.php?rid=3177200&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20360 In conclusion, the in vitro effects of tapentadol suggest mixed ion channel activities on potassium, calcium, and sodium channels at supra-pharmacological concentrations. These activities may be neutralizing, resulting in lack of a net effect of tapentadol on cardiac repolarization. Drug Dev Res 1-12, 2010 © 2010 Wiley-Liss, Inc. (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3177200 Sat, 16 Jan 2010 00:00:00 +0100 3177200 http://www.medworm.com/index.php?rid=3177201&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20343 Antimalarial medicines constitute important tools to cure and prevent malaria infections, thereby averting death and disability; their role in reducing the transmission of malaria is becoming increasingly important. Effective medicines that are currently available include artemisinin-based combination therapies (ACTs) for uncomplicated malaria, parenteral and rectal formulations of artemisinin derivatives and quinine injectables for severe malaria, and primaquine as an anti-relapse agent. These medicines are not optimal, however, owing to safety considerations in specific risk groups, complex regimens, and less than optimal formulations. The efficacy of antimalarial medicines including currently used ACTs is threatened by parasite resistance. Resistance to artemisinins has recently been id... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3177201 Fri, 15 Jan 2010 00:00:00 +0100 3177201 http://www.medworm.com/index.php?rid=4068643&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20389 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4068643 Fri, 01 Jan 2010 00:00:00 +0100 4068643 http://www.medworm.com/index.php?rid=4068642&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20387 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4068642 Fri, 01 Jan 2010 00:00:00 +0100 4068642 http://www.medworm.com/index.php?rid=4041670&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20394 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4041670 Fri, 01 Jan 2010 00:00:00 +0100 4041670 http://www.medworm.com/index.php?rid=4019486&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20391 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4019486 Fri, 01 Jan 2010 00:00:00 +0100 4019486 http://www.medworm.com/index.php?rid=4019485&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20388 Abstract (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=4019485 Fri, 01 Jan 2010 00:00:00 +0100 4019485 http://www.medworm.com/index.php?rid=3878309&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20379 (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3878309 Fri, 01 Jan 2010 00:00:00 +0100 3878309 http://www.medworm.com/index.php?rid=3878308&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20380 (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3878308 Fri, 01 Jan 2010 00:00:00 +0100 3878308 http://www.medworm.com/index.php?rid=3850727&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20372 (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850727 Fri, 01 Jan 2010 00:00:00 +0100 3850727 http://www.medworm.com/index.php?rid=3850726&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20373 (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850726 Fri, 01 Jan 2010 00:00:00 +0100 3850726 http://www.medworm.com/index.php?rid=3850725&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20376 (Source: Drug Development Research) Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3850725 Fri, 01 Jan 2010 00:00:00 +0100 3850725 http://www.medworm.com/index.php?rid=3116587&cid=s_33623_13_f&fid=33623&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fddr.20357 Eleven amino-substituted 1,4-naphthoquinones were synthesized via the reaction of 1,4-naphthoquinone with different primary and secondary mono- and diamines in the presence of dichloromethane ethanol (1:2) solvent at room temperature. All compounds were purified by flash column chromatography, characterized by TLC, HPLC, 13C-NMR, 1H-NMR, and FT-IR spectral analysis and were evaluated in vitro for antifilarial activity using adult bovine filarial worm Setaria digitata by assessing worm motility and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction. Seven of the 11 compounds had macrofilaricidal activity with compounds 9 (2-[(1,3-dimethylbutyl) amino] naphthalene-1,4-dione) and 11 (2-(4-methylpiperazin-1-yl) naphthalene-1,4-dione) having maximum activity (ED50 valu... Drug Development Research journals http://www.medworm.com/rss/comments.php?id=3116587 Thu, 24 Dec 2009 00:00:00 +0100 3116587