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Journals Current Opinion in Investigati...

Current Opinion in Investigational Drugs

https://read.qxmd.com/read/21157647/oligonucleotides-new-therapeutic-approaches-for-asthma-and-chronic-obstructive-pulmonary-disease
#21
JOURNAL ARTICLE
Mark Parry-Billings, Nicolay Ferrari, Rosanne Seguin
Asthma and COPD are significant lung diseases for which anti-inflammatories, including inhaled corticosteroids and leukotriene- targeted drugs, represent a key element of current therapy. Oligonucleotides comprise a diverse family of emerging drug candidates for the treatment of these diseases. There is a commonality in the chemistry of oligonucleotide drug molecules but, importantly, individual candidates are distinct in their molecular targets and also possess different mechanisms of action. Oligonucleotides may be divided in two groups based on their main mechanism of action: (i) RNA-targeting; and (ii) protein-targeting...
November 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/21157646/resetting-autoimmunity-in-the-nervous-system-the-role-of-hematopoietic-stem-cell-transplantation
#22
JOURNAL ARTICLE
Paolo A Muraro, Sofia V Abrahamsson
According to current concepts for multiple sclerosis (MS), a fundamental pathogenic role is played by T- and B-cells that inappropriately recognize self antigens and initiate a cell-mediated or humoral inflammatory reaction that injures myelin and axons, and results in neural dysfunction and loss. Transplantation of bone marrow-derived hematopoietic stem cells following high-dose immunosuppression is being evaluated as an experimental treatment for severe forms of immune-mediated disorders, including MS. The primary goal of this therapeutic approach is to induce medication-free remission from new disease activity by correcting the immune aberrations that promote the attack against self tissue; this approach is termed 'immune repair'...
November 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/21157645/novel-treatments-for-systemic-lupus-erythematosus
#23
JOURNAL ARTICLE
Mary Gayed, Caroline Gordon
Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with the production of autoantibodies, and with considerable morbidity and mortality. There has been much interest in developing more specific therapies for this disease, which is currently managed with immunosuppressive drugs, predominantly corticosteroids, azathioprine, methotrexate and cyclophosphamide, in combination with hydroxychloroquine. Mycophenolate mofetil has been demonstrated to be as efficacious as cyclophosphamide in patients with lupus nephritis, and is being used increasingly in the clinic despite not being licensed for this indication...
November 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/21157644/function-of-nod-like-receptors-in-immunity-and-disease
#24
JOURNAL ARTICLE
Maryse Dagenais, Jeremy Dupaul-Chicoine, Maya Saleh
Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are cytosolic pattern-recognition receptors that sense microbial invasion, cell stress and physiological perturbations, and elicit an inflammatory response to alert the system to the presence of danger. Most NLRs exert their functions by assembling inflammasomes that recruit and activate caspase-1, whereas a few engage the NFκB and MAPK pathways. In the past few years, significant insights have been gained into the regulatory mechanisms of these innate immunity effectors and their role in health and disease that, notably, have led to direct therapeutic applications in the clinic...
November 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/21157643/muscarinic-receptors-as-targets-for-anti-inflammatory-therapy
#25
JOURNAL ARTICLE
María Elena Sales
ACh, the main neurotransmitter in the neuronal cholinergic system, is synthesized by pre-ganglionic fibers of the sympathetic and parasympathetic autonomic nervous system and by post-ganglionic parasympathetic fibers. There is increasing experimental evidence that ACh is widely expressed in prokaryotic and eukaryotic non-neuronal cells. The neuronal and non-neuronal cholinergic systems comprise ACh, choline acetyltransferase and cholinesterase, enzymes that synthesize and catabolize ACh, and the nicotinic and muscarinic ACh receptors (nAChRs and mAChRs, respectively), which are the targets for ACh action...
November 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/21157642/targeting-th2-cytokines-in-fibrotic-diseases
#26
JOURNAL ARTICLE
Yuko Morishima, Yukio Ishii
Fibrosis is characterized by the excessive accumulation of extracellular matrix components, leading to tissue scarring. Fibrosis can occur in various tissue and organ systems, and is considered a leading cause of morbidity and mortality. Because of unsatisfactory results with currently available therapies for fibrotic diseases, the development of new therapies that target fibrosis directly is warranted. This review focuses on the importance of an imbalance in T-helper type 1 (Th1)/Th2 cell responses in fibroproliferation in several major fibrotic diseases, and discusses the prospects of novel therapeutic options targeting the Th2-type inflammatory response and cytokines...
November 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/21157641/the-growth-receptors-and-their-role-in-wound-healing
#27
JOURNAL ARTICLE
Kerstin J Rolfe, Adriaan O Grobbelaar
Abnormal wound healing is a major problem in healthcare today, with both scarring and chronic wounds affecting large numbers of individuals worldwide. Wound healing is a complex process involving several variables, including growth factors and their receptors. Chronic wounds fail to complete the wound healing process, while scarring is considered to be an overzealous wound healing process. Growth factor receptors and their ligands are being investigated to assess their potential in the development of therapeutic strategies to improve wound healing...
November 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/21157640/targeting-the-il-1-family-members-in-skin-inflammation
#28
JOURNAL ARTICLE
Liselotte E Jensen
The IL-1 family of cytokines comprises 11 proteins with pro- and anti-inflammatory functions that are mediated through an equally large group of receptors and coreceptors. Dysregulation of the IL-1 system may lead to diseases such as psoriasis, atopic dermatitis, contact dermatitis and cutaneous lupus erythematosus. These inflammatory skin conditions greatly affect quality of life and life expectancy, and their frequencies are increasing. However, treatment options for these diseases are unsatisfactory. This review briefly summarizes new findings, reported in the past 2 years, implicating IL-1 family members in skin inflammation...
November 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20882712/mutations-in-the-melanocortin-3-receptor-mc3r-gene-impact-on-human-obesity-or-adiposity
#29
REVIEW
Ya-Xiong Tao
The melanocortin-3 receptor (MC3R), together with the related melanocortin-4 receptor (MC4R), are important regulators of energy homeostasis. Rodent studies have demonstrated that the two receptors have non-redundant roles in regulating energy balance. However, while mutations for the MC4R have been established as a cause of monogenic obesity, mutations in the MC3R gene remain controversially associated with human obesity pathogenesis. This editorial summarizes the current status of MC3R in rodent energy homeostasis and human obesity pathogenesis...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872321/bi-10773-a-sodium-glucose-cotransporter-2-inhibitor-for-the-potential-oral-treatment-of-type-2-diabetes-mellitus
#30
REVIEW
Inês Aires, Joaquim Calado
BI-10773, being developed by Boehringer Ingelheim Corp, is a sodium-glucose cotransporter (SGLT)2 inhibitor for the oral treatment of type 2 diabetes mellitus (T2DM). Preclinical and clinical research has demonstrated that inhibition of SGLT2, the major pathway of renal glucose reabsorption, leads to increased urinary glucose excretion with concomitant reductions in fasting and postprandial plasma glucose levels, HbA1c levels and body mass. In phase I clinical trials in patients with T2DM, once-daily BI-10773 increased urinary glucose excretion resulting in dose-proportional reductions in fasting plasma glucose and mean daily glucose levels...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872320/eliglustat-tartrate-an-orally-active-glucocerebroside-synthase-inhibitor-for-the-potential-treatment-of-gaucher-disease-and-other-lysosomal-storage-diseases
#31
REVIEW
Timothy M Cox
Eliglustat tartrate (Genz-112638), currently under development by Genzyme Corp, is a glucocerebroside (glucosylceramide) synthase inhibitor for the treatment of Gaucher disease and other lysosomal storage disorders. Gaucher disease is an inherited defect of lysosomal functions caused by mutations in the GBA1 gene leading to accumulation of glucocerebroside, primarily in macrophages. Gaucher disease is characterized by visceromegaly and skeletal complications, including osteoporosis and painful episodes of osteonecrosis...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872319/sirtuin-targeting-drugs-mechanisms-of-action-and-potential-therapeutic-applications
#32
REVIEW
Ahmad Aljada, Lynn Dong, Shaker A Mousa
The sirtuins are NAD+-dependent histone/protein deacetylases that are similar to Saccharomyces cerevisiae silent information regulator 2 (Sir2). Sirtuins regulate various normal and abnormal cellular and metabolic processes, including tumorigenesis, neurodegeneration, and processes associated with type 2 diabetes and obesity. Several age-related diseases, such as Alzheimer's disease, and longevity have also been linked to the functions of sirtuins. A thorough understanding of the mechanisms of action of the sirtuins may therefore yield novel therapeutic strategies targeting these processes; several small-molecule and naturally occurring inhibitors and activators of these enzymes have been identified...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872318/the-mechanism-of-action-for-oxyntomodulin-in-the-regulation-of-obesity
#33
REVIEW
Katie Wynne, Benjamin Ct Field, Stephen R Bloom
Oxyntomodulin, a product of the proglucagon gene, is released from the enteroendocrine L-cells of the gastrointestinal tract after the digestion of food, and acts via glucagon-like peptide 1 receptors in the arcuate nucleus to induce satiety. The administration of oxyntomodulin to animals and humans causes weight loss by reducing food intake in combination with increasing energy expenditure. Thus, the development of potent and long-acting analogs of oxyntomodulin is an exciting new therapeutic avenue for addressing the global obesity epidemic...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872317/growth-hormone-releasing-factor-agonists-for-the-treatment-of-hiv-associated-lipodystrophy
#34
REVIEW
Miao Hu, Brian Tomlinson
HIV-associated lipodystrophy characterized by body composition changes and associated metabolic abnormalities, including dyslipidemia and insulin resistance, is a major challenge in the treatment of HIV infection. Growth hormone-releasing factor (GRF) analogs with greater stability than the natural hormone can induce growth hormone secretion in a physiological manner, and appear to be promising candidate therapies for these conditions. The most promising GRF agonist in development is tesamorelin (EMD Serono/Theratechnologies), which has exhibited efficacy for the treatment of excess visceral adipose tissue in patients with HIV infection in two recent phase III, randomized, placebo-controlled clinical trials...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872316/thyroid-hormone-receptor-and-lipid-regulation
#35
REVIEW
Paul Webb
The concept of thyroid hormone (TH) analogs that retain the beneficial effects of TH excess on lipid lowering and fat metabolism, while avoiding any harmful effects on the heart, muscle, bone and other tissues, has interested scientists and physicians for several decades. While there have been many attempts to develop selective TH receptor (TR) modulators (STRMs) for safe lipid lowering, these approaches have failed consistently. This review details recent advances in the development of TRβ subtype- and liver-selective STRM analogs, and presents the results of preliminary clinical trials with one of these compounds, eprotirome (KB-2115; Karo Bio AB)...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872315/s-nitrosothiol-biology-and-therapeutic-potential-in-metabolic-disease
#36
REVIEW
Christopher G Kevil, Rakesh P Patel
S-Nitrosothiols (RSNOs) have been used widely as experimental nitric oxide (NO) donors, but the clinical use of these agents remains limited. Recent data support a role for endogenous RSNOs as mediators of NO signaling via the post-translational modification of proteins. This review discusses the increased understanding of the role of RSNOs in NO signaling, as well as emerging insights into NO donor-dependent and -independent mechanisms of action of RSNOs, in the context of emerging and potential therapeutics that target endogenous RSNOs or use synthetic RSNOs to stimulate NO signaling...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872314/testosterone-therapy-in-women-with-androgen-deficiency-its-time-has-come
#37
REVIEW
André Guay, Abdulmaged Traish
The concept that women may have a testosterone deficiency is controversial, as is the possibility of testosterone replacement therapy for women. It has been stated that androgen deficiency is a new concept; however, women have been treated off-label for more than 50 years. A number of objections to such therapy in women have been reviewed and discussed, including the lack of a normal age-related concentration range for androgens, the lack of randomized, placebo-controlled clinical trials, and the possibility of chronic adverse effects, particularly the risk of cardiovascular disease and breast cancer...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872313/plant-derived-therapeutics-for-the-treatment-of-metabolic-syndrome
#38
REVIEW
Brittany L Graf, Ilya Raskin, William T Cefalu, David M Ribnicky
Metabolic syndrome is defined as a set of coexisting metabolic disorders that increase an individual's likelihood of developing type 2 diabetes, cardiovascular disease and stroke. Medicinal plants, some of which have been used for thousands of years, serve as an excellent source of bioactive compounds for the treatment of metabolic syndrome because they contain a wide range of phytochemicals with diverse metabolic effects. In order for botanicals to be effectively used against metabolic syndrome, however, botanical preparations must be characterized and standardized through the identification of their active compounds and respective modes of action, followed by validation in controlled clinical trials with clearly defined endpoints...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20872312/appetite-and-volume-regulating-neuropeptides-role-in-treating-alcohol-dependence
#39
REVIEW
Thomas Hillemacher, Kai G Kahl, Annemarie Heberlein, Marc An Muschler, Christian Eberlein, Helge Frieling, Stefan Bleich
Recent studies have demonstrated a role for appetite- and volume-regulating neuropeptides in alcohol dependence, particularly in association with alcohol craving. The peptides leptin, ghrelin, adiponectin, vasopressin and the atrial natriuretic peptide (ANP) have been of particular interest because of their central effects on various brain circuits, including the hypothalamic-pituitary-adrenocortical (HPA) axis. In addition, pro-opiomelanocortin (POMC) plays an important role in linking appetite regulation with the HPA axis...
October 2010: Current Opinion in Investigational Drugs
https://read.qxmd.com/read/20730702/macitentan-a-tissue-targeting-endothelin-receptor-antagonist-for-the-potential-oral-treatment-of-pulmonary-arterial-hypertension-and-idiopathic-pulmonary-fibrosis
#40
JOURNAL ARTICLE
Shahzad G Raja
Macitentan (ACT-064992), under development by Actelion Ltd in collaboration with Japanese licensee Nippon Shinyaku Co Ltd, is an orally active, non-peptide dual endothelin (ET)(A) and ET(B) receptor antagonist for the potential treatment of idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Scientific evidence suggests that the ET system may play an important role in the pathobiology of several cardiovascular diseases. A major therapeutic advance for the treatment of patients with PAH and IPF has been the pharmacological control of the activated ET system with ET receptor antagonists...
September 2010: Current Opinion in Investigational Drugs
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