1,943 results match your criteria Current Opinion in Pharmacology[Journal]


Tumor targeting peptides: novel therapeutic strategies in glioblastoma.

Authors:
Drazen Raucher

Curr Opin Pharmacol 2019 Feb 15;47:14-19. Epub 2019 Feb 15.

Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, United States. Electronic address:

Peptides are a promising new therapeutic approach for glioblastoma with potential for more effective targeting and fewer devastating side effects compared to conventional cancer therapies. With the specificity to target receptors which are uniquely or overexpressed on cancer cells as well as accurately targeting dysregulated signaling pathways, peptides demonstrate a high potential for the treatment of even the most aggressive cancers. By binding to these targets, peptides can be used to deliver drugs, serve as antagonists to various ligands, or, given some inherent anticancer activity, provide additional treatment options alone or in combination therapy. Read More

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http://dx.doi.org/10.1016/j.coph.2019.01.006DOI Listing
February 2019

Recent advances of anti-cancer therapies including the use of cell-penetrating peptides.

Curr Opin Pharmacol 2019 Feb 13;47:8-13. Epub 2019 Feb 13.

University of Cologne, Department of Chemistry, Biochemistry, Zülpicher Str. 47a, 50674 Cologne, Germany. Electronic address:

Cancer is one of the major growing public health problems making the development of new anti-cancer treatment strategies still compulsory. Conventionally used chemotherapies are quite often associated with severe side effects. One reason is limited cell-permeability of the used drugs resulting in only poor overall bioavailability. Read More

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http://dx.doi.org/10.1016/j.coph.2019.01.003DOI Listing
February 2019
8 Reads

Pharmacological advances in pemphigoid.

Curr Opin Pharmacol 2019 Feb 12;46:34-43. Epub 2019 Feb 12.

Department of Dermatology, Philipps University, Baldingerstr., Marburg, Germany. Electronic address:

Pemphigoid is the most common autoimmune blistering disease. IgG and IgE autoantibodies against the hemidesmosomal antigens Bullous Pemphigoid (BP) 180 and BP230 are of pathogenic relevance, since autoantibody-antigen binding results in complement activation, immune cells infiltration, impaired hemidesmosomal function, and loss of dermal-epidermal adhesion. Systemic steroids and immunosuppressants are frontline therapies in pemphigoid, but result in substantial morbidity and increased mortality. Read More

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http://dx.doi.org/10.1016/j.coph.2018.12.007DOI Listing
February 2019
1 Read

Therapeutic strategies for eosinophilic dermatoses.

Curr Opin Pharmacol 2019 Feb 8;46:29-33. Epub 2019 Feb 8.

Institute of Pharmacology, University of Bern, Bern, Switzerland; Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia.

Eosinophil infiltration is observed in a broad spectrum of skin diseases of various origins. Eosinophils are thought to actively contribute to pathogenesis as they are able to defend against microbes, to regulate inflammation, cause tissue damage, promote remodeling and fibrosis, and initiate pruritus. Therefore, targeting eosinophils would seem a worthwhile therapeutic approach. Read More

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http://dx.doi.org/10.1016/j.coph.2019.01.002DOI Listing
February 2019
2 Reads

Modern sun protection.

Curr Opin Pharmacol 2019 Feb 4;46:24-28. Epub 2019 Feb 4.

Department of Dermatology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.

So far sun protection meant ultraviolet (UV) protection. But there is preliminary data that beside UV radiation also visible light (VIS) and near infrared A (IRA) radiation may have harmful effects on our skin resulting in photoaging and even cancer induction. Therefore, some authors claim that modern sun protection should also include shielding against longer wavelengths such as VIS and IRA. Read More

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February 2019
4 Reads

Protein-driven nanomedicines in oncotherapy.

Curr Opin Pharmacol 2019 Jan 24;47:1-7. Epub 2019 Jan 24.

CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, 08193, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.

Proteins are organic macromolecules essential in life but exploited, mainly in recombinant versions, as drugs or vaccine components, among other uses in industry or biomedicine. In oncology, individual proteins or supramolecular complexes have been tailored as small molecular weight drug carriers for passive or active tumor cell-targeted delivery, through the de novo design of appropriate drug stabilizing vehicles, or by generating constructs with different extents of mimesis of natural cell-targeted entities, such as viruses. In most of these approaches, a convenient nanoscale size is achieved through the oligomeric organization of the protein component in the drug conjugate. Read More

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http://dx.doi.org/10.1016/j.coph.2018.12.004DOI Listing
January 2019
2 Reads

Identification of anti-prion drugs and targets using toxicity-based assays.

Curr Opin Pharmacol 2019 Jan 23;44:20-27. Epub 2019 Jan 23.

Boston University School of Medicine, Boston, MA 02118, United States. Electronic address:

Prion diseases are untreatable and invariably fatal, making the discovery of effective therapeutic interventions a priority. Most candidate molecules have been discovered based on their ability to reduce the levels of PrP, the infectious form of the prion protein, in cultured neuroblastoma cells. We have employed an alternative assay, based on an abnormal cellular phenotype associated with a mutant prion protein, to discover a novel class of anti-prion compounds, the phenethyl piperidines. Read More

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http://dx.doi.org/10.1016/j.coph.2018.12.005DOI Listing
January 2019

Trends in the treatment and prevention of keratinocyte carcinoma (non-melanoma skin cancer).

Authors:
Alexander Zink

Curr Opin Pharmacol 2019 Jan 17;46:19-23. Epub 2019 Jan 17.

Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany; Clinical Unit Allergology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany. Electronic address:

Keratinocyte carcinoma (KC), previously also known as non-melanoma skin cancer, is the most common malignancy worldwide. It comprises basal cell carcinoma, squamous cell carcinoma (SCC), and actinic keratoses as carcinoma in situ or precursors of SCC. With solar ultraviolet radiation being the main risk factor, several countries have accepted KC as an occupational disease of outdoor professions. Read More

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http://dx.doi.org/10.1016/j.coph.2018.12.002DOI Listing
January 2019
4 Reads

Clinical effectiveness of novel rosacea therapies.

Curr Opin Pharmacol 2019 Jan 10;46:14-18. Epub 2019 Jan 10.

Center for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC, United States.

Rosacea is a common inflammatory skin disease that is difficult to manage because of the unknown etiology and due to its variable manifestations. These facts and the few new available treatment options make it difficult to select a really effective treatment. This review aims to assess the efficacy and safety of novel treatment options for rosacea. Read More

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http://dx.doi.org/10.1016/j.coph.2018.12.001DOI Listing
January 2019
5 Reads

Current pharmaceutical developments in atopic dermatitis.

Curr Opin Pharmacol 2019 Jan 2;46:7-13. Epub 2019 Jan 2.

Aarhus University Hospital, Department of Dermatology, Aarhus, Denmark.

Atopic dermatitis (AD) is an inflammatory, pruritic, chronic or chronically relapsing skin disease that typically begins in early childhood and is occurring frequently in families with other atopic diseases (bronchial asthma and/or allergic rhino-conjunctivitis). Thanks to immunological and neurobiological research, the era of new treatments is coming as well as it occurred with psoriasis 15 years ago. Many treatments targeting cytokines (IL-4, IL-13, IL-31, TSLP) or neurotransmitters (substance P, opioids) or their respective receptors as well as phosphodiesterase-4 or the Jak/Stat pathways are under development. Read More

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http://dx.doi.org/10.1016/j.coph.2018.12.003DOI Listing
January 2019
3 Reads

Current treatment strategies in refractory chronic pruritus.

Curr Opin Pharmacol 2018 Dec 6;46:1-6. Epub 2018 Dec 6.

Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany.

Chronic pruritus is a highly prevalent, debilitating disease, which is often refractory to conventional therapies. A step-wise, guideline-driven approach should be adopted in the management of these patients. Emollients as well as topical corticosteroids if appropriate should be initiated whilst looking for the cause underlying the pruritus. Read More

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http://dx.doi.org/10.1016/j.coph.2018.11.007DOI Listing
December 2018
1 Read

Therapeutic strategies for prion disease: a practical perspective.

Curr Opin Pharmacol 2018 Nov 30;44:15-19. Epub 2018 Nov 30.

Department of Neurology, University Hospitals Cleveland Medical Center, 3619 Park East Drive, Suite 206, Beachwood, OH 44122, USA.

Human prion diseases are usually rapid neurodegenerative illnesses that are invariably fatal. Despite several clinical trials, no effective treatment has been discovered in humans. Although prior clinical trials have not been successful, they provided information that is vital for the formation of future clinical trials. Read More

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http://dx.doi.org/10.1016/j.coph.2018.11.006DOI Listing
November 2018
2 Reads

Impact of currently used anti-diabetic drugs on myoendothelial communication.

Curr Opin Pharmacol 2018 Nov 28;45:1-7. Epub 2018 Nov 28.

Departments of Pharmacology and Medical Education, Weill Cornell Medicine - Qatar, Qatar Foundation, Education City, Doha, Qatar. Electronic address:

Diabetes is associated with a high risk of cardiovascular complications and ideally anti-diabetic drugs should not only reduce metabolic abnormalities but also reduce the negative impact of diabetes on vascular function; however, lowering blood glucose levels does not necessarily reduce cardiovascular events. Endothelial dysfunction, defined as a reduction in endothelium-dependent vasodilation, is the earliest indicator of vascular disease and this raises the question: Do the currently used anti-diabetic drugs protect endothelial function? Metformin, in use for 60 years, is the first choice drug for type 2 diabetes and based on pre-clinical and clinical data metformin has proven cardiovascular protective actions; in contrast SGLT2 inhibitors were only introduced in 2013 but show great promise. This review compares metformin with SGLT2 inhibitors and the data supporting their protective effects on the endothelium. Read More

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http://dx.doi.org/10.1016/j.coph.2018.11.002DOI Listing
November 2018
1 Read
4.595 Impact Factor

Editorial.

Curr Opin Pharmacol 2018 Dec 27;43:150. Epub 2018 Nov 27.

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http://dx.doi.org/10.1016/j.coph.2018.11.004DOI Listing
December 2018
2 Reads

Editorial.

Curr Opin Pharmacol 2018 Dec 27;43:151. Epub 2018 Nov 27.

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http://dx.doi.org/10.1016/j.coph.2018.11.003DOI Listing
December 2018
1 Read

Editorial overview.

Curr Opin Pharmacol 2018 Dec 24;43:vi-vii. Epub 2018 Nov 24.

Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.

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http://dx.doi.org/10.1016/j.coph.2018.11.005DOI Listing
December 2018
1 Read

Cell-based therapy against prion diseases.

Curr Opin Pharmacol 2018 Nov 22;44:8-14. Epub 2018 Nov 22.

Institute for Regenerative Medicine and Biotherapies (IRMB), Neural Stem Cell, MSC and Neurodegenerative Diseases - U1183 INSERM (Institut National de la Santé et de la Recherche Médicale), 80 rue Augustin Fliche, 34295 Montpellier, France. Electronic address:

Despite multiple efforts to find treatments, prion diseases are still incurable. The currently available therapeutic strategies are mostly based on compounds to inhibit pathological PrP (PrPSc) accumulation, and cellular PrP (PrP) conversion into PrP. However, they cannot reverse the pathological changes already present in the brain. Read More

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http://dx.doi.org/10.1016/j.coph.2018.11.001DOI Listing
November 2018
3 Reads

Editorial overview: Endocrine and metabolic diseases Druggable diabetes: identification of therapeutic opportunities.

Curr Opin Pharmacol 2018 Dec 13;43:iii-v. Epub 2018 Nov 13.

Department of Diabetes, School of Life Course Sciences King's College London, London SE1 1UL, UK.

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http://dx.doi.org/10.1016/j.coph.2018.10.002DOI Listing
December 2018
1 Read

Cell-free prion protein conversion assays in screening for anti-prion drug candidates.

Curr Opin Pharmacol 2018 Nov 6;44:1-7. Epub 2018 Nov 6.

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States. Electronic address:

The search for medications to treat prion diseases has lasted more than 30 years but no clinically validated treatments for prion diseases of humans or livestock have been realized. A primary strategy has been to identify molecules that can inhibit the formation of pathological forms of prion protein, for example, protease-resistant forms called PrP. Such inhibitors can prolong the lives of experimental animals inoculated peripherally with prions, but the practical therapeutic efficacy of known inhibitors against ongoing brain infections has so far been limited by toxicity, insufficient bioavailability to the CNS, and/or strain specificities. Read More

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November 2018
10 Reads

The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis.

Curr Opin Pharmacol 2018 Dec 16;43:152-165. Epub 2018 Oct 16.

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA; The Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Cystic fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR dysfunction is characterized by abnormal mucociliary transport due to a dehydrated airway surface liquid (ASL) and hyperviscous mucus, among other pathologies of host defense. ASL depletion is caused by the absence of CFTR mediated chloride secretion along with continued activity of the epithelial sodium channel (ENaC) activity, which can also be affected by CFTR mediated anion conductance. Read More

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http://dx.doi.org/10.1016/j.coph.2018.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294660PMC
December 2018
13 Reads

Stem cell therapy in severe pediatric motility disorders.

Curr Opin Pharmacol 2018 Dec 16;43:145-149. Epub 2018 Oct 16.

Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK; Neurogastroenterology and Motility Unit, Department of Paediatric Gastroenterology, Great Ormond Street Hospital NHS Foundation Trust, London, WC1N 3JH, UK. Electronic address:

Pediatric gastrointestinal motility disorders represent a range of severe developmental or acquired conditions that disrupt enteric neuromuscular function. Current medical and surgical therapeutic options are very limited but recent advances have highlighted the possibility of improved or curative stem cell-based treatments. Not only has the ability to harvest, propagate and transplant human-derived enteric neural stem cells (ENSCs) been demonstrated but recent in vivo transplantation studies have confirmed that ENSCs are capable of engraftment within recipient intestine of animal models of enteric neuropathy and effecting functional rescue. Read More

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http://dx.doi.org/10.1016/j.coph.2018.09.004DOI Listing
December 2018
2 Reads

Medical and dietary treatments in eosinophilic esophagitis.

Curr Opin Pharmacol 2018 Dec 16;43:139-144. Epub 2018 Oct 16.

Department of Gastroenterology & Hepatology, University Hospital Zurich, Switzerland.

Eosinophilic esophagitis (EoE) refers to a relatively new chronic inflammatory disease of the esophagus, which according to the current understanding underlies an immune-mediated pathogenesis driven by exposure to allergens. While several open questions remain regarding ethiopathogenesis as well as treatment options and their positioning, one thing has increasingly been recognized. The disease is on the rise and will increasingly be of importance in everyday's clinical practice, not only in expert physicians but also gastroenterologists with a broad clinical spectrum, allergologists and even general practitioners. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.013DOI Listing
December 2018
9 Reads

Use of dietary interventions for functional gastrointestinal disorders.

Curr Opin Pharmacol 2018 Dec 9;43:132-138. Epub 2018 Oct 9.

Department of Rehabilitation, Nutrition and Sport, La Trobe University, Melbourne, Australia. Electronic address:

The role of food in the development of symptoms experienced within functional gastrointestinal disorders (FGIDs) is well recognised. This review aims to describe the evidence base for dietary interventions in the different functional esophageal, duodenal and bowel disorders. Randomised controlled trials are lacking for many of the FGIDs, with the exception of irritable bowel syndrome (IBS). Read More

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December 2018
4 Reads

Treatment of diverticular disease, targeting symptoms or underlying mechanisms.

Curr Opin Pharmacol 2018 Dec 3;43:124-131. Epub 2018 Oct 3.

Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Hospital Sant'Andrea, University Sapienza, Rome, Italy.

Diverticular disease (DD) is a highly prevalent disease in western industrialized countries that encompasses a complex set of disorders. Because of its complexity and heterogeneity, both from a pathogenic and a clinical point of view, the management of this disease represent a challenge in clinical practice. This review aims to analyze and summarize the most recent evidence on the medical strategies for DD, considering separately the different stages of the disease, from prevention of diverticula formation to treatment of acute diverticulitis and prevention of recurrences. Read More

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December 2018
5 Reads

Applications of peptide hormone ligands for the treatment of dumping and short bowel syndrome.

Curr Opin Pharmacol 2018 Dec 28;43:118-123. Epub 2018 Sep 28.

Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, 3000 Leuven, Belgium; Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address:

Dumping syndrome is a common and debilitating complication of upper gastrointestinal surgery. Accelerated gastric emptying and dysregulated secretion of gastrointestinal (GI) hormones are involved in its pathophysiology. Pasireotide, a novel somatostatin analogue, improved dumping in a phase-2 study. Read More

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http://dx.doi.org/10.1016/j.coph.2018.09.005DOI Listing
December 2018
5 Reads

Editorial overview: Tuberculosis, malaria and schistosomiasis; understanding resistance and development of new drugs.

Curr Opin Pharmacol 2018 Oct 24;42:iv-vi. Epub 2018 Sep 24.

Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit & DST/NRF Centre of Excellence for Biomedical TB Research, Department of Pathology, University of Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, South Africa.

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http://dx.doi.org/10.1016/j.coph.2018.09.002DOI Listing
October 2018
2 Reads

New developments in the treatment of gastroparesis and functional dyspepsia.

Curr Opin Pharmacol 2018 Dec 21;43:111-117. Epub 2018 Sep 21.

Mayo Clinic, Rochester, MN, USA.

Functional dyspepsia (FD) and gastroparesis are frequent causes of upper gastrointestinal symptoms such as postprandial fullness, early satiation, epigastric pain or burning, upper abdominal bloating, bothersome belching, nausea and vomiting. The underlying pathophysiological mechanisms are heterogeneous and involved mechanisms such as abnormal gastric motility (accommodation, emptying), visceral hypersensitivity, low grade mucosal inflammation and cellular changes in enteric nerves, muscle or interstitial cells of Cajal. Patient-reported outcomes for evaluating treatment efficacy in these conditions were recently developed and validated. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.015DOI Listing
December 2018
6 Reads

Targeting protein misfolding to protect pancreatic beta-cells in type 2 diabetes.

Authors:
Safia Costes

Curr Opin Pharmacol 2018 Dec 21;43:104-110. Epub 2018 Sep 21.

IGF, CNRS, INSERM, University of Montpellier, Montpellier, France. Electronic address:

The islet in type 2 diabetes is characterized by beta-cell dysfunction and deficit, increased beta-cell apoptosis and amyloid deposits that derived from islet amyloid polypeptide (IAPP). In species such as humans that are vulnerable to developing type 2 diabetes, IAPP has the propensity to form toxic oligomers that contribute to beta-cell dysfunction and apoptosis, defining type 2 diabetes as a protein misfolding disorder. In this report, we review mechanisms known to contribute to protein misfolding and formation of toxic oligomers, and the deleterious consequences of these oligomers on beta-cell function and survival. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.016DOI Listing
December 2018
3 Reads

Editorial overview: New technologies: multidisciplinary evolutions for drug discovery.

Curr Opin Pharmacol 2018 Oct 18;42:vii-ix. Epub 2018 Sep 18.

Scientific Director, Center of Excellence Research and Biopharmacy, Servier Research and Development, 50 Rue Carnot, 92284 Suresnes Cedex, France.

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http://dx.doi.org/10.1016/j.coph.2018.08.014DOI Listing
October 2018
3 Reads

Refractory GERD, beyond proton pump inhibitors.

Curr Opin Pharmacol 2018 Dec 18;43:99-103. Epub 2018 Sep 18.

Université de Lyon, Hospices Civils de Lyon, Digestive Physiology, Hopital E Herriot, F-69437, Lyon, France; Université de Lyon, Lyon I University, Digestive Physiology, F-69008, Lyon, France; Université de Lyon, Inserm U1032, LabTAU, F-69008, Lyon, France.

Pharmacologic therapy, surgery, minimally invasive therapies, and alternative therapies are different options available for the management of refractory GERD. The choice may depend on the cause of refractoriness. Increased gastric acid suppression therapy might be useful in the rare patients with persistent elevated esophageal acid exposure on proton pump inhibitors (PPI). Read More

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http://dx.doi.org/10.1016/j.coph.2018.09.001DOI Listing
December 2018
7 Reads

The gut-liver axis in hepatocarcinoma: a focus on the nuclear receptor FXR and the enterokine FGF19.

Curr Opin Pharmacol 2018 Dec 14;43:93-98. Epub 2018 Sep 14.

Department of Interdisciplinary Medicine, `Aldo Moro' University of Bari, Italy; National Cancer Center, IRCCS Istituto Tumori `Giovanni Paolo II', Bari, Italy. Electronic address:

Elevated bile acid (BA) concentrations in the liver is associated with severe disease, including cholestasis and hepatocellular carcinoma. The nuclear Farnesoid X Receptor (FXR) is the master regulator of BAs homeostasis. In the ileum, BA-dependent FXR activation induces the production of the fibroblast growth factor FGF19, a hormone that reaches the liver through the portal system where it represses the expression of CYP7A1, the rate limiting enzyme in the process of hepatic BAs synthesis. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.005DOI Listing
December 2018
3 Reads

Pre- and probiotic overview.

Curr Opin Pharmacol 2018 Dec 13;43:87-92. Epub 2018 Sep 13.

Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy. Electronic address:

The dynamic relationship between gut microbiota and its human host is also known as a trophic association that might range from commensalism, where only the microbe enjoys a positive effect from the relationship, to intestinal symbiosis where both host and microbe benefit from their interaction. In the last years, we have started to understand how alterations of the gut microbiota composition leading to the disruption of host-microbial interactions are associated and/or predispose individuals to disease conditions ranging from inflammatory bowel diseases to allergy and functional gastrointestinal disorders, such as irritable bowel syndrome. While we await important insights in this field, the microbiota is already a therapeutic target. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.010DOI Listing
December 2018
22 Reads
4.595 Impact Factor

Endocannabinoids in the treatment of gasytrointestinal inflammation and symptoms.

Curr Opin Pharmacol 2018 Dec 12;43:81-86. Epub 2018 Sep 12.

Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy. Electronic address:

The evolving policies regarding the use of therapeutic Cannabis have steadily increased the public interest in its use as a complementary and alternative medicine in several disorders, including inflammatory bowel disease. Endocannabinoids represent both an appealing therapeutic strategy and a captivating scientific dilemma. Results from clinical trials have to be carefully interpreted owing to possible reporting-biases related to cannabinoids psychotropic effects. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.009DOI Listing
December 2018
2 Reads

Fecal microbiota transfer for bowel disorders: efficacy or hype?

Curr Opin Pharmacol 2018 Dec 12;43:72-80. Epub 2018 Sep 12.

Division of Gastroenterology, Department of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States.

Purpose Of Review: Dysbiosis has been related to the pathophysiology of disorders of - gut-brain interaction (DGBI) including irritable bowel syndrome (IBS) and functional constipation (FC). Accordingly, modulation of gut microbiota has been proposed as a potential treatment for these disorders. Gut microbiota modulation can be effected by probiotics, prebiotics, symbiotics, postbiotics, antibiotics and fecal transplantation (FMT) or bacteriotherapy. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.012DOI Listing
December 2018
26 Reads

Mucosal permeability and mast cells as targets for functional gastrointestinal disorders.

Curr Opin Pharmacol 2018 Dec 11;43:66-71. Epub 2018 Sep 11.

Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology, Linköping University, Linköping, Sweden; Department of Surgery, County Council of Östergötland, Linköping, Sweden.

The intestinal mucosa is constantly exposed to harmful luminal content, and uptake is closely controlled and regulated by neuro-immune factors. If control is broken, it might lead to ongoing enhanced mucosal permeability, potentially resulting in functional gastrointestinal disorders. The importance of mast cells in the regulation of the mucosal barrier has become obvious, and increased numbers and more activated mast cells have been observed in irritable bowel syndrome, functional dyspepsia and gastroesophageal reflux disease. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.011DOI Listing
December 2018
1 Read

In silico models in drug development: where we are.

Curr Opin Pharmacol 2018 Oct 8;42:111-121. Epub 2018 Sep 8.

Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences (DCEXS), Hospital del Mar Medical Research Institute (IMIM), Universitat Pompeu Fabra (UPF), Carrer Dr. Aiguader 88, 08003 Barcelona, Spain. Electronic address:

The use and utility of computational models in drug development has significantly grown in the last decades, fostered by the availability of high throughput datasets and new data analysis strategies. These in silico approaches are demonstrating their ability to generate reliable predictions as well as new knowledge on the mode of action of drugs and the mechanisms underlying their side effects, altogether helping to reduce the costs of drug development. The aim of this review is to provide a panorama of developments in the field in the last two years. Read More

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October 2018
1 Read

Placental peptides regulating islet adaptation to pregnancy: clinical potential in gestational diabetes mellitus.

Curr Opin Pharmacol 2018 Dec 7;43:59-65. Epub 2018 Sep 7.

Department of Diabetes, School of Life Course Sciences, King's College London, Guy's Campus, London SE1 1UL, UK. Electronic address:

Pregnancy involves a progressive increase in insulin resistance and the β-cells must adapt to compensate and prevent gestational diabetes (GDM). In this review we discuss the evidence for placental peptides, including placental lactogen, hepatocyte growth factor, adiponectin and leptin, playing a role in the islet adaptation to pregnancy. The difficulties of translating data from rodent models into human pregnancy are covered and we summarise studies investigating associations between serum placental peptides and GDM risk. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.004DOI Listing
December 2018
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Recent advances in combinatorial drug screening and synergy scoring.

Curr Opin Pharmacol 2018 Oct 5;42:102-110. Epub 2018 Sep 5.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria; Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraße 17A, 1090 Vienna, Austria. Electronic address:

Treatment of complex diseases such as cancer, cardiovascular disease, diabetes or neurological disorders frequently warrants the utilization of drug combinations for therapeutic intervention. In fact, the most successful example is the current standard of care for HIV patients. However, identification of successful drug cocktails is not a simple task and is hampered by lack of standardization in terminology, experimental protocols and models as well as data analysis. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S14714892173020
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http://dx.doi.org/10.1016/j.coph.2018.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219891PMC
October 2018
15 Reads

Opioid receptors in the GI tract: targets for treatment of both diarrhea and constipation in functional bowel disorders?

Curr Opin Pharmacol 2018 Dec 3;43:53-58. Epub 2018 Sep 3.

NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK. Electronic address:

Opioids have been used for centuries, mostly as a sedative and to treat pain. Currently, they are used on a global scale for the treatment of acute and chronic pain in diseases as osteoarthritis, fibromyalgia, and low back pain. Binding of opioids on opioid receptors can cause a range of different effects such as changes in stress response, analgesia, motor activity and autonomic functions. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S14714892183001
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http://dx.doi.org/10.1016/j.coph.2018.08.008DOI Listing
December 2018
29 Reads

Turning omics data into therapeutic insights.

Curr Opin Pharmacol 2018 Oct 24;42:95-101. Epub 2018 Aug 24.

Computational & Systems Biology Program and the Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address:

Omics technologies have made it easier and cheaper to evaluate thousands of biological molecules at once. These advances have led to novel therapies approved for use in the clinic, elucidated the mechanisms behind disease-associated mutations, led to increased accuracy in disease subtyping and personalized medicine, and revealed novel uses and treatment regimes for existing drugs through drug repurposing and pharmacology studies. In this review, we summarize some of these milestones and discuss the potential of integrative analyses that combine multiple data types for further advances. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204089PMC
October 2018
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Islet microRNAs in health and type-2 diabetes.

Curr Opin Pharmacol 2018 Dec 23;43:46-52. Epub 2018 Aug 23.

Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University and Clinical Research Centre, SUS, Malmö, Sweden. Electronic address:

Failure of the β-cell to secrete enough insulin is a major contributing factor in the pathogenesis of type-2 diabetes (T2D). MicroRNAs provide an extra layer in the regulation of protein expression, and are thus involved in β-cell compensation during development of the disease. In this review, we discuss how microRNAs can regulate their target protein expression and phenotypic output, present the status of nutritional regulation of microRNA expression, and summarize work on microRNA expression in human islets. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.003DOI Listing
December 2018
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The present state of the tuberculosis drug development pipeline.

Curr Opin Pharmacol 2018 Oct 23;42:81-94. Epub 2018 Aug 23.

Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address:

Tuberculosis now ranks as the leading cause of death in the world due to a single infectious agent. Current standard of care treatment can achieve very high cure rates for drug-sensitive disease but requires a 6-month duration of chemotherapy. Drug-resistant disease requires significantly longer treatment durations with drugs associated with a higher risk of adverse events. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204086PMC
October 2018
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Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?

Curr Opin Pharmacol 2018 Dec 22;43:40-45. Epub 2018 Aug 22.

ULB Center for Diabetes Research, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium. Electronic address:

Type 2 diabetes is a common complex disease. Relatively little is known about the underlying pathophysiology. Mild islet inflammation has been suggested to play a pathogenic role; here we review the available evidence. Read More

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http://dx.doi.org/10.1016/j.coph.2018.08.002DOI Listing
December 2018
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Mechanisms of resistance to the partner drugs of artemisinin in the malaria parasite.

Curr Opin Pharmacol 2018 Oct 22;42:71-80. Epub 2018 Aug 22.

Research School of Biology, Australian National University, Canberra 2601, Australia.

The deployment of artemisinin-based combination therapies (ACTs) has been, and continues to be, integral to reducing the number of malaria cases and deaths. However, their efficacy is being increasingly jeopardized by the emergence and spread of parasites that are resistant (or partially resistant) to the artemisinin derivatives and to their partner drugs, with the efficacy of the latter being especially crucial for treatment success. A detailed understanding of the genetic determinants of resistance to the ACT partner drugs, and the mechanisms by which they mediate resistance, is required for the surveillance of molecular markers and to optimize the efficacy and lifespan of the partner drugs through resistance management strategies. Read More

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http://dx.doi.org/10.1016/j.coph.2018.07.010DOI Listing
October 2018
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Editorial overview: Immunomodulation: Striking the right balance: using immunomodulators to target infectious diseases, cancer, and autoimmunity.

Curr Opin Pharmacol 2018 Aug;41:vii-ix

Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.

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http://dx.doi.org/10.1016/j.coph.2018.07.013DOI Listing
August 2018
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The continuing evolution of strategies for cancer therapeutics.

Authors:
Elizabeth Yeh

Curr Opin Pharmacol 2018 Aug;41:iv-vi

Medical University of South Carolina (MUSC), Charleston, SC, USA.

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http://dx.doi.org/10.1016/j.coph.2018.07.012DOI Listing
August 2018
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Potential of mesenchymal stromal cells for improving islet transplantation outcomes.

Curr Opin Pharmacol 2018 Dec 10;43:34-39. Epub 2018 Aug 10.

Department of Diabetes, School of Life Course Sciences, King's College London, Guy's Campus, London SE1 1UL, UK.

Allogeneic islet transplantation as a therapy for Type 1 Diabetes (T1D) is restricted by the limited availability of donor islets, loss of functional islets during pre-transplantation culture in vitro and further extensive loss during the immediate post-transplantation period when islet function and survival is compromised by the hypoxic, inflammatory host environment. In the longer term pathogenic T cell responses drive autoimmunity and chronic allograft rejection. Experimental studies have demonstrated that mesenchymal stromal cells (MSCs) have significant potential to improve the outcomes of clinical islet transplantation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S14714892183007
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http://dx.doi.org/10.1016/j.coph.2018.07.011DOI Listing
December 2018
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How scientific literature analysis yields innovative therapeutic hypothesis through integrative iterations.

Curr Opin Pharmacol 2018 Oct 6;42:62-70. Epub 2018 Aug 6.

Bio-Modeling Systems, Tour CIT, 3 Rue de l'Arrivée, 75015, Paris, France.

It is becoming generally accepted that the current diagnostic system often guarantees, rather than diminishes, disease heterogeneity. In effects, syndrome-dominated conceptual thinking has become a barrier to understanding the biological causes of complex, multifactorial diseases characterized by clinical and therapeutic heterogeneity. Furthermore, not only is the flood of currently available medical and biological information highly heterogeneous, it is also often conflicting. Read More

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http://dx.doi.org/10.1016/j.coph.2018.07.005DOI Listing
October 2018
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Identifying novel therapeutic targets for diabetes through improved understanding of islet adhesion receptors.

Curr Opin Pharmacol 2018 Dec 4;43:27-33. Epub 2018 Aug 4.

Department of Diabetes, School of Life Course Sciences, King's College London, Guy's Campus, London SE1 1UL, UK.

Adhesion receptors are transmembrane proteins that mediate cell-cell and cell-matrix communications. In addition to their adhesive role in maintaining islet architecture, they are also important for promoting islet cell survival, proliferation and secretory function. Their capacity for improving β-cell mass and insulin secretion suggest that they may be suitable targets for pharmacological intervention, and their interactions with extracellular matrix proteins hold promise in improving islet transplantation outcomes. Read More

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http://dx.doi.org/10.1016/j.coph.2018.07.009DOI Listing
December 2018
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Will iPSC-cardiomyocytes revolutionize the discovery of drugs for heart disease?

Curr Opin Pharmacol 2018 Oct 3;42:55-61. Epub 2018 Aug 3.

The Cardiovascular Institute and Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

Cardiovascular disease remains the largest single cause of mortality in the Western world, despite significant advances in clinical management over the years. Unfortunately, the development of new cardiovascular medicines is stagnating and can in part be attributed to the difficulty of screening for novel therapeutic strategies due to a lack of suitable models. The advent of human induced pluripotent stem cells and the ability to make limitless numbers of cardiomyocytes could revolutionize heart disease modeling and drug discovery. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S14714892183004
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http://dx.doi.org/10.1016/j.coph.2018.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261432PMC
October 2018
14 Reads