Role of the P2X4 receptor in neuropathic pain.
Abstract Neuropathic pain is the most important type of chronic pain because it is refractory to available medications. Neuropathic pain occurs after peripheral nerve injury (PNI) or nerve damage by various reasons. In recent decades, a growing body of evidence shows that spinal microglia and P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, play a principal role in evoking this pain. Understanding the functions of microglial P2X4R in evoking this pain provides potential strategies for developing new treatments for neuropathic pain. PMID: 30878800 [PubMed - as supplied by publisher] (Source: Curre...
Source: Current Opinion in Pharmacology - March 14, 2019 Category: Drugs & Pharmacology Authors: Inoue K Tags: Curr Opin Pharmacol Source Type: research

Editorial: Alzheimer's Disease, aged-related dementias and the search for effective therapeutics.
PMID: 30878393 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - March 13, 2019 Category: Drugs & Pharmacology Authors: Trist DG Tags: Curr Opin Pharmacol Source Type: research

Experimental models to study prion disease pathogenesis and identify potential therapeutic compounds.
Abstract Prion diseases are devastating neurodegenerative disorders for which no drugs are available. The successful development of therapeutics depends on drug screening platforms and preclinical models that recapitulate key molecular and pathological features of the disease. Innovative experimental tools have been developed over the last few years that might facilitate drug discovery, including cell-free prion replication assays and prion-infected flies. However, there is still room for improvement. Animal models of genetic prion disease are few, and only partially recapitulate the complexity of the human disord...
Source: Current Opinion in Pharmacology - March 13, 2019 Category: Drugs & Pharmacology Authors: Vorberg I, Chiesa R Tags: Curr Opin Pharmacol Source Type: research

The future of peptides in cancer treatment.
ml; Abstract Peptides hold great potential for the cancer therapy and diagnostics. In the current review, the main and most influential areas of peptide cancer therapeutics are overviewed. These include the development of anticancer peptides, use of peptides for drug delivery, and cancer targeting. PMID: 30856511 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - March 8, 2019 Category: Drugs & Pharmacology Authors: Kurrikoff K, Aphkhazava D, Langel Ü Tags: Curr Opin Pharmacol Source Type: research

Peptides as cancer vaccines.
er PR Abstract Cancer vaccines based on synthetic peptides are a safe, well-tolerated immunotherapy able to specifically stimulate tumor-reactive T cells. However, their clinical efficacy does not approach that achieved with other immunotherapies such as immune checkpoint blockade. Nevertheless, major advances have been made in selecting tumor antigens to target, identifying epitopes binding to classical and non-classical HLA molecules, and incorporating these into optimal sized peptides for formulation into a vaccine. Limited potency of currently used adjuvants and the immunosuppressive tumor microenvironment are...
Source: Current Opinion in Pharmacology - March 1, 2019 Category: Drugs & Pharmacology Authors: Calvo Tardón M, Allard M, Dutoit V, Dietrich PY, Walker PR Tags: Curr Opin Pharmacol Source Type: research

The de-Alzheimerization of age-related dementias: implications for drug targets and approaches to effective therapeutics.
Abstract Alzheimer's disease (AD) was differentiated from senile dementia (SD) in 1910 due to its early onset and pathological severity. In 1976, this distinction was upended when SD was redesignated as AD to focus efforts and funding in dementia-related research. AD then became conflated with amyloid plaques and, to a lesser degree, neurofibrillary tangles complicating efforts in understanding dementia causality and its treatment. The resultant four-decade search for therapies-based almost exclusively on amyloid was an exercise in futility. While dementia is a complex, multifactorial syndrome, AD is viewed as a h...
Source: Current Opinion in Pharmacology - February 19, 2019 Category: Drugs & Pharmacology Authors: Mullane K, Williams M Tags: Curr Opin Pharmacol Source Type: research

Tumor targeting peptides: novel therapeutic strategies in glioblastoma.
Abstract 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...
Source: Current Opinion in Pharmacology - February 15, 2019 Category: Drugs & Pharmacology Authors: Raucher D Tags: Curr Opin Pharmacol Source Type: research

Recent advances of anti-cancer therapies including the use of cell-penetrating peptides.
f I Abstract 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. During the last thirty years, cell-penetrating peptides (CPPs) have extensively been studied as efficient vehicles for several classes of cargos, and the development of novel therapeutic applications including CPPs has gained a major role in current cancer research. This rev...
Source: Current Opinion in Pharmacology - February 13, 2019 Category: Drugs & Pharmacology Authors: Klimpel A, Lützenburg T, Neundorf I Tags: Curr Opin Pharmacol Source Type: research

Pharmacological advances in pemphigoid.
Abstract 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. A large randomized multicenter study highlighted doxycycline as a feasible alternative to systemic corticostero...
Source: Current Opinion in Pharmacology - February 12, 2019 Category: Drugs & Pharmacology Authors: Maglie R, Hertl M Tags: Curr Opin Pharmacol Source Type: research

Therapeutic strategies for eosinophilic dermatoses.
Abstract 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. A promising strategy is to target the production, activation and survival of eosinophils, example with antibodies directed against IL-5 or its receptor, and Siglec-8. Dexpramipexole and tyrosine kinase inhibitors have been shown ...
Source: Current Opinion in Pharmacology - February 8, 2019 Category: Drugs & Pharmacology Authors: Simon D, Simon HU Tags: Curr Opin Pharmacol Source Type: research

Modern sun protection.
Abstract 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. Therefore, avoidance of sun exposure at peak times and textile sun protection are important pillars of a modern prophylactic approach. Besides, antioxidants and DNA repair enzymes may be added to topical sunscreens i...
Source: Current Opinion in Pharmacology - February 4, 2019 Category: Drugs & Pharmacology Authors: Singer S, Karrer S, Berneburg M Tags: Curr Opin Pharmacol Source Type: research

Protein-driven nanomedicines in oncotherapy.
uez E Abstract 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 thro...
Source: Current Opinion in Pharmacology - January 24, 2019 Category: Drugs & Pharmacology Authors: Casanova I, Unzueta U, Arroyo-Solera I, Céspedes MV, Villaverde A, Mangues R, Vazquez E Tags: Curr Opin Pharmacol Source Type: research

Identification of anti-prion drugs and targets using toxicity-based assays.
Abstract 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 PrPSc, 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. Using an assay that monitors the acute toxic effects of PrPSc on the synapses of cultured hippocampal neurons, we h...
Source: Current Opinion in Pharmacology - January 23, 2019 Category: Drugs & Pharmacology Authors: Mercer RC, Harris DA Tags: Curr Opin Pharmacol Source Type: research

Trends in the treatment and prevention of keratinocyte carcinoma (non-melanoma skin cancer).
Abstract 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. The prevalence in these high-risk groups is substantial, but awareness and preventive behavior remains inadequate. Parallel to the development of improved treatments, such as daylight photodynamic therapy and PD1 ...
Source: Current Opinion in Pharmacology - January 17, 2019 Category: Drugs & Pharmacology Authors: Zink A Tags: Curr Opin Pharmacol Source Type: research

Clinical effectiveness of novel rosacea therapies.
Abstract 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. The topical alpha adrenergic agonist oxymetazoline reduces rosacea-related erythema. Topical ivermectin improves lesion count, inflammation, and maintenance of remission of rosacea compared to topical metronidazole. Procedural therapies including pulsed dye las...
Source: Current Opinion in Pharmacology - January 10, 2019 Category: Drugs & Pharmacology Authors: Feaster B, Cline A, Feldman SR, Taylor S Tags: Curr Opin Pharmacol Source Type: research

Current pharmaceutical developments in atopic dermatitis.
n M Abstract 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...
Source: Current Opinion in Pharmacology - January 2, 2019 Category: Drugs & Pharmacology Authors: Misery L, Huet F, Gouin O, Ständer S, Deleuran M Tags: Curr Opin Pharmacol Source Type: research

Current treatment strategies in refractory chronic pruritus.
r S Abstract 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. If these measures fail, and the origin of the pruritus remains unknown, cannot be treated or does not respond to therapy, systemic therapies as for example gabapentinoids, antidepressants, mu-opioid-receptor antagonists or, in case of inflammatory conditions, immu...
Source: Current Opinion in Pharmacology - December 6, 2018 Category: Drugs & Pharmacology Authors: Pereira MP, Mittal A, Ständer S Tags: Curr Opin Pharmacol Source Type: research

Therapeutic strategies for prion disease: a practical perspective.
Abstract 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. Among these findings is the realization that there are several prion disease-specific aspects that must be considered when conducting clinical trials. The rarity, rapidity, and clinical heterogeneity of prion disease affect study enrollment and the ability to measure treatment effects. In...
Source: Current Opinion in Pharmacology - November 30, 2018 Category: Drugs & Pharmacology Authors: Appleby BS, Connor A, Wang H Tags: Curr Opin Pharmacol Source Type: research

Impact of currently used anti-diabetic drugs on myoendothelial communication.
Abstract 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 ...
Source: Current Opinion in Pharmacology - November 28, 2018 Category: Drugs & Pharmacology Authors: Ding H, Ye K, Triggle CR Tags: Curr Opin Pharmacol Source Type: research

Editorial.
PMID: 30502021 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - November 27, 2018 Category: Drugs & Pharmacology Authors: Trist D, Williams M Tags: Curr Opin Pharmacol Source Type: research

Editorial.
PMID: 30502022 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - November 27, 2018 Category: Drugs & Pharmacology Authors: Trist D, Williams M Tags: Curr Opin Pharmacol Source Type: research

Editorial overview.
PMID: 30482447 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - November 24, 2018 Category: Drugs & Pharmacology Authors: Tack J, Sarnelli G Tags: Curr Opin Pharmacol Source Type: research

Cell-based therapy against prion diseases.
S, Crozet C Abstract 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 (PrPC) conversion into PrPSc. However, they cannot reverse the pathological changes already present in the brain. Cell-based therapeutic strategies could promote the repair of the pre-existing brain damage. The few available data come mostly from preclinical studies using neural stem cells, bone marrow-derived microglia and mesenchymal stem cells, as cell sources. Moreover...
Source: Current Opinion in Pharmacology - November 22, 2018 Category: Drugs & Pharmacology Authors: Relaño-Ginés A, Lehmann S, Crozet C Tags: Curr Opin Pharmacol Source Type: research

Editorial overview: Endocrine and metabolic diseases Druggable diabetes: identification of therapeutic opportunities.
PMID: 30446351 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - November 13, 2018 Category: Drugs & Pharmacology Authors: Persaud SJ, Bowe JE Tags: Curr Opin Pharmacol Source Type: research

Cell-free prion protein conversion assays in screening for anti-prion drug candidates.
Abstract 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 PrPres. 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...
Source: Current Opinion in Pharmacology - November 6, 2018 Category: Drugs & Pharmacology Authors: Ferreira NDC, Caughey B Tags: Curr Opin Pharmacol Source Type: research

The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis.
Abstract 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. Therefore, ENaC has been proposed as a therapeutic target to ameliorate ASL d...
Source: Current Opinion in Pharmacology - October 16, 2018 Category: Drugs & Pharmacology Authors: Shei RJ, Peabody JE, Kaza N, Rowe SM Tags: Curr Opin Pharmacol Source Type: research

Stem cell therapy in severe pediatric motility disorders.
Abstract 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 neurop...
Source: Current Opinion in Pharmacology - October 16, 2018 Category: Drugs & Pharmacology Authors: McCann CJ, Borrelli O, Thapar N Tags: Curr Opin Pharmacol Source Type: research

Medical and dietary treatments in eosinophilic esophagitis.
Abstract 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 pract...
Source: Current Opinion in Pharmacology - October 15, 2018 Category: Drugs & Pharmacology Authors: Biedermann L, Straumann A Tags: Curr Opin Pharmacol Source Type: research

Use of dietary interventions for functional gastrointestinal disorders.
Abstract 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). Restricting rapidly fermentable, short-chain carbohydrates (FODMAPs) provides an evidence based dietary approach for the management of symptoms of IBS. Recent evidence shows the upper GI motility response varies betwee...
Source: Current Opinion in Pharmacology - October 8, 2018 Category: Drugs & Pharmacology Authors: Manning LP, Biesiekierski JR Tags: Curr Opin Pharmacol Source Type: research

Treatment of diverticular disease, targeting symptoms or underlying mechanisms.
Abstract 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. Based on some evidence, dietary ...
Source: Current Opinion in Pharmacology - October 3, 2018 Category: Drugs & Pharmacology Authors: Cuomo R, Cargiolli M, Cassarano S, Carabotti M, Annibale B Tags: Curr Opin Pharmacol Source Type: research

Applications of peptide hormone ligands for the treatment of dumping and short bowel syndrome.
Abstract 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. Preliminary data suggest that the glucagon-like peptide-1 (GLP-1) analogue liraglutide can also improve dumping. Short bowel syndrome is the most common cause of intestinal failure and involves not only a loss of mucosal absorptive area but also hypersecretion and accelerated transit. GLP-2 is the best studie...
Source: Current Opinion in Pharmacology - September 28, 2018 Category: Drugs & Pharmacology Authors: Wauters L, Vanuytsel T Tags: Curr Opin Pharmacol Source Type: research

Editorial overview: Tuberculosis, malaria and schistosomiasis; understanding resistance and development of new drugs.
PMID: 30262186 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - September 24, 2018 Category: Drugs & Pharmacology Authors: Egan TJ, Warner DF Tags: Curr Opin Pharmacol Source Type: research

Targeting protein misfolding to protect pancreatic beta-cells in type 2 diabetes.
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. Finally, we will consider approaches to prevent protein misfolding and formation of toxic oligomers as potential novel therapeutic targets for type 2 diabetes and other protein misfolding diseases. PMID: 30245473 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - September 20, 2018 Category: Drugs & Pharmacology Authors: Costes S Tags: Curr Opin Pharmacol Source Type: research

New developments in the treatment of gastroparesis and functional dyspepsia.
Abstract 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...
Source: Current Opinion in Pharmacology - September 20, 2018 Category: Drugs & Pharmacology Authors: Tack J, Camilleri M Tags: Curr Opin Pharmacol Source Type: research

Editorial overview: New technologies: multidisciplinary evolutions for drug discovery.
PMID: 30241695 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - September 18, 2018 Category: Drugs & Pharmacology Authors: Bril A, Nosjean O Tags: Curr Opin Pharmacol Source Type: research

Refractory GERD, beyond proton pump inhibitors.
Abstract 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). Potassium-competitive acid blockers (P-CAB) might induce a more important acid inhibition than PPI. Baclofen might act as a reflux inhibitor and demonstrates a significant efficacy in rumination syndrome. The role of topical antacid-alg...
Source: Current Opinion in Pharmacology - September 18, 2018 Category: Drugs & Pharmacology Authors: Roman S, Mion F Tags: Curr Opin Pharmacol Source Type: research

The gut-liver axis in hepatocarcinoma: a focus on the nuclear receptor FXR and the enterokine FGF19.
Abstract 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. This gut-liver FXR-FGF19 dual action is the paradigm of physiological BA regulation and it is currently targeted in ...
Source: Current Opinion in Pharmacology - September 14, 2018 Category: Drugs & Pharmacology Authors: Piglionica M, Cariello M, Moschetta A Tags: Curr Opin Pharmacol Source Type: research

Pre- and probiotic overview.
Abstract 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 disorder...
Source: Current Opinion in Pharmacology - September 13, 2018 Category: Drugs & Pharmacology Authors: Cremon C, Barbaro MR, Ventura M, Barbara G Tags: Curr Opin Pharmacol Source Type: research

Fecal microbiota transfer for bowel disorders: efficacy or hype?
Abstract 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. The latter is currently used for recurrent or severe Clostridium difficile colitis and has been the focus of recent research in IBS and FC. RECENT FINDI...
Source: Current Opinion in Pharmacology - September 12, 2018 Category: Drugs & Pharmacology Authors: Schmulson M, Bashashati M Tags: Curr Opin Pharmacol Source Type: research

Endocannabinoids in the treatment of gasytrointestinal inflammation and symptoms.
Abstract 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. Moreover, discriminating between symptomatic improvement and the real gain on the underlying inflammatory process is often challenging. This r...
Source: Current Opinion in Pharmacology - September 12, 2018 Category: Drugs & Pharmacology Authors: Pesce M, Esposito G, Sarnelli G Tags: Curr Opin Pharmacol Source Type: research

Mucosal permeability and mast cells as targets for functional gastrointestinal disorders.
rholm JD Abstract 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. To target the disturbed mucosal permeability, directly or via mast ce...
Source: Current Opinion in Pharmacology - September 11, 2018 Category: Drugs & Pharmacology Authors: Keita ÅV, Söderholm JD Tags: Curr Opin Pharmacol Source Type: research

In silico models in drug development: where we are.
anz F Abstract 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. PMID: 30205360 [PubMed - as supplied by pub...
Source: Current Opinion in Pharmacology - September 8, 2018 Category: Drugs & Pharmacology Authors: Piñero J, Furlong LI, Sanz F Tags: Curr Opin Pharmacol Source Type: research

Placental peptides regulating islet adaptation to pregnancy: clinical potential in gestational diabetes mellitus.
In conclusion, current data support important roles for placental peptides interacting to support β-cells during pregnancy, however mechanisms involved in humans are unclear. Further work in humans is required, but placental peptides have clinical potential from both a diagnostic and therapeutic perspective. PMID: 30199758 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - September 7, 2018 Category: Drugs & Pharmacology Authors: Simpson S, Smith L, Bowe J Tags: Curr Opin Pharmacol Source Type: research

Recent advances in combinatorial drug screening and synergy scoring.
Abstract 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. Here we discuss the most recent developments in combinatorial drug screening by covering technological advancements in screening strategies,...
Source: Current Opinion in Pharmacology - September 4, 2018 Category: Drugs & Pharmacology Authors: Pemovska T, Bigenzahn JW, Superti-Furga G Tags: Curr Opin Pharmacol Source Type: research

Opioid receptors in the GI tract: targets for treatment of both diarrhea and constipation in functional bowel disorders?
Abstract 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. This review provide a synthetic summary of the most recent literature on the use of drugs acting on mu-receptors to treat two prevalent functional bowel disorders, presenting with opposite bowel habit. Eluxadoline and ...
Source: Current Opinion in Pharmacology - September 3, 2018 Category: Drugs & Pharmacology Authors: Pannemans J, Corsetti M Tags: Curr Opin Pharmacol Source Type: research

Turning omics data into therapeutic insights.
Abstract 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. PMID: 30149217...
Source: Current Opinion in Pharmacology - August 24, 2018 Category: Drugs & Pharmacology Authors: Kedaigle A, Fraenkel E Tags: Curr Opin Pharmacol Source Type: research

The present state of the tuberculosis drug development pipeline.
Abstract 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. Thus, there is a pressing need for a drug regimen that is safer, shorter in duration and superior to current front-line chemotherapy in terms of efficacy. The TB drug pipeline contains several candidates that address one or more of the...
Source: Current Opinion in Pharmacology - August 22, 2018 Category: Drugs & Pharmacology Authors: J Libardo MD, Boshoff HI, Barry CE Tags: Curr Opin Pharmacol Source Type: research

Islet microRNAs in health and type-2 diabetes.
In conclusion, current data lend support to microRNAs being essential regulators of insulin secretion. Future work will describe microRNAs in α-cell function, details of the microRNA-mRNA network, and possibilities to use microRNAs as biomarkers and in therapeutic treatment of T2D and complications. PMID: 30144686 [PubMed - as supplied by publisher] (Source: Current Opinion in Pharmacology)
Source: Current Opinion in Pharmacology - August 22, 2018 Category: Drugs & Pharmacology Authors: Wendt A, Esguerra JL, Eliasson L Tags: Curr Opin Pharmacol Source Type: research

Mechanisms of resistance to the partner drugs of artemisinin in the malaria parasite.
Abstract 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 surveil...
Source: Current Opinion in Pharmacology - August 21, 2018 Category: Drugs & Pharmacology Authors: Martin RE, Shafik SH, Richards SN Tags: Curr Opin Pharmacol Source Type: research

Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?
Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes? Curr Opin Pharmacol. 2018 Aug 21;43:40-45 Authors: Lytrivi M, Igoillo-Esteve M, Cnop M Abstract 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. Mild islet inflammation is histologically detected in pancreas sections of type 2 diabetic patients. In experimental models, it can be triggered by excess nutrients, amyloid, lipopolysaccharide, and endop...
Source: Current Opinion in Pharmacology - August 21, 2018 Category: Drugs & Pharmacology Authors: Lytrivi M, Igoillo-Esteve M, Cnop M Tags: Curr Opin Pharmacol Source Type: research