Pharmacology

Diphenyl Ditelluride-Induced Cell Cycle Arrest And Apoptosis: A Relation With Topoisomerase I Inhibition
The diphenyl ditelluride (DPDT) is a prototype for the development of new biologically active molecules. In previous studies, DPDT showed an elevated cytotoxicity in Chinese hamster fibroblast (V79) cells but the mechanisms for reduction of cell viability still remain unknown. DPDT showed mutagenic properties by induction of frameshift mutations in bacterium Salmonella typhimurium and yeast Sac...


Compliance with Recommendations on Outpatient Antibiotic Prescribing for Respiratory Tract Infections: The Case of Spain
Inappropriate antibiotic use in primary care, such as in Respiratory Tract Infections (RTIs), is an important cause of bacterial resistance. This study aimed at describing the current pattern of outpatient antibiotic use in acute RTIs in Spain and evaluating adherence to national recommendations. A retrospective observational study was performed including all the episodes of RTIs registered dur...
Confidence intervals for the difference between independent binomial proportions: comparison using a graphical approach and moving averages
This paper uses graphical methods to illustrate and compare the coverage properties of a number of methods for calculating confidence intervals for the difference between two independent binomial proportions. We investigate both small-sample and large-sample properties of both two-sided and one-sided coverage, with an emphasis on asymptotic methods. In terms of aligning the smoothed coverage pr...


Re-evaluating the PCP challenge as a pre-clinical model of impaired cognitive flexibility in schizophrenia
Nmda-r antagonists are a popular translational pharmacological challenge to induce cognitive deficits associated with schizophrenia. Amongst their many cognitive and non-cognitive effects is an ability to impair cognitive flexibility in general, and reversal learning in particular. Here, we test the hypothesis that the nmda-r antagonist phencyclidine when given acutely selectively effects rever...
Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice
Social behavior plays a fundamental role in life of many animal species, allowing the interaction between individuals and sharing of experiences, needs, and goals across them. In humans, some neuropsychiatric diseases, including anxiety, posttraumatic stress disorder and autism spectrum disorders, are often characterized by impaired sociability. Here we report that N-Methyl-3,4-methylenedioxyam...


Modulation of K2P2.1 and K2P10.1 K+ channel sensitivity to carvedilol by alternative mRNA translation initiation
The β-receptor antagonist carvedilol blocks a range of ion channels. K2P2.1 (TREK1) and K2P10.1 (TREK2) channels are expressed in the heart and regulated by alternative translation initiation (ATI) of their mRNA, producing functionally distinct channel variants. The first objective was to investigate acute effects of carvedilol on human K2P2.1 and K2P10.1 channels. Second, we sought to study A...
In vitro, in vivo and ex-vivo characterization of ibrutinib: A potent inhibitor of MRP1 efflux function
Multidrug resistance protein 1 (MRP1, ABCC1) plays a critical role in the development of multidrug resistance (MDR). Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). Here we investigated the reversal effect of ibrutinib on MRP1-mediated MDR. EXPERIMENTAL APPROACHCytotoxicity was determined by M assay. The expression of protein was detected by Western blot. RT-PCR and Q-PCR were perf...

A nonerythropoietic peptide derivative of erythropoietin decreases susceptibility to diet-induced insulin resistance in mice
The hematopoietic activity of erythropoietin (EPO) is mediated by the classic EPO receptor (EpoR) homodimer, whereas the tissue-protective effects by a hetero-complex between EpoR and the β-common receptor (βcR). Here, we investigated the effects of a novel, selective ligand of the hetero-complex EpoR/βcR (pyroglutamate helix B surface peptide [pHBSP]) in mice chronically exposed to a diet e...
Maternal and foetal adverse events with tumour necrosis factor-alpha inhibitors in inflammatory bowel disease
Transplacental transfer of tumour necrosis factor-alpha (TNF-α) inhibitors has been shown in mothers receiving therapy for inflammatory bowel disease (IBD). To examine reports of adverse events of these medications in pregnancy. Individual Safety Reports of adverse events (Jan 2003–June 2012) were accessed from the Food and Drug Administration Adverse Event Reporting System. The study data s...

Sevoflurane post-conditioning increases nuclear factor erythroid 2-related factor and haemoxygenase-1 expression via protein kinase C pathway in a rat model of transient global cerebral ischaemia
The antioxidant mechanism of sevoflurane post-conditioning-induced neuroprotection remains unclear. We determined whether sevoflurane post-conditioning induces nuclear factor erythroid 2-related factor (Nrf2, a master transcription factor regulating antioxidant defence genes) and haemoxygenase-1 (HO-1, an antioxidant enzyme) expression, and whether protein kinase C (PKC) is involved in Nrf2 act...
The Phosphatidylinositol(4,5)Bisphosphate-Binding Sequence of Transient Receptor Potential Channel Canonical 4alpha Is Critical for Its Contribution to Cardiomyocyte Hypertrophy
Cardiomyocyte hypertrophy requires a source of Ca2+ distinct from the Ca2+ that regulates contraction. The canonical transient receptor potential channel (TrpC) family, a family of cation channels regulated by activation of phospholipase C (PLC), has been implicated in this response. Cardiomyocyte hypertrophy downstream of Gq-coupled receptors is mediated specifically by PLCβ1b that is sca...

G-Protein betagamma Subunit Dimers Modulate Kidney Repair after Ischemia-Reperfusion Injury in Rats
Heterotrimeric G-proteins play a crucial role in the control of renal epithelial cell function during homeostasis and in response to injury. In this report, G-protein β subunit (Gβ) dimer activity was evaluated during the process of tubular repair after renal ischemia-reperfusion injury (IRI) in male Sprague Dawley rats. Rats were treated with a small molecule inhibitor of Gβ act...
IPX066, a mixed immediate/sustained-release levodopa preparation for Parkinson’s disease
L-DOPA has long been the ‘gold standard’ treatment for Parkinson’s disease (PD), but suffers from poor oral bioavailability and rapid pharmacokinetic elimination. A longer acting preparation has long been sought. Areas covered: We conducted PubMed search for IPX066 and reviewed abstracts from meetings that included the topic of PD. IPX066 is a novel mixed immediate release (IR) and sustai...
The need to improve current psychopharmacotherapy before developing new drugs
CNS research has become unprofitable, and several pharmaceutical companies have reduced financial support for developing new CNS drugs. Until the situation can be changed, it is our duty to optimize the usage of the currently available psychoactive drugs. Several tools for optimizing pharmacotherapy are available, such as therapeutic drug monitoring and genotyping and phenotyping CYP enzymes. F...
Effects of the D1 Dopamine Receptor Agonist Dihydrexidine (DAR-0100A) on Working Memory in Schizotypal Personality Disorder
Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D1 receptor agonist dihydrexidine (DAR-0100A) could attenuate wor...