Pharmacology

Addiction, families and treatment: A critical realist search for theories that can improve practice
The stress–strain-coping-support (SSCS) model and the social-ecological (SE) model were analysed in a search for theories that can serve as a foundation for improving the assistance and support provided to families affected by addiction and alcohol and drug (AOD) problems. The basis for the analyses was a critical realist one, viewing addiction as a multilayered and necessarily laminated phen...


Development of a bifunctional filter for prion protein and leukoreduction of red blood cell components
Leukofiltration of blood components is currently implemented worldwide as a precautionary measure against white blood cell–associated adverse effects and the potential transmission of variant Creutzfeldt-Jakob disease (vCJD). A newly developed bifunctional filter (Sepacell Prima, Asahi Kasei Medical) was assessed for prion removal, leukoreduction (LR), and whether the filter significantly aff...
A Universal Framework for the Benefit-Risk Assessment of Medicines: Is This the Way Forward?
A universal framework for the evaluation of the benefit-risk assessment of medicines during development by pharmaceutical companies and in the regulatory review by regulatory authorities is considered of value, as it would result in the systematic structured approach to support transparency in decision making. Several organizations have developed frameworks over the past few years, including th...


Long-Term (1 Year) Safety and Efficacy of Methylphenidate Modified-Release Long-Acting Formulation (MPH-LA) in Adults with Attention-Deficit Hyperactivity Disorder: A 26-Week, Flexible-Dose, Open-Label Extension to a 40-Week, Double-Blind, Randomised, Pla
Previously, in a 40-week, randomised, double-blind, placebo-controlled core study comprising three phases (9-week dose confirmation, 5-week open-labeldose optimisation and 6-month maintenance of effect) in adults with attention-deficit/hyperactivity disorder (ADHD), methylphenidate modified-release long-acting formulation (MPH-LA) at 40–80 mg/day controlled ADHD symptoms as well as decreased...
Fresh from the designation pipeline: orphan drugs recently designated in the EU (March–April 2014)
Many rare diseases could benefit from a therapeutic point of view; examples include targeted gene therapies or ‘borrowing’ therapies from other diseases based on their mechanism of action, which is similar to that of the rare disease in question. Areas covered: This paper discusses five of the most recent orphan drug designations in the EU. Their corresponding compounds are to treat severe ...


Phosphodiesterase type 5 inhibitors for stuttering priapism: recent advances
Stuttering priapism is a recognized clinical problem in patients afflicted with sickle-cell disease. It is both distressing physically and psychologically due to its recurrent nature and the need for emergent treatment, that is, corporal aspiration. The use of phosphodiesterase type 5 inhibitors (PDE5i) is counterintuitive, as this class of drugs is used for the treatment of erectile dysfunctio...
Potential role of cardiac chloride channels and transporters as novel therapeutic targets
The heart and blood vessels express a range of anion currents (e.g. I Cl. PKA) and symporter/antiporters (e.g. Cl−/HCO3 − exchanger) that translocate chloride (Cl−). They have been proposed to contribute to a variety of physiological processes including cellular excitability, cell volume homeostasis and apoptosis. Additionally there is evidence that Cl− currents or transporters may play...

Targeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28
The Wnt signaling pathways are a group of signal transduction pathways that play an important role in cell fate specification, cell proliferation and cell migration. Aberrant signaling in these pathways has been implicated in the development and progression of multiple cancers by allowing increased proliferation, angiogenesis, survival and metastasis. Activation of the Wnt pathway also contribu...
Small molecule Mcl-1 inhibitors for the treatment of cancer
The Bcl-2 family of proteins serves as primary regulators of apoptosis. Myeloid cell leukemia 1 (Mcl-1), a pro-survival member of the Bcl-2 family of proteins, is overexpressed and the Mcl-1 gene is amplified in many tumor types. Moreover, the overexpression of Mcl-1 is the cause of resistance to several chemotherapeutic agents. Thus, Mcl-1 is a promising cancer target. This review highlights t...

Cells and secretome – towards endogenous cell re-activation for cartilage repair
Regenerative medicine approaches to cartilage tissue repair have mainly been concerned with the implantation of a scaffold material containing monolayer expanded cells into the defect, with the aim to differentiate the cells into chondrocytes. While this may be a valid approach, the secretome of the implanted cells and its effects on the endogenous resident cells, is gaining in interest. This r...
Engineering strategies to mimic the glioblastoma microenvironment
Glioblastoma multiforme (GBM) is the most common and deadly brain tumor, with a mean survival time of only 21months. Despite the dramatic improvements in our understanding of GBM fueled by recent revolutions in molecular and systems biology, treatment advances for GBM have progressed inadequately slowly, which is due in part to the wide cellular and molecular heterogeneity both across tumors an...

Biomechanical forces in the skeleton and their relevance to bone metastasis: Biology and engineering considerations
Bone metastasis represents the leading cause of breast cancer related-deaths. However, the effect of skeleton-associated biomechanical signals on the initiation, progression, and therapy response of breast cancer bone metastasis is largely unknown. This review seeks to highlight possible functional connections between skeletal mechanical signals and breast cancer bone metastasis and their contr...
Naturally derived and synthetic scaffolds for skeletal muscle reconstruction
Skeletal muscle tissue has an inherent capacity for regeneration following injury. However, severe trauma, such as volumetric muscle loss, overwhelms these natural muscle repair mechanisms prompting the search for a tissue engineering/regenerative medicine approach to promote functional skeletal muscle restoration. A desirable approach involves a bioscaffold that simultaneously acts as an induc...
Inhaled antimicrobial therapy – Barriers to effective treatment
Inhaled antibiotics dramatically improve targeting of drug to the site of respiratory infections, while simultaneously minimizing systemic exposure and associated toxicity. The high local concentrations of antibiotic may enable more effective treatment of multi-drug resistant pathogens. This review explores barriers to effective treatment with inhaled antibiotics. In addition, potential opportu...
Hypothermia after cardiac arrest does not affect serum levels of neuron-specific enolase and protein S-100b
We investigated the brain-derived proteins neuron-specific enolase (NSE) and protein S-100b (S-100b) in survivors of cardiac arrest who had either received therapeutic hypothermia (TH) or had not. In a retrospective cohort study, we analysed serum levels of these two proteins over 5 days in 201 adult cardiac arrest survivors admitted to our intensive care unit between 2003 and 2010. These were ...