Long-term use of deferiprone significantly enhances left-ventricular ejection function in thalassemia major patients

A multicenter randomized open-label long-term sequential deferiprone–deferoxamine (DFP-DFO) versus DFP alone trial (sequential DFP-DFO) performed in patients with thalassemia major (TM) was retrospectively reanalyzed to assess the variation in the left ventricular ejection fraction (LVEF) [1].     

Successful long-term outcome after renal transplantation in a patient with atypical haemolytic uremic syndrome with combined membrane cofactor protein CD46 and complement factor I mutations

Background

Atypical haemolytic uremic syndrome (aHUS) is often associated with a high risk of disease recurrence and subsequent graft loss after isolated renal transplantation. Evidence-based recommendations for a mutation-based management after renal transplantation in aHUS caused by a combined mutation with complement factor I (CFI) and membrane cofactor protein CD46 (MCP) are limited.

Case-diagnosis/Treatment

We describe a 9-year-old boy with a first manifestation of aHUS at the age of 9 months carrying combined heterozygous mutations in the CFI and MCP genes. At the age of 5 years, he underwent isolated cadaveric renal transplantation. Fresh frozen plasma was administered during and after transplantation, tapered and finally stopped after 3 years.

Conclusions

During the 5-year follow-up after transplantation there have been no signs of aHUS recurrence and graft function has remained good. The combination of heterozygous MCP and CFI mutations with aHUS might have a positive impact on the post-transplant course, possibly predicting a lower risk of aHUS recurrence after an isolated cadaveric renal transplantation     

Proteomic and metabolomic profiling reveals time-dependent changes in hippocampal metabolism upon paroxetine treatment and biomarker candidates

Most of the commonly used antidepressants block monoamine reuptake transporters to enhance serotonergic or noradrenergic neurotransmission. Effects besides or downstream of monoamine reuptake inhibition are poorly understood and yet presumably important for the drugs' mode of action. In the present study we aimed at identifying hippocampal cellular pathway alterations in DBA/2 mice using paroxetine as a representative Selective Serotonin Reuptake Inhibitor (SSRI). Furthermore we identified biomarker candidates for the assessment of antidepressant treatment effects in plasma. Hippocampal protein levels were compared between chronic paroxetine- and vehicle-treated animals using in vivo¹⁵N metabolic labeling combined with mass spectrometry. We also studied the time course of metabolite level changes in hippocampus and plasma using a targeted polar metabolomics profiling platform. In silico pathway analyses revealed profound alterations related to hippocampal energy metabolism. Glycolytic metabolite levels acutely increased while Krebs cycle metabolite levels decreased upon chronic treatment. Changes in energy metabolism were influenced by altered glycogen metabolism rather than by altered glycolytic or Krebs cycle enzyme levels. Increased energy levels were reflected by an increased ATP/ADP ratio and by increased ratios of high-to-low energy purines and pyrimidines. In the course of our analyses we also identified myo-inositol as a biomarker candidate for the assessment of antidepressant treatment effects in the periphery. This study defines the cellular response to paroxetine treatment at the proteome and metabolome levels in the hippocampus of DBA/2 mice and suggests novel SSRI modes of action that warrant consideration in antidepressant development efforts.     

Modern drug delivery strategies applied to natural active compounds

Introduction: Colloidal drug delivery systems (CDDSs) are innovative carriers that have been studied in pharmaceutical field from many years to overcome unfavorable physical and chemical features of synthetic drugs. Recently the use of CDDS as carriers for phytochemicals has seen an exponential increase which, in some cases, has led to the rediscovery of ancient and forgotten natural molecules.

Area covered: This article focuses on the main features of CDDS, particularly micro- and nanoemulsions, vesicular carriers and micro- and nanoparticles, loaded with natural active compounds. A detailed review of the literature is presented, introducing the importance of these systems in terms of their capability to optimize the stability of phytochemicals, their absorption through biological membranes and their bioavailability.

Expert opinion: The delivery of phytochemicals is problematic due to poor solubility, poor permeability, low bioavailability, instability in biological milieu and extensive first-pass metabolism. Global research efforts investigating nanotechnology have attempted to overcome these limitations rediscovering and, in some cases, ‘discovering ex novo’ unexpected virtues and benefits associated to these compounds. The ‘nanotechnological approach’ can definitely enhance the pharmacokinetics and therapeutic index of natural active compounds and improve their performance in therapy.     

Evidence of early development of action planning in the human foetus: a kinematic study

The aim of the present study was to investigate whether foetal hand movements are planned and how they are executed. We performed a kinematic analysis of hand movements directed towards the mouth and the eyes in the foetuses of eight women with normally evolving pregnancies. At 14, 18 and 22 weeks of gestation, eight foetuses underwent a 20-min four-dimensional-ultrasound session. The video recordings for these movements were then imported into in-house software developed to perform kinematic analysis. We found that spatial and temporal characteristics of foetal movements are by no means uncoordinated or unpatterned. By 22 weeks of gestation the movements seem to show the recognizable form of intentional actions, with kinematic patterns that depend on the goal of the action, suggesting a surprisingly advanced level of motor planning.     

High throughput functional microdissection of pathogen-specific T-cell immunity using antigen and lymphocyte arrays

The analysis of the human T-cell response specific for relevant pathogens is useful for diagnostic purposes and for research. Several methods enumerate antigen specific T-cells and measure their functions. Since screening of numerous antigens from pathogens is often needed to evaluate immunocompetence, lymphocytes, labor and cost are limiting factors. To examine pathogen-specific T-cell immunity, we have miniaturized the analysis of T-cell responses using an array approach in 384- and 1536-well plates with as few as 10 x 10(3) PBMC per well instead of the 500 x 10(3) PBMC used for current assays. Secreted cytokines were detected in the same wells used for lymphocyte cultures. The method can detect about ten CMV specific T-cells diluted into 50 x 10(3) PBMC (0.02%), and can quantify secreted cytokines. The microarray approach allowed evaluation of T-cell immunity in children with a sensitivity higher than current methods. When applied to CMV epitope mapping, the data obtained with conventional methods were confirmed. The assay could be automated, allowing high throughput processing. The assay provides quantitative information on cytokines induced by antigen stimulation and can be applied in a simplified format as a field test to monitor T-cell immunity in vaccine trials or in veterinary medicine.     

Borrelia lusitaniae in immature Ixodes ricinus (Acari: Ixodidae) feeding on common wall lizards in Tuscany, central Italy

Lizards and small rodents were live captured in Tuscany, central Italy, from May through August 2005. Prevalence of infestation by larval Ixodes ricinus L. (Acari: Ixodidae) and mean numbers of larvae per host were not significantly different for common wall lizards, Podarcis muralis Laurenti, and Apodemus spp. mice, whereas infestation levels by nymphs were significantly greater on lizards. Borrelia lusitaniae, which was previously shown to be dominant in host-seeking I. ricinus in the same study area, was detected by polymerase chain reaction (PCR) in 19.8% (95% confidence interval: 14.4, 26.0) of larval ticks and in 52.9% (27.8, 77.0) of nymphs that were collected from lizards. Moreover, 18.8% (7.2, 36.4) and 25.0 (3.2, 65.1) of lizards' tail biopsies and blood samples, respectively, were positive for B. lusitaniae. Conversely, attached ticks and ear biopsies from Apodemus spp. mice were PCR negative. Passerine birds belonging to 10 species were live captured in March 2005, and Borrelia valaisiana was detected in 57.1% (18.4, 90.1) of I. ricinus nymphs feeding on Eurasian blackbirds, Turdus merula L. Results of this study suggest that lizards play an important role as reservoirs for B. lusitanae and may affect the dominance of this genospecies in the Mediterranean area.