Neuropilins in physiological and pathological angiogenesis

Neuropilin-1 (Np1) and neuropilin-2 (Np2) are transmembrane glycoproteins with large extracellular domains that interact with both class 3 semaphorins and vascular endothelial growth factor (VEGF), and are involved in the regulation of many physiological pathways, including angiogenesis. The neuropilins also interact directly with the classical receptors for VEGF, VEGF-R1 and -R2, mediating signal transduction. The heart, glomeruli and osteoblasts express both Np1 and Np2, but there is differential expression in the adult vasculature, with Np1 expressed mainly by arterial endothelium, whereas Np2 is only expressed by venous and lymphatic endothelium. Both neuropilins are commonly over-expressed in regions of physiological (wound-healing) and pathological (tumour) angiogenesis, but the signal transduction pathways, neuropilin-mediated gene expression and the definitive role of neuropilins in angiogenic processes are not fully characterized. This review details the current evidence for the role of neuropilins in angiogenesis, and suggests future research directions that may enhance our understanding of the mechanisms of action of this unique family of proteins.     

Iodinated curcumin bearing dermal cream augmented drug delivery,antimicrobial and antioxidant activities

Objectives: Curcumin (Cur) exhibits weak microbicidal activity owing to high lipophilicity and low cell permeability. Therefore, in the present investigation, Cur was iodinated using elemental iodine (I₂) to synthesise Cur–I₂ powder that was later formulated as Cur–I₂ dermal cream and characterised in vitro for antimicrobial and antioxidant activities.

Methods and results: Electrophilic addition of I₂ saturated the olefinic bonds of Cur, as confirmed by UV/visible spectroscopy, FT-IR, ¹H NMR and DSC techniques. In addition, in vitro skin permeation and retention analysis indicated that Cur–I₂ cream followed the first order and Higuchi model for drug release through the rat skin. The minimum inhibitory concentration (MIC) of Cur–I₂ powder was measured to be 60 and 90?µg/ml significantly (p?Staphylococcus aureus and Escherichia coli, respectively. Moreover, Cur–I₂ also exhibited strong antioxidant potential.

Conclusions: Cur–I₂ cream warrants further in vivo study to scale up the technology for clinical translation.     

DNA interaction,anti-proliferative effect of copper oxide nanocolloids prepared from metallosurfactant based microemulsions acting as precursor,template and reducing agent

In the present study, we have synthesized mixed cuprous/copper oxide nanosuspensions by metallosurfactant based microemulsion technique. Three metallosurfactants were synthesized which includes two non-ionic double chained metallosurfactants with C₁₂, C₁₆ chains with coordinated copper i.e. Cudda and Cuhexa, respectively. Another cationic double chained metallosurfactant with loosely bound metal (Cuctac) was also prepared. The prepared metallocomplexes were characterized using FTIR, elemental analysis, and NMR. The effect of the position of metallosurfactant in microemulsion on the fabrication and properties of nanosuspensions was elucidated. In this method, no external reducing agent and capping agent were added and tween 80 acted both as reducing and stabilizing agent for the nanoparticles. The synthesized nanoparticles were characterized and it was observed that mixed copper and cuprous oxide particles are present in colloidal suspension for all the three studied metallosurfactants. The kinetics of formation of mixed copper/cuprous oxide nanosuspensions (Ns) and their stability was estimated using Uv-visible spectroscopy. Further, the binding and interactions of copper nanosuspensions with calf Thymus DNA (CT-DNA) were assessed using Uv–vis spectroscopy, circular dichroism and gel electrophoresis. Additionally, the antioxidant activity of the Cu Ns was checked using DPPH assay. The role of positive charge on nanoparticles as evaluated from Zeta potential was responsible for DNA affinity. The DNA conformational changes in the presence of nanosuspensions and relevant scavengers were investigated. Further, the anti-proliferative activity of copper Ns was assessed using HeLa cells and Cuhexa derived Ns were proved to be active with highest activity at a low concentration and were nontoxic towards normal cell lines. In summary, this work demonstrates a softer approach for the synthesis of copper nanosuspensions with a size range of 2–5?nm and evaluated the role of type and structure of metallosurfactant on size, stability of particles and anti-proliferative activity.     

Regional variation in hospitalisation and mortality in heart failure: comparison of England and Lombardy using multistate modelling

Heart failure (HF) is a common, serious chronic condition with high morbidity, hospitalisation and mortality. The healthcare systems of England and the northern Italian region of Lombardy share important similarities and have comprehensive hospital administrative databases linked to the death register. We used them to compare admission for HF and mortality for patients between 2006 and 2012 (n = 37,185 for Lombardy, 234,719 for England) with multistate models. Despite close similarities in age, sex and common comorbidities of the two sets of patients, in Lombardy, HF admissions were longer and more frequent per patient than in England, but short- and medium-term mortality was much lower. English patients had more very short stays, but their very elderly also had longer stays than their Lombardy counterparts. Using a three-state model, the predicted total time spent in hospital showed large differences between the countries: women in England spent an average of 24 days if aged 65 at first admission and 19 days if aged 85; in Lombardy these figures were 68 and 27 days respectively. Eight-state models suggested disease progression that appeared similar in each country. Differences by region within England were modest, with London patients spending more time in hospital and having lower mortality than the rest of England. Whilst clinical practice differences plausibly explain these patterns, we cannot confidently disentangle the impact of alternatives such as coding, casemix, and the availability and use of non-hospital settings. We need to better understand the links between rehospitalisation frequency and mortality.