Capsulotomy worsens diabetic retinopathy in the Ins2Akitamice

Purpose: Cataract surgery increases the risk of developing diabetic retinopathy (DR) and accelerates the progression of pre-existing DR. Recent evidence suggests that cataract surgery elicits retinal pro-inflammatory gene expression, although the underlying pathogenic mechanisms remain ill-defined. In this study, we investigated the effect of capsulotomy on visual function, retinal immune cell activation and photoreceptor stress in the Ins2Akita mice, a mouse model of Type-1 diabetes. Methods: Male heterozygous Ins2Akita mice (2 months of hyperglycemia) and C57BL/6J age-matched siblings were used in this study. An incision (1mm) was made in the peripheral cornea and Capsulotomy was performed in the anterior lens capsule of the right eye. Control mice received corneal incision without capsulotomy in the right eye. The unoperated left eyes were used as internal controls. Forty days following surgery, retinal function was assessed by electroretinography (ERG). Neuronal retinal damage and microglial activation were assessed by imunohistochemistry. Results: The Ins2Akita mice receiving capsulotomy presented lower scotopic a-wave, b-wave and oscillatory potentials amplitudes compared to other experimental groups. Fundus images, SD-OCT and H&E staining did not show significant changes between different groups. Immunostaining of Iba-1 and CD68 revealed exacerbated microglial activation and giant cell immune cell infiltration in eyes receiving capsulotomy in Ins2Akita mice. This was accompanied by a disruption of cone photoreceptor outer segments and abnormal rhodopsin expression at the outer nuclear layer. Conclusions: Our results suggest that capsulotomy induces retinal microglial activation and worsens retinal neuropathy in diabetic eyes.

A comparison of carbon flow from pre-labelled and pulse-labelled plants

Perennial rye-grass was subjected to two different¹⁴C labelling regimes to enable a partitioning of the carbon sources contributing to rhizosphere carbon-flow. Plant/soil microcosms were designed which enabled rye-grass plants to either receive a single pulse of¹⁴C-CO₂ or to be pre-labelled using a series of¹⁴C-CO₂ pulses, allowing the fate of newly photoassimilated carbon and carbon lost by root decomposition to be followed into the soil. For young rye-grass plants grown over a short period, rhizosphere carbon flow was found to be dominated by newly photoassimilated carbon. Evidence for this came from the observed percentage of the total¹⁴C budget (i.e. total¹⁴C-CO₂ fixed by the plants) lost from the root/soil system, which was 30 times greater for the pulse labelled compared to pre-labelled plants. Root decomposition was found to be less at 10°C compared to 20-25°C, though input of¹⁴C into the soil was the same at both temperatures. © 1988 Kluwer Academic Publishers.

Using Flory-Huggins phase diagrams as a pre-formulation tool for the production of amorphous solid dispersions; a comparison between hot-melt extrusion and spray drying

Objectives: Amorphous drug forms provide a useful method of enhancing the dissolution performance of poorly water-soluble drugs; however, they are inherently unstable. In this article, we have used Flory–Huggins theory to predict drug solubility and miscibility in polymer candidates, and used this information to compare spray drying and melt extrusion as processes to manufacture solid dispersions.
Method:  Solid dispersions were characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry) and spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods. 
Key Findings: Spray drying permitted generation of amorphous solid dispersions to be produced across a wider drug concentration than melt extrusion. Melt extrusion provided sufficient energy for more intimate mixing to be achieved between drug and polymer, which may improve physical stability. It was also confirmed that stronger drug–polymer interactions might be generated through melt extrusion. Remixing and dissolution of recrystallised felodipine into the polymeric matrices did occur during the modulated differential scanning calorimetry analysis, but the complementary information provided from FTIR confirms that all freshly prepared spray-dried samples were amorphous with the existence of amorphous drug domains within high drug-loaded samples. 
Conclusion: Using temperature–composition phase diagrams to probe the relevance of temperature and drug composition in specific polymer candidates facilitates polymer screening for the purpose of formulating solid dispersions.

A Correlation between the Dynamic Viscosity and Crystallisation of Felodipine from its Amorphous Polymer Solid Dispersion

Purpose Previously, it has been reported that molecular mobility determines the rate of molecular approach to crystal surfaces, while entropy relates to the probability of that approaching molecule having the desirable configuration for further growth of the existing crystal; and the free energy dictates the probability of that molecule not returning to the liquid phase1. If we plot the crystal growth rate and viscosity of a supercooled liquid in a log-log format, the relationship between the two is linear, indicating the influence viscosity has upon crystal growth rate. However, such approximation has been derived from pure drug compounds and it is apparent that further understanding of crystallization from drug-polymer solid dispersion is required in order to stabilise drugs embedded within amorphous polymeric solid dispersions. Methods Mixtures of felodipine and polymer (HPMCAS-HF, PVPK15 and Soluplus®) at specified compositions were prepared using a Restch MM200 ball mill. To examine crystal growth within amorphous solid dispersions, samples were prepared by melting 5-10 mg of ball milled mixture at 150°C for 3-5 minutes on a glass slip pre-cleaned with methanol and acetone. All prepared samples were confirmed to be crystal free by visual observation using a polarised light microscope (Olympus BX50). Prepared samples were stored at 0% RH (P2O5), inside desiccators, maintained in ovens at 80°C. For the dynamic viscosity measurement, approximately 100-200mg ball milled mixture was heated on the base plate of a rotational rheometer at 150°C for 5 minutes and the top plate was lowered to a defined gap to form a good contact with the material. The sandwiched amorphous material was heated to 80°C and the viscosity was measured. Results The equation was used to probe the correlation of viscosity to crystal growth rate. In comparison to the value of xi in log-log equation reported from pure drug compound, a value of 1.63 was obtained for FD-polymer solid dispersions irrespective of the polymer involved. &#8733 Conclusion The high xi value suggests stronger viscosity dependence may exist for amorphous FD once incorporated with amorphous polymer.

Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms pre-exposed to sub-inhibitory concentrations of vancomycin

Staphylococcus epidermidis biofilm formation is responsible for the persistence of orthopedic implant infections. Previous studies have shown that exposure of S. epidermidis biofilms to sub-MICs of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC-vancomycin-treated S. epidermidis biofilms was impeded compared to that of control, untreated biofilms. Further experiments showed an increase in the extracellular DNA (eDNA) concentration in biofilms preexposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added, S. epidermidis DNA increased the planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (ITC) revealed that the binding constant of DNA and vancomycin was 100-fold higher than the previously reported binding constant of vancomycin and its intended cellular D-Ala-D-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC-vancomycin-treated S. epidermidis biofilms, which might be an important factor for the persistence of biofilm infections.

The significance of bruising in the pre-mobile infant

The majority of children in our society are loved andcherished. The occasional cases of intentional injury to a childresulting in death or significant harm evoke powerful anduncomfortable feelings (Devaney et al, 2013), and the publicoutcry may result in health and social workers facing criticism.Identifying whether an infant is at risk of abuse is a challengefor practitioners, and can be a source of stress and anxiety(Brandon et al, 2011). Bruising is a strong indicator of childabuse involving intentional injury (Kemp et al, 2014). Theincidence of bruising correlates to developmental stage, withnon-mobile infants least likely to incur bruising. Therefore, itspresence in pre-mobile infants requires immediate assessment.A search of the literature around bruising in pre-mobile infantsrevealed themes of missed opportunities for early intervention,the role of the father in the family and the significance of childdevelopment. Sharing of knowledge and expertise within themultidisciplinary team is key to safeguarding infants.