Control of osmotic pressure to improve cell viability in cell‐laden tissue engineering constructs

Design of tissue engineering strategies deals with the need to balance both biomaterials characteristics and techniques specificities, often resulting in cell‐compromising processing conditions. One important factor often disregarded is the osmotic pressure to which cells are exposed. An in‐house microfluidic system was used to prove that addition of an osmotic regulator significantly benefits the generation of viable cell‐laden hydrogels under harsh processing conditions. Human adipose‐derived stem cells were resuspended in 1.5% alginate and 1% gellan gum (GG; w/v) solutions containing different concentrations (0.12 m , 0.25 m and 1.5 m ) of sucrose as osmotic regulator. GG (in water) and alginate (in water or phosphate‐buffered saline) solutions were used to vary the conditions under which cells were kept prior processing. Independently of the polymer, addition of sucrose did not affect the processing conditions or the viscosity of the solutions, except at 1.5 m . The obtained results clearly demonstrate that inclusion of 0.25 m sucrose during processing of the cell‐laden hydrogels allowed to keep cell viability around 80%, in opposition to the 20% observed in its absence, both for GG and alginate‐derived hydrogels prepared in water. Impressively, the level of cell viability observed with the inclusion of 0.25 m sucrose, 76% for GG and 86% for alginate, was similar to that obtained with the standard alginate solution prepared in phosphate‐buffered saline (82%). The beneficial effect of sucrose was observed within the first 5 min of processing and was maintained for prolonged experimental setups with viability values above 50%, even after a 2‐h time‐frame and independently of the material.     

High-dose contrast-enhanced MRI in multiple sclerosis

Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-D03A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-D03A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions.     

Ethical questions in the treatment of subjects with dementia. Part I. Respecting autonomy: awareness, competence and behavioural disorders

The document deals with some ethical issues raised by the treatment of demented people. In particular the conceptual and empirical aspects of the assessment of awareness and competence of these patients are analysed, as well as the dilemmas related to the treatment of behavioral disorders.     

Gadolinium enhanced MRI predicts clinical and MRI disease activity in relapsing-remitting multiple sclerosis.

The aim of the study was to evaluate the predictive power of baseline gadolinium (Gd) enhanced MRI in relation to subsequent clinical and MRI activity. Sixty eight patients with clinically definite relapsing-remitting multiple sclerosis had a baseline Gd enhanced MRI and were followed up clinically and by monthly Gd enhanced MRI for six months. The occurrence of relapses during the follow up period was predicted by the presence of at least one enhancing lesion on the baseline MRI (P < 0.05). The number and volume of enhancing lesions at baseline were significantly associated with both enhancing lesions observed during the follow up period (P < 0.0001) and the accumulation of abnormality on T2 weighted images (P < 0.0001). Moreover, the presence of three or more enhancing lesions at baseline scan was consistently associated with the development of permanent abnormalities on T2 weighted images six months later. The study suggests that the number and volume of Gd enhancing lesions at a single examination are strong short term predictors of subsequent clinical and MRI activity.     

Small hepatic veins Budd–Chiari syndrome

Budd–Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction at any level from the small hepatic veins to the atrio-caval junction, in the absence of heart failure or constrictive pericarditis. Various imaging modalities are available for investigating the gross hepatic vascular anatomy but there are rare forms of this disease where the obstruction is limited to the small intrahepatic veins, with normal appearance of the large hepatic veins at imaging. In this cases only a liver biopsy can demonstrate the presence of a small vessels outflow block. We report two cases of small hepatic veins Budd–Chiari syndrome.