Structural characterisation of poly(amidoamine) networks via high-resolution magic angle spinning NMR.

A comprehensive structural characterisation of cross-linked insoluble poly(amidoamine) (PAA) networks was performed by high-resolution magic angle spinning (HRMAS) NMR spectroscopy. Model samples with 20%, 40% and 80% cross-linking degrees were prepared and the best conditions to obtain high-resolution spectra in the gel phase determined. Whereas the samples with 20% and 40% cross-linking degrees could be exhaustively resolved and described, the sample with 80% cross-linking degree could not be characterised by this technique owing to insufficient mobility of the polymer segments. Even with this limitation, the method developed in this study can be reasonably considered as a general one, which enables exhaustive characterisation of cross-linked PAA networks of biomedical interest.

Understanding the mechanism of action of poly(amidoamine)s as endosomolytic polymers: correlation of physicochemical and biological properties.

Bioresponsive poly(amidoamine)s (PAA)s are currently under development as endosomolytic polymers for intracellular delivery of proteins and genes. Here for the first time, small-angle neutron scattering (SANS) is used to systematically investigate the pH-dependent conformational change of an endosomolytic polymer, the PAA ISA 23. The radius of gyration of the ISA23 was determined as a function of pH and counterion, the aim being to correlate changes in polymer conformation with membrane activity assessed using a rat red blood cell haemolysis assay. With decreasing pH, the ISA23 radius of gyration increased to a maximum (R(g) approximately 80 A) around pH = 3, before subsequently decreasing once more. At high pH and therefore high ionic strengths, the polymer is negatively charged and adopts a rather compact structure (R(g) approximately 20 A), presumably with the dissociated carboxylic groups on the exterior of the polymer coil. At low pH, the coil again collapses (R(g) < 20 A), presumably due to the effects of the high ionic strength. It is concluded that the nature of the salt form has no direct bearing on the size of the polymer coil, but it does indirectly determine the prevailing pH and, hence, polymer conformation. Pulsed-gradient spin-echo NMR measurements were in good agreement with the SANS estimates of the radius of gyration, although ISA23 polydispersity does complicate the data interpretation/comparison. These results support the proposed mode of action of PAAs, namely a coil expansion on passing from a neutral pH (extracellular) to an acidic pH (endosomal and lysosomal) environments. The results do, however, suggest that the charge on the polymer shows a closer correlation with the haemolysis activity rather than the polymer conformation.

[Evaluation of long term care institutions for the aged in the Federal District. A critical viewpoint]. / Evaluación de instituciones de cuidados prolongados para ancianos en el Distrito Federal. Una visión crítica.

OBJECTIVE: To critically analyze the level and quality of infrastructure, human resources and organization of long term care institutions for the elderly in Mexico City and to describe the functional status and care requirements of their residents. MATERIAL AND METHODS: A census was made of the institutions located in the metropolitan area of Mexico City which totalled 115. These were classified according to their belonging to the public or private sector (for profit and non-profit). In each category we made a random selection of 33 institutions which were all assessed according to the methodology described by Firevicius and applied by PAHO in several countries in Latin-America. This questionnaire was applied by a single interviewer. Within the selected institutions, 30% of the residents, who were also randomly selected were assessed by means of the Kuntzman's care requirements scale. Out of a total population of 1955, 617 (34%) residents were assessed. RESULTS: The mean score obtained by the institutions was under 50% of the maximum possible score with a great deal of dispersion of the results. The lowest scores were identified in the private for profit sector and in a subgroup of public institutions. The highest scores were found among private non-profit institutions and a sector of the public institutions. The most important shortcomings identified were related to infrastructure and quality of human resources. The mean age of the institutionalized elderly is 76; 48.1% are functionally independent, 21.3% partially dependent and 30.6% totally dependent. When trying to correlate the mean functional status of the population of a given institution with its resources for care-giving we usually found no correlation. It is commonplace to find highly dependent populations living in poorly staffed or inadequately equipped institutions and vice versa CONCLUSIONS: Quality of care in long term care institutions in Mexico City is often poor and this is particularly true for private for profit institutions. Lack of norms and supervision pertaining to the functioning of such institutions contributes greatly to this reality.