Changes in the brain and plasma Aß peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

Double transgenic mice expressing mutant amyloid precursor protein (APPswe) and mutant presenilin 1 (PS1dE9) are a model of Alzheimer-type amyloidosis and are widely used in experimental studies. In the present work, the relationships between brain and plasma amyloid-ß peptide (Aß) levels and cognitive impairments were examined in male APPswe/PS1dE9 double transgenic mice at different ages. When compared with non-transgenic littermates, APPswe/PS1dE9 mice exhibited significant learning deficits from the age of 6months (M6), which were aggravated at later stages of life (M8 and M12). Sporadic brain amyloid plaques were observed in mice as early as M3 and progressively increased in number and size up to M12. A similar increase was observed in brain insoluble Aß levels as assessed by enzyme-linked immunosorbent assay (ELISA). In particular, the levels of brain insoluble Aß peptides rose steeply from M4 to M6. Interestingly, this pronounced amyloid deposition was accompanied by a temporary fall in the concentration of brain soluble and membrane-bound Aß peptides at M6 that rose again at M8 and M12. The plasma levels of Aß40 and Aß42 decreased with advancing age up to M8, when they stabilized at M12. This decrease in plasma Aß levels coincided with the observed increase in insoluble brain Aß levels. These results could be useful for developing plasma Aß levels as possible biomarkers of the cerebral amyloidosis and provide advances in the knowledge of the Aß peptide biochemical changes that occur in the brain of Alzheimer's disease patients.

Dopamine transporter down-regulation following repeated cocaine: implications for 3,4-methylenedioxymethamphetamine-induced acute effects and long-term neurotoxicity in mice.

BACKGROUND AND PURPOSE: 3,4-Methylenedioxymethamphetamine (MDMA) and cocaine are two widely abused psychostimulant drugs targeting the dopamine transporter (DAT). DAT availability regulates dopamine neurotransmission and uptake of MDMA-derived neurotoxic metabolites. We aimed to determine the effect of cocaine pre-exposure on the acute and long-term effects of MDMA in mice. EXPERIMENTAL APPROACH: Mice received a course of cocaine (20 mg*kg(-1), x2 for 3 days) followed by MDMA (20 mg*kg(-1), x2, 3 h apart). Locomotor activity, extracellular dopamine levels and dopaminergic neurotoxicity were determined. Furthermore, following the course of cocaine, DAT density in striatal plasma membrane and endosome fractions was measured. KEY RESULTS: Four days after the course of cocaine, challenge with MDMA attenuated the MDMA-induced striatal dopaminergic neurotoxicity. Co-administration of the protein kinase C (PKC) inhibitor NPC 15437 prevented cocaine protection. At the same time, after the course of cocaine, DAT density was reduced in the plasma membrane and increased in the endosome fraction, and this effect was prevented by NPC 15437. The course of cocaine potentiated the MDMA-induced increase in extracellular dopamine and locomotor activity, following challenge 4 days later, compared with those pretreated with saline. CONCLUSIONS AND IMPLICATIONS: Repeated cocaine treatment followed by withdrawal protected against MDMA-induced dopaminergic neurotoxicity by internalizing DAT via a mechanism which may involve PKC. Furthermore, repeated cocaine followed by withdrawal induced behavioural and neurochemical sensitization to MDMA, measures which could be indicative of increased rewarding effects of MDMA.

[Standardizing care. When the intervention is valid]. / Estandarizar los cuidados. Cuando lo hecho es válido.

The objectives of this study were: A) to assemble a Standard Care Plan Guide taken from both nursing care records as well as data from a bibliography review; B) to know the number of nursing interventions and evaluate their suitability according to the stated nursing diagnosis. These results can then be compared before and after using the Standard Care Plan Guide. An analysis of 1827 nursing care records was performed. The first phase, after studying 1255 records, consisted of standardizing the care to correspond with 36 nursing diagnoses previously selected from the NANDA taxonomy. The second phase saw the standard care practice incorporated by the nursing staff. And finally, a comparison was made of the results between phase one and three (before and after the incorporation of the Standard Care Plan Guide.) The number of nursing interventions notably increased, jumping from 3263 in the first phase up to 4271 in the third. The average nursing action per patient rose from 3.03 to 9.09. Also, the diagnostic categories increased, going from 930 in the first phase up to 1624 in the third. The average number of correctly stated diagnoses per patient climbed from 1.56 to 2.78. The authors state that better nursing care and attention to the patient can occur if the nurses are given the conceptual instruments and training that will facilitate their daily tasks.