Middle-age abolishes cardioprotection conferred by thioredoxin-1 in mice.

Thioredoxin-1 (Trx1) has cardioprotective effects on ischemia/reperfusion (I/R) injury, although its role in ischemic postconditioning (PostC) in middle-aged mice is not understood. This study aimed to evaluate if combining two cardioprotective strategies, such as Trx1 overexpression and PostC, could exert a synergistic effect in reducing infarct size in middle-aged mice. Young or middle-aged wild-type mice (Wt), transgenic mice overexpressing Trx1, and dominant negative (DN-Trx1) mutant of Trx1 mice were used. Mice hearts were subjected to I/R or PostC protocol. Infarct size, hydrogen peroxide (H2O2) production, protein nitration, Trx1 activity, mitochondrial function, and Trx1, pAkt and pGSK3ß expression were measured. PostC could not reduce infarct size even in the presence of Trx1 overexpression in middle-aged mice. This finding was accompanied by a lack of Akt and GSK3ß phosphorylation, and Trx1 expression (in Wt group). Trx1 activity was diminished and H2O2 production and protein nitration were increased in middle-age. The respiratory control rate dropped after I/R in Wt-Young and PostC restored this value, but not in middle-aged groups. Our results showed that Trx1 plays a key role in the PostC protection mechanism in young but not middle-aged mice, even in the presence of Trx1 overexpression.

Effect of lithium in pyramidal neurons of Cornu Ammonis in an animal model.

Bipolar disorder has been associated with a decrease in hippocampal size, and lithium appears to reverse this neuroanatomical abnormality. The objective of this work was to evaluate, at a cellular level, the size of both cell body and nucleus of pyramidal neurons located throughout the Cornu Ammonis (CA1 to CA4 regions). To perform this duty, we used 16 rats that were randomized into two groups: control and dietary lithium-treated. After one month, they were sacrificed and their brains removed for histopathological analysis. Serial photos of the entire Cornu Ammonis were taken and, after dividing them into 4 regions of interest, we measured the cell body and nucleus on each pyramidal neuron belonging to the first 5 photos of each region of interest. As a result of this histological analysis, cell body area and nuclear area were significantly larger in the experimental group in a specific area of the Cornu Ammonis that could correspond to CA2 or the transition between CA1 and CA2. These results suggest that the effect of lithium is not homogeneous throughout the hippocampus and allows directing future studies to a specific area of this structure.

Impaired cardiac mitochondrial function and contractile reserve following an acute exposure to environmental particulate matter.

BACKGROUND: It has been suggested that mitochondrial function plays a central role in cardiovascular diseases associated with particulate matter inhalation. The aim of this study was to evaluate this hypothesis, with focus on cardiac O2 and energetic metabolism, and its impact over cardiac contractility. METHODS: Swiss mice were intranasally instilled with either residual oil fly ash (ROFA) (1.0 mg/kg body weight) or saline solution. After 1, 3 or 5 h of exposure, O2 consumption was evaluated in heart tissue samples. Mitochondrial respiration, respiratory chain complexes activity, membrane potential and ATP content and production rate were assessed in isolated mitochondria. Cardiac contractile reserve was evaluated according to the Langendorff technique. RESULTS: Three hours after ROFA exposure, tissue O2 consumption was significantly decreased by 35% (from 1180 +/- 70 to 760 +/- 60 ng-at O/min g tissue), as well as mitochondrial rest (state 4) and active (state 3) respiration, by 30 and 24%, respectively (control state 4: 88 +/- 5 ng-at O/min mg protein; state 3: 240 +/- 20 ng-at O/min mg protein). These findings were associated with decreased complex II activity, mitochondrial depolarization and deficient ATP production. Even though basal contractility was not modified (control: 75 +/- 5 mm Hg), isolated perfused hearts failed to properly respond to isoproterenol in ROFA-exposed mice. Tissue O2 consumption rates positively correlated with cardiac contractile state in controls (r2 = 0.8271), but not in treated mice (r2 = 0.1396). GENERAL SIGNIFICANCE: The present results show an impaired mitochondrial function associated with deficient cardiac contractility, which could represent an early cardiovascular alteration after the exposure to environmental particulate matter.

[The activation of A1 adenosine receptors attenuates myocardial stunning in the rabbit]. / La activación de los receptores A1 de adenosina atenúa el atontamiento de miocardio en el conejo.

Hearts exposed to a prolonged period of ischemia (> or = 30 minutes) present smaller infarct size when reperfused in the presence of adenosine. However, when the period of ischemia is shorter, the infarct areas are not very significant, but a postischemic ventricular dysfunction persists. The objective of this study was to determine the effect of adenosine, (administered only during reperfusion) on systolic and diastolic alterations present in postischemic ventricular dysfunction, as well as to determine whether A1 receptors participate in this effect. Isolated isovolumic rabbit hearts were subjected to 15 minutes of global ischemia followed by 30 minutes of reperfusion. Before ischemia and during reperfusion ventricular function was evaluated. In the control group, the left ventricular developed pressure (LVDP) reached 56 +/- 2% of recovery at 30 minutes of reperfusion. The administration of adenosine improved LVDP 75 +/- 3% (P < 0.05 vs. control). However, when adenosine was given in presence of an A1 receptor selective antagonist (DPCPX), LVDP reached 50 +/- 2% (P < 0.05 vs. control). In the control group, left ventricular end diastolic pressure (LVEDP) (diastolic stiffness), increased 293 +/- 4%, at 30 minutes of reperfusion. Only a 15 +/- 8% (P < 0.05 vs. control) increase in LVEDP was observed with adenosine. Reperfusion with adenosine plus DPCPX did not attenuate an increase of 493 +/- 9% (P < 0.05 vs. control) in diastolic stiffness. Adenosine administered from the beginning of reperfusion attenuated both systolic alterations and diastolic stiffness in postischemic dysfunction. This effect was abolished by DPCPX, suggesting an important role for the A1 receptors in adenosine protection.

Context trees: representing co-operative healthcare activities in IREP.

The IREP Project is based on the concept of 'rehabilitation programme' (LLP--Life Long Programme). It consists in a global vision of the patient's therapeutic-rehabilitative path, that is realised by the description, selection, adaptation and evaluation of generalised protocols. This paper discusses the issues arising in the definition of multidisciplinary rehabilitation programmes involving the co-operation of independent teams. A methodology to formalise and collect descriptions of programmes is presented. A programme is considered as a set of interconnected activities, represented as a graph of Activity Modules, organised in Context Trees; the resulting structured representation is the framework to implement timely and effective communication services in a global information system on rehabilitation. Based on this experience, a set of possible requirements for software tools to formalise and manage programmes have been suggested; it was the basis for the realisation of a first prototype under field test in a rehabilitation environment by other partners of the IREP Project.

Percutaneous microcompression of the gasserian ganglion: personal experience.

The effectiveness of percutaneous microcompression of the gasserian ganglion, performed according to the technique proposed by Mullan and Lichtor, was evaluated in 74 patients affected by essential trigeminal neuralgia and compared to the results obtained with the RF thermocoagulation of Sweet and Wepsic. Similar results were obtained with the two methods but adverse side-effects were less common with microcompression. It is concluded that the microcompression should be recommended as a first choice among the different percutaneous procedures in the treatment of trigeminal neuralgia.