Heat shock response by EBV-immortalized B-lymphocytes from centenarians and control subjects: a model to study the relevance of stress response in longevity

'Successful aging', i.e. the ability to attain old age in relatively good health, is believed to be related to the capability to cope with different environmental stresses. Independently of their specific differentiation, all body cells respond to hyperthermia and other stresses with the production of Heat Shock Proteins (HSPs) that play an important role in cell survival. We investigated the heat shock response in B-lymphoid cell lines from 44 centenarians and 23 younger subjects, by studying both HSP70 synthesis and cell survival after hyperthermic treatment. Interestingly, no significant difference could be found between the two age groups as far as HSP70 synthesis was concerned; moreover, cell lines from centenarians appeared to be less prone to heat-induced apoptosis than lines from younger controls. These results, which are in contrast with previous findings showing an age-related decrease of the HSP70 synthesis and of hyperthermic response, corroborate the above mentioned hypothesis that the biological success of centenarians is due to the preservation of the capability to cope with stresses. An A/C polymorphism identified in the promoter region of HSP70-1 gene had been previously shown to affect the probability to attain longevity in females. To investigate if this effect was related to any influence of this polymorphism on HSP70 protein synthesis the correlation between A/C polymorphism and protein synthesis was investigated. We found that cells from AA centenarian females displayed a lower synthesis of HSP70.     

Successful selective ablation of fast atrioventricular node pathway by cryothermal energy application

This paper reports the experience of successful cryoablation of fast atrioventricular nodal pathway in a patient with recurrent atrioventricular nodal reentrant tachycardia after previous unsuccessful attempts of slow pathway ablation. Slow formation of a permanent lesion by cryothermal energy application allowed precise modulation of atrioventricular nodal conduction until the endpoints of complete fast pathway ablation were met with long-term cure of the arrhythmia.     

Determinants of atrial fibrillation development in patients with hypertrophic cardiomyopathy

Predictors of the development of atrial fibrillation (AF) in patients who have hypertrophic cardiomyopathy (HC) have not been extensively studied, although, in these patients, AF contributes to the exacerbation of symptoms and the development of heart failure. The present study determined the role of left atrial (LA) function in the development of AF in patients who have HC. One hundred fifty consecutive patients who had HC, had no history of AF, and who were followed for 5.2 +/- 2.9 years constituted the study population. Using M-mode echocardiography, we measured LA function as global LA fractional shortening and LA diameter. LA volume was measured from 2-dimensional 4-chamber views by the method of disks. During follow-up, 20 patients developed AF. LA function was an independent predictor of AF (odds ratio 0.716, p = <0.001), whereas LA diameter and volume were predictors in addition to age. Kaplan-Meier analysis showed that LA dysfunction carried a high risk of AF. Thus, in patients who have HC, LA function is a strong predictor of AF development and is independent of age.     

Effects of physical activity on intestinal gas transit and evacuation in healthy subjects

PURPOSE: To determine the effects of mild physical activity on intestinal gas transit and clearance. METHODS: In 8 healthy adults, a gas mixture was infused continuously into the jejunum (12 mL/min) for 120 minutes with simultaneous duodenal lipid perfusion (1 kcal/min). Gas evacuation, perception of abdominal sensations (on a scale of 0 [none] to 6 [pain]), and abdominal girth were measured at 15-minute intervals during rest and intermittent pedalling, with subjects in a supine position. RESULTS: Mean (+/- SD) intestinal gas retention was lower during exercise than at rest (-84 +/- 303 mL vs. 143 +/- 219 mL, P <0.05). Gas retention during rest was associated with significant abdominal distension (8 +/- 6 mm, P <0.01 vs. basal), which was decreased with exercise (3 +/- 7 mm, P <0.05 vs. rest). The gas challenge test was well tolerated both during exercise and rest (perception score: 0.6 +/- 0.5 vs. 0.9 +/- 0.4, P = 0.25). CONCLUSION: In healthy subjects, gut transit of intraluminal gas is enhanced by mild physical activity.     

Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis

Alpha-lipoic acid (alpha-LA) is a neuroprotective metabolic antioxidant that has been shown to cross the blood brain barrier. We tested whether alpha-LA is capable to prevent MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). Daily oral administration of alpha-LA, starting at the time of immunization, significantly prevented EAE progression as compared to control mice. This was associated with a reduction of CNS infiltrating T cells and macrophages as well as decreased demyelination. We then tested alpha-LA in a therapeutic protocol aimed at suppressing EAE after its onset. Intraperitoneal (i.p.), but not oral, administration of alpha-LA significantly prevented disease progression when compared to vehicle-treated controls. Similarly, we observed significant reduction of demyelination and inflammatory infiltration. This clinical effect was not due to an impairment of MOG35-55 recognition by encephalitogenic T cells. In contrast, MOG-specific T cells showed a decreased production of IFNgamma and IL-4, suggesting an immunosuppressive activity on both Th1 and Th2 cytokines. In addition, alpha-LA inhibited the proteolytic activity of MMP2 and MMP9 only at very high doses. Our data indicate that alpha-LA can effectively interfere with the autoimmune reaction associated with EAE through mechanisms other than its antioxidant activity and supports further studies on the use of alpha-LA as a potential therapy for MS.     

Quetiapine regulates FGF-2 and BDNF expression in the hippocampus of animals treated with MK-801

Fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF) are trophic factors, widely distributed in the adult brain, whose expression can be modulated by psychoactive drugs. Administration of the atypical antipsychotic quetiapine resulted in a marked elevation of FGF-2 and BDNF mRNA levels in the rat hippocampus, but only under conditions of reduced NMDA receptor activity. These effects were drug-specific, given that they were not observed with the conventional antipsychotic haloperidol; and anatomically defined, since no similar effect was observed in striatum, prefrontal or frontal cortex. These results suggest that quetiapine may promote neuroplasticity via the up-regulation of neurotrophic factors when NMDA-mediated transmission is perturbed.