Aging-related Decrease of Human ASC Angiogenic Potential Is Reversed by Hypoxia Preconditioning Through ROS Production

Adipose stroma/stem cells (ASC) represent an ideal source of autologous cells for cell-based therapy. Their transplantation enhances neovascularization after experimental ischemic injury. Aging is associated with a progressive decrease in the regenerative potential of mesenchymal stem cells (MSCs) from bone marrow. This work aims to determine the aging effect on human ASC capacities. First, we show that aging impairs angiogenic capacities of human ASC (hASC) in a mouse ischemic hindlimb model. Although no change in hASC number, phenotype, and proliferation was observed with aging, several mechanisms involved in the adverse effects of aging have been identified in vitro combining a concomitant decrease in (i) ASC ability to differentiate towards endothelial cells, (ii) secretion of proangiogenic and pro-survival factors, and (iii) oxidative stress. These effects were counteracted by a hypoxic preconditioning that improved in vivo angiogenic capacities of hASC from older donors, while hASC from young donors that have a strong ability to manage hypoxic stress were not. Finally, we identified reactive oxygen species (ROS) generation as a key signal of hypoxia on hASC angiogenic capacities. This study demonstrates for the first time that age of donor impaired angiogenic capacities of hASC in ischemic muscle and change in ROS generation by hypoxic preconditioning reverse the adverse effect of aging.     

Prevalence of Thoracic Aortic Aneurysms in Patients with Degenerative Abdominal Aortic Aneurysms: Results from the Prospective ACTA Study

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Are anti-Chlamydia pneumoniae antibodies prognosis indicators for peripartum cardiomyopathy?

BACKGROUND: The authors recently pointed out an epidemiological relation between specific anti-Chlamydia pneumoniae antibodies and peripartum cardiomyopathy in Niamey (Republic of Niger). DESIGN: In this work, they studied the prognosis value of such specific antibodies. METHODS: The serological status for specific IgG, IgA and IgM anti-C. pneumoniae antibodies of 50 African women (age, mean+/-SD = 30.2 +/- 7 years) hospitalized in Niamey, with peripartum cardiomyopathy, was determined at the time of diagnosis. The diagnosis was categorized as 'complete remission' (13 patients, age = 29.3 +/- 6.5 years, observation delay = 27 months), 'incomplete remission' (27 patients, age = 30.7 +/- 7.6 years, observation delay = 14 months) and 'deceased' (10 patients, age = 30.3 +/- 6.2 years, observation delay = 13 months). The control group comprised 27 African women (age = 25.2 +/- 4.6 years), living in the same area. The Mann-Whitney and Fisher's exact tests were used for the statistical comparison. RESULTS: The dilution of IgG specific anti-C. pneumoniae antibodies was higher (P = 0.047) in the 'incomplete remission' compared with 'complete remission'. The dilution of IgA specific anti-C. pneumoniae antibodies was higher (P = 0.033) in the patients with a severe evolution ('deceased' + 'incomplete remission') compared with 'complete remission'. There was no significant difference between patients in 'complete remission' compared with 'controls'. CONCLUSIONS: At the time of peripartum cardiomyopathy diagnosis the specific IgG and IgA anti-C. pneumoniae antibodies are of prognosis value: a high dilution is more often associated with a poor prognosis. This is the first identified prognosis factor during the precocious evolution of peripartum cardiomyopathy.     

Diagnostic criteria in predicting a biliary origin of acute pancreatitis in the era of endoscopic ultrasound: multicentre prospective evaluation of 213 patients.

BACKGROUND: No study on bioclinical criteria predicting a biliary origin for acute pancreatitis has included endosonography as a reference examination. Re-examination of bioclinical parameters deserves consideration in the era where other causes are known (e.g. hereditary, autoimmune). AIM AND METHODS: To determine the performance of bioclinical markers in predicting a biliary origin of acute pancreatitis where the diagnosis of biliary lithiasis was established or ruled out using endosonography. Only patients with a first acute episode of pancreatitis were included. RESULTS: 213 patients (male: 55%; median age: 56 years) were prospectively included in 14 centres. Causes of acute pancreatitis were: biliary (62%), alcoholic (25%), other (13%). Delay between symptom-onset and admission was <48 h in 80%. Endosonography was the sole method establishing the diagnosis of biliary pancreatitis in 15% of patients. At univariate analysis, age, female sex, declared alcohol consumption, elevated aspartate and alanine transaminases on admission, gammaglutamyl transferase, alkaline phosphatase, total bilirubin, lipase, mean corpuscular volume were predictive of a biliary origin. Only age (p < 0.0001), sex (p < 0.0008) and alanine transaminase (p < 0.0004) remained significant at multivariate analysis. At age 50, the respective sensitivity and specificity were 73 and 65%. With an elevated alanine transaminase at 2 times the upper limit of normal range, the respective sensitivity and specificity were 74 and 84%. The probability of a biliary origin of acute pancreatitis could be estimated by the following formula: = 1/1 + exp(4.6967 - 0.0656 x age + 1.1208 x sex - 0.6909 x alanine transaminase). CONCLUSION: When endosonography is performed to confirm or exclude a biliary origin of acute pancreatitis, age, sex and alanine transaminase at admission are the only factors predictive of a biliary cause.     

Bradycardia and syncope as manifestations of partial epilepsy

Although transient increases in heart rate typically occur, bradycardia has infrequently been noted in association with partial seizures. Five patients with temporal lobe epilepsy are described in whom sinus bradyarrhythmias and syncope were prominent manifestations of seizure activity. Partial improvement occurred in one of two patients in whom a permanent pacemaker was implanted before a diagnosis of epilepsy was established. Treatment with phenytoin or carbamazepine resulted in nearly complete resolution of symptoms in all five patients. Because pacemaker implantation does not prevent recurrent symptoms, but anticonvulsant therapy does, this experience underscores the importance of considering the diagnosis of partial epilepsy in selected patients with sinus bradyarrhythmias and syncope.     

L-carnitine supplementation and physical exercise restore age-associated decline in some mitochondrial functions in the rat

In mammals, during the aging process, an atrophy of the muscle fibers, an increase in body fat mass, and a decrease in skeletal muscle oxidative capacities occur. Compounds and activities that interact with lipid oxidative metabolism may be useful in limiting damages that occur in aging muscle. In this study, we evaluated the effect of L-carnitine and physical exercise on several parameters related to muscle physiology. We described that supplementing old rats with L-carnitine at 30 mg/kg body weight for 12 weeks (a) allowed the restoration of L-carnitine level in muscle cells, (b) restored muscle oxidative activity in the soleus, and (c) induced positive changes in body composition: a decrease in abdominal fat mass and an increase in muscle capabilities without any change in food intake. Moderate physical exercise was also effective in (a) limiting fat mass gain and (b) inducing an increase in the capacities of the soleus to oxidize fatty acids.     

Toward immunomodulatory and anti-inflammatory properties of statins

Over the past decade, a large number of studies reported a prominent role of inflammation and immune response in atherosclerosis. Thus, therapeutic strategies to reduce inflammation could exert beneficial effects in the prevention of atherosclerosis progression. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) have demonstrated their capacity to greatly reduce coronary morbidity and mortality in both primary and secondary intervention trials. Furthermore, originally described as the most efficient drugs to reduce serum cholesterol, recent reports suggest that statins also confer cardiovascular benefits by their ability to modulate immuno-inflammatory processes. This review summarizes in vitro and in vivo evidence of immunomodulatory properties of statins.     

Effect of bipolar electrode orientation on local electrogram properties

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Adiponutrin: A new gene regulated by energy balance in human adipose tissue

Adiponutrin is a newly identified nonsecreted adipocyte protein regulated by changes in energy balance in rodents. We documented the influence of energy balance modification on adiponutrin gene expression in humans. We investigated the mRNA expression in sc adipose tissue of nonobese women and in obese women during 2-d very low-calorie diet (VLCD) and subsequent refeeding as well as before and after a VLCD of 3 wk (21-d VLCD). The adiponutrin mRNA levels of the nonobese and obese women were not different (P > 0.05). Two-day VLCD reduced the average level of adiponutrin mRNA expression by 36% (P = 0.0016), whereas refeeding elevated the mRNA level by 31% (P = 0.004). The 3-wk VLCD caused a dramatic 58% fall of the adiponutrin mRNA expression level (P = 0.001). The mRNA level was negatively correlated with fasting glucose (Rho = -0.62; P < 0.0001), and subjects with high adiponutrin mRNA level had an increased insulin sensitivity. Compared with other adipocyte proteins such as leptin and adiponectin, adiponutrin mRNA did not show correlation with either adiposity indexes or with leptin or adiponectin mRNAs. These results indicate that adiponutrin gene expression in humans is highly regulated by changes in energy balance.