Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase.

Recent studies have uncovered important cross talk between inflammation, generation of reactive oxygen and nitrogen species, and lipid metabolism in the pathogenesis of cardiovascular aging. Inhibition of the endocannabinoid anandamide metabolizing enzyme, the fatty acid amide hydrolase (FAAH), is emerging as a promising novel approach for the treatment of various inflammatory disorders. In this study, we have investigated the age-associated decline of cardiac function and changes in inflammatory gene expression, nitrative stress, and apoptosis in FAAH knockout (FAAH(-/-)) mice and their wild-type (FAAH(+/+)) littermates. Additionally, we have explored the effects of anandamide on TNF-alpha-induced ICAM-1 and VCAM-1 expression and monocyte-endothelial adhesion in human coronary artery endothelial cells (HCAECs). There was no difference in the cardiac function (measured by the pressure-volume conductance catheter system) between 2- to 3-mo-old (young) FAAH(-/-) and FAAH(+/+) mice. In contrast, the aging-associated decline in cardiac function and increased myocardial gene expression of TNF-alpha, gp91phox, matrix metalloproteinase (MMP)-2, MMP-9, caspase-3 and caspase-9, myocardial inducible nitric oxide synthase protein expression, nitrotyrosine formation, poly (ADP-ribose)polymerase cleavage and caspase-3/9 activity, observed in 28- to 31-mo-old (aging) FAAH(+/+) mice, were largely attenuated in knockouts. There was no difference in the myocardial cannabinoid CB(1) and CB(2) receptor gene expression between young and aging FAAH(-/-) and FAAH(+/+) mice. Anandamide dose dependently attenuated the TNF-alpha-induced ICAM-1 and VCAM-1 expression, NF-kappaB activation in HCAECs, and the adhesion of monocytes to HCAECs in a CB(1)- and CB(2)-dependent manner. These findings suggest that pharmacological inhibition of FAAH may represent a novel protective strategy against chronic inflammation, oxidative/nitrative stress, and apoptosis associated with cardiovascular aging and atherosclerosis

Effects of aerobic workout on the changes in the characteristics of dynamics of the center of gravity in different age categories

Introduction The quality and function of movements undergo deterioration due to weight gain. Aerobic training normalizes body weight, improves the health status, and in addition, it is expected to improve the dynamics of movements. The aims of this study were to prove the beneficial effects of recreational physical activities on the movements. Methods Participants were divided into five different age categories: second childhood, adolescence, mature age I, mature age II, and aging. Squatting and vertical jumping of the participants were measured at the beginning and at the end of a 5-month training program. These movements simulated ordinary daily movements. Changes in the body were determined by InBody230. APAS 3D system was used for movement analysis. Results The results showed significant improvements in body weight, fat mass, muscle mass, fat mass–body weight ratio, muscle mass–body weight ratio, body mass index, body fat percentage, and waist–hip ratio. During jumping, the lifting and sinking of the center of gravity’s (CG) position and its velocity and acceleration were improved. In case of squatting, the results showed significant improvements in the velocity and acceleration of dynamical characteristics of the CG. Other correlations were observed between changes in body composition and the dynamics of movements. Discussion The research proved that recreational training optimized body composition and improved the characteristics of CG’s dynamics. The study suggests considerable connection between body composition and the characteristics of the movements’ dynamics. From this point of view, our training program was the most effective in the working age groups

Comparison of clinical characteristics of patients with pandemic SARS-CoV-2-related and community-acquired pneumonias in Hungary – a pilot historical case-control study

The distinction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related and community-acquired pneumonias poses significant difficulties, as both frequently involve the elderly. This study aimed to predict the risk of SARS-CoV-2-related pneumonia based on clinical characteristics at hospital presentation. Case-control study of all patients admitted for pneumonia at Semmelweis University Emergency Department. Cases (n = 30) were patients diagnosed with SARS-CoV-2-related pneumonia (based on polymerase chain reaction test) between 26 March 2020 and 30 April 2020; controls (n = 82) were historical pneumonia cases between 1 January 2019 and 30 April 2019. Logistic models were built with SARS-CoV-2 infection as outcome using clinical characteristics at presentation. Patients with SARS-CoV-2-related pneumonia were younger (mean difference, 95% CI: 9.3, 3.2–15.5 years) and had a higher lymphocyte count, lower C-reactive protein, presented more frequently with bilateral infiltrate, less frequently with abdominal pain, diarrhoea, and nausea in age- and sex-adjusted models. A logistic model using age, sex, abdominal pain, C-reactive protein, and the presence of bilateral infiltrate as predictors had an excellent discrimination (AUC 0.88, 95% CI: 0.81–0.96) and calibration (p = 0.27–Hosmer-Lemeshow test). The clinical use of our screening prediction model could improve the discrimination of SARS-CoV-2 related from other community-acquired pneumonias and thus help patient triage based on commonly used diagnostic approaches. However, external validation in independent datasets is required before its clinical use

IGF-1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging

Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cognitive impairment. To establish the link between IGF-1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF-1 deficiency (Igf1f/f -TBG-Cre-AAV8) and accelerated vascular aging. We found that IGF-1-deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal-dependent spatial memory test, mimicking the aging phenotype. IGF-1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF-1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment

Rule-Based Models of the Interplay between Genetic and Environmental Factors in Childhood Allergy

Peer reviewe

Cardiac electrophysiological effects of citalopram in guinea pig papillary muscle comparison with clomipramine.

The effect of citalopram, a selective serotonin reuptake inhibitor (SSRI) antidepressant, was studied on cardiac action potential configuration and compared with that of the tricyclic antidepressant (TCA) clomipramine. Conventional microelectrode techniques were used in right ventricular papillary muscle preparations of the guinea pig. Citalopram caused a concentration-dependent (10-100 microM) shortening of action potential duration (APD), depression of plateau and overshoot potential, and reduction of maximum velocity of depolarization (V(max)). No significant changes in resting membrane potential were observed. Similar results were obtained with clomipramine; however, reduction of V(max) and overshoot was more pronounced with clomipramine, whereas citalopram caused relatively greater shortening of APD. Effects of both drugs were partly reversible. The results indicate that the SSRI antidepressant citalopram, similarly to TCA compounds, alters cardiac action potential configuration in guinea pig ventricular muscle, probably owing to inhibition of cardiac Na(+) and Ca(2+) channels. Differences in cardiac side effects of the two drugs may be related to their different actions on cardiac action potential configuration