Arterial compliance and its dynamics in obese adolescents.

Arterial compliance (AC) decrease with aging is accelerated by factors associated with the progression of atherosclerotic process, including obesity. Prevalence of obesity increases not only in adult population but also in children and adolescents. The results of studies characterizing the effect of obesity on AC (often indirectly estimated by pulse wave velocity (PWV)) are contradictory. Considering the limitations of previously applied methods and the need to interpret AC values in the context of potential confounders or during various physiological states, the aim of this study was to compare AC of control and obese adolescents during four different physiological states: supine rest, head-up tilt (HUT), supine recovery and mental arithmetic (MA). AC was assessed by the method based on two-element Windkessel model as the ratio of a time constant t characterizing diastolic blood pressure decay and total peripheral resistance (TPR). In total, fifty healthy and normotensive subjects (40 females, 10 males, age 17.5 years (SD=1.1 years)) were examined - 25 obese and 25 age- and sex-matched control subjects. We observed significantly increased AC values during all phases in obese group. An increase in AC was also preserved after controlling for blood pressure influence. These results were confirmed using PWV based AC estimation. Interestingly, AC decreased similarly during stress phases (HUT, MA) in both groups. Lastly, TPR was decreased throughout the study protocol in obese subjects. In conclusion, AC is increased in young obese subjects consistently during various physiological states. Furthermore, changes of physiological states evoke similar response of AC in both groups indicating preserved autonomic control of elastic arteries. A decreased TPR in obese subjects points towards the influence of different maturation state of the arterial tree and/or changes in vasomotion possibly counterbalancing acceleration of atherosclerosis process.

Beta-adrenergic receptors gene polymorphisms are associated with cardiac contractility and blood pressure variability.

Beta-adrenergic receptors (beta-ARs) play a pivotal role in the cardiovascular regulation. In the human heart beta1- and beta2-ARs dominate in atria as well as in ventricle influencing heart rate and myocardial contractility. Some single nucleotide polymorphisms (SNPs) of beta-ARs might influence cardiovascular function. However, the influence of beta-AR genes SNPs on hemodynamic parameters at rest and their reactivity under stress is still not well known. We aimed to explore the associations between four selected beta-ARs gene polymorphisms and selected cardiovascular measures in eighty-seven young healthy subjects. While in beta1-AR polymorphism rs1801252 no significant association was observed, second beta1-AR polymorphism rs1801253 was associated with decreased cardiac output and cardiac index during all phases and with decreased flow time corrected and ejection time index at rest and during mental arithmetics. Polymorphism rs1042713 in beta2-AR was associated with alterations in blood pressure variability at rest and during head-up-tilt, while rs1042714 was associated predominantly with decreased parameters of cardiac contractility at rest and during mental arithmetics. We conclude that complex analysis of various cardiovascular characteristics related to the strength of cardiac contraction and blood pressure variability can reveal subtle differences in cardiovascular sympathetic nervous control associated with beta-ARs polymorphisms.

Short-term arterial compliance changes in the context of systolic blood pressure influence.

Arterial compliance (C) is a complex parameter influencing ventricular-arterial coupling depending on structural (arterial wall remodeling) and functional (blood pressure, smooth muscles tone) changes. Based on Windkessel model, C can be calculated as the ratio of a time constant Tau characterizing diastolic blood pressure decay and total peripheral resistance (TPR). The aim of this study was to assess changes of C in the context of systolic arterial pressure (SAP) perturbations during four physiological states (supine rest, head-up tilt, supine recovery, mental arithmetic). In order to compare pressure independent changes of C a new index of C120 was proposed predicting C value at 120 mm Hg of SAP. Eighty-one healthy young subjects (48 f, average age 18.6 years) were examined. Hemodynamic parameters were measured beat-to-beat using volume-clamp photoplethysmographic method and impedance cardiography. We observed that C was strongly related to SAP values on the beat-to-beat time scale. Interestingly, C120 decreased significantly during stress phases. In conclusion, potential changes of SAP should be considered when measuring C. Arterial compliance changes in the opposite direction to TPR pointing towards influence of vascular tone changes on its value.

Noninvasive arterial compliance estimation.

Arterial compliance is an important cardiovascular parameter characterizing mechanical and structural properties of arteries and significantly influencing ventricular-arterial coupling. Decreased arterial compliance is associated with several physiological states and pathological processes. Furthermore, arterial compliance is influenced by other cardiovascular parameters even at short time scales. Today, there are numerous noninvasive methods of estimation arterial compliance in vivo introducing some level of confusion about selection of the best method for particular application and measurement setting. In this review, the most common noninvasive methods of arterial compliance estimation are summarized, discussed and categorized. Finally, interpretation of estimated arterial compliance in the context of other possible confounders is discussed.

Differential amplicons (ΔAmp)-a new molecular method to assess RNA integrity.

Integrity of the mRNA in clinical samples has major impact on the quality of measured expression levels. This is independent of the measurement technique being next generation sequencing (NGS), Quantitative real-time PCR (qPCR) or microarray profiling. If mRNA is highly degraded or damaged, measured data will be very unreliable and the whole study is likely a waste of time and money. It is therefore common strategy to test the quality of RNA in samples before conducting large and costly studies. Most methods today to assess the quality of RNA are ignorant to the nature of the RNA and, therefore, reflect the integrity of ribosomal RNA, which is the dominant species, rather than of mRNAs, microRNAs and long non-coding RNAs, which usually are the species of interest. Here, we present a novel molecular approach to assess the quality of the targeted RNA species by measuring the differential amplification (ΔAmp) of an Endogenous RNase Resistant (ERR) marker relative to a reference gene, optionally combined with the measurement of two amplicons of different lengths. The combination reveals any mRNA degradation caused by ribonucleases as well as physical, chemical or UV damage. ΔAmp has superior sensitivity to common microfluidic electrophoretic methods, senses the integrity of the actual targeted RNA species, and allows for a smoother and more cost efficient workflow.

The effect of dehydroepiandrosterone on Zucker rats selected for fat food preference.

When allowed to select between macronutrients in a 1-h-a-day meal paradigm, Zucker rats consume 20-80% of their total caloric intake as fat. If they receive an intraperitoneal injection of DHEA 2 h before such a test meal, they consume fewer total calories. The magnitude of this effect on each macronutrient depends upon the animal's initial preference for fat; the higher the initial fat preference, the more profound is the decrease in caloric intake and the more pronounced the effect on fat consumption. Doses as low as 25 mg DHEA/kg body weight are effective. Lean Zucker rats that prefer to consume a high-fat diet have higher epinephrine and dopamine levels in select regions of the hypothalamus known to control food intake. Administration of DHEA to such animals 2 h before decapitation reduces the content of norepinephrine and these monoamines to levels that mimic the values found in the low-fat-preferring animals. It is hypothesized that exogenous DHEA causes the acute release of norepinephrine, epinephrine, and dopamine in select regions of the hypothalamus, and this release causes a decrease in food intake, particularly fat.

IgE synthesis in man. I. Development of specific IgE antibodies after immunization with tetanus-diphtheria (Td) toxoids.

Specific IgE and IgG antibodies were measured in 39 adolescent and adult humans preselected to have less than 0.125 antitoxin units (AU) ml to tetanus antitoxin (IgG) irrespective of previous immunization history. Mean antitoxin values (IgG) measured by sheep red cell hemagglutination (SRBC) increased by 2 logs to 1.49 AU/ml sera for tetanus and by 1 log to 0.025 AU/ml sera for diphtheria. Specific tetanus IgE was noted to increase after immunization from a mean 2.0 +/- 0.2% counts bound to 3.1 +/- 0.6% counts bound, but was not statistically significant. Diphtheria-specific IgE rose significantly (p less than 0.05) from a mean 1.5 +/- 0.2% counts bound to a mean 4.0 +/- 1.2% counts bound in atopic individuals and from a mean 1.2 +/- 0.0% counts bound to a mean 2.2 +/- 0.5% counts bound in nonatopics. These data document the development of tetanus and diphtheria IgE antibodies after booster immunization.