The mechanism of injury-induced [Ca2+]i oscillations in the endothelium of excised rat aorta

Endothelial injury is the primary event that leads to a variety of severe vascular disorders. The signal transduction pathway which drives the subsequent healing process is far from being fully elucidated. Mechanical injury elicits a Ca2+ response in the endothelium of intact rat aorta, which comprises an initial Ca2+ release from inositol-1,4,5-trisphosphate-sensitive (IP3Rs) stores followed by a long-lasting decay phase due to Ca2+ entry through uncoupled connexons. In a minor fraction of cells, the Ca2+ signal adopts an oscillatory pattern whose molecular underpinnings are yet to be elucidated. In the light of the role played by repetitive Ca2+ spikes in regulating tissue regeneration, the present study aims at elucidating the mechanisms underlying injury-induced Ca2+ oscillations. The repetitive Ca2+ signal reversibly ceased upon removal of extracellular Ca2+ or addition of the inorganic cations, La3+ and Ni2+. Moreover, the spiking response was abolished by the gap-junction blockers, heptanol and 18 beta-glycyrrhetinic acid and by interfering with the Ca2+ entry-mode mode of the Na+/Ca2+ exchanger (NCX). The InsP3-producing agonist, ATP, resumed Ca2+ oscillations in silent cells, while the phospholipase C inhibitor, U73122, inhibited the oscillatory signal. The latter was also prevented by the SERCA inhibitors, thapsigargin and cyclopiazonic acid acid. These data show that injury-induced [Ca2+]i oscillations require the coordinated interplay between NCX-mediated Ca2+ entry and InsP3-dependent Ca2+ release. Besides directly gating Ca2+ inflow, uncoupled connexons might let Na+ into the cells and stimulate Ca2+ entry through NCX by increasing submembranal Na+ levels

Heart Rate Variability as Biomarker for Prognostic of Metabolic Disease

Lifestyle emerging diseases like obesity, metabolic syndrome (MeS), and diabetes mellitus are considered high-risk factors for lethal arrhythmias and side effects. A Poincaré plot is constructed with the time series of RR and PP electrocardiogram (ECG) intervals, using two stages: the new phase and the old phase. We proposed this diagram of two dimensions, a way to quantify and observe the regularity of events in space and time. Therefore, the heart rate variability (HRV) can be used as a biomarker for early prognostic and diagnostic of several metabolic diseases; additionally, this biomarker is obtained by a noninvasive tool like the electrocardiogram

Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health

Environmental pollution nowadays has not only a direct correlation with human health changes but a direct social impact. Epidemiological studies have evidenced the increased damage to human health on a daily basis because of damage to the ecological niche. Rapid urban growth and industrialized societies importantly compromise air quality, which can be assessed by a notable accumulation of air pollutants in both the gas and the particle phases. Of them, particulate matter (PM) represents a highly complex mixture of organic and inorganic compounds of the most variable size, composition, and origin. PM being one of the most complex environmental pollutants, its accumulation also varies in a temporal and spatial manner, which challenges current analytical techniques used to investigate PM interactions. Nevertheless, the characterization of the chemical composition of PM is a reliable indicator of the composition of the atmosphere, the quality of breathed air in urbanized societies, industrial zones and consequently gives support for pertinent measures to avoid serious health damage. Epigenomic damage is one of the most promising biological mechanisms of air pollution-derived carcinogenesis. Therefore, this review aims to highlight the implication of PM exposure in diverse molecular mechanisms driving human diseases by altered epigenetic regulation. The presented findings in the context of pan-organic cancer, fibrosis, neurodegeneration and metabolic diseases may provide valuable insights into the toxicity effects of PM components at the epigenomic level and may serve as biomarkers of early detection for novel targeted therapies

Metabolic syndrome remodels electrical activity of the sinoatrial node and produces arrhythmias in rats

"In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats"

Multiple effects of 4-aminopyridine on feline and rabbit sinoatrial node myocytes and multicellular preparations

"4-aminopyridine (4-AP) is commonly used to block the transient outward potassium current, I(to), in cardiac and noncardiac tissues. In the present work, we found that 4-AP inhibited the rapid component of the delayed rectifier potassium current, I(Kr), in rabbit-isolated sinoatrial node myocytes by 25% (1 mM) and 51% (5 mM) and inhibited the slow component of the delayed rectifier potassium current, I(Ks), in cat- isolated sinoatrial node myocytes by 39% (1 mM) and 62% (5 mM). In cat- and rabbit-isolated sinoatrial node myocytes, 4-AP activated muscarinic receptors in a voltage-dependent manner to increase the acetylcholine-activated potassium current, I(KACh). In multicellular preparations of the central region of the sinoatrial node from nonreserpinized rabbits, 4-AP produced an increase in action potential overshoot, frequency, and rate of diastolic depolarization. In the presence of the beta-adrenergic antagonist propranolol, 4-AP produced a marked increase in duration and a marked decrease in maximum diastolic potential and eventually, cessation of the spontaneous activity in preparations from the sinoatrial central region. In multicellular preparations from reserpinized rabbits, 4-AP produced similar effects to those observed in the presence of propranolol. We conclude that 4-AP inhibits multiple cardiac K(+) currents, including I(to), I(Kr), and I(Ks), and that these activities mask I(KACh) activation"

Seguimiento farmacoterapéutico de antiparasitarios para pacientes pediátricos de Santa María Acuexcomac-México

"El Método Dáder para el seguimiento farmacoterapéutico ha sido una herramienta que permite detectar y solucionar problemas relacionados con la medicación y puede adaptarse a las condiciones de la población mexicana que vive en comunidades rurales. El programa se ofreció a 300 infantes de la comunidad de Santa María Acuexcomac, de los cuales solo 102 aceptaron participar. En la primera etapa se diagnosticaron 62 casos de parasitosis causada por Entamoeba histolytica, Himenolepis nana y/o Giardia lamblia. Se prescribieron quinfamida para los casos de amibiasis, albendazol para himenolepiasis y giardiasis, o ambos medicamentos para amibiasis en conjunción con himenolepiasis y/o giardiasis. Al finalizar esta etapa la adherencia al tratamiento farmacoterapeutico de los pacientes que se les realizo el seguimiento farmacoterapéutico fue en promedio de 96.9%, mientras que 76 % de estos pacientes no presentaron parasitosis en un segundo análisis coproparasitoscópico. En la segunda etapa se administró metronidazol para el tratamiento de amibiasis y/o giardiasis, y prazicuantel para el tratamiento de himenolepiasis. A todos los pacientes se les realizó el seguimiento farmacoterapéutico obteniéndose una adherencia del 81.8%. Al finalizar el programa ninguno de los pacientes a los cuales se les brindo el seguimiento farmacoterapéutico, presentaron parasitosis"

The mechanism of injury-induced [Ca2+]i oscillations in the endothelium of excised rat aorta

Endothelial injury is the primary event that leads to a variety of severe vascular disorders. Mechanical injury elicits a Ca(2+) response in the endothelium of excised rat aorta, which comprises an initial Ca(2+) release from inositol-1,4,5-trisphosphate (InsP(3))-sensitive stores followed by a long-lasting decay phase due to Ca(2+) entry through uncoupled connexons. The Ca(2+) signal may also adopt an oscillatory pattern, the molecular underpinnings of which are unclear. In the light of the role played by Ca(2+) spiking in tissue regeneration, this study aimed to unveil the mechanisms underlying injury-induced Ca(2+) oscillations. The latter reversibly ceased upon removal of extracellular Ca(2+) or addition of the gap junction blockers heptanol, 18 α,β-glycyrrhetinic acid, La(3+) and Ni(2+), but were insensitive to BTP-2 and SKF 96365. The spiking response was abolished by inhibiting the Ca(2+) entry mode of the Na(+)/Ca(2+) exchanger (NCX). The InsP(3)-producing agonist ATP resumed Ca(2+) oscillations in silent cells, while the phospholipase C inhibitor U73122 suppressed them. Injury-induced Ca(2+) transients were prevented by the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA) blockers thapsigargin and cyclopiazonic acid, while they were unaffected by suramin and genistein. These data show for the first time that the coordinated interplay between NCX-mediated Ca(2+) entry and InsP(3)-dependent Ca(2+) release contributes to injury-induced intracellular Ca(2+) concentration oscillations

The role of the autonomic nervous system on cardiac rhythm during the evolution of diabetes mellitus using heart rate variability as a biomarker

"Heart rate variability (HRV) is highly influenced by the Autonomic Nervous System (ANS). Several illnesses have been associated with changes in the ANS, thus altering the pattern of HRV. However, the variability of the heart rhythm is originated within the Sinus Atrial Node (SAN) which has its own variability. Still, although both oscillators produce HRV, the influence of the SAN on HRV has not yet been exhaustively studied. On the other hand, the complications of diabetes mellitus (DM), for instance, nephropathy, retinopathy, and neuropathy, increase cardiovascular morbidity and mortality. Traditionally, these complications are diagnosed only when the patient is already suffering from the negative symptoms these complications implicate. Consequently, it is of paramount importance to develop new techniques for early diagnosis prior to any deterioration on healthy patients. HRV has been proved to be a valuable, noninvasive clinical evidence for evaluating diseases and even for describing aging and behavior. In this study, several ECGs were recorded and their RR and PP intervals were analyzed to detect the interpotential interval (ii) of the SAN. Additionally, HRV reduction was quantified to identify alterations in the nervous system within the nodal tissue via measuring the SD1/SD2 ratio in a Poincaré plot"

MeS increased risk of suffering arrhythmias.

<p>(<b>A</b>) Upper trace, representative electrocardiogram (ECG) of control rats. Lower trace; rats with MeS presented irregular sinusal rhythm (see asterisks). (<b>B</b>) Poincaré plot of ECG R-R interval evidenced an increase in the heart rate variability in MeS (n = 7; black) vs. control animals (n = 8; grey). The line dot represents the length and width of the area surrounding the points in Poincaré plot. (This plot was built with each interval R-R of ECG as a function of the previous R-R interval).</p