Study of Harris Lines at the »Prat de la Riba« Necropolis – Third to Fifth Century AD

Harris lines (HL) are considered a nutritional or pathological stress factor in the study of past populations. This study attempts to contribute to the knowledge of the causal agents for HL in terms of assessing the health state of the population of Tarragona in the Roman period. The presence of HL has been analyzed in 614 long bones (214 humeri, 150 femurs and 250 tibias) from 243 skeletons. No HL have been observed in humeri. The frequencies of HL in femurs are higher than 27% and in tibias more than 48%. Although no significant differences in the presence of HL is found among age categories, it seems that the causal agents of these marks acted on individuals from the age of 5, an age from which the long bones of the lower extremities are more prone to producing HL. The hardened living conditions in the Dark Age of the Roman period in Spain between the third to fifth centuries A.D. may be the cause of the high prevalence of HL in this population

Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.

Inhibition of Extracellular Matrix degradation by nitric oxide (NO) induces cardiac protection against coronary ischemia/reperfusion (IR). Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) stimulates enzymatic activation of matrix metalloproteinases (MMPs) in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN) in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2) knockout (KO) mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO) in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9), in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF). NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6). The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5), or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.Ministerio de Economía y CompetitividadInstituto de Salud Carlos II

EMMPRIN-targeted magnetic nanoparticles for In vivo visualization and regression of acute myocardial infarction.

Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to CONTROL and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs CONTROL 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury.Ministerio de Economía y CompetitividadInstituto de Salud Carlos II

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (–5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. –19.7% variation, p < 0.01). Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (–5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. – 19.7% variation, p < 0.01). Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.pre-print2533 K

Autoanticossos contra receptors de folat i estat en folats a la població general, durant l'embaràs i efecte sobre la subfertilitat en dones

Folate receptor blocking autoantibodies (FR-AuAb), that impede transmembranal folate transport by this route, have been associated with neuronal developmental anomalies.The prevalences of FR-AuAb in the population and in pregnant women, their association with folate status, the cause of their production and effect on female subfertility were investigated.7.2% of the population and 6.3% of pregnant women were carriers, but folate status was not impaired. However higher cord folate status indicated the presence of a compensatory mechanism. Birth weight of carriers' offspring was 4.6 times more likely to be below the 25th percentile. The presence of FR-AuAb in the cord (7.5%) was not associated with maternal presence, cord folate status, or birth weight. High milk consumers had 2.4 times more risk of having FR-AuAb than the rest of consumers.FR-AuAb carriers at preconception were 12 times more likely to have subfertility than non-carriers.Els autoanticossos contra receptors de folat (AuAc-RF), que impedeixen el transport transmembranal de folat per aquesta ruta, s'han associat amb anomalies del desenvolupament neuronal. S'ha investigat les prevalences de portadors d'AuAc-RF i l'estat en folats a la població i a l'embaràs, la causa de la seva producció i l'efecte sobre la subfertilitat femenina.El 7.2% de la població i 6.3% de gestants eren portadors, sense perjudicar l'estat en folats. Peró el folat plasmàtic major dels cordons, indicava presència d'un mecanisme de compensació. Les portadores tenien 4.6 vegades major risc de tenir un nadó amb un pes al n¨¦ixer ¡ÜP25. AuAc-RF al cordó (7.5%) no sassociava amb presència materna, estat en folats del cordó ni amb pes de naixement. Alts consumidors de llet tenien 2.4 major risc de ser portadors respecte la resta de consumidors .Les portadores a la preconcepció, tenien 12 vegades major risc per subfertilitat respecte les no-portadores

Low folate status enhances pregnancy changes in plasma betaine and dimethylglycine concentrations and the association between betaine and homocysteine

10.3945/ajcn.112.05418

Exposure to Folate Receptor Alpha Antibodies during Gestation and Weaning Leads to Severe Behavioral Deficits in Rats: A Pilot Study

<div><p>The central nervous system continues to develop during gestation and after birth, and folate is an essential nutrient in this process. Folate deficiency and folate receptor alpha autoantibodies (FRα-AuAb) have been associated with pregnancy-related complications and neurodevelopmental disorders. In this pilot study, we investigated the effect of exposure to FRα antibodies (Ab) during gestation (GST), the pre-weaning (PRW), and the post weaning (POW) periods on learning and behavior in adulthood in a rat model. In the open field test and novel object recognition task, which examine locomotor activity and anxiety-like behavior, deficits in rats exposed to Ab during gestation and pre-weaning (GST+PRW) included more time spent in the periphery or corner areas, less time in the central area, frequent self-grooming akin to stereotypy, and longer time to explore a novel object compared to a control group; these are all indicative of increased levels of anxiety. In the place avoidance tasks that assess learning and spatial memory formation, only 30% of GST+PRW rats were able to learn the passive place avoidance task. None of these rats learned the active place avoidance task indicating severe learning deficits and cognitive impairment. Similar but less severe deficits were observed in rats exposed to Ab during GST alone or only during the PRW period, suggesting the extreme sensitivity of the fetal as well as the neonatal rat brain to the deleterious effects of exposure to Ab during this period. Behavioral deficits were not seen in rats exposed to antibody post weaning. These observations have implications in the pathology of FRα-AuAb associated with neural tube defect pregnancy, preterm birth and neurodevelopmental disorders including autism.</p></div