Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Attachment to Caregivers and Type 1 Diabetes in Children

Attachment is a behavioral and physiological system, which enables individual’s dynamic adaptation to its environment. Attachment develops in close interaction between an infant and his/her mother, plays an important role in the development of the infant’s brain, and influences the quality of interpersonal relationships throughout life.Security of attachment is believed to influence individual response to stress, exposing insecurely organized individuals to deregulated autonomic nervous system and exaggerated hypothalamic-pituitary-adrenal activity, which, in turn, produces increased and prolonged exposure to stress-hormones. Such stress responses may have considerable implications for the development of diverse health-risk conditions, such as insulin resistance and hyperlipidemia, shown by numerous studies.Although the mechanisms are not yet fully understood, there is compelling evidence highlighting the role of psychological stress in the development of type 1 diabetes (T1D). One of the possible contributing factors for the development of T1D may be the influence of attachment security on individual stress reactivity. Thus, the suggestion is that insecurely attached individuals are more prone to experience increased and prolonged influence of stress hormones and other mechanisms causing pancreatic beta-cell destruction.The present paper opens with a short overview of the field of attachment in children, the principal attachment classifications and their historic development, describes the influence of attachment security on individual stress-reactivity and the role of the latter in the development of T1D. Following is a review of recent literature on the attachment in patients with T1D with a conclusion of a proposed role of attachment organization in the etiology of T1D.     

Macroporous thin membranes for cell transplant in regenerative medicine

The aim of this paper is to present a method to produce macroporous thin membranes made of poly (ethyl acrylate-co-hydroxyethyl acrylate) copolymer network with varying cross-linking density for cell transplantation and prosthesis fabrication. The manufacture process is based on template techniques and anisotropic pore collapse. Pore collapse was produced by swelling the membrane in acetone and subsequently drying and changing the solvent by water to produce 100 microns thick porous membranes. These very thin membranes are porous enough to hold cells to be transplanted to the organism or to be colonized by ingrowth from neighboring tissues in the organism, and they present sufficient tearing stress to be sutured with surgical thread. The obtained pore morphology was observed by Scanning Electron Microscope, and confocal laser microscopy. Mechanical properties were characterized by stress–strain experiments in tension and tearing strength measurements. Morphology and mechanical properties were related to the different initial thickness of the scaffold and the cross-linking density of the polymer network. Seeding efficiency and proliferation of mesenchymal stem cells inside the pore structure were determined at 2 h, 1, 7, 14 and 21 days from seeding.     

Contribution to the rheological testing of pharmaceutical semisolids

Rheological behaviour of pharmaceutical semisolid preparations significantly affects manufacturing process, administration, stability, homogeneity of incorporated drug, accuracy of dosing, adhesion in the place of application, drug release, and resulting therapeutic effect of the product. We performed test of consistency by penetrometry, rotational, oscillation and creep tests, and squeeze and tack tests of model samples to introduce methods suitable for characterization and comparison of semisolids in practice. Penetrometry is a simple method allowing sorting the semisolids to low and high stress-resistant materials but deficient for rheological characterization of semisolids. Value of yield stress, generally considered to be appropriate feature of semisolids, is significantly influenced by the method of testing and the way of evaluation. The hysteresis loops of model semisolids revealed incomplete thixotropy, therefore, three-step thixotropy test was employed. Semisolids showed nonlinear response in the creep phase of tests and partial recovery of structure by storing energy in the recovery phase. Squeeze and tack tests seem to be convenient ways for comparison of semisolids. Our study can contribute to a better understanding of different flow behaviour of semisolids given by different physicochemical properties of excipients and can bring useful approaches to evaluation and comparison of semisolids in practice.     

Tissue tracking of segmental strain as a predictor of provoked dynamic left ventricular outflow tract obstruction

BackgroundLeft ventricular outflow tract obstruction (LVOTO) is commonly observed in patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy (LVH). Some patients develop LVOTO provoked by physical exertion, and hence termed dynamic LVOTO (DLVOTO). However, its precise prevalence and mechanism are still unclear.AimTwo-dimensional speckle tracking echocardiography (2D STE) seems to be helpful for the detection of early LV structural abnormalities. This study aimed to examine the possible role of segmental as well as global longitudinal strain in identifying DLVOTO non-HCM patients as detected by dobutamine stress echocardiography (DSE).Methods and resultsTwo hundred and fifty patients without structural heart disease had undergone conventional transthoracic echocardiography, 2D STE, and DSE. All patients with non-ischemic evidence were divided into two groups according to the DSE results; DLVOTO (+) and DLVOTO (?).Among 250 patients, 50 patients (36%) had shown DLVOTO after DSE (15 males, 35 females; mean age 55±7years). They were compared with 90 non -LVOTO obstruction patients (43 males, 47 females; mean age 57±6years). Based on multivariate logistic regression analysis, the independent predictors of provoked DLVOTO during DSE were resting basal septal longitudinal strain BS-LS _average (p < 0.001), resting LA reservoir strain (p < 0.001), and systolic LVOT diameter (p = 0.03). Resting BS-LS _average with cut-off - 17.5% was recognized as a critical indicator of DLVOTO, with sensitivity 78%, and specificity 95% (better than systolic LVOT diameter of sensitivity 76%, and specificity 15% and resting LA reservoir strain which showed poor AUC at ROC curve 0.007).ConclusionWe demonstrate that provoked LVOTO during DSE in non HCM symptomatic patients is directly correlated to resting regional LS, where the increased BS-LS of ≥ ?17.5% was a key determinant of LVOT gradient provocation. Assessment of baseline BS-LS _average might be a bedside simple tool for detection of patients with DLVOTO not able to do DSE.     

Antioxidant and anti-inflammatory activities of lycopene against 5-fluorouracil-induced cytotoxicity in Caco2 cells

5-fluorouracil (5FU) is widely used to treat colorectal cancer (CC) and its main mechanisms of anticancer action are through generation of ROS which often result in inflammation. Here, we test the effect of Lycopene against 5FU in Caco2 cell line. Caco2 cells were exposed to 3 µg/ml of 5FU alone or with 60, 90, 120 µg/ml of lycopene. This was followed by assessment of cytotoxicity, oxidative stress, and gene expression of inflammatory genes. Our findings showed that Lycopene and 5FU co-exposure induced dose-dependent cytotoxic effect without compromising the membrane integrity based on the LDH assay. Lycopene also significantly enhanced 5FU-induced SOD activity and GSH level compared to control for all mixture concentrations (p < 0.01). Lycopene alone and combination with 5FU-induced expression of IL-1β, TNF-α, and IL-6. Furthermore, IFN-γ expression was significantly enhanced by only mixture of lycopene (90 µg/ml) and 5FU (p < 0.05). In conclusion, Lycopene supplementation with 5FU therapy resulted in improvement in antioxidant parameters such as catalase and GSH levels giving the cell capacity to cope with 5FU-mediated oxidative stress. Lycopene also enhanced IFN-γ expression in the presence of 5FU, which may activate antitumor effects further enhancing the cancer killing effect of 5FU.