Mechanisms involved in the aging-induced vascular dysfunction

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permissionVascular aging is a key process determining health status of aged population. Aging is an independent cardiovascular risk factor associated to an impairment of endothelial function, which is a very early and important event leading to cardiovascular disease. Vascular aging, formerly being considered an immutable and inexorable risk factor, is now viewed as a target process for intervention in order to achieve a healthier old age. A further knowledge of the mechanisms underlying the age-related vascular dysfunction is required to design an adequate therapeutic strategy to prevent or restore this impairment of vascular functionality. Among the proposed mechanisms that contribute to age-dependent endothelial dysfunction, this review is focused on the following aspects occurring into the vascular wall: (1) the reduction of nitric oxide (NO) bioavailability, caused by diminished NO synthesis and/or by augmented NO scavenging due to oxidative stress, leading to peroxynitrite formation (ONOO -); (2) the possible sources involved in the enhancement of oxidative stress; (3) the increased activity of vasoconstrictor factors; and (4) the development of a low-grade pro-inflammatory environment. Synergisms and interactions between all these pathways are also analyzed. Finally, a brief summary of some cellular mechanisms related to endothelial cell senescence (including telomere and telomerase, stress-induced senescence, as well as sirtuins) are implemented, as they are likely involved in the age-dependent endothelial dysfunction, as well as in the lower vascular repairing capacity observed in the elderly. Prevention or reversion of those mechanisms leading to endothelial dysfunction through life style modifications or pharmacological interventions could markedly improve cardiovascular health in older peopleThis study is supported by grants from Ministerio de Ciencia e Innovación (Instituto de Salud Carlos III, RETICEF RD06/0013; PI08/1649; SAF2011-28011; SAF2011-24684, Spanish Government, and Sociedad Española de Farmacología/Almirall Prodesfarm

A New Generating Family of Distributions: Properties and Applications to the Weibull Exponential Model

A new method for generating family of distributions was proposed. Some fundamental properties of the new proposed family include the quantile, survival function, hazard rate function, reversed hazard and cumulative hazard rate functions are provided. This family contains several new models as sub models, such as the Weibull exponential model which was defined and discussed its properties. The maximum likelihood method of estimation is using to estimate the model parameters of the new proposed family. The flexibility and the importance of the Weibull-exponential model is assessed by applying it to a real data set and comparing it with other known models

On Construction of Tri-Concept Lattices

The main point is to define the structure of a Tri-Concept lattice to deal with data given by different sources and represent it by less complex structures without loosing knowledge. We suggest the algorithm TRI-NEST to form the nested diagrams corresponding to the Tri-Concept lattices. Adding the ICE-T algorithm enables us to generate all frequently closed concepts, which leads to simplifying the Tri-Concept lattices and using the Iceberg Concept lattices as a reduction method to the big data while preserving all information

Bridging Explainability and Interpretability in AI-driven SCM Projects to Enhance Decision-Making

New AI-based systems implementation in companies is steadily expanding, paving the way for novel organizational sequences. The increasing involvement of end-users has also garnered interest in AI explainability. However, AI explainability continues to be a serious concern, particularly in conventional fields of activity where end-users play an essential role in the large-scale deployment of AI-based solutions. To address this challenge, managing the close relationship between explainability and interpretability deserves particular attention to enable end-users to act and decide with confidence

Purification of kappa (k)-carrageenase from locally isolated Cellulosimicrobium cellulans

Partial purification of the crude kappa (k)-carrageenase present in the culture filtrates of Cellulosimicrobium cellulans was carried out by fractional precipitation, using ammonium sulphate, acetone and ethanol individually. The highest recovered protein (37.08%) combined with enzyme activity was obtained with ammonium sulphate. The fraction precipitated by 90% ammonium sulphate was re-purified by anion exchange chromatography diethylaminoethyl (DEAE) cellulose, A-52 and 79 fractions were obtained. The loaded protein was separated into 4 peaks. The third protein peak was the major one which contained the most recovered enzyme activity (84.95%) from the eluted fractions. The collected fractions of this peak were subjected to further purification by re-chromatography on Sephadex G-100. The k-carrageenase activity was fractionated into 2 peaks. The first peak was the major one containing 95.622% of the total recovered activity. The pooled fractions of the major protein component showed a specific k-carrageenase activity of 46.22 U/mg protein, yielding about 4.6 fold purification of the crude enzyme preparation. Some properties of purified k-carrageenase obtained from cellusimicrobium cellulans cultures were studied. The optimum reaction temperature of the purified k-carrageenase was 30°C and the maximum activity occurred at a reaction pH of 6.Key words: Cellulosimicrobium cellulans, k-carrageenase, purification, sephadex G-100, diethylaminoethyl (DEAE) sephadex A-52

Effect of relining, cement type, and thermocycling on push-out bond strength of fiber reinforced posts.

Statement of the problem: Improving the adaptation of fiber reinforced posts through relining may affect the retention of the posts. Purpose: To investigate the effect of post relining, cement type, and thermocycling on the push-out bond strength of fiber reinforced posts. Materials and methods: (48) endodontically treated human teeth were excessively flared using diamond stones. The teeth were divided into two groups; group (1) (n ¼ 24) received glassix glass fiber posts adapted to the flared canals by relining with composite resin and group (2) (n ¼ 24) received non-relined glassix glass fiber post. Samples of each group were divided into three subgroups (n ¼ 8) according to the type of cement used; subgroup (a): luted using Metacem Refill, a total etch resin cement, subgroup (b): luted using Rely X Unicem, a self-adhesive resin cement and subgroup (c): luted using RelyX Luting, a resin modified glass ionomer cement. Half the samples of each subgroup (n ¼ 4) were subjected to thermocycling. The samples were sectioned horizontally into 2 mm thick slices yielding 3 sections for each sample. Retention was evaluated using push out bond strength test using universal testing machine. The maximum failure load was recorded and used to calculate the push-out bond strength. Data was statistically analyzed and mode of failure was assessed using magnifying glass. Results: Relined posts showed statistically significantly higher mean push-out bond strength than non-relined posts. Rely X Unicem showed the statistically significantly highest mean push-out bond strength among tested cements. Metacem showed significantly lower mean push-out bond strength than Rely X Unicem. Rely X Luting showed the statistically significantly lowest mean push-out bond strengths. There was no statistically significant difference between mean push-out bond strength with and without thermocycling. Most failures occurred at the cementedentin interface in the relined group, while adhesive failure occurred at the cement-post interface in non-relined group

HYPOGLYCEMIC AND HYPOLIPIDEMIC EFFECTS OF SPIRULINA PLATENSIS, PHYCOCYANIN, PHYCOCYANOPEPTIDE AND PHYCOCYANOBILIN ON MALE DIABETIC RATS

This study aimed to evaluate hypoglycemic and hypolipidemic activities of Spirulina Platensis and its bioactive components (phycocyanin (PC), phycocyanopeptide (PCP) and phycocyanobilin (PCB)) on male diabetic Rats compared to controls and glibenclamide drug. For this reason, male Albino rats were equally divided into seven groups designated as normal control, diabetic control, diabetic + glibenclamide (Glyburide) drug (600 µg kg−1 body weight), diabetic + Spirulina biomass suspension (50 mg/ml/ kg−1 body weight), diabetic + phycocyanin (50 mg kg−1 body weight), diabetic + phycocyanopeptide (49 mg kg−1 body weight) and diabetic + phycocyanobilin (982 µg kg−1 body weight). The results show a statistically significant reduction (P < 0.05) level of fasting blood glucose, insulin resistance and lipids levels in diabetic animals administration with Spirulina Platensis, phycocyanin, phycocyanopeptide and phycocyanobilin compared with diabetic control.  Also, there were an increase in HDL–cholesterol levels and β-cell function in these treatments. Histopathologically, diabetic rats treated with spirulina, PC, PCP induced a slight improve of pancreatic cells and an obvious recovery of pancreatic cells.  The expression of insulin secretion from cells (β-cells) of diabetic rats was improved in the groups treated with Spirulina, phycocyanin, phycocyanopeptide. While, diabetic rats treated with phycocyanobilin recorded insulin levels lower than them.  From this study it can be concluded that Spirulina Platensis, phycocyanin, phycocyanopeptide and phycocyanobilin possessed hypoglycemic, insulin sensitivity and hypolipidemic effects. Hypoglycemic and hypolipidemic effects of Spirulina Platensis may be attributed to phenolic compounds and phycocyanin. The antidiabetic effect of PC is most likely due to its ability to reduction of insulin resistance, enhance β-cell function and recovery of β-cells. The effect of PC may be attributed to selenium-binding phycocyanopeptide or/ and phycocyanobilin responsible for the antioxidant activity and chromium-binding phycocyanopeptide which activates insulin receptors

Upregulation of Orai Channels Contributes to Aging-Related Vascular Alterations in Rat Coronary Arteries.

Vascular territories display heterogeneous sensitivity to the impacts of aging. The relevance of the STIM/Orai system to vascular function depends on the vascular bed. We aimed to evaluate the contribution of the STIM/Orai system to aging-related vascular dysfunction in rat coronary circulation. Vascular function was evaluated according to myography in coronary arteries from young (three-month-old) and older (twenty-month-old) rats. The effects of aging and STIM/Orai inhibition on the contraction and relaxation of the coronary arteries and on the protein expression of STIM-1, Orai1, and Orai3 in these vessels were determined. Aging-related hypercontractility to serotonin and endothelin-1 in arteries from male rats was reversed by STIM/Orai inhibition with YM-58483 or by specifically blocking the Orai1 channel with Synta66. The inhibitory effects of Synta66 on coronary vasoconstriction were also observed in older female rats. YM-58483 relaxed serotonin- but not KCl-contracted arteries from males. STIM/Orai inhibition improved defective endothelial vasodilations in aged arteries, even in the presence of NO synthase and cyclooxygenase inhibitors, but not in KCl-contracted segments. YM-58483 significantly enhanced relaxations to calcium-activated potassium channel stimulation in aged vessels. Increased protein expression of Orai1 and Orai3 was detected in arterial homogenates and sections from older rats. Upregulation of the Orai channel contributes to aging-related coronary dysfunction, revealing a potential target in reducing CVD risk.post-print455 K