Diabetes and Ischemic Stroke: An Old and New Relationship an Overview of the Close Interaction between These Diseases

Diabetes mellitus is a comprehensive expression to identify a condition of chronic hyperglycemia whose causes derive from different metabolic disorders characterized by altered insulin secretion or faulty insulin effect on its targets or often both mechanisms. Diabetes and atherosclerosis are, from the point of view of cardio- and cerebrovascular risk, two complementary diseases. Beyond shared aspects such as inflammation and oxidative stress, there are multiple molecular mechanisms by which they feed off each other: chronic hyperglycemia and advanced glycosylation end-products (AGE) promote ‘accelerated atherosclerosis’ through the induction of endothelial damage and cellular dysfunction. These diseases impact the vascular system and, therefore, the risk of developing cardio- and cerebrovascular events is now evident, but the observation of this significant correlation has its roots in past decades. Cerebrovascular complications make diabetic patients 2–6 times more susceptible to a stroke event and this risk is magnified in younger individuals and in patients with hypertension and complications in other vascular beds. In addition, when patients with diabetes and hyperglycemia experience an acute ischemic stroke, they are more likely to die or be severely disabled and less likely to benefit from the one FDA-approved therapy, intravenous tissue plasminogen activator. Experimental stroke models have revealed that chronic hyperglycemia leads to deficits in cerebrovascular structure and function that may explain some of the clinical observations. Increased edema, neovascularization, and protease expression as well as altered vascular reactivity and tone may be involved and point to potential therapeutic targets. Further study is needed to fully understand this complex disease state and the breadth of its manifestation in the cerebrovasculature.     

Pathogenetic Mechanisms of Hypertension–Brain-Induced Complications: Focus on Molecular Mediators

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.     

Cancer-Related Cachexia: The Vicious Circle between Inflammatory Cytokines,Skeletal Muscle,Lipid Metabolism and the Possible Role of Physical Training

Cachexia is a multifactorial and multi-organ syndrome that is a major cause of morbidity and mortality in late-stage chronic diseases. The main clinical features of cancer-related cachexia are chronic inflammation, wasting of skeletal muscle and adipose tissue, insulin resistance, anorexia, and impaired myogenesis. A multimodal treatment has been suggested to approach the multifactorial genesis of cachexia. In this context, physical exercise has been found to have a general effect on maintaining homeostasis in a healthy life, involving multiple organs and their metabolism. The purpose of this review is to present the evidence for the relationship between inflammatory cytokines, skeletal muscle, and fat metabolism and the potential role of exercise training in breaking the vicious circle of this impaired tissue cross-talk. Due to the wide-ranging effects of exercise training, from the body to the behavior and cognition of the individual, it seems to be able to improve the quality of life in this syndrome. Therefore, studying the molecular effects of physical exercise could provide important information about the interactions between organs and the systemic mediators involved in the overall homeostasis of the body.     

Effect of polythene film activated with enterocin EJ97 in combination with EDTA against Bacillus coagulans

Polythene films coated with the enterococcal bacteriocin enterocin EJ97 alone or in combination with EDTA were tested against Bacillus coagulans CECT 12. Bacteriocin activity was clearly enhanced by EDTA, as shown by viable staining and epifluorescence microscopy observation of treated cells. Activated films were tested in liquids from canned corn and canned peas inoculated with B. coagulans cell suspensions and stored at 4 °C and 20 °C for 24 h. The bacteriocin alone showed highest activity in samples stored at 4 °C, while the maximum performance of EDTA was observed at 20 °C. Films activated with a combination of both antimicrobials showed highest bactericidal activity at 4 °C. In liquid from canned corn and peas stored at 4 °C, the combined treatment reduced the concentrations of viable cells progressively over incubation time. Viable staining revealed an increase in the percentage of dead cells at 20 °C, avoiding proliferation of the bacilli. The bactericidal effect of the combined antimicrobial agents was higher in the liquid of canned peas than that of canned corn. The combined use of viable staining and classical viable cell counts allowed a better estimation of cell damage caused by the antimicrobial treatments.     

Profiling selected phytochemicals and nutrients in different tissues of the multipurpose tree Moringa oleifera L., grown in Ghana

The purpose of this new study was to determine the types and levels of major phytochemicals (non-nutrients) and nutrients in the different tissues from vegetative and flowering Moringa oleifera L. an important multipurpose crop. Rhamnose and acetyl-rhamnose-substituted glucosinolates were found in all of the M. oleifera tissues with different profiles depending on the tissue. In addition the tissues of M. oleifera had a relatively complex flavonoid profile consisting of glucosides, rutinosides, malonylglucosides and traces of acetylglucosides of kaempferol, quercetin and isorhamnetin. Fatty acid profiling of the different tissues showed that leaves were rich in palmitic (16:0) and linolenic (18:3) acid whereas seeds were predominated by oleic acid (18:1). Roots were rich in palmitic and oleic acid, whereas stems and twigs predominately contained palmitic acid. Potassium, magnesium and calcium were the predominant minerals in all of the tissues. Low levels of selenium were detected only in whole seeds.     

Investigating the chlorination of acidic pharmaceuticals and by-product formation aided by an experimental design methodology

The degradation of seven acidic drugs and two metabolites during chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). A triple-quadrupole (QqQ) system was used to follow the time course of the pharmaceuticals and by-products, while a quadrupole time-of-flight (Q-TOF) system was also used for the identification of the by-products. Under strong chlorination conditions (10 mg/L Cl₂, 24 h), only four of the target compounds were significantly degraded: salicylic acid, naproxen, diclofenac and indomethacine. The degradation kinetics of these four compounds were investigated at different concentrations of chlorine, bromide and pH by means of a Box-Behnken experimental design. Depending on these factors, measured pseudo-first order half-lives were in the ranges: 23-573 h for salicylic acid, 13-446 min for naproxen, 5-328 min for diclofenac and 0.4-13.4 min for indomethacine. Also, it was observed that chlorine concentration was the overall most significant factor, followed by the bromide concentration (except for indomethacine), resulting in increased degradation kinetics as they are increased. The degradation path of salicylic acid, naproxen and diclofenac consisted of aromatic substitution of one or two hydrogens by chlorine and/or bromide. Moreover, for diclofenac, two other by-products corresponding to a decarboxylation/hydroxylation pathway from the monohalogenated products were also identified. On the other hand, indomethacine degradation did not lead to halogenation products but to oxidation ones. The investigation of these by-products in real samples by LC-MS/MS (QqQ) showed that the halogenated derivates of salicylic acid occurred in all the drinking water and wastewater samples analysed.     

Determination of anthocyanin content in C.V Monastrell grapes during ripening period using several procedures

The accumulation of anthocyanins in grape skin and their evolution during ripening were evaluated in Monastrell grapes grown at four different sites growing season. Of the different techniques used for this purpose, we used one chromatographic [high‐performance liquid chromatography (HPLC)] and three spectrophotometric (Saint‐Cricq, Fragoso‐García and Lamadon) methods. The grapes from two of the sites (Agüeros and Rubializas) presented much higher values of anthocyanin (1279 and 1207 mg kg^?1 respectively) compounds than the grapes from the other two sites. Of the different methods used, HPLC proved to be an invaluable tool for identifying and quantifying individual anthocyanins in a sample, while the Fragoso‐García technique was the best of the spectrophotometric methods for laboratories that do not have access to HPLC equipment. Application of principal component determination (PCA) to our experimental data resulted satisfactory classification of wines in terms of their geographical origin. High correlation coefficients were observed among the different spectrophotometric techniques (0.88 between Fragoso‐García and Saint Cricq; and 0.92 between Lamadon and Saint Cricq) and lower coefficients between HPLC and the spectrophotometric techniques.     

Matrices of water-soluble drug using natural polymer and direct compression method

The objective of this research was to find an optimum Carrageenan matrix formulation with the desired drug release and physical properties prepared by direct compression. In order to achieve this, matrices containing 10% theophylline, different Carrageenan level, and different excipient were prepared and evaluated. A selected matrix containing 40% Carrageenan and lactose fast flo was tested for dissolution in three different dissolution media (distilled water, 0.1 N HCl, and phosphate buffer pH 7.4). The same formulation was also tested for dissolution at 50 rpm, 100 rpm, and 150 rpm, and using different dissolution apparatus (Apparatus 1 and 2).

All matrices showed a decrease in drug release as the polymer level was increased. Only Avicel PH-101 did not show any significant difference between matrices prepared with 30% and 40% polymer. At 10% polymer level, it appears that the type of diluent used controls the drug release. However, at high polymer level, 30% and 40%, it appears that the polymer level controls the drug release. Phosphate buffer pH 7.4 and 0.1 N HCl increase drug release and appear to increase Carrageenan solubility and decrease gel formation. Also, as the rotational speed of the apparatus was increased, the integrity of the gel layer was decreased, and the release of drug was increased. The drug release from Carrageenan matrices appears to follow the diffusion model for inert matrix up to 90 min. After 90 min, the drug release follows a zero-order model.

This study demonstrated that matrices using Carrageenan can be successfully prepared by direct compression.     

A Bayesian framework for sensory adaptation

Adaptation allows biological sensory systems to adjust to variations in the environment and thus to deal better with them. In this article, we propose a general framework of sensory adaptation. The underlying principle of this framework is the setting of internal parameters of the system such that certain prespecified tasks can be performed optimally. Because sensorial inputs vary probabilistically with time and biological mechanisms have noise, the tasks could be performed incorrectly. We postulate that the goal of adaptation is to minimize the number of task errors. This minimization requires prior knowledge of the environment and of the limitations of the mechanisms processing the information. Because these processes are probabilistic, we formulate the minimization with a Bayesian approach. Application of this Bayesian framework to the retina is successful in accounting for a host of experimental findings.     

Common pediatric esophageal disorders

Esophageal disorders in children can result in significant morbidity. The most common esophageal disorder seen in children is gastroesophageal reflux. Other common disorders affecting the esophagus include peptic esophageal strictures, esophageal atresia with or without tracheoesophageal fistula, caustic and foreign body ingestions, achalasia, and cricopharyngeal achalasia. We discuss what is currently known about these common pediatric esophageal disorders with regard to pathophysiology, clinical presentation, and diagnostic and treatment strategies.