Efficiency of Expired Drugs Used as Corrosion Inhibitors: A Review.

Corrosion inhibitors represent one of the most commonly used methods for significantly reducing the corrosion rate of metals and alloys. Adsorption inhibitors have a wide range of applications in cooling water systems, deicing solutions for aircrafts, airports and ways, etching and degreasing solutions, oil pipelines, paints and coatings and metal processing solutions. Adsorption corrosion inhibitors of metals and alloys are generally organic compounds that contain structures with heteroatoms (N, P, S, As, O) in their molecules, having lone pair electrons or π electrons in aromatic rings or multiple bonds. They enable relatively strong interactions between the metal atoms and organic molecules, resulting in a protective layer of organic molecules adsorbed at the metal-corrosive solution interface. Most molecules of active substances from drugs contain similar structures, which is why many drugs have been already tested as corrosion inhibitors. One of the major disadvantages of using drugs for this purpose is their particularly high price. To overcome this impediment, the possibility of using expired drugs as corrosion inhibitors has been investigated since 2009. The present paper is an exhaustive compilation of the scientific published papers devoted to the use of expired drugs as corrosion inhibitors in various aggressive solutions. The inhibitory efficiencies of expired drugs are presented as a function of the studied metal or alloy and the nature of the aggressive solution, as well as the concentration of the inhibitor in such a solution. Research has especially been focused on mild and carbon steel and less on stainless steel, as well as on some metals such as copper, zinc, nickel, tin and aluminum and its alloys. The experimental methods used to assess the inhibitory efficiencies of expired drugs are briefly discussed. Also, the available information on the stability of the active substances in the drugs is presented, although most authors were not concerned with this aspect. Finally, several actions are revealed that must be undertaken by researchers so that the results obtained in the study of the anticorrosive action of expired drugs can be applied at the industrial level and not remain only an academic concern.

In Vitro Study of the Multimodal Effect of Na+/K+ ATPase Blocker Ouabain on the Tumor Microenvironment and Malignant Cells.

Na+/K+ ATPase is a protein involved in the active transport of ions across the cellular membrane. Ouabain is a cardiotonic glycoside that, by inhibiting the Na+/K+ pump, interferes with cell processes mediated directly by the pump, but also indirectly influences other cellular processes such as cell cycle and proliferation, growth, cell differentiation, angiogenesis, migration, adhesion, and invasion. We used the SK-BR-3 breast cancer cell line, mesenchymal stem cells (MSCs), and tumor-associated fibroblasts (TAFs) in vitro to determine the effects of ouabain exposure on these cellular types. The results showed a multi-level effect of ouabain mainly on tumor cells, in a dose-dependent manner, while the TAFs and their normal counterparts were not significantly influenced. Following exposure to ouabain, the SK-BR-3 cells changed their morphologic appearance, decreased the expression of immunophenotypic markers (CD29, Her2, VEGF), the proliferation rate was significantly decreased (Ki67 index), the cells were blocked in the G0 phase of the cell cycle and suffered necrosis. These data were correlated with the variable expression of α and ß Na+/K+ pump subunits in tumor cells, resulting in decreased ability to adhere to the VCAM-1 substrate in functional flow chamber studies. Being indicative of the pro-apoptotic and inhibitory effect of ouabain on tumor invasion and metastasis, the results support the addition of ouabain to the oncological therapeutic arsenal, trailing the "repurposing drugs" approach.

Study on the Biodegradation Process of D-Mannose Glycopolymers in Liquid Media and Soil.

Polymers derived from natural raw materials have become of great interest due to their increased biodegradable features and possible biocompatibility. Our group has successfully synthesized and characterized polymers derived from D-mannose oligomer (M), 2-hydroxy propyl acrylate (HPA), and methacrylate (HPMA) in different weight ratios. Their biodegradation was studied in liquid media with pure Proteus mirabilis inoculum for the samples with the most sugar residue, and the results show that the methacrylate derivative M_HPMA1 lost about 50% of its weight during incubation. SEM/EDX techniques were employed to display the modifications of the samples during the biodegradation process. The glycopolymers were buried in garden soil, and the experiment proved that more than 40% of the weight of the M_HPA1 sample was lost during biodegradation, while the other samples encountered an average of about 32% weight loss. The biodegradation profile was fitted against linear and polynomial mathematical models, which enabled an estimate of about a year for the total degradation of the D-mannose glycopolymers sample in soil.

Urine Metabolomic Signature of People Diagnosed with Balkan Endemic Nephropathy and Other Types of Chronic Kidney Disease Compared with Healthy Subjects in Romania.

Metabolomic analysis methods were employed to determine biomarkers for various chronic kidney diseases (CKDs). Modern analytical methods were developed and applied successfully to find a specific metabolomic profile in urine samples from CKD and Balkan endemic nephropathy (BEN) patients. The aim was to explore a specific metabolomic profile defined by feasible/easy-to-identify molecular markers. Urine samples were collected from patients with CKDs and BEN, and from healthy subjects from endemic and nonendemic areas in Romania. Metabolomic analysis of urine samples, extracted by the liquid-liquid extraction (LLE) method, was performed by gas chromatography-mass spectrometry (GC-MS). The statistical exploration of the results was performed through a principal component analysis (PCA) evaluation. Urine samples were statistically analyzed using a classification based on six types of metabolites. Most urinary metabolites are distributed in the center of a loading plot, meaning that these compounds do not represent significant markers for BEN. One of the most frequent and higher-concentration urinary metabolites in BEN patients was p-Cresol, a phenolic compound that implies a severe injury of the renal filtration function. The presence of p-Cresol was associated with protein-bound uremic toxins, which have specific functional groups such as indole and phenyl. In prospective studies for future investigation, prevention, and disease treatment, we suggest a larger sample size, sample extraction using other methods, and analysis using other chromatography techniques coupled with mass spectrometry, which can generate a more significant data set for statistical analysis.

Automation and Optimization of Rat Heart Decellularization Using a Vibrating Fluid Column.

This paper presents the validation of a software application to optimize the discoloration process in simulated hearts and to automate and determine the final moment of decellularization in rat hearts using a vibrating fluid column. The implemented algorithm specifically for the automated verification of a simulated heart's discoloration process was optimized in this study. Initially, we used a latex balloon containing enough dye to reach the opacity of a heart. The complete discoloration process corresponds to complete decellularization. The developed software automatically detects the complete discoloration of a simulated heart. Finally, the process stops automatically. Another goal was to optimize the Langendorff-type experimental apparatus, which is pressure-controlled and equipped with a vibrating fluid column that shortens the decellularization time by mechanically acting directly on cell membranes. Control experiments were performed with the designed experimental device and the vibrating liquid column using different decellularization protocols for hearts taken from rats. In this work, we used a commonly utilized solution based on sodium dodecyl sulfate. Ultraviolet spectrophotometry was used to measure the evolution of the dye concentration in the simulated hearts and, similarly, to determine the concentrations of deoxyribonucleic acid (DNA) and proteins in the rat hearts.

Decellularized Extracellular Matrix Scaffolds for Cardiovascular Tissue Engineering: Current Techniques and Challenges.

Cardiovascular diseases are the leading cause of global mortality. Over the past two decades, researchers have tried to provide novel solutions for end-stage heart failure to address cardiac transplantation hurdles such as donor organ shortage, chronic rejection, and life-long immunosuppression. Cardiac decellularized extracellular matrix (dECM) has been widely explored as a promising approach in tissue-regenerative medicine because of its remarkable similarity to the original tissue. Optimized decellularization protocols combining physical, chemical, and enzymatic agents have been developed to obtain the perfect balance between cell removal, ECM composition, and function maintenance. However, proper assessment of decellularized tissue composition is still needed before clinical translation. Recellularizing the acellular scaffold with organ-specific cells and evaluating the extent of cardiomyocyte repopulation is also challenging. This review aims to discuss the existing literature on decellularized cardiac scaffolds, especially on the advantages and methods of preparation, pointing out areas for improvement. Finally, an overview of the state of research regarding the application of cardiac dECM and future challenges in bioengineering a human heart suitable for transplantation is provided.

Optimization of Complete Rat Heart Decellularization Using Artificial Neural Networks.

Whole organ decellularization techniques have facilitated the fabrication of extracellular matrices (ECMs) for engineering new organs. Unfortunately, there is no objective gold standard evaluation of the scaffold without applying a destructive method such as histological analysis or DNA removal quantification of the dry tissue. Our proposal is a software application using deep convolutional neural networks (DCNN) to distinguish between different stages of decellularization, determining the exact moment of completion. Hearts from male Sprague Dawley rats (n = 10) were decellularized using 1% sodium dodecyl sulfate (SDS) in a modified Langendorff device in the presence of an alternating rectangular electric field. Spectrophotometric measurements of deoxyribonucleic acid (DNA) and total proteins concentration from the decellularization solution were taken every 30 min. A monitoring system supervised the sessions, collecting a large number of photos saved in corresponding folders. This system aimed to prove a strong correlation between the data gathered by spectrophotometry and the state of the heart that could be visualized with an OpenCV-based spectrometer. A decellularization completion metric was built using a DCNN based classifier model trained using an image set comprising thousands of photos. Optimizing the decellularization process using a machine learning approach launches exponential progress in tissue bioengineering research.

An Empirical Model for Predicting Biodegradation Profiles of Glycopolymers.

Pollution caused by plastic materials has a great impact on the environment. The biodegradation process is a good treatment solution for common polymers and biodegradation susceptible ones. The present work introduces new insight into the biodegradation process from a mathematical point of view, as it envisions a new empirical model for this complex process. The model is an exponential function with two different time constants and a time delay, which follows the weight loss profile of the polymer during the biodegradation process. Moreover, this function can be generated as the output variable of a dynamic exogenous system described through state equations. The newly developed models displayed a good fit against the experimental data, as shown by statistical indicators. In addition, the new empirical model was compared to kinetics models available in the literature and the correlation coefficients were closest to 1 for the new empirical model in all discussed cases. The mathematical operations were performed in the MATLAB Simulink environment.

3D Bioprinting of Model Tissues That Mimic the Tumor Microenvironment.

The tumor microenvironment (TME) influences cancer progression. Therefore, engineered TME models are being developed for fundamental research and anti-cancer drug screening. This paper reports the biofabrication of 3D-printed avascular structures that recapitulate several features of the TME. The tumor is represented by a hydrogel droplet uniformly loaded with breast cancer cells (106 cells/mL); it is embedded in the same type of hydrogel containing primary cells-tumor-associated fibroblasts isolated from the peritumoral environment and peripheral blood mononuclear cells. Hoechst staining of cryosectioned tissue constructs demonstrated that cells remodeled the hydrogel and remained viable for weeks. Histological sections revealed heterotypic aggregates of malignant and peritumoral cells; moreover, the constituent cells proliferated in vitro. To investigate the interactions responsible for the experimentally observed cellular rearrangements, we built lattice models of the bioprinted constructs and simulated their evolution using Metropolis Monte Carlo methods. Although unable to replicate the complexity of the TME, the approach presented here enables the self-assembly and co-culture of several cell types of the TME. Further studies will evaluate whether the bioprinted constructs can evolve in vivo in animal models. If they become connected to the host vasculature, they may turn into a fully organized TME.

Biodegradation Pattern of Glycopolymer Based on D-Mannose Oligomer and Hydroxypropyl Acrylate.

Glycopolymers are polymers with sugar moieties which display biodegradable and/or biocompatible character. They have emerged as an environmentally-friendly solution to classical synthetic polymers and have attracted significant research interest in the past years. Herein, we present the synthesis of a D-mannose based glycopolymer with biodegradable features. The glycopolymer was synthesized by radical copolymerization between a D-mannose oligomer bearing polymerizable double bonds and 2-hydroxypropyl acrylate, in a weight ratio of 1:2. The copolymerization kinetics was investigated by differential scanning calorimetry (DSC) and the activation energy of the process was comparatively assessed by Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa methods. The obtained glycopolymer displayed good thermal behavior, fact proven by thermogravimetrical (TG) analysis and it was submitted to biodegradation inside a bioreactor fed with water from the Bega River as the source of microbial inoculum. The glycopolymer sample degraded by approximately 60% in just 23 days. The biodegradation pattern of the glycopolymer was successfully fitted against a modified sigmoidal exponential function. The kinetic model coefficients and its accuracy were calculated using Matlab and the correlation coefficient is more than promising. The changes inside glycopolymer structure after biodegradation were studied using TG and FTIR analyses, which revealed that the sugar moiety is firstly attacked by the microbial consortia as nutrient source for proliferation.

Acute inhibition of monoamine oxidase and ischemic preconditioning in isolated rat hearts: interference with postischemic functional recovery but no effect on infarct size reduction.

Monoamine oxidases (MAOs) have recently emerged as important mitochondrial sources of oxidative stress in the cardiovascular system. Generation of reactive oxygen species during the brief episodes of ischemic preconditioning (IPC) is responsible for the cardioprotection at reperfusion. The aim of this study was to assess the effects of two MAO inhibitors (clorgyline and pargyline) on the IPC-related protection in isolated rat hearts. Animals subjected to 30 min global ischemia and 120 min reperfusion were assigned to the following groups: (i) Control, no additional intervention; (ii) IPC, 3 cycles of 5 min ischemia and 5 min reperfusion before the index ischemia; (iii) IPC-clorgyline, IPC protocol bracketed for 5 min with clorgyline (50 µmol/L); (iv) IPC-pargyline, IPC protocol bracketed for 5 min with pargyline (0.5 mmol/L). The postischemic functional recovery was assessed by the left ventricular developed pressure (LVDP) and the indices of contractility (+dLVP/dt max) and relaxation (-dLVP/dt max). Infarct size (IS) was quantified by TTC staining. In both genders, IPC significantly improved functional recovery that was further enhanced in the presence of either clorgyline or pargyline. IS reduction was comparable among all the preconditioned groups, regardless of the presence of MAO inhibitors. In isolated rat hearts, acute inhibition of MAOs potentiates the IPC-induced postischemic functional recovery without interfering with the anti-necrotic protection.

Revealing a Pre-neoplastic Renal Tubular Lesion by p-S6 Protein Immunohistochemistry after Rat Exposure to Aristolochic Acid.

Aristolochic acid (AA) has, in the last decade, become widely promoted as the cause of the Balkan endemic nephropathy and associated renal or urothelial tumours, although without substantial focal evidence of the quantitative dietary exposure via bread in specific households in hyperendemic villages. Occasional ethnobotanical use of Aristolochia clematitis might be a source of AA, and Pliocene lignite contamination of well-water is also a putative health risk factor. The aim of this study was two-fold: to verify if extracts of A. clematitis and Pliocene, or AA by itself, could induce the development of renal or urothelial tumours, and to test the utility of the ribosomal protein p-S6 to identify preneoplastic transformation. Rats were given extracts of A. clematitis in drinking water or AA I, by gavage. After seven months, renal morphology was studied using conventional haematoxylin and eosin and immunohistochemistry for ribosomal p-S6 protein. Plant extracts (cumulative AA approximately 1.8 g/kg b.w.) were tolerated and caused no gross pathology or renal histopathological change, with only faint diffuse p-S6 protein (except in the papilla) as in controls. Cumulative AA I (150 mg/kg b.w. given over 3 days) was also tolerated for seven months by all recipients, without gross pathology or kidney tumours. However, p-S6 protein over-expression was consistent particularly within the renal papilla. In one case given AA I, intense p-S6 protein staining of a proximal tubule fragment crucially matched the pre-neoplastic histology in an adjacent kidney section. We briefly discuss these findings, which compound uncertainty concerning the cause of the renal or upper urinary tract tumours of the Balkan endemic nephropathy.

Development of a high-performance anesthesia ventilator for research in small animals.

INTRODUCTION: Small animal models are used extensively in basic research because of their low cost and possibility to mimic several human pathologies. These models are used to either analyze the underlying mechanisms and/or assess therapeutic approaches. In this respect, gentle and safe artificial ventilation is mandatory, especially for prolonged experimental procedures that require the survival of the animals. The aim of the present paper was to develop and validate a high-performance anesthesia ventilator for small animals. METHODS: A pressure-controlled ventilator with assisted ventilation and deep breath modulated on a scheduled basis and a PEEP facility for an improved anesthetic management was developed. Parameters of acid-base balance and arterial blood gases were measured initially at the end of arterial catheterization and monitored throughout the experiment. RESULTS: Our data show the following average values (mmHg) for pO2: 440 +/- 45 (initial), 378 +/- 24 (2 h), 373 +/- 22 (4 h), and 375 +/- 28 (6 h) and for pCO2: 35 +/- 3 (initial), 34 +/- 5 (2 h), 38 +/- 5 (4 h), and 40 +/- 6 (6 h), respectively. CONCLUSIONS: We describe the procedure for the manufacture of a reliable, high-performance anesthesia ventilator that facilitates recovery of spontaneous respiration at animal arousal with preservation of normal blood gases values and no damage to the lungs.

Enucleation: a possible mechanism of cancer cell death.

There are few major morphologies of cell death that have been described so far: apoptosis (type I), cell death associated with autophagy (type II), necrosis (type III) and anchorage-dependent mechanisms-anoikis. Here, we show for the first time a possibly novel mechanism inducing tumour cell death under in vitro conditions-enucleation. We pursued the influence of colloidal suspensions of Fe3 O4 nanoparticles on tumour cell lines (SK-BR-3 and MCF-7 breast cancer cell lines) grown according to standard cell culture protocols. Magnetite nanoparticles were prepared by combustion synthesis and double layer coated with oleic acid. Scanning and transmission electron microscopy revealed that tumour cells developed a network of intracytoplasmic stress fibres, which induce extrusion of nuclei, and enucleated cells die. Normal adult mesenchymal stem cells, used as control, did not exhibit the same behaviour. Intact nuclei were found in culture supernatant of tumour cells, and were visualized by immunofluorescence. Enucleation as a potential mechanism of tumour cell death might open new horizons in cancer biology research and development of therapeutic agents capable of exploiting this behaviour.

Activation of prosurvival signaling pathways during the memory phase of volatile anesthetic preconditioning in human myocardium: a pilot study.

According to a compelling body of evidence anesthetic preconditioning (APC) attenuates the deleterious consequences of ischemia-reperfusion and protects the heart through a mechanism similar to ischemic preconditioning. The present study was purported to investigate the intracellular signaling pathways activated in human myocardium in response to a preconditioning protocol with two different volatile anesthetics, namely isoflurane and sevoflurane. To this aim, phosphorylation of PKCα and -δ, ERK1/2, Akt, and GSK3ß was determined at the end of the APC protocol, in human atrial samples harvested from patients undergoing open-heart surgery. The results demonstrate that preconditioning with volatile anesthetics triggers the activation of PKCδ and -α isoforms and of prosurvival kinases, ERK1/2, and Akt, while inhibiting their downstream target GSK3ß during the memory phase.

Anti-hyperglycemic effect of bilberry, blackberry and mulberry ultrasonic extracts on diabetic rats.

Small fruits like bilberry, blackberry and mulberry are rich sources of anthocyanins and other phenols, compounds with a certified antioxidant activity and spectacular effects in some chronic diseases. Romanian bilberry, blackberry and mulberry extracts were tested as anti-hyperglycemic agents on diabetic rats. Anthocyanins extraction was carried out with 80 % acidified ethanol in ultrasonically conditions at 23 ± 2 °C and 40 kHz. Monomeric anthocyanins content was determined by pH differential method and varied between 1200 and 2800 mg/L. The analyses of anthocyanins were achieved using high performance liquid chromatography and mass spectrometry. Phenolics content was determined by Folin-Ciocalteu procedure and values varied between 2320 and 4250 mg/L gallic acid. Antioxidant activities of extracts were estimated by DPPH scavenging method and the values varied between 8 and 16 miliequivalents Trolox. In order to evaluate the toxicology of the extracts, the heavy metals concentration and pesticides content were analyzed. The extracts were administrated to diabetic rats in drinking water for five weeks. The administration of bilberry extract offered no satisfactory results. Treatment with blackberry extract determined a significant decrease of glucose level from 360 to about 270 mg/dL (p < 0.05). The mulberry extract administration determined a significant decrease of glucose level from 252 mg/dL at the start day to 155 mg/dL at the final of experiment (p < 0.05).

Volatile anaesthetics and cardioprotection: lessons from animal studies.

Volatile anaesthetics emerged as important cardioprotective agents in both animal models of ischaemia/reperfusion injury and humans with coronary artery disease. Their administration before a prolonged ischaemic episode is known as anaesthetic preconditioning, whereas when given at the very onset of reperfusion, the strategy is termed anaesthetic postconditioning. Both types of anaesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. They share similar, albeit not identical, intracellular signal transduction pathways with their widely investigated counterparts, ischaemic pre- and postconditioning. Despite a wealth of preclinical evidence for cardioprotection for anaesthetic conditioning strategies, their translation into clinical therapy has been rather disappointing. This review highlights the major findings on the cardioprotective effects of volatile anaesthetics in experimental settings. It explores hypotheses that may explain the lack of efficacy observed in several past clinical studies paving the way for future preclinical and translational studies.

Corrosion inhibitors from expired drugs.

This paper presents a method of expired or unused drugs valorization as corrosion inhibitors for metals in various media. Cyclic voltammograms were drawn on platinum in order to assess the stability of pharmaceutically active substances from drugs at the metal-corrosive environment interface. Tafel slope method was used to determine corrosion rates of steel in the absence and presence of inhibitors. Expired Carbamazepine and Paracetamol tablets were used to obtain corrosion inhibitors. For the former, the corrosion inhibition of carbon steel in 0.1 mol L(-1) sulfuric acid solution was about 90%, whereas for the latter, the corrosion inhibition efficiency of the same material in the 0.25 mol L(-1) acetic acid-0.25 mol L(-1) sodium acetate buffer solution was about 85%.

Adipocytes differentiated in vitro from rat mesenchymal stem cells lack essential free fatty acids compared to adult adipocytes.

Adult bone marrow mesenchymal stem cells (BMSCs) can be differentiated in vitro to become adipocyte-like cells with lipid vacuoles, similar to adipocytes derived from adult adipose tissue. Little is known regarding the composition of free fatty acids (FFAs) of the in vitro-differentiated adipocytes, or whether it resembles that of native adult adipocytes. We used gas chromatography-mass spectrometry to identify FFA species in BMSC-derived adipocytes and compared them with FFAs found in adipocytes derived from adult adipose tissue. We found that adult adipocytes contained significant percentages of saturated and monounsaturated FFAs, including palmitic acid (C16:0), stearic acid (C18:0), and oleic acid (C18:1); some polyunsaturated FFAs, such as linoleic acid (C18:2), a small percentage of arachidonic acid (C20:4), and very little linolenic acid (C18:3). In comparison, 80%-90% confluent BMSCs contained comparable percentages of palmitic and oleic acids, significantly more arachidonic and stearic acids, very little linoleic acid, and no linolenic acid. After differentiation, compared with adult adipocytes, BMSC-derived adipocytes contained a comparable percentage of palmitic acid, more stearic and arachidonic acids, less oleic acid, almost no linoleic acid, and no detectable linolenic acid. This composition was quite similar to that of undifferentiated BMSCs. The differentiation medium contained only palmitic and stearic acids, with traces of oleic acid; it did not contain the essential polyunsaturated fatty acids. Thus, the composition of FFAs in BMSC-derived adipocytes was altered compared with adult adipocytes. BMSC-derived adipocytes had an altered composition of saturated and monounsaturated FFAs and lacked essential FFAs that may directly affect signaling related to their lipolysis/lipogenesis functions.