Macrovascular Complications of Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has emerged as a pandemic. It has different complications, both microvascular and macrovascular. OBJECTIVE: The purpose of this review is to summarize the different types of macrovascular complications associated with T2DM. METHODS: A comprehensive review of the literature was performed to identify clinical studies, which determine the macrovascular complications associated with T2DM. RESULTS: Macrovascular complications of T2DM include coronary heart disease, cardiomyopathy, arrhythmias and sudden death, cerebrovascular disease and peripheral artery disease. Cardiovascular disease is the primary cause of death in diabetic patients. Many clinical studies have shown a connection between T2DM and vascular disease, but almost always other risk factors are present in diabetic patients, such as hypertension, obesity and dyslipidaemia. CONCLUSION: T2DM causes a variety of macrovascular complications through different pathogenetic pathways that include hyperglycaemia and insulin resistance. The association between T2DM and cardiovascular disease is clear, but we need more clinical studies in order to identify the pure effect of T2DM.

The effect of surface charge and pH on the physiological behaviour of cobalt, copper, manganese, antimony, zinc and titanium oxide nanoparticles in vitro.

The precise knowledge on various interactions of metal nanoparticles (NP) in a living organism is scarce. It is expected that metals can bind to nucleic acids, peptides and proteins (e.g. enzymes), and modify the functioning of vital cellular compartments after entering the organism. The predictive factors for quantitative nanostructure-activity relationship (QNAR) analysis could enhance efficient and harmless usage of nanoparticles (NPs) in the industry as well in the medicine. The studies value the composition of the NP corona determined by time, temperature and source of protein which has been found to implicate the physiological behaviour of NPs. One has largely been ignored: the NPs specific isoelectric point (IEP) and pH at the state of measurement. Herein, this study investigates the effect of pH and surface charge of six metal oxide (MeOx) NPs on time dependency of cytotoxicity. Several aspects of the characterization of ultrafine particles in the actual test system which is the most relevant for the interpretation of the toxicological data are referred: (i) the difference of pH in the room temperature and in the incubation conditions (ii) the difference of dispersions in MilliQ and complete cell media; (iii) the need to exemplify also the pH and isoelectric point when the hydrodynamic size is measured; (iv) the importance of time due to the time-dependent equilibration and changes of NPs corona. The surface charge determines the formation of corona and could be modified by pH. MeOx NPs without fully charge equilibrated corona might play the main role of MeOx NPs entering into the cell and consequently the time dependent manifestation of the cellular effect.

Bacterial polysaccharide levan as stabilizing, non-toxic and functional coating material for microelement-nanoparticles.

Levan, fructose-composed biopolymer of bacterial origin, has potential in biotechnology due to its prebiotic and immunostimulatory properties. In this study levan synthesized by levansucrase from Pseudomonas syringae was thoroughly characterized and used as multifunctional biocompatible coating material for microelement-nanoparticles (NPs) of selenium, iron and cobalt. Transmission electron microscopy (TEM), hydrodynamic size measurements (DLS) and X-ray photoelectron spectroscopy (XPS) showed the interaction of levan with NPs. Levan stabilized the dispersions of NPs, decreased their toxicity and had protective effect on human intestinal cells Caco-2. In addition, levan attached to cobalt NPs remained accessible as a substrate for the colon bacteria Bacteroides thetaiotaomicron. We suggest that the combination of levan and nutritionally important microelements in the form of NPs serves as a first step towards a novel "2 in 1" approach for food supplements to provide safe and efficient delivery of microelements for humans and support beneficial gut microbiota with nutritional oligosaccharides.

Toxicity of 11 Metal Oxide Nanoparticles to Three Mammalian Cell Types In Vitro.

The knowledge on potential harmful effects of metallic nanomaterials lags behind their increased use in consumer products and therefore, the safety data on various nanomaterials applicable for risk assessment are urgently needed. In this study, 11 metal oxide nanoparticles (MeOx NPs) prepared using flame pyrolysis method were analyzed for their toxicity against human alveolar epithelial cells A549, human epithelial colorectal cells Caco2 and murine fibroblast cell line Balb/c 3T3. The cell lines were exposed for 24 h to suspensions of 3-100 µg/mL MeOx NPs and cellular viability was evaluated using. Neutral Red Uptake (NRU) assay. In parallel to NPs, toxicity of soluble salts of respective metals was analyzed, to reveal the possible cellular effects of metal ions shedding from the NPs. The potency of MeOx to produce reactive oxygen species was evaluated in the cell-free assay. The used three cell lines showed comparable toxicity responses to NPs and their metal ion counterparts in the current test setting. Six MeOx NPs (Al2O3, Fe3O4, MgO, SiO2, TiO2, WO3) did not show toxic effects below 100 µg/mL. For five MeOx NPs, the averaged 24 h IC50 values for the three mammalian cell lines were 16.4 µg/mL for CuO, 22.4 µg/mL for ZnO, 57.3 µg/mL for Sb2O3, 132.3 µg/mL for Mn3O4 and 129 µg/mL for Co3O4. Comparison of the dissolution level of MeOx and the toxicity of soluble salts allowed to conclude that the toxicity of CuO, ZnO and Sb2O3 NPs was driven by release of metal ions. The toxic effects of Mn3O4 and Co3O4 could be attributed to the ROS-inducing ability of these NPs. All the NPs were internalized by the cells according to light microscopy studies but also proven by TEM, and internalization of Co3O4 NPs seemed to be most prominent in this aspect. In conclusion, this work provides valuable toxicological data for a library of 11 MeOx NPs. Combining the knowledge on toxic or non-toxic nature of nanomaterials may be used for safe-by-design approach.

5'-Nucleotidase from Vipera lebetina venom.

5'-Nucleotidase (5'-NT) is widely represented in animal tissues (CD73) as well as in almost all snake venoms. In the present study, a 5'-NT isoform has been isolated from Vipera lebetina venom. The homodimeric isoform consists of monomers with molecular masses of 60 kDa. The enzyme is thermolabile and has pH optimum at 7.5. The 5'-NT activity is inhibited by metal ions Fe(3+), Cu(2+) and Zn(2+), enhanced by Mn(2+) while Mg(2+) and Ca(2+) have no remarkable effect. In addition to 120-kDa protein there are higher molecular forms of 5'-NT present in the V. lebetina venom. The cloning and sequencing of the 5'-NT coding cDNA resulted in 5'-truncated construct. MALDI-TOF and Orbitrap mass-spectrometry of the tryptic peptides confirmed the translated N-terminally truncated protein sequence concordance to the 5'-NT isolated from the venom. The isolated protein strongly inhibited ADP- or collagen-induced platelet aggregation.

Size-dependent toxicity of silver nanoparticles to bacteria, yeast, algae, crustaceans and mammalian cells in vitro.

The concept of nanotechnologies is based on size-dependent properties of particles in the 1-100 nm range. However, the relation between the particle size and biological effects is still unclear. The aim of the current paper was to generate and analyse a homogenous set of experimental toxicity data on Ag nanoparticles (Ag NPs) of similar coating (citrate) but of 5 different primary sizes (10, 20, 40, 60 and 80 nm) to different types of organisms/cells commonly used in toxicity assays: bacterial, yeast and algal cells, crustaceans and mammalian cells in vitro. When possible, the assays were conducted in ultrapure water to minimise the effect of medium components on silver speciation. The toxic effects of NPs to different organisms varied about two orders of magnitude, being the lowest (∼0.1 mg Ag/L) for crustaceans and algae and the highest (∼26 mg Ag/L) for mammalian cells. To quantify the role of Ag ions in the toxicity of Ag NPs, we normalized the EC50 values to Ag ions that dissolved from the NPs. The analysis showed that the toxicity of 20-80 nm Ag NPs could fully be explained by released Ag ions whereas 10 nm Ag NPs proved more toxic than predicted. Using E. coli Ag-biosensor, we demonstrated that 10 nm Ag NPs were more bioavailable to E. coli than silver salt (AgNO3). Thus, one may infer that 10 nm Ag NPs had more efficient cell-particle contact resulting in higher intracellular bioavailability of silver than in case of bigger NPs. Although the latter conclusion is initially based on one test organism, it may lead to an explanation for "size-dependent" biological effects of silver NPs. This study, for the first time, investigated the size-dependent toxic effects of a well-characterized library of Ag NPs to several microbial species, protozoans, algae, crustaceans and mammalian cells in vitro.