Chitosan-based Nanosystems as Drug Carriers

The formation and application of polymeric nanomaterials is great demandin science, industry, biotechnology, and medicine due to the possibility ofachieving a significant improvement in the physicochemical, mechanical,and barrier properties of polymers and using them as drug carriers andfillers, which is especially promising for biodegradable polymers such aschitosan and their derivatives. The article presents methods for creatingpolymer nanostructures based on polysaccharides and, in particular,chitosan. Obtaining nanostructured samples of chitosan using theapproaches of chemical transformation and modification of polysaccharidesis an urgent scientific problem, the solution of which makes it possible toobtain new polymer systems of great practical interest. The medical aspectsof the use of polymer carriers based on chitosan for the treatment of variousdiseases are discussed. The unique specificity of the properties of chitosanand nanomaterials derived from it, with the properties inherent in thisnatural polymer, can serve as a promising future, especially in the field ofmedicine

Bioavailable Trace Metals in Neurological Diseases

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron

Alterations in Energy/Redox Metabolism Induced by Mitochondrial and Environmental Toxins: A Specific Role for Glucose-6-Phosphate-Dehydrogenase and the Pentose Phosphate Pathway in Paraquat Toxicity

Parkinson’s disease (PD) is a multifactorial disorder with a complex etiology including genetic risk factors, environmental exposures, and aging. While energy failure and oxidative stress have largely been associated with the loss of dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental toxins, very little is known regarding the alterations in energy metabolism associated with mitochondrial dysfunction and their causative role in cell death progression. In this study, we investigated the alterations in the energy/redox-metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP+], and 6-hydroxydopamine [6-OHDA]) in order to identify common and/or different mechanisms of toxicity. A combined metabolomics approach using nuclear magnetic resonance (NMR) and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to identify unique metabolic profile changes in response to these neurotoxins. Paraquat exposure induced the most profound alterations in the pentose phosphate pathway (PPP) metabolome. 13C-glucose flux analysis corroborated that PPP metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5-lactone, and erythrose-4-phosphate were increased by paraquat treatment, which was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis also found an increase in the expression of glucose-6-phosphate dehydrogenase (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively increased paraquat toxicity, while its inhibition with 6-aminonicotinamide inhibited paraquat-induced oxidative stress and cell death. These results suggest that paraquat “hijacks” the PPP to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. Our study clearly demonstrates that alterations in energy metabolism, which are specific for distinct mitochondiral/environmental toxins, are not bystanders to energy failure but also contribute significant to cell death progression

The Importance of Scaling for an Agent Based Model: An Illustrative Case Study with COVID-19 in Zimbabwe

Agent-based models frequently make use of scaling techniques to render the simulated samples of population more tractable. The degree to which this scaling has implications for model forecasts, however, has yet to be explored; in particular, no research on the spatial implications of this has been done. This work presents a simulation of the spread of Covid-19 among districts in Zimbabwe and assesses the extent to which results vary relative to the samples upon which they are based. It is determined that in particular, different geographical dynamics of the spread of disease are associated with varying population sizes, with implications for others seeking to use scaled populations in their research