Probing Amphotericin B Single Channel Activity by Membrane Dipole Modifiers

The effects of dipole modifiers and their structural analogs on the single channel activity of amphotericin B in sterol-containing planar phosphocholine membranes are studied. It is shown that the addition of phloretin in solutions bathing membranes containing cholesterol or ergosterol decreases the conductance of single amphotericin B channels. Quercetin decreases the channel conductance in cholesterol-containing bilayers while it does not affect the channel conductance in ergosterol-containing membranes. It is demonstrated that the insertion of styryl dyes, such as RH 421, RH 237 or RH 160, in bilayers with either cholesterol or ergosterol leads to the increase of the current amplitude of amphotericin B pores. Introduction of 5α-androstan-3β-ol into a membrane-forming solution increases the amphotericin B channel conductance in a concentration-dependent manner. All the effects are likely to be attributed to the influence of the membrane dipole potential on the conductance of single amphotericin B channels. However, specific interactions of some dipole modifiers with polyene-sterol complexes might also contribute to the activity of single amphotericin B pores. It has been shown that the channel dwell time increases with increasing sterol concentration, and it is higher for cholesterol-containing membranes than for bilayers including ergosterol, 6-ketocholestanol, 7-ketocholestanol or 5α-androstan-3β-ol. These findings suggest that the processes of association/dissociation of channel forming molecules depend on the membrane fluidity

Cognitive impairment in patients with type 2 diabetes mellitus: prevalence, pathogenetic mechanisms, the effect of antidiabetic drugs

In recent years, a large amount of data has been accumulated on the relationship between cognitive impairment, dementia and diabetes mellitus. This article presents an overview of modern literature, including the definition of cognitive functions, the modern classification of cognitive impairment, pathogenetic mechanisms of diabetes mellitus influence on the development of cognitive impairment and dementia (neurogenesis, integrity of the blood-brain barrier, systemic inflammatory reactions, hyper- and hypoglycemia, insulin resistance, vascular dysfunction of the microvasculature and increase in glucocorticosteroids). The influence of anti-diabetic medications on cognitive functions has been examined in detail: insulin preparations, oral hypoglycemic agents of the biguanide group (metformin), thiazolidinediones (rosiglitazone and pioglitazone), sulfonylurea derivatives (glycazide, glipizide), a-glucosidase (acarbose) inhibitors, incretin-directed therapy (receptor agonists glucan-like peptide (exenatide and liraglutide) and inhibitors of dipeptidylpeptidase type 4 (sitagliptin, vildagliptin and alogliptin)), sodium glucose inhibitors cotransporter type 2. The data demonstrating a multidirectional effect on the cognitive functions of various antidiabetic drugs is presented, the possible influence on the rate of progression of cognitive impairment and the risk of dementia of intensive control of plasma glucose level in comparison with the standard decrease in patients with type 2 diabetes is analyzed

Hypoglycemia and the risk of cognitive impairment and dementia in elderly and senile patients with type 2 diabetes

Research results show that poor glycemic control and recurrent episodes of severe hypoglycaemia are associated with a decrease in cognitive function in elderly people with type 2 diabetes mellitus (T2DM). On the other hand, patients with diabetes mellitus associated with cognitive impairment/dementia are most at risk of developing hypoglycaemic conditions. It is obvious that the relationship between hypoglycaemia and dementia is very complex and has a mutually aggravating nature. Studies also show that individuals of older age groups with diabetes and cognitive impairment have a high risk of developing hypoglycaemic conditions, such as unwanted side effects from glucose-lowering therapy. In this case, of particular interest is the question that is being actively studied at the present time, which is concerning the effect of different groups of glucose-lowering antidiabetic drugs on the cognitive status and the rate of cognitive decline in diabetic patients with cognitive impairment. In this review, we attempted to summarise, systematise, and present data available in the literature concerning the effect of hypoglycaemia on the risk of cognitive impairment and dementia in elderly and senile patients with type-2 diabetes, as well as the degree of participation in this process of of various groups of sugar-lowering antidiabetic drugs

Soluble Cyanobacterial Carotenoprotein as a Robust Antioxidant Nanocarrier and Delivery Module

To counteract oxidative stress, antioxidants including carotenoids are highly promising, yet their exploitation is drastically limited by the poor bioavailability and fast photodestruction, whereas current delivery systems are far from being efficient. Here we demonstrate that the recently discovered nanometer-sized water-soluble carotenoprotein from Anabaena sp. PCC 7120 (termed AnaCTDH) transiently interacts with liposomes to efficiently extract carotenoids via carotenoid-mediated homodimerization, yielding violet–purple protein samples. We characterize the spectroscopic properties of the obtained pigment–protein complexes and the thermodynamics of liposome–protein carotenoid transfer and demonstrate the delivery of carotenoid echinenone from AnaCTDH into liposomes with an efficiency of up to 70 ± 3%. Most importantly, we show efficient carotenoid delivery to membranes of mammalian cells, which provides protection from reactive oxygen species (ROS). Incubation of neuroblastoma cell line Tet21N in the presence of 1 μM AnaCTDH binding echinenone decreased antimycin A ROS production by 25% (p < 0.05). The described carotenoprotein may be considered as part of modular systems for the targeted antioxidant delivery.BMBF, 01DJ15007, Carotenoidbindende photoschaltbare Proteine: Lichtinduzierte Dynamik und Anwendungen in modernen mikroskopischen Verfahre

Is the Membrane Lipid Matrix a Key Target for Action of Pharmacologically Active Plant Saponins?

This study was focused on the molecular mechanisms of action of saponins and related compounds (sapogenins and alkaloids) on model lipid membranes. Steroids and triterpenes were tested. A systematic analysis of the effects of these chemicals on the physicochemical properties of the lipid bilayers and on the formation and functionality of the reconstituted ion channels induced by antimicrobial agents was performed. It was found that digitonin, tribulosin, and dioscin substantially reduced the boundary potential of the phosphatidylcholine membranes. We concluded that saponins might affect the membrane boundary potential by restructuring the membrane hydration layer. Moreover, an increase in the conductance and lifetime of gramicidin A channels in the presence of tribulosin was due to an alteration in the membrane dipole potential. Differential scanning microcalorimetry data indicated the key role of the sapogenin core structure (steroid or triterpenic) in affecting lipid melting and disordering. We showed that an alteration in pore forming activity of syringomycin E by dioscin might be due to amendments in the lipid packing. We also found that the ability of saponins to disengage the fluorescent marker calcein from lipid vesicles might be also determined by their ability to induce a positive curvature stress

Emotion Regulation in Patients with Essential Hypertension: Subjective-evaluative, Physiological, and Behavioral Aspects

AbstractThe primary aim of this research was to study characteristic features of emotion regulation in a stressful situation displayed by patients with essential hypertension (HTN). We examined 170 patients with HTN and 82 healthy individuals. In a situation modulating experimental stress HTN patients demonstrate a specific complex of physiological, subjective-evaluative and behavioral reactions and also aspiration level (AL) specifics, which reliably differs them from healthy people. 52.3% of HTN patients showed the growth of anxiety which disorganizes behavior, it is accompanied by open emotion expression and a variety of behavioral manifestations. 47.7% of patients with HTN characteristically display the mechanisms of suppression and denial of situations causing anxiety, as well as repression of emotions generated in stressful situations