Material engineering for atopic dermatitis treatment

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a prevalence of 30% for children and to 17% for adults. There is observed an increasing trend of occurring AD over time in the world. Many factors contribute to the development of the disease, such as environmental, genetic and psychological factors. The proper AD treatment should be complexed and consists of skin care with emollients and pharmacological treatment. Most of the topical corticosteroids and other drugs have unpleasant side effects, therefore, developing new therapies is very useful. To minimalize side effects with a simultaneous reduction in the duration, a NPs (nanoparticles) therapy application is highly proposed. On the other hand, hydrogels and their shielding properties with high hydrating level and drug delivery capability are also widely studied. Some works report on the combination of these two solutions with promising results. Material engineering for biomedical applications is a dynamically growing field which offers new drug delivery systems (DDS). In this paper, based on the literature we discuss the new methods of AD treatment using hydrogels and nanotechnology

Effect of temperature on tolbutamide binding to glycated serum albumin

Glycation process occurs in protein and becomes more pronounced in diabetes when an increased amount of reducing sugar is present in bloodstream. Glycation of protein may cause conformational changes resulting in the alterations of its binding properties even though they occur at a distance from the binding sites. The changes in protein properties could be related to several pathological consequences such as diabetic and nondiabetic cardiovascular diseases, cataract, renal dysfunction and Alzheimer's disease. The experiment was designed to test the impact of glycation process on sulfonylurea drug tolbutamide-Albumin binding under physiological (T = 309 K) and inflammatory (T = 311 K and T = 313 K) states using fluorescence and UV-VIS spectroscopies. It was found in fluorescence analysis experiments that the modification of serum albumin in tryptophanyl and tyrosyl residues environment may affect the tolbutamide (TB) binding to albumin in subdomain IIA and/or IIIA (Sudlow's site I and/or II), and also in subdomains IB and IIB. We estimated the binding of tolbutamide to albumin described by a mixed nature of interaction (specific and nonspecific). The association constants (Lmol-1) for tolbutamide at its high affinity sites on non-glycated albumin were in the range of 1.98-7.88 × 104 Lmol-1 (λex = 275 nm), 1.20-1.64 × 104 Lmol-1 (λex = 295 nm) and decreased to 1.24-0.42 × 104 Lmol-1 at λex = 275 nm (T = 309 K and T = 311 K) and increased to 2.79 × 104 Lmol-1 at λex = 275 nm (T = 313 K) and to 4.43-6.61 × 104 Lmol-1 at λex = 295 nm due to the glycation process. Temperature dependence suggests the important role of van der Waals forces and hydrogen bonding in hydrophobic interactions between tolbutamide and both glycated and non-glycated albumin. We concluded that the changes in the environment of TB binding of albumin in subdomain IIA and/or IIIA as well as in subdomains IB and IIB influence on therapeutic effect and therefore the studies of the binding of tolbutamide (in diabetes) to transporting protein under glycation that refers to the modification of a protein are of great importance in pharmacology and biochemistry. This information may lead to the development of more effective drug therapy in people with diabetes

Analysis of antibiotic resistance genetic conditioning of Enterobacteriaceae NDM-1 family members and the related epidemiological threat in Poland

Antibiotic resistance is an extremely serious threat to the modern world. Since 2008, Gram-negativerods from the Enterobacteriaceae family gained the possibility of b-lactam degradation using NDM-1carbapenemase, encoded by the blaNDM gene. It often occurs in the genome of Klebsiella pneumoniaeand can occur on both bacterial chromosome and plasmids. This creates a very high risk due to thewidespread occurrence of bacteria from this family both in the environment and in human microflora.Lack of sensitivity to popular b-lactam antibiotics is especially dangerous for patients hospitalised for along time with reduced immunity. In Poland, since 2011, the number of registered NDM+ isolates andrelated infections are constantly increasing, reaching 1780 cases in 2016. Bacilli showing the presence ofthe blaNDM gene are registered very often in the Mazowieckie and Podlaskie regions, while the numberof such cases is the lowest in the Opolskie region. Inhibiting the growing number of infections caused byEnterobacteriaceae NDM+ is extremely difficult, and one of the methods to reduce this phenomenon isstrict compliance with hygiene rules

In Vitro Investigations of Acetohexamide Binding to Glycated Serum Albumin in the Presence of Fatty Acid

The interaction of drugs with human serum albumin (HSA) is an important element of therapy. Albumin affects the distribution of the drug substance in the body, as well as its pharmacokinetic and pharmacodynamic properties. On the one hand, inflammation and protein glycation, directly associated with many pathological conditions and old age, can cause structural and functional modification of HSA, causing binding disorders. On the other hand, the widespread availability of various dietary supplements that affect the content of fatty acids in the body means that knowledge of the binding activity of transporting proteins, especially in people with chronic diseases, e.g., diabetes, will achieve satisfactory results of the selected therapy. Therefore, the aim of the present study was to evaluate the effect of a mixture of fatty acids (FA) with different saturated and unsaturated acids on the affinity of acetohexamide (AH), a drug with hypoglycaemic activity for glycated albumin, simulating the state of diabetes in the body. Based on fluorescence studies, we can conclude that the presence of both saturated and unsaturated FA disturbs the binding of AH to glycated albumin. Acetohexamide binds more strongly to defatted albumin than to albumin in the presence of fatty acids. The competitive binding of AH and FA to albumin may influence the concentration of free drug fraction and thus its therapeutic effect

Influence of Piracetam on Gliclazide—Glycated Human Serum Albumin Interaction. A Spectrofluorometric Study

Advanced Glycation End-Products (AGEs) are created in the last step of protein glycation and can be a factor in aging and in the development or worsening of many degenerative diseases (diabetes, chronic kidney disease, atherosclerosis, Alzheimer’s disease, etc.). Albumin is the most susceptible to glycation plasma protein. Modified albumin by AGEs may be more resistant to enzymatic degradation, which further increases the local accumulation of AGEs in tissues. The aim of the present study was to analyze in vitro glycation of serum albumin in the presence of piracetam (PIR) and the gliclazide (GLZ)-glycated albumin interaction. The analysis of PIR as an inhibitor and GLZ interaction with nonglycated human albumin (HSA) and glycated by fructose human albumin (gHSAFRC), in the absence and presence of piracetam (gHSAFRC-PIR), was performed by fluorescence quenching of macromolecules. On the basis of obtained data we concluded that under the influence of glycation, association constant ( K a ) of gliclazide to human serum albumin decreases and GLZ binds to HSA with less strength than under physiological conditions. PIR strongly inhibited the formation of AGEs in the system where the efficiency of HSA glycation was the largest. The analysis of piracetam influence on the GLZ-glycated albumin interaction has shown that piracetam increases the binding strength of GLZ to glycated albumin and weakens its therapeutic effect. Based on the obtained data we concluded that monitoring therapy and precautions are required in the treatment when the combinations of gliclazide and piracetam are used at the same time

In Vitro Investigation of the Interaction of Tolbutamide and Losartan with Human Serum Albumin in Hyperglycemia States

Serum albumin is exposed to numerous structural modifications which affect its stability and activity. Glycation is one of the processes leading to the loss of the original properties of the albumin and physiological function disorder. In terms of long lasting states of the hyperglycemia, Advanced Glycation End-products (AGEs) are formed. AGEs are responsible for cellular and tissue structure damage that cause the appearance of a number of health consequences and premature aging. The aim of the present study was to analyze the conformational changes of serum albumin by glycation—“fructation”—using multiple spectroscopic techniques, such as absorption (UV-Vis), fluorescence (SFM), circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy and evaluate of possible alteration of binding and competition between tolbutamide (TB, a first-generation sulfonylurea oral hypoglycemic drug) and losartan (LOS, an angiotensin II receptor (AT1) blocker used in hypertension (1st line with a coexisting diabetes)) in binding to non-glycated (HSA) and glycated (gHSAFRC) human serum albumin in high-affinity binding sites. The studies allowed us to indicate the structural alterations of human serum albumin as a result of fructose glycation. Changes in binding parameters, such as association ( K a ) or Stern-Volmer ( K S V ) constants suggest that glycation increases the affinity of TB and LOS towards albumin and affects interactions between them. The process of albumin glycation influences the pharmacokinetics of drugs, thus monitored pharmacotherapy is reasonable in the case of diabetes and hypertension polypharmacy. This information may lead to the development of more effective drug treatments based on personalized medicine for patients with diabetes. Our studies suggest the validity of monitored polypharmacy of diabetes and coexisting diseases

The differences between the antioxidant activity of vitamin products

Antioxidants are compounds naturally found in many products i.e. fruits, vegetables, and herbs. Antioxidants naturally occurring in plants include vitamins A, C, and E, polyphenols, and mineral compounds. These compounds are also found in many dietary supplements. This study aimed to determine the total antioxidant capacity (TAC) and total polyphenol content (TPC) of selected juices and dietary supplements. 1.1-diphenyl-2-picrylhydrazyl (DPPH) assay is a research method that allows antioxidant activity analysis. The TPC in test samples was measured by the Folin-Ciocalteu method. The study showed that all selected for the analysis products have antioxidant properties. The values of TAC corresponded to TPC with 0.94 (juices) and 0.98 (diet supplements) correlation coefficients. The highest value of TAC was obtained for juice consisting of apples, beets, cherries, and the lowest for juice containing only carrots and products containing vitamin C composition. The tested juices have higher values of TAC compared to dietary supplements, and therefore juices should be the basic prevention of civilization diseases

Changes in Glycated Human Serum Albumin Binding Affinity for Losartan in the Presence of Fatty Acids In Vitro Spectroscopic Analysis

Conformational changes in human serum albumin due to numerous modifications that affect its stability and biological activity should be constantly monitored, especially in elderly patients and those suffering from chronic diseases (which include diabetes, obesity, and hypertension). The main goal of this study was to evaluate the effect of a mixture of fatty acids (FA) on the affinity of losartan (LOS, an angiotensin II receptor (AT1) blocker used in hypertension, a first-line treatment with coexisting diabetes) for glycated albumin—simulating the state of diabetes in the body. Individual fatty acid mixtures corresponded to the FA content in the physiological state and in various clinical states proceeding with increased concentrations of saturated (FAS) and unsaturated (FAUS) acids. Based on fluorescence studies, we conclude that LOS interacts with glycated human serum albumin (af)gHSA in the absence and in the presence of fatty acids ((af)gHSAphys, (af)gHSA4S, (af)gHSA8S, (af)gHSA4US, and (af)gHSA8US) and quenches the albumin fluorescence intensity via a static quenching mechanism. LOS not only binds to its specific binding sites in albumins but also non-specifically interacts with the hydrophobic fragments of its surface. Incorrect contents of fatty acids in the body affect the drug pharmacokinetics. A higher concentration of both FAS and FAUS acids in glycated albumin reduces the stability of the complex formed with losartan. The systematic study of FA and albumin interactions using an experimental model mimicking pathological conditions in the body may result in new tools for personalized pharmacotherapy

Collagen - structure, properties and application

Collagen is the dominant component of the extracellular matrix of mammals. It occurs almost in all animal tissues. Collagen is a highly heterogeneous protein. The collagen protein family is characterized by great diversity in terms of structure, occurrence, and function. Up till now, 29 types of collagens proteins have been classified. The representation of individual types of collagen has certain common features. The most important property is the above-average mechanical strength that results directly from the spatial structure. Collagen is a building material for most tissues and organs. It also plays an important role in the process of cell growth and differentiation, which results from the specific structure of collagen fibers as well as their ability to adhere. The development of research techniques allowed to study in detail the molecular structure and properties of collagen. Therefore, collagen has become a subject of interest in many branches of science. Synthetic recombinant collagen fibers were developed as the basis of collagen biomaterials for medical applications, including implantology or gynecology. The specific structure of collagen also makes it applicable as a protein carrier in drug delivery systems (DDS), particularly in the treatment of cancer and genetic diseases. The use of tissue regenerative abilities and an interdisciplinary look at the properties of collagen and collagen-based biomaterials may constitute the future of medical development

The Influence of Oxidative Stress on Serum Albumin Structure as a Carrier of Selected Diazaphenothiazine with Potential Anticancer Activity

Albumin is one of the most important proteins in human blood. Among its multiple functions, drug binding is crucial in terms of drug distribution in human body. This protein undergoes many modifications that are certain to influence protein activity and affect its structure. One such reaction is albumin oxidation. Chloramine T is a strong oxidant. Solutions of human serum albumin, both non-modified and modified by chloramine T, were examined with the use of fluorescence, absorption and circular dichroism (CD) spectroscopy. 10H-3,6-diazaphenothiazine (DAPT) has anticancer activity and it has been studied for the first time in terms of binding with human serum albumin—its potential as a transporting protein. Using fluorescence spectroscopy, in the presence of dansylated amino acids, dansyl-l-glutamine (dGlu), dansyl-l-proline (dPro), DAPT binding with two main albumin sites—in subdomain IIA and IIIA—has been evaluated. Based on the conducted data, in order to measure the stability of DAPT complexes with human (HSA) and oxidized (oHSA) serum albumin, association constant (Ka) for ligand-HSA and ligand-oHSA complexes were calculated. It has been presumed that oxidation is not an important issue in terms of 10H-3,6-diazaphenothiazine binding to albumin. It means that the distribution of this substance is similar regardless of changes in albumin structure caused by oxidation, natural occurring in the organism