Etiopathogenetic parallels and unresolved issues of pathogenesis of comorbidity COPD and metabolic syndrome (review)

The review analyzes the etiological and pathogenetic factors (including immunopathogenesis factors) of chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MS), cites data on clinical and pathogenetic characteristics of combined pathology, emphasizes the commonality of risk factors and individual links of pathogenesis in syntropy.The clinical and pathogenetic features of the comorbidity of COPD and MS are closely related to the severity of chronic “metabolic” inflammation induced by elements of adipose tissue. Functional and biochemical disorders recorded in metabolic syndrome (insulin resistance, hyperglycemia, dyslipidemia) are considered as factors contributing to dysfunction of the components of innate and adaptive immunity.The review formulates a number of unresolved issues of the pathogenesis of comorbid pathology, the study of which is necessary to search for the mutual aggravating effect of COPD and MS mechanisms. In view of the clinical and laboratory metabolic syndrome equivalents variety, the authors emphasize the relevance of future studies of the pathogenetic features of chronic inflammation associated with the comorbidity of the main components of metabolic syndrome and COPD, to develop effective methods of prevention and pathogenetic therapy of comorbid pathology

Iron metabolism parameters and inflammatory status in patients with diabetes mellitus and dyslipidemia

Background: Investigating the inflammatory status and iron metabolism in patients with impaired carbohydrate metabolism seems quite relevant, while only few studies are devoted to the relationship between metabolic parameters, including lipid profile, inflammatory status indicators and the state of ferrokinetics in diabetes mellitus types 1 and 2 in a comparative aspect.Aims: To establish the direction of changes in the inflammatory status and the state of ferrokinetics in patients with type 1 and type 2 diabetes mellitus depending on lipid metabolism disorders.Materials and methods: The study included 48 patients with type 1 diabetes, 81 patients with type 2 diabetes; 11 people with obesity without impaired carbohydrate metabolism made up the comparison group, 17 healthy volunteers - the control group. Low-grade inflammation was assessed by the levels of high-sensitive C-reactive protein (CRP), tumor necrosisfactor-а (TNF-а), ferritin, and erythrocyte sedimentation rate (ESR). The state of iron metabolism was evaluated by the main hematological parameters (hemoglobin, red blood cell count, hematocrit), serum iron concentrations, transferrin, ferritin and hepcidin concentrations. In all patients lipid metabolism parameters, glycated hemoglobin, and microalbuminuria were measured.Results: Patients with type 1 and type 2 diabetes mellitus had significantly higher inflammatory markers concentrations-TNF-а, ESR, and CRP - in relation to obese patients without impaired carbohydrate metabolism and those in the control group. The highest production of TNF-а was observed in patients with type 1 diabetes mellitus (15.28 [12.41-24.41] pg/ml), whereas CRP (7.00 [3.00-11.85] ng/ml) and ESR (18.00 [9.00-27.00] mm/h) were higher in patients with type 2 diabetes. In the structure of the examined individuals with diabetes mellitus (regardless of its type), dyslipidemia type IIb in comparison with less atherogenic type IIa dyslipidemia was characterized by a higher production of CRP (6.9 [3.00-12.35] and 3.00 [1.80-8.70] ng/ml, respectively), ESR (20.00 [10.00-30.00] and 15.00 [5.00-24.50] mm/h, respectively) and ferritin (114.80 [48.90-196.45] and 50.90 [19.58-114.10] ng/ml, respectively). Compared to iron deficiency anemia, anemia of chronic diseases in diabetes mellitus patients was more often accompanied by dyslipidemia llb (χ2=2.743; p=0.098) and was characterized by a higher content of atherogenic fractions of cholesterol.Conclusions: Patients with type 2 diabetes mellitus and a more atherogenic dyslipidemia profile (type IIb) have a phenotype of the local inflammatory mesenchymal reaction of the liver with an increase in acute-phase proteins predominantly of hepatic origin (CRP, ferritin), whereas individuals suffering from type 1 diabetes and less atherogenic lipid profile (type IIa) have a phenotype of an autoimmune, genetically determined inflammatory response. It has been established that anemia of chronic diseases developing in the background of diabetes mellitus is associated with a more atherogenic lipid profile, compared with iron deficiency anemia

Pathogenetic aspects of hepcidin metabolism and ferrocinetics dysregulation in carbohydrate metabolism disorders

Hepcidin, a hormone regulating iron metabolism, has received attention for its role in the pathogenesis of dysregulations in carbohydrate metabolism. Hepcidin disorders in patients with diabetes mellitus are bi-directional: manifesting as iron overload syndrome in cases of decreased hepcidin production and as anaemia of chronic disease in cases of hepcidin hypersecretion. However, till date, detailed analyses of mechanisms underlying hepcidin dysregulation have not been conducted nor have the interactions of ferrocinetic and carbohydrate-metabolic disorders been examined. An association between diabetes mellitus and neurodegenerative diseases as well as the role of iron metabolism in Alzheimer or Parkinson diseases is a subject of ongoing research. This review provides a summary of the current understanding of hepcidin regulation and its disorders in various diseases, including diabetes mellitus and neurodegenerative diseases. In addition, we provide an overview of the available therapies that address ferrocinetic disorders resulting from the dysregulation of hepcidin

Correlations between Iron Metabolism Parameters, Inflammatory Markers and Lipid Profile Indicators in Patients with Type 1 and Type 2 Diabetes Mellitus

This study aims to establish relationships between inflammatory status, ferrokinetics and lipid metabolism in patients with diabetes mellitus. Subclinical inflammation was assessed by levels of high-sensitive C-reactive protein, tumor necrosis factor-α and erythrocyte sedimentation rate. Iron metabolism parameters included complete blood count, serum iron, transferrin and ferritin. Metabolic status assessment included lipid profile, glycated hemoglobin and microalbuminuria measurement. As a result of the study it was possible to establish both general (universal) and diabetes mellitus (DM) type-dependent relationships between the parameters of lipid profile and metabolic control in DM. High-density lipoprotein cholesterol (HDL-C) levels negatively correlated with microalbuminuria (r = −0.293; p ˂ 0.05 for type 1 diabetes and r = −0.272; p ˂ 0.05 for type 2 diabetes). Ferritin concentration positively correlated with triglyceride level (r = 0.346; p ˂ 0.05 for type 1 diabetes and r = 0.244; p ˂ 0.05 for type 2 diabetes). In type 1 diabetes, a negative correlation was discovered between estimated glomerular filtration rate (eGFR) and LDL-C (r = −0.480; p ˂ 0.05), very low-density-lipoprotein cholesterol (VLDL-C) (r = −0.490; p ˂ 0.05) and triglycerides (r = −0.553; p ˂ 0.05), and a positive one between C-reactive protein concentration and triglyceride level (r = 0.567; p ˂ 0.05). Discovered relationships between lipid profile indices, inflammatory status and microalbuminuria confirmed mutual influence of hyperlipidemia, inflammation and nephropathy in diabetes patients. Obtained results justify the strategy of early hypolipidemic therapy in patients with diabetes mellitus to prevent the development and progression of microvascular complications

UMAOH calcium phosphate coatings designed for drug delivery: vancomycin, 5-fluorouracil, interferon α-2b case

Drug delivery systems based on calcium phosphate (CaP) coatings have been recently recognized as beneficial drug delivery systems in complex cases of bone diseases for admission of drugs in the localized area, simultaneously inducing osteoinduction because of the bioavailable Ca and P ions. However, micro-arc oxidation (MAO) deposition of CaP does not allow for the formation of a coating with sufficient interconnected porosity for drug delivery purposes. Here, we report on the method to deposit CaP-based coatings using a new hybrid ultrasound-assisted MAO (UMAOH) method for deposition of coatings for drug delivery that could carry various types of drugs, such as cytostatic, antibacterial, or immunomodulatory compositions. Application of UMAOH resulted in coatings with an Ra roughness equal to 3.5 mu m, a thickness of 50-55 mu m, and a combination of high values of internal and surface porosity, 39 and 28%, respectively. The coating is represented by the monetite phase that is distributed in the matrix of amorphous CaP. Optimal conditions of coating deposition have been determined and used for drug delivery by impregnation with Vancomycin, 5-Fluorouracil, and Interferon-alpha-2b. Cytotoxicity and antimicrobial activity of the manufactured drug-carrying coatings have been studied using the three different cell lines and methicillin-resistant S. aureus

Coal-Derived Humic Substances: Insight into Chemical Structure Parameters and Biomedical Properties

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the “swim exhaustion” test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement