Structure-activity relationship studies of functionalized aromatic peptidomimetics as neurolysin activators.

Modulating peptidase neurolysin (Nln) has been identified as a potential cerebroprotective target for the development of therapeutics for ischemic stroke. Continued structure-activity relationship studies on peptidomimetic small molecule activators of Nln bearing electron-donating and electron- withdrawing functionalized phenyls are explored. Incorporation of fluorine or trifluoromethyl groups produces Nln activators with enhanced A50, while methoxy substitution produces derivatives with enhanced Amax. Selected activators containing methoxy or trifluoromethyl substitution are selective for Nln over related peptidases and possess increased blood-brain barrier penetrability than initial hits.

Bee Venom Effect on Glioblastoma Cells Viability and Gelatinase Secretion.

BACKGROUND: The involvement of MMP-2 and MMP-9 in the pathogenesis of various kinds of cancers including glioblastoma is well documented. The evaluation of the anticancer potential of honey bee (Apis mellifera) venom (BV) consisting of the inhibition of MMP-2 and MMP-9 secretion in a glioblastoma cell culture model was the aim of the study. METHODS: 8-MG-BA and GAMG human primary glioblastoma cell lines vs. HT-22 mouse hippocampal neuronal cells were applied for the study. The BV dose (0.5, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, and 5.0 µg/ml) and time-dependent (24, 48, 72 h) cytotoxicity was evaluated with the tetrazolium-based colorimetric assay (MTT test). MMP-2 and MMP-9 activities in the cell culture medium under different BV concentrations were determined by gelatin zymography. RESULTS: A dose and time-dependent BV effect on cytotoxicity of both glioblastoma cell lines and hippocampus line was observed. The weakest, but statistically important effect was exerted by BV on HT-22 cells. The greatest cytotoxic effect of BV was observed on the 8-MG-BA line, where a statistically significant reduction in viability was observed at the lowest BV dose and the shortest incubation time. The reduction of both gelatinases secretion was observed at 8-MG-BA and GAMG lines without significant effect of HT-22 cell line. CONCLUSION: In vitro studies indicate that BV has both cytotoxic and inhibitory effects on the secretion of MMP-2 and MMP-9 in selected lines of glioma, suggesting anticancer properties of BV.

Identification and Characterization of Two Structurally Related Dipeptides that Enhance Catalytic Efficiency of Neurolysin.

Neurolysin (Nln) is a recently recognized endogenous mechanism functioning to preserve the brain from ischemic injury. To further understand the pathophysiological function of this peptidase in stroke and other neurologic disorders, the present study was designed to identify small molecule activators of Nln. Using a computational approach, the structure of Nln was explored, which was followed by docking and in silico screening of ∼140,000 molecules from the National Cancer Institute Developmental Therapeutics Program database. Top ranking compounds were evaluated in an Nln enzymatic assay, and two hit histidine-dipeptides were further studied in detail. The identified dipeptides enhanced the rate of synthetic substrate hydrolysis by recombinant (human and rat) and mouse brain-purified Nln in a concentration-dependent manner (micromolar A50 and Amax ≥ 300%) but had negligible effect on activity of closely related peptidases. Both dipeptides also enhanced hydrolysis of Nln endogenous substrates neurotensin, angiotensin I, and bradykinin and increased efficiency of the synthetic substrate hydrolysis (Vmax/Km ratio) in a concentration-dependent manner. The dipeptides and competitive inhibitor dynorphin A (1-13) did not affect each other's affinity for Nln, suggesting differing nature of their respective binding sites. Lastly, drug affinity responsive target stability (DARTS) and differential scanning fluorimetry (DSF) assays confirmed concentration-dependent interaction of Nln with the activator molecule. This is the first study demonstrating that Nln activity can be enhanced by small molecules, although the peptidic nature and low potency of the activators limit their application. The identified dipeptides provide a chemical scaffold to develop high-potency, drug-like molecules as research tools and potential drug leads. SIGNIFICANCE STATEMENT: This study describes discovery of two molecules that selectively enhance activity of peptidase Nln-a newly recognized cerebroprotective mechanism in the poststroke brain. The identified molecules will serve as a chemical scaffold for development of drug-like molecules to further study Nln and may become lead structures for a new class of drugs. In addition, our conceptual and methodological framework and research findings might be used for other peptidases and enzymes, the activation of which bears therapeutic potential.

Discovery of First-in-Class Peptidomimetic Neurolysin Activators Possessing Enhanced Brain Penetration and Stability.

Peptidase neurolysin (Nln) is an enzyme that functions to cleave various neuropeptides. Upregulation of Nln after stroke has identified the enzyme as a critical endogenous cerebroprotective mechanism and validated target for the treatment of ischemic stroke. Overexpression of Nln in a mouse model of stroke results in dramatic improvement of stroke outcomes, while pharmacological inhibition aggravates them. Activation of Nln has therefore emerged as an intriguing target for drug discovery efforts for ischemic stroke. Herein, we report the discovery and hit-to-lead optimization of first-in-class Nln activators based on histidine-containing dipeptide hits identified from a virtual screen. Adopting a peptidomimetic approach provided lead compounds that retain the pharmacophoric histidine moiety and possess single-digit micromolar potency over 40-fold greater than the hit scaffolds. These compounds exhibit 5-fold increased brain penetration, significant selectivity over highly homologous peptidases, greater than 65-fold increase in mouse brain stability, and 'drug-like' fraction unbound in the brain.

Activity of selected metalloproteinases in neurodegenerative diseases of the central nervous system as exemplified by dementia and schizophrenia. / Aktywnosc wybranych metaloproteinaz w chorobach neurodegeneracyjnych osrodkowego ukladu nerwowego na przykladzie otepienia i schizofrenii.

OBJECTIVES: The aim of the study was to determine and analyze the correlation between the concentrations of selected metalloproteinases and their inhibitors (TIMP-1 and TIMP-2) in patients with dementia and schizophrenia. METHODS: The concentration of two collagenases and metalloendopeptidase was determined in the study. The study included 29 patients with lateonset dementia, 25 patients with paranoid schizophrenia and 25 healthy controls who were age-matched with the study groups. Symptoms of dementia were evaluated using the Short Mental State Assessment Scale, whereas the symptoms of schizophrenia were assessed using the Positive and Negative Assessment Scale. Blood samples were collected from the participants and the concentrations of MMP-1, MMP7, MMP-13, TIMP-1, and TIMP-2 in the blood serum were evaluated using ELISA method. RESULTS: A two-fold increase in the concentration of MMP-1 and a slight increase in MMP-13 was observed in dementia patients compared to other groups, as well as a lower level of MMP-7 and TIMP-1 and a higher level of TIMP-2 compared to the control group. Patients with schizophreniashowed lower MMP-7 and higher TIMP-2 serum level compared to the controls. No differences in the concentration of MMP-1, MMP-13 and TIMP-1 levels were noticed. In people with late onset dementia an increase in collagenolytic activity was demonstrated. CONCLUSIONS: Increase in collagenolytic activity may indicate an increased remodeling within the central nervous system in late onset dementia. The differencein the fluctuation of the concentrations of the studied enzymes and their inhibitors in dementia and schizophrenia indicates their different involvement in the pathogenesis of these disorders.

Author Correction: An open data infrastructure for the study of anthropogenic hazards linked to georesource exploitation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An open data infrastructure for the study of anthropogenic hazards linked to georesource exploitation.

Mining, water-reservoir impoundment, underground gas storage, geothermal energy exploitation and hydrocarbon extraction have the potential to cause rock deformation and earthquakes, which may be hazardous for people, infrastructure and the environment. Restricted access to data constitutes a barrier to assessing and mitigating the associated hazards. Thematic Core Service Anthropogenic Hazards (TCS AH) of the European Plate Observing System (EPOS) provides a novel e-research infrastructure. The core of this infrastructure, the IS-EPOS Platform (tcs.ah-epos.eu) connected to international data storage nodes offers open access to large grouped datasets (here termed episodes), comprising geoscientific and associated data from industrial activity along with a large set of embedded applications for their efficient data processing, analysis and visualization. The novel team-working features of the IS-EPOS Platform facilitate collaborative and interdisciplinary scientific research, public understanding of science, citizen science applications, knowledge dissemination, data-informed policy-making and the teaching of anthropogenic hazards related to georesource exploitation. TCS AH is one of 10 thematic core services forming EPOS, a solid earth science European Research Infrastructure Consortium (ERIC) (www.epos-ip.org).

Decreased nitric oxide serum level after pituitary adenoma resection.

BACKGROUND: Nitric oxide (NO) is synthesized by the conversion of Arginine (Arg) into the NO and Citrulline (Cit). Although the NO is involved into the pathogenesis of several physiological and pathological processes, the role of NO in pituitary adenomas (PA) progression is not determined. Our purpose was to evaluate the relationship between NO and PA as well as the effect of tumor resection on NO metabolites level in serum. METHODS: The study group consisted of 21 patients with PA, 18 patients with macroadenomas and 3 with microadenomas. Venous blood samples were collected at two time-points; 1) before the surgery and 2) 3-5 days after PA resection. Arg and Cit levels were determined by the automated ion-exchange chromatography with usage of Amino Acids Analyser (AAA 400). Commercially available kit for the evaluation of nitrate/nitrite serum levels was applied for indirect assessment of serum NO level. RESULTS: Significant decrease in NO concentration after the surgery was observed in comparison with the time-point 1. Arg level did not significantly change during the study period. Cit level was ranged below the detection limit of applied method. CONCLUSIONS: The decrease of NO level after the pituitary adenoma resection indicates the relationship between NO synthesis and PA occurrence.

Peptidase neurolysin functions to preserve the brain after ischemic stroke in male mice.

Previous studies documented up-regulation of peptidase neurolysin (Nln) after brain ischemia, however, the significance of Nln function in the post-stroke brain remained unknown. The aim of this study was to assess the functional role of Nln in the brain after ischemic stroke. Administration of a specific Nln inhibitor Agaricoglyceride A (AgaA) to mice after stroke in a middle cerebral artery occlusion model, dose-dependently aggravated injury measured by increased infarct and edema volumes, blood-brain barrier disruption, increased levels of interleukin 6 and monocyte chemoattractant protein-1, neurological and motor deficit 24 h after stroke. In this setting, AgaA resulted in inhibition of Nln in the ischemic hemisphere leading to increased levels of Nln substrates bradykinin, neurotensin, and substance P. AgaA lacked effects on several physiological parameters and appeared non-toxic to mice. In a reverse approach, we developed an adeno-associated viral vector (AAV2/5-CAG-Nln) to overexpress Nln in the mouse brain. Applicability of AAV2/5-CAG-Nln to transduce catalytically active Nln was confirmed in primary neurons and in vivo. Over-expression of Nln in the mouse brain was also accompanied by decreased levels of its substrates. Two weeks after in vivo transduction of Nln using the AAV vector, mice were subjected to middle cerebral artery occlusion and the same outcome measures were evaluated 72 h later. These experiments revealed that abundance of Nln in the brain protects animals from stroke. This study is the first to document functional significance of Nln in pathophysiology of stroke and provide evidence that Nln is an endogenous mechanism functioning to preserve the brain from ischemic injury.

Respiratory health problems in adolescents living near main roads in the Upper Silesian industrial zone, Poland.

OBJECTIVES: This study explores the association between self-reported exposure to traffic-related air pollution and respiratory health symptoms, as well as lung functions and skin prick tests in adolescents living in the vicinity of main roads. MATERIAL AND METHODS: The data in the study were acquired using a cross-sectional study conducted between 2004-2005 in Chorzów (Silesia, Poland) among adolescents (N = 936) aged 13-15 years, attending junior high schools. Adverse respiratory health symptoms and exposure to traffic-related air pollution were determined on the basis of a questionnaire. Moreover, all children underwent spirometry and skin prick tests. Multivariable logistic regression with multiple imputation for missing data was used to assess the prevalence of adverse respiratory symptoms in relation to self-reported exposure to traffic-related air pollution, adjusted for socioeconomic and environmental factors. RESULTS: Among respiratory tract diseases, asthma and allergic rhinitis associations were statistically significant (OR = 2.16, 95% CI: 1.12-4.15 and OR = 1.69, 95% CI: 1.08-2.64, respectively). Likewise, among respiratory disorders, statistically significant associations were found in the case of wheezes and dyspnea attack (OR = 1.58, 95% CI: 1.10-2.26 and OR = 2.39, 95% CI: 1.56-3.66, respectively), with respect to the vicinity of the main road. Living in the area with high traffic intensity was statistically significantly associated with a higher prevalence of asthma and wheezes (OR = 2.31, 95% CI: 1.22-4.39 and 1.48, 95% CI: 1.09-2.01, respectively). The results obtained did not confirm the relationship between the adopted way of exposure to traffic-related air pollution and lung function indices or skin prick tests. CONCLUSIONS: Results of the study suggest that children living in the area with intense traffic are more likely to develop respiratory disorders. Moreover, the vicinity of a main road as well as traffic intensity could be suitable in assessing the relationship between road transport and potential health problems among exposed inhabitants. Int J Occup Med Environ Health. 2019;32(4):553-67.

The impact of changes in serum levels of metalloproteinase-2 and metalloproteinase-9 on pain perception in patients with disc herniation before and after surgery.

Purpose: The aim of our research was to investigate the link between serum levels of metalloproteinase-2 (MMP-2) and MMP-9, and the degree of pain experienced before and 1 and 3 months after microdiscectomy in 70 patients with disc herniation (DH). Patients and methods: The control group (group C) consisted of 70 healthy subjects and the DH group consisted of 70 patients with sciatica pain caused by lumbar DH. Before (DH0) and 1 and 3 months after surgery, the patients were assessed in terms of the following biochemical parameters: MMP-2, tissue inhibitors of metalloproteinases-2 (TIMP-2), MMP-2/TIMP-2, MMP-9, TIMP-1, and MMP-9/TIMP1, and the following clinical parameters: Numeric Rating Scale for the back (NRS-B) and the leg (NRS-L) and the Pain Rating Index (PRI) and Present Pain Intensity (PPI) of the McGill Pain Questionnaire. Results: No statistically significant correlations were observed following the biochemical and clinical assessments performed in group C and the DH group before surgery. After surgery (1 month), higher levels of TIMP-1 correlated with higher levels of NRS-B (rs =0.27; p<0.05). At 3 months after surgery higher levels of TIMP-2 and lower levels of MMP-2/TIMP-2 were correlated with higher levels of NRS-L (rs =0.27, p<0.05 and rs =-0.31, p<0.05, respectively) and higher levels of TIMP-2 were correlated with higher PRI scores (rs =0.27; p<0.005) and PPI scores (rs =0.35; p<0.01). Conclusion: The results showed that MMPs are involved in DH and play a significant role in the perception of pain after DH surgery. However, the value of MMPs as a potential therapeutic target in pain treatment should be considered cautiously.

The Oxidative Stress in Knee Osteoarthritis Patients. An Attempt of Evaluation of Possible Compensatory Effects Occurring in the Disease Development.

Background and Objective: Osteoarthritis (OA) is a disorder of the musculoskeletal system resulting in worsening of life condition. The research revealed the involvement of oxidative stress into both OA pathogenesis and the effects of therapeutic agents applied in OA cases. The activities of the most important antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant status (TAS), in blood of the knee OA patients were studied, with the aim of clarifying which enzymatic antioxidants are involved into osteoarthritis (OA)-related oxidative stress and whether any compensatory effects occur. The results were additionally analyzed with regard to gender. Methods: Whole blood SOD (U/mL), plasma GPx (U/L) and CAT (U/mL) activities as well as plasma TAS (mmol/L)) in knee OA patients were investigated. Sixty-seven patients (49 females and 18 males) with primary knee OA were enrolled. The control comprised 21 subjects (10 females and 11 males) free of osteoarthritis or inflammation. Results: TAS was decreased in OA subjects (4.39 0.53 vs. 4.70 0.60), with this effect being more significant in OA females (4.31 0.51 vs. 5.02 0.54). GPx was depressed in all OA patients (518 176 vs. 675 149). In both genders, GPx was decreased, significantly in males (482 185 vs. 715 105). SOD was decreased in all OA patients (109 32 vs. 127 42). CAT showed no difference in all OA subjects vs. control, while in OA females it was depleted (20.2 (11.6-31.6) vs. 38.5 (27.9-46.6)) and in OA men it increased (26.9 (23.3-46.5) vs. 14.0 (7.0-18.6)). Conclusions: The obtained results suggest that in men some compensatory mechanisms towards OA-related oxidative stress occurred. Based on the obtained data, the introduction of antioxidant supplements into OA therapy could be suggested with further research concerning the choice of agents.

Correlations among plasma silicon, magnesium and calcium in patients with knee osteoarthritis - analysis in consideration of gender.

INTRODUCTION AND OBJECTIVE: Osteoarthrits (OA) is a complex, chronic disorder of cartilage and bone, related to homeostasis of bioelements. The current study aimed at evaluation of correlations between plasma silicon, magnesium and ionized calcium in OA patients in consideration to gender. MATERIAL AND METHODS: The study comprised 59 patients aged 69.5±9.0 years (18 males aged 66.8±9.2; 41 females aged 70.7±8.8), admitted to the Trauma and Orthopaedic Ward of the Independent Public Health Care Centre in Leczna, Poland, due to OA and qualified to surgery. Control group consisted of 19 subjects without OA (54.5±8.6 years; 10 males aged 41.3±9.3; 9 females aged 69.1±14.9). Plasma concentrations of silicon and magnesium (spectrophotometric methods) and ionized calcium (potentiometric method) were determined. RESULTS: Silicon in OA patients was significantly increased vs. control. In OA males and OA females, silicon was enhanced vs. the respective controls, but it was statistically significant only in males. Magnesium in OA patients was not significantly different from control group. In females, a significant decrease vs. the respective control was observed. No significant differences were observed in the case of ionized calcium. Positive correlations between silicon and magnesium in healthy control, both in the whole group and in male and female subgroups, were noted, while no such effect was observed in OA subjects. CONCLUSIONS: The results might suggest some connection between higher OA incidence in women and the depleted magnesium in the organism. Silicon increase in OA patients, especially in men, may indicate its intense metabolism during the articular inflammatory process, likely dependent on sex hormones. It remains open whether the plasma Si increase is the effect or cause of OA.

Serum Level of Metalloproteinase-2 but not Metalloproteinase-9 Rises in Patients With Failed Back Surgery Syndrome After Spinal Cord Stimulation.

OBJECTIVES: The impact of spinal cord stimulation (SCS) on serum levels of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was assessed in a group of patients with failed back surgery syndrome (FBSS). The study was to give new insights into the SCS mechanism of action and the role of MMP-2 and MMP-9 in the development of NP. MATERIAL AND METHODS: Clinical assessments were performed and biochemical markers were determined in two groups of patients: the control group (24 individuals) and the FBSS group (24 patients). Seventeen patients with the FBSS had SCS implanted and were examined before surgical procedure, one month after (17 patients), and three months after operation (12 patients). Clinical status was assessed with the use numeric rating scale, pain rating index of McGill pain questionnaire, Oswestry disability index and Beck depression inventory. MMP-2 and MMP-9 serum levels were determined using gelatin zymography. Immunoenzymatic method was employed to determine plasma concentrations of tissue inhibitors of metalloproteinases (TIMPs). RESULTS: Levels of MMP-2 and TIMP-2 were higher in the FBSS group compared to the control group. The difference was statistically significant (p < 0.001 and p = 0.004, respectively). The concentration of MMP-2 was significantly increased (p = 0.0135) one-month post-SCS and remained elevated but stable up to three months after implantation. TIMP-2, MMP-2/TIMP-2, MMP-9, TIMP-1, and MMP-9/TIMP-1 serum levels did not change significantly. CONCLUSIONS: MMPs may play a role in the development of FBSS. SCS increases the already elevated MMP-2 serum levels which are associated with neuroinflammatory processes in FBSS patients.

Lithium disturbs homeostasis of essential microelements in erythrocytes of rats: Selenium as a protective agent?

BACKGROUND: Selenium is an essential element which shows protective properties against diverse harmful factors. Lithium compounds are widely used in medicine, but, in spite of undoubted beneficial effects, treatment with these compounds may lead to severe side effects, including renal, gastrointestinal, neurological, endocrine and metabolic disorders. This study was aimed at evaluating the influence of selenium and/or lithium on lithium, iron, zinc and copper content in rats' erythrocytes as well as estimate the action of additional selenium on lithium exposure effects. METHODS: The experiment was performed on four groups of rats (six animals each): control - received saline; Li - received 2.7mg Li/kg b.w. as lithium carbonate; Se - received 0.5mg Se/kg b.w. as sodium selenite; Se+Li - received simultaneously 0.5mg Se/kg b.w. and 2.7mg Li/kg b.w. (sodium selenite and lithium carbonate). The administration was performed for three weeks, once a day by stomach tube, in form of water solutions. In erythrocytes the content of lithium, iron, zinc and copper was determined using flame atomic absorption spectroscopy. RESULTS: Lithium treatment insignificantly disturbed iron and zinc homeostasis as well as markedly increased lithium accumulation and copper content in rat erythrocytes. Selenium coadministration reversed those effects. CONCLUSIONS: The beneficial effect of selenium on disturbances of studied microelements homeostasis as well as on preventing lithium accumulation in erythrocytes in Li receiving animals allows suggesting that further research on selenium application as an adjuvant in lithium therapy is worth carrying on.

Antioxidant Potential of Propolis, Bee Pollen, and Royal Jelly: Possible Medical Application.

Honeybees products comprise of numerous substances, including propolis, bee pollen, and royal jelly, which have long been known for their medicinal and health-promoting properties. Their wide biological effects have been known and used since antiquity. Bee products are considered to be a potential source of natural antioxidants such as flavonoids, phenolic acids, or terpenoids. Nowadays, the still growing concern in natural substances capable of counteracting the effects of oxidative stress underlying the pathogenesis of numerous diseases, such as neurodegenerative disorders, cancer, diabetes, and atherosclerosis, as well as negative effects of different harmful factors and drugs, is being observed. Having regarded the importance of acquiring drugs from natural sources, this review is aimed at updating the current state of knowledge of antioxidant capacity of selected bee products, namely, propolis, bee pollen, and royal jelly, and of their potential antioxidant-related therapeutic applications. Moreover, the particular attention has been attributed to the understanding of the mechanisms underlying antioxidant properties of bee products. The influence of bee species, plant origin, geographic location, and seasonality as well as type of extraction solutions on the composition of bee products extracts were also discussed.

Health inequalities among students of lower secondary schools in Bytom, Poland.

INTRODUCTION AND OBJECTIVE: Poverty and low level of education pose the biggest threats to public health. Moreover, they generate inequalities in public healthThe aim of the study was to check if there are any inequalities in health among teenagers living in Bytom, Poland. MATERIAL AND METHODS: In 2011 and 2012, an epidemiological cross-sectional study was conducted on 1,099 students from lower secondary schools from Bytom. The students completed a questionnaire which was based on an earlier Health Behaviour in School-aged Children study (HBSC). Socio-Economic Status of teenagers (SES) was determined according to the Family Affluence Scale (FAS), the intensity of possible problems in the place of residence and on parents' education. Impact of SES on health self-assessment, asthma, pneumonia, bronchitis with addition to spinal deformities were also investigated. RESULTS: A good or very good level of health was declared by students from families representing a high level of FAS and residing in a more peaceful, less troubled neighbourhood. The highest level of asthma prevalence (10.9%) occurred among students from families with a low level of FAS. The students from families with high FAS were less affected by spinal deformities (34.6%). Students living in a troubled neighbourhood more often suffered from bronchial asthma, pneumonia, bronchitis and spinal deformities. CONCLUSIONS: The level of family affluence depends on the parents' education and all the analysed health problems occurred more frequently in children whose parents had completed at least general secondary education. A high economic standard of living and a peaceful neighbourhood determined good or very good health self-assessment among the surveyed students.

Selenium - a fascinating antioxidant of protective properties.

Selenium is a trace element which fulfils important functions in the organism. Its deficit may cause acute disorders, but an overdose can also lead to severe consequences. The functions of selenium in the organism are mainly connected with its antioxidant properties, as it is an essential part of important antioxidant enzymes. Disturbances of oxidant balance have been found to be involved in the activity of numerous harmful factors as well as in the pathogenesis of diverse illnesses. Selenium administration has proved to be effective against the toxicity of many agents and the side effects of drugs. However, the narrow range between therapeutic and toxic doses of selenium, as well as the dependence of its effect on the applied form, dose and method of treatment, makes the choice of the most effective supplement a very complex issue. Divergent forms of selenium are still being studied, including both inorganic and organic compounds as well as Se-enriched natural products. The newest research has also involved selenium nanoparticles. The aim of this review is to present the great potential of selenium for protecting the organism against a wide variety of environmental pollutants, drugs and physical factors.

Adipokine Profile in Patients with Type 2 Diabetes Depends on Degree of Obesity.

BACKGROUND The fast pace of life, promoting fast food consumption and low physical activity, has resulted in obesity and/or diabetes as being serious social problems. The aim of the present study was to evaluate concentrations of selected adipokines (leptin, adiponectin, resistin, and visfatin) and to assess the leptin/adiponectin ratio in plasma of type 2 diabetes (T2D) patients in relation to degree of obesity. MATERIAL AND METHODS The study comprised 92 T2D subjects divided into 4 groups according to BMI value - I (normal body weight), II (overweight), III (obesity), and IV (severe obesity) - and 20 healthy volunteers (control group). Each group was divided into male and female subgroups. Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. RESULTS In women, leptin concentration was significantly higher in group IV, whereas in men it was higher in groups III and IV than in the control group and groups I and II. Irrespective of sex, a significant decrease in adiponectin level was observed in group III vs. CONTROL: There was no significant difference in resistin levels. In women visfatin was markedly enhanced in group III, whereas in men in groups II, III and IV vs. CONTROL: Leptin/adiponectin ratio was increased in groups III and IV vs. control in women, whereas in men vs. both control and group I. CONCLUSIONS The obese type 2 diabetic patients presented a disturbed adipokine profile, which seems to be an important link between obesity and T2D. The future studies concerning the question if regulating of adipokines' concentrations could be a promising approach for managing metabolic disorders seem to be well-grounded.