The effect of IL10 gene polymorphism on obesity parameters in highly physically active young men.

The main aim of this study was to investigate the association between 5 polymorphisms of the interleukin 10 (IL10) gene and body composition parameters in physically active young men. A cohort of 131 young men was enrolled and the following IL10 single-nucleotide polymorphisms (SNPs) were analysed: rs1518111, rs1878672, rs3024496, rs3024498 and rs3024505. The subjects were divided into groups depending on obesity parameters: body mass index (BMI) and percentage of body fat tissue (fat %). Statistical analysis was conducted for alleles, genotypes and haplotypes, and an association between SNPs and body composition parameters was analysed using four genetic models: dominant, recessive, codominant and overdominant mode of inheritance (MOI). The only statistically significant result in polymorphisms was found for rs3024505 in the over-dominant model with BMI (p = 0.04) and with fat % (p = 0.02). The haplo.score function showed an association between BMI and CCGTA (respectively) haplotype in the additive model (score = -2.00, p = 0.04) and in the dominant model (score = -2.30, p = 0.02). The obtained results indicate a statistically significant contribution of selected IL10 polymorphisms in the regulation of body weight in physically active individuals.

Association of Interleukin Genes IL10 and IL10RB with Parameters of Overweight in Military Students.

BACKGROUND: To date, nearly 300 single-nucleotide polymorphisms (SNPs) associated with BMI, waist-to-hip ratio, and other adiposity traits have been identified by GWAS. With regards to IL10, at least 49 IL10-associated polymorphisms have been reported. However, little is known regarding the relationship between SNPs of the IL10 gene and the risk of obesity in young men. The aim of the present study was to investigate the relationship between SNPs of the IL10 and IL10RB genes and the risk of obesity in young men. METHODS: A cohort of 139 male students were enrolled and the following IL10 and IL10RB SNPs were analyzed: IL10 (rs1518110), IL10 (rs3024491), IL10RB (rs2834167). The subjects were divided into groups depending on obesity parameters: body mass index (BMI), fat mass index (FMI) and fat percentage (Fat%). Statistical analysis was conducted for a single locus and haplotypes, an association between SNPs and body composition parameters was tested with four genetic models: dominant, recessive, codominant and overdominant mode of inheritance (MOI). RESULTS: Significant association was found for interaction IL10 (rs1518110) × IL10RB (rs2834167) with Fat% value exceeding 20 in codominant (p-value = 0.03, OR = 0.34, 95% CI 0.08 1.44) and dominant model (p-value = 0.03, OR = 0.34, 95% CI 0.08 1.44) Conclusion: Our study shows for the first time that there is a correlation between the occurrence of specific polymorphisms of IL10 gene (rs1518110, rs3024491 and rs2834167) and the possibility of obesity.

The interactions between interleukin-1 family genes: IL1A, IL1B, IL1RN, and obesity parameters.

BACKGROUND: Obesity has been recognized as a worldwide growing problem, producing many pathologies including the promotion of "proinflammatory state." The etiology of human obesity is still only partially understood; however, the genetic background has been proved. Its nature is complex, and currently, it appears that the combined effects of the interactions among multiple genes should receive more attention. Due to the fact that obesity promotes proinflammatory conditions, in this study, we investigated the genetic polymorphism of IL-1 family genes in healthy people with normal and elevated body mass index (BMI) and fat %. RESULTS: The single-nucleotide polymorphisms (SNPs) within the IL1A -889C > T (rs1800587), IL1B + 3954 T > C (rs1143634), and IL1RN -87G > A (rs2234677) genes alone were associated neither with BMI nor fat % values in tested group. The associations between SNP-SNP interaction and BMI for the IL1B × IL1RN interactions were significant for dominant model (p = 0.02) and codominant model (p = 0.03). The same SNP-SNP interaction (IL1B × IL1RN) was associated also with fat % for codominant (p = 0.01) and recessive (p = 0.002) models. CONCLUSIONS: This study further confirmed that IL-1 family genes are involved in genetic background of obesity. It has been shown that interaction IL1B × IL1RN was associated with both BMI and fat % with rare T allele protecting form higher values. Thus, even if certain polymorphisms in single genes of IL-1 family cannot be defined as related to obesity in examined population, the genetic interrelationships should be analyzed.

IL-6 Polymorphisms Are Not Related to Obesity Parameters in Physically Active Young Men.

Interleukin 6 (IL-6) is a cytokine with both pro- and anti-inflammatory actions, but is also considered as a "metabolic hormone" involved in immune responses, affecting glucose, protein and lipid metabolism. It has been proposed to be related to obesity, but various results have been presented. Thus, in this study, the very homogenous population of young, male military professionals, living in the same conditions involving high physical activity, has been selected to avoid the influence of environmental factors. The subjects were divided into groups depending on the obesity parameters BMI (body mass index) and fat percentage (fat%), and the following IL-6 SNPs (Single Nucleotide Polymorphisms) were analyzed: rs1800795, rs1800796 and rs13306435. No relation was found between obesity parameters and IL-6 polymorphisms rs1800795, rs1800796 and rs13306435. It may be postulated that even if a genetic predisposition involves IL-6 genes, this effect in individuals with obesity of a low grade is minor, or can be avoided or at least markedly reduced by changes in lifestyle.

The effects of radio-frequency radiation (RFR) exposure on the analgesic efficacy of morphine in healthy rats and rats with inflammation.

OBJECTIVES: The aim of this study, conducted at the Military Institute of Hygiene and Epidemiology in Warsaw in 2017, was to evaluate the effects of a single (15 min) and repeated (5 times for 15 min) radio-frequency radiation (RFR) exposure of 1800 MHz frequency on the analgesic efficacy of morphine in healthy rats and rats with complete Freund's adjuvant (CFA) induced inflammation. MATERIAL AND METHODS: Rats were injected intraperitoneally with morphine (MF) in the dose of 8 mg/kg or drug vehicle 15 min before RFR exposure. The authors used the plantar analgesia meter and the radiant heat paw-withdrawal test to assess the pain threshold. RESULTS: A single RFR exposure slightly influenced paw withdrawal latency (PWL) in healthy rats in the single exposure baseline group, and influenced PWL, 30 and 60 min after morphine or vehicle injection, in the repeated exposure group. There were differences between the sham-exposed groups (vehicle), 30, 60 and 90 min after injection, both in the single and repeated RFR-exposure groups. The antinociceptive effect of morphine in healthy rats was slightly decreased by RFR exposure at 60 and 90 min, both in the single and repeated exposure groups. The PWL was slightly decreased, both in the single and repeated exposure groups with inflammation (CFA and CFA/MF), at 30, 60 and 90 min, and PWL was increased in the sham-exposed groups (CFA and CFA/MF), both in the single and repeated exposure groups, at 30, 60 and 90 min. The antinociceptive effect of morphine in healthy rats was significantly increased by RFR exposure at 30 min after drug injection in the single exposure group, and increased at 30 and 60 min in the repeated exposure group. CONCLUSIONS: The authors observed a minor influence of RFR exposure on the antinociceptive effects of morphine in healthy rats after repeated exposures and a statistically significant influence of repeated exposure on morphine mediated antinociceptive effects in the inflammation group. Int J Occup Med Environ Health. 2019;32(4):465-74.

Does kisspeptin participate in GABA-mediated modulation of GnRH and GnRH receptor biosynthesis in the hypothalamic-pituitary unit of follicular-phase ewes?

BACKGROUND: The inverse relationship between GnRH transcript level and GABA neurons activity has suggested that GABA at the hypothalamic level may exert a suppressive effect on subsequent steps of the GnRH biosynthesis. In the present study, we analyzed the effects of GABA type A receptor agonist (muscimol) or antagonist (bicuculline) on molecular mechanisms governing GnRH/LH secretion in follicular-phase sheep. METHODS: ELISA technique was used to investigate the effects of muscimol and/or bicuculline on levels of post-translational products of genes encoding GnRH ligand and GnRH receptor (GnRHR) in the preoptic area (POA), anterior (AH) and ventromedial (VMH) hypothalamus, stalk/median eminence (SME), and GnRHR in the anterior pituitary (AP). Real-time PCR was chosen for determination of the effect of drugs on kisspeptin (Kiss 1) mRNA level in POA and VMH including arcuate nucleus (VMH/ARC), and on Kiss1 receptor (Kiss1r) mRNA abundance in POA-hypothalamic structures. These analyses were supplemented by RIA method for measurement of plasma LH concentration. RESULTS: The study demonstrated that muscimol and bicuculline significantly decreased or increased GnRH biosynthesis in all analyzed structures, respectively, and led to analogous changes in plasma LH concentration. Similar muscimol- and bicuculline-related alterations were observed in levels of GnRHR. However, the expression of Kiss 1 and Kiss1r mRNAs in selected POA-hypothalamic areas of either muscimol- and bicuculline-treated animals remained unaltered. CONCLUSIONS: Our data suggest that GABAergic neurotransmission is involved in the regulatory pathways of GnRH/GnRHR biosynthesis and then GnRH/LH release in follicular-phase sheep conceivably via indirect mechanisms that exclude involvement of Kiss 1 neurons.

Assessment of exogenous melatonin action on mouse liver cells after exposure to soman.

Melatonin is a hormone with many different biological activities and therefore seems to be an important factor reducing the harmful effects caused by toxic organophosphorus compounds. In this study, we attempted to evaluate the protective effect of melatonin on liver cells of mice challenged with chemical warfare agent-soman. The study was conducted at the level of ultrastructural and biochemical changes (analysis of the activity of model lysosomal enzymes and assessment of the level of lipid peroxidation). Significant biochemical and ultrastructural changes were found in the studied mouse hepatocytes after administration of soman alone, and soman in combination with melatonin, and the scope of the disclosed changes was dependent on the time of action of the examined factors. Melatonin has shown protective action, shielding liver cells from toxic effects of soman, which may result from its antioxidant properties and stimulation of the lysosomal compartment, the system coordinating the isolation and removal of cell-threatening processes.

The effect of 1800MHz radio-frequency radiation on NMDA receptor subunit NR1 expression and peroxidation in the rat brain in healthy and inflammatory states.

BACKGROUND: The aim of this study was to evaluate the effect of repeated exposure (5 times for 15min) of 1800MHz radio-frequency radiation (RFR) on N-methyl-d-aspartate receptor subunit NR1 (NMDA-NR1) expression in the brains of rats in a persistent inflammatory state. We also measured the effect of RFR combined with tramadol (TRAM) to determine the potential antioxidant capacity of this agent. METHODS: The effects of the Global System for Mobile Communication (GSM) modulated 1800MHz RFR exposure on the expression and activity of glutamate receptor channels with antioxidative activity in brain tissue was measured using oxygen radical absorbance capacity (ORAC) and electron spin resonance (ESR) detection of the hydroxyl radical generated by the Fenton reaction. NMDA-NR1 was measured in the cerebral tissue of rats with inflammation (complete Freund's adjuvent) and those injected with tramadol after RFR exposure (RFR, RFR/TRAM) and in non-exposed (baseline, TRAM) rats. RESULTS: No differences between the baseline group and the exposed group (RFR) were observed. NMDA-NR1 expression decreased after CFA injection and RFR exposure, and an elevated expression of NMDA-NR1 was observed in healthy control rats of both groups: TRAM/RFR and RFR. CONCLUSIONS: ORAC assessment revealed a robust effect of RFR, however the other experiments revealed equivocal effects. Further studies examining the combination of ORAC with NMDA are warranted to elucidate more clearly the effect of RFR on the brain.

Influence of electromagnetic field (1800 MHz) on lipid peroxidation in brain, blood, liver and kidney in rats.

OBJECTIVES: The aim of this study is the evaluation of the influence of repeated (5 times for 15 min) exposure to electromagnetic field (EMF) of 1800 MHz frequency on tissue lipid peroxidation (LPO) both in normal and inflammatory state, combined with analgesic treatment. MATERIAL AND METHODS: The concentration of malondialdehyde (MDA) as the end-product of the lipid peroxidation (LPO) was estimated in blood, liver, kidneys, and brain of Wistar rats, both healthy and those with complete Freund's adjuvant (CFA)-induced persistent paw inflammation. RESULTS: The slightly elevated levels of the MDA in blood, kidney, and brain were observed among healthy rats in electromagnetic field (EMF)-exposed groups, treated with tramadol (TRAM/EMF and exposed to the EMF). The malondialdehyde remained at the same level in the liver in all investigated groups: the control group (CON), the exposed group (EMF), treated with tramadol (TRAM) as well as exposed to and treated with tramadol (TRAM/EMF). In the group of animals treated with the complete Freund's adjuvant (CFA) we also observed slightly increased values of the MDA in the case of the control group (CON) and the exposed groups (EMF and TRAM/EMF). The MDA values concerning kidneys remained at the same levels in the control, exposed, and not-exposed group treated with tramadol. Results for healthy rats and animals with inflammation did not differ significantly. CONCLUSIONS: The electromagnetic field exposure (EMF), applied in the repeated manner together with opioid drug tramadol (TRAM), slightly enhanced lipid peroxidation level in brain, blood, and kidneys.

Antinociceptive effect of D-Lys(2), Dab(4)N-(ureidoethyl)amide, a new cyclic 1-4 dermorphin/deltorphin analog.

BACKGROUND: A preliminary evaluation of antinociceptive activity of a new cyclic dermorphin/deltorphin tetrapeptide analog restricted via a urea bridge and containing C-terminal ureidoethylamid {[H-Tyr-d-Lys(&(1))-Phe-Dab(&(2))-CH2CH2NHCONH2][&(1)CO&(2)]} (cUP-1) revealed a significant and long-lasting increase of pain threshold to thermal stimulation after systemic application. The current studies were aimed at further evaluation of cUP-1 activity in animal models of somatic and visceral pain. The influence of cUP-1 on motor functions was also investigated. METHODS: The influence of cUP-1 (0.5-2mgkg(-1), iv) on nociceptive threshold to mechanical pressure and analgesic efficacy in formalin and acetic acid-induced writhing tests were estimated. The antinociceptive effect of cUP-1 was compared to that of morphine (MF). The influence of cUP-1 (1, 4 and 8mgkg(-1), iv) on locomotor activity, motor coordination and muscle strength was estimated using open field and rota-rod tests and a grip strength measurement. RESULTS: Administration of cUP-1 in doses of 1 and 2mgkg(-1) elicited a significant increase of nociceptive threshold to mechanical pressure. MF applied in the same doses induced an antinociceptive effect only at the higher dose (2mgkg(-1)). There were no marked differences between the effect of cUP-1 and MF at each dose, at relative time points. In the writhing test and both phases of the formalin test, cUP-1 showed a significant, dose-dependent antinociceptive effect which did not markedly differ from that of MF. cUP-1 did not significantly affect motor functions of mice. CONCLUSIONS: Systemic application of cUP-1 elicited a dose-dependent antinociceptive effect. The analgesic efficacy of cUP-1 on mechanical nociception, visceral and formalin-induced pain was comparable to that of MF. cUP-1 did not impair motor functions of mice.

Changes in antioxidant capacity of blood due to mutual action of electromagnetic field (1800 MHz) and opioid drug (tramadol) in animal model of persistent inflammatory state.

BACKGROUND: The biological effects and health implications of electromagnetic field (EMF) associated with cellular mobile telephones and related wireless systems and devices have become a focus of international scientific interest and world-wide public concern. It has also been proved that EMF influences the production of reactive oxygen species (ROS) in different tissues. METHODS: Experiments were performed in healthy rats and in rats with persistent inflammatory state induced by Complete Freund's Adjuvant (CFA) injection, which was given 24 h before EMF exposure and drug application. Rats were injected with CFA or the same volume of paraffin oil into the plantar surface of the left hind paw. Animals were exposed to the far-field range of an antenna at 1800 MHz with the additional modulation which was identical to that generated by mobile phone GSM 1800. Rats were given 15 min exposure, or were sham-exposed with no voltage applied to the field generator in control groups. Immediately before EMF exposure, rats were injected intraperitoneally with tramadol in the 20 mg/kg dose or vehicle in the 1 ml/kg volume. RESULTS: Our study revealed that single EMF exposure in 1800 MHz frequency significantly reduced antioxidant capacity both in healthy animals and those with paw inflammation. A certain synergic mode of action between applied electromagnetic fields and administered tramadol in rats treated with CFA was observed. CONCLUSIONS: The aim of the study was to examine the possible, parallel/combined effects of electromagnetic radiation, artificially induced inflammation and a centrally-acting synthetic opioid analgesic drug, tramadol, (used in the treatment of severe pain) on the antioxidant capacity of blood of rats. The antioxidant capacity of blood of healthy rats was higher than that of rats which received only tramadol and were exposed to electromagnetic fields.

Synthesis, biological activity and resistance to proteolytic digestion of new cyclic dermorphin/deltorphin analogues.

A series of novel cyclic ureidopeptides, analogues of dermorphine/deltorphine tetrapeptide, were synthesized by solid phase peptide synthesis and/or in solution. The antinociceptive activity of N-substituted amides 1-10 was evaluated using hot-plate and tail-flick tests. Analogue 1 showed significant, stronger than morphine, antinociceptive effect after systemic applications. All analogues were also tested for their in vitro resistance to proteolysis by means of mass spectroscopy and it was found that all substituted amides 1-10 showed full stability during incubation with large excess of chymotrypsin and pepsin. Compound 1 is a lead molecule for further evaluation.

Ephedrine-caffeine mixture in wet-cold stress.

Our investigations were aimed at studying the possibility of enhancement of homeostatic processes protecting against excessive body cooling by using thermogenic drugs. We studied the influence of ephedrine (1 mg/kg) and caffeine (2.5 mg/kg) mixture in males immersed in cold water (12 degrees C) on core temperature and plasma catecholamines, cortisol, energy substrates and chosen cognitive functions in subjects without or after previous submission to short cold acclimation procedure by five repeated brief cold-water immersions. The tested drugs did not significantly influence core temperature during immersion both in acclimated and non-acclimated subjects, however, they enhanced metabolic response. There were observed faster mobilization and higher increase in energy substrates, more pronounced in acclimated subjects (free fatty acids, glucose). Tested drugs slightly improved some psychosomatic reactions. Although the results of our study suggest that a single application of ephedrine-caffeine mixture might probably support physiological mechanisms protecting against excessive body cooling when used in people in wet-cold conditions, further research is needed to confirm the clinical significance.