Influence of the Apelinergic System on Conduction Disorders in Patients after Myocardial Infarction.

BACKGROUND: There is a growing body of evidence for an important role of the apelinergic system in the modulation of cardiovascular homeostasis. The aim of our study was to (1) examine the relationship between apelin serum concentration at index myocardial infarction (MI) and atrioventricular conduction disorders (AVCDs) at 12-month follow-up, and (2) investigate the association between initial apelin concentration and the novel marker of post-MI scar (Q/QRS ratio) at follow-up. METHODS: In 84 patients with MI with complete revascularization, apelin peptide serum concentrations for apelin-13, apelin-17, elabela (ELA) and apelin receptor (APJ) were measured on day one of hospitalization; at 12-month follow-up, 54 of them underwent thorough examination that included 12-lead electrocardiography (ECG), Holter ECG monitoring and echocardiography. RESULTS: The mean age was 58.9 years. At 12-month follow-up, AVCDs were diagnosed in 21.4% of subjects, with AV first-degree block in 16.7% and sinoatrial arrest in 3.7%. ELA serum concentration at index MI correlated positively with the occurrence of AVCD (p = 0.003) and heart rate (p = 0.005) at 12-month follow-up. The apelin-13 serum concentration at index MI correlated negatively with the Q/QRS ratio. CONCLUSIONS: The apelin peptide concentration during an acute phase of MI impacts the development of AVCD and the value of Q/QRS ratio in MI survivors.

The Effect of Oleanolic Acid and Its Four New Semisynthetic Derivatives on Human MeWo and A375 Melanoma Cell Lines.

This study aimed to synthesize four new semisynthetic derivatives of natural oleanolic acid (OA) and, based on an analysis of their cytotoxic and anti-proliferative effects against human MeWo and A375 melanoma cell lines, select those with anti-cancer potential. We also screened the treatment time with the concentration of all four derivatives. We synthesized oxime 2 and performed its acylation with carboxylic acids into new derivatives 3a, 3b, 3c and 3d according to the methods previously described. Colorimetric MTT and SRB assays were used to measure the anti-proliferative and cytotoxic activity of OA and its derivatives 3a, 3b, 3c and 3d against melanoma cells. Selected concentrations of OA, the derivatives, and different time periods of incubation were used in the study. The data were analyzed statistically. The present results revealed the possible anti-proliferative and cytotoxic potential of two selected OA derivatives 3a and 3b, on A375 and MeWo melanoma cells, especially at concentrations of 50 µM and 100 µM at 48 h of incubation (p < 0.05). Further studies will be necessary to analyze the proapoptotic and anti-cancer activities of 3a and 3b against skin and other cancer cells. The bromoacetoxyimine derivative (3b) of OA morpholide turned out to be the most effective against the tested cancer cells.

Effect of a Single and Triple Dose of Levamisole on Hematological Parameters in Controlled Inflammation Model.

This study aimed to evaluate the impact of single and triple administration of levamisole on the dynamics of hematological parameters during experimental pleuritis. The experiment was performed on female Buffalo rats. Rats were randomly assigned to two equal groups that received 1 and 3 doses of levamisole every 2, 24 and 48 h, respectively. Following the experiment, blood samples for the measurement of hematological parameters were collected. The study group receiving three doses of levamisole observed a significant reduction of red blood cell count at 48 h post administration and an increase in mean corpuscular volume compared to the control inflammation group. The administration of a single dose of levamisole results in a significant increase in hematocrit at 72 h, an increase in white blood cell count at 24 h and 72 h, and an increase in neutrophil count at 72 h compared to the control inflammation group. Administration of a single and triple dose of levamisole showed statistically significant modification of some hematological parameters and thus modulates the inflammatory process. In the lungs, this results in a reduction in leukocyte infiltrations around the bronchi and blood vessels.

A Study of the Impact of Graphene Oxide on Viral Infection Related to A549 and TC28a2 Human Cell Lines.

Graphene has been one of the most tested materials since its discovery in 2004. It is known for its special properties, such as electrical conductivity, elasticity and flexibility, antimicrobial effect, and high biocompatibility with many mammal cells. In medicine, the antibacterial, antiviral, and antitumor properties of graphene have been tested as intensively as its drug carrying ability. In this study, the protective effect of graphene oxide against Rubella virus infection of human lung epithelial carcinoma cells and human chondrocyte cells was examined. Cells were incubated with graphene oxide alone and in combination with the Rubella virus. The cytopathic effect in two incubation time periods was measured using DAPI dye as a percentage value of the changed cells. It was shown that the graphene oxide alone has no cytopathic effect on any of tested cell lines, while the Rubella virus alone is highly cytopathic to the cells. However, in combination with the graphene oxide percentage of the changed cells, its cytotopathicity is significantly lower. Moreover, it can be concluded that graphene oxide has protective properties against the Rubella virus infection to cells, lowering its cytopathic changes to the human cells.

The Improvement of the Adaptation Process of Tocopherol and Acetylsalicylic Acid in Offspring of Mothers Exposed to TCDD.

Dioxins are chemical compounds that may cause an inflammatory reaction. During dioxin-induced inflammation, generated reactive oxygen species lead to morphological changes in various tissues and in biochemical parameters. The aim of this study was to demonstrate the changes in the livers of rats whose mothers were exposed to dioxins and the protective role of α-tocopherol and acetylsalicylic acid in liver inflammation. The study material consisted of Buffalo rats who were the offspring of females treated with dioxin, dioxin + α-tocopherol, or dioxin + acetylsalicylic acid. Livers and blood samples were taken from the rats' offspring, and then histopathological and biochemical analyses were performed. The histopathological analysis showed that the changes observed in the livers of neonates were the result of the dioxins derived from their mother. The biochemical analysis showed that the morphological changes in the liver affected its function, which manifested in a higher total protein concentration in the dioxin-treated group, and that the creatinine level in this group was significantly higher than that in the other groups. This effect was reduced by the protective role of α-tocopherol and acetylsalicylic acid. Based on these results, we came to the conclusion that dioxins significantly affect the structure of the liver, which negatively affects its function, mainly in the scope of the metabolism of plasma proteins and hepatic enzymes.

Plasma Levels of Apelinergic System Components in Patients with Chronic and Acute Coronary Syndromes-A Pilot Study.

The effects of the apelinergic system components apelin (AP) and elabela (ELA) in the regulation of human cardiovascular homeostasis, and data concerning the relationship between ELA and AP and coronary artery disease (CAD) are yet unknown. The aim of the study was the evaluation of AP, ELA and APJ-receptor levels in the plasma of patients with chronic coronary syndromes (CCS) and acute coronary syndromes (ACS). The study group consisted of 114 patients with CAD and 33 healthy controls. Patients were divided into two groups: with CCS (n = 30) and ACS (n = 84). Routine laboratory tests and plasma ELA, AP-17, AP-13 and APJ receptor levels were measured. Echocardiographic data were analyzed in all patients. Levels of AP-17 and ELA were significantly lower in CCS than in healthy controls and ACS patients. We demonstrated significant increase of levels of plasma apelinergic system peptides, especially ELA and AP-17 in ACS patients compared with healthy controls and CCS, suggestive of compensating up-regulation mechanisms. There is a relationship between circulating ELA and AP-17 levels and classical, biochemical markers of ischemia and left ventricular ejection faction as well.

The effect of biologically active compounds in the mucus of slugs Limax maximus and Arion rufus on human skin cells.

Molluscs are one of the sources of biologically active substances, which are now intensively studied, especially for their anti-cancer properties. Malignant melanoma originates from melanocytes, develops very quickly and is associated with poor prognosis. Therefore, the aim of the study was to assess the properties of biologically active compounds in sterile mucus isolated from slugs Limax maximus and Arion rufus. Tested mucus were isolated using the new self-developed method which is safe for the environment and the animal donors. The impact of the mucus on human keratinocytes CCD 1106 KERTr and malignant melanoma cells A-375 was examined using MTT assay and SRB assay, which allowed us to determine the cell metabolic activity and cell number after treating them with slug mucus isolated from Limax maximus and Arion rufus decreased human keratinocytes and melanoma cells metabolic activity as well as manifested properties of reducing the number of cells in both tested cell lines, and therefore can be a source of biologically active substances with anticancer potential.

Xanthohumol Effect on 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Treated Japanese Quails in Terms of Serum Lipids, Liver Enzymes, Estradiol, and Thyroid Hormones.

Dioxins are compounds classified as persistent organic pollutants, from which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic to living organisms. TCDD is considered a carcinogen and has proinflammatory influence on animals and humans, promoting free radicals' formation, and binding with the aryl hydrocarbon receptor (AhR) leads to expression of cytochrome p-450 genes that in turn predisposes to mutations. Natural flavonoids, in this case xanthohumol (XN), have been reported to attenuate TCDD toxicity through inhibition of the transformation of the AhR. Moreover, XN shows antioxidant properties. The aim of the study was to compare the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and XN on lipid, liver enzyme, estradiol, and thyroid enzyme levels in the serum of Japanese quails. Adult, six-month-old, Japanese quails were divided into eight groups according to treatment procedures. Serum levels of total cholesterol (TCh), high-density lipoproteins (HDLs), triglycerides (TGs), estradiol, triiodothyronine, and thyroxine, and activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were measured. In comparison with the control group, 2,3,7,8-tetrachlorodibenzo-p-dioxin significantly decreased concentrations of serum HDLs and thyroid hormones and significantly increased the serum TCh level. Levels of serum TGs, liver enzymes, and estradiol were not changed after 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment. Based on our data, XN treatment may also increase the levels of thyroid hormones. Moreover, the tested dioxin disrupts the liver function, especially changing lipids' metabolism. Therefore, more studies are needed for better understanding the mechanism of toxic influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin on key metabolic pathways and organs in living organisms.

The Protective Effect of Xanthohumol on the Content of Selected Elements in the Bone Tissue for Exposed Japanese Quails to TCDD.

Dioxins (including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are highly toxic and persistent chemicals widely distributed in the environment in trace amounts, and are side products of industrial and chemical processes. Exposure to dioxins leads to multiorgan morphological and functional abnormalities, including within the bone tissue, disrupting its microarchitecture and mechanical properties. Xanthohumol (XN) is a chemical compound classified as a prenylated flavonoid, distinguished by multidirectional biological action. The aim of the study is to assess whether xanthohumol, as a substance with strong antioxidant and anti-inflammatory properties, has the ability to eliminate the negative effects of TCDD on bone tissue. The experiment was conducted on adult Japanese quails. Two different doses of TCDD and xanthohumol were administered to birds. After euthanasia of animals, the research material in the form of cranial vault and hind limb bone was collected, and their mineral compositions of calcium, phosphorus, magnesium, zinc, and iron concentrations were determined using atomic emission spectrometry in an acetylene-air flame method. Our results indicate that the administration of TCDD at a low dose causes more dynamic changes in the concentration of elements in bone, in comparison to a higher dose of dioxin. Results show also that higher doses of the XN cause the linear increase in the concentration of phosphorus and iron in the bone of the hind limb, and calcium in the bones of the cranial vault. In conclusion, our experiment shows that the use of TCDD and XN in Japanese quails together in various doses influences the content of phosphorus, magnesium, zinc, and iron in the research material.

Thermographic evaluation of experimental pleurisy induced by carrageenan and modified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

PURPOSE: The use of a thermal imaging camera may improve the detection of changes during inflammation process propagation in animals and humans that could be caused by numerous factors like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). METHODS: Rats were randomised and divided into two groups, C group, in which experimental pleural inflammatory reaction was evoked and TCDD group, in which a single dose was applied 21 days before administration of 1% carrageenan solution. Infrared thermograms were taken with a microbolometer thermal imaging camera MobIR M8. The surface temperature distribution was measured in three randomly selected animals. RESULTS: In the analysis of correlation we found negative results between both groups. In the C group, the pleurisy was developed and allowed to develop freely. It can be observed that both the average maximum temperature and the average minimum temperature were the highest after 48 hours after injection of the 1% carrageenan in solution. In TCDD group, lowered temperature in all days of experiments was noted. However, the increase of temperature after carrageenan injection was similar. The main changes observed in the lungs were oedema, hyperemia with clot formation and changes in lung structure. Several proliferative changes in the lungs were noted. Moreover, increased number of goblet cells as well and increased release of the surfactant was observed. The activation of fibroblasts and synthesis of collagen fibers was noted. CONCLUSIONS: The TCDD administration results in the reduction of superficial temperature, which is easily detectable by thermal imaging camera that can be effectively used in monitoring the course of inflammation.

The The influence of high doses of α-tocopherol on the content of selected trace elements in the liver of developing chicken embryos in experimentally induced 2,3,7,8-tetrachlorodibenzo-p-dioxin intoxication.

A chicken embryo develops in ovo without access to a constant circulating maternal nutrient supply, and therefore all necessary nutrients are initially stored in the yolk, and with progressive development are transferred to the liver, where they are taken up in response to various needs. Fluctuations in hepatic trace elements correlate with their mobilization from egg stores. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) intoxication causes liver damage by production of free radicals, while α-tocopherol is a well-known antioxidant and may play a protective role. In the experiment presented here, a solution containing only TCDD, TCDD and α-tocopherol, as well as α-tocopherol exclusively, was administrated into the yolk sac. The iron, zinc, copper and magnesium distribution was evaluated using histological and chemical methods. It has been found that α-tocopherol has no influence on magnesium and zinc content in the liver. The observed increase in iron content may be caused by antagonistic action of iron and α-tocopherol. On the other hand, synergistic action of α-tocopherol and TCDD has been noted with respect to the copper content.

Co-expression of the aryl hydrocarbon receptor and estrogen receptor in the developing teeth of rat offspring after rat mothers' exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and the protective action of α-tocopherol and acetylsalicylic acid.

BACKGROUND: Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can cause adverse effects in many organs. Toxic effects are caused due to the formation of a TCDD complex with the cytoplasmatic aryl hydrocarbon receptor (AhR), whose mechanism of action is similar to that of the estrogen receptor (ER). Some substances, including α-tocopherol (E) and acetylsalicylic acid (ASA), can reduce the toxic effects of TCDD in offspring. OBJECTIVES: The objective of this study was to evaluate the co-expression of AhR and ER in the incisors of rat offspring whose mothers were exposed to TCDD, using immunohistochemical and histological techniques. Moreover, the possible protective role of E and ASA was investigated. MATERIAL AND METHODS: Four groups of 2-day-old rat offspring, whose mothers were intoxicated by TCDD before mating, were established: control group (C), TCDD group, TCDD+E group and TCDD+ASA group. RESULTS: In the TCDD group, there was an increase in ER expression and a decrease in AhR expression in comparison with the C group. In the TCDD+E and TCDD+ASA groups, there was a weak or negative ER expression and slightly stronger expression of AhR than in the TCDD group. CONCLUSIONS: The co-expression of AhR and ER during tooth development suggests the role of AhR and ER in the control of this process. Both receptors are also involved in the process of detoxification of TCDD. The increase in AhR in TCDD+E and TCDD+ASA groups indicate a preventive action of antioxidant and antiinflammatory pharmaceutics, which may limit negative effects of TCDD.

Indirect study of the effect of α-tocopherol and acetylsalicylic acid on the mineral composition of bone tissue in the offspring of female rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: long-term observations.

This paper discusses problems related to the influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the mineral composition of the calvaria in the offspring of female rats. The female rats were administered with a single dose of TCDD and subsequently, after three-weeks, with α-tocopherol or acetylsalicylic acid. The research focused on analysis of the main mineral elements (Ca, Mg, Fe, Zn). The aim of the study was to determine the effect of dioxins and various doses of drugs on bone mineral composition in a six-month observation period. The mineral composition was analyzed using an atomic spectrometry method. Data were statistically analyzed and verified at a significance level of p = 0.05. The use of α-tocopherol normalizes bone resorption and formation disturbed by TCDD, maintaining the content of the studied elements at the physiological level. In turn, administration of acetylsalicylic acid limits the bone resorption process, which affects the element content.

The Protective Effect of α-Tocopherol on the Content of Selected Elements in the Calvaria for Exposed Hens to TCDD in the Early Embryonic Period.

This paper focuses on negative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on element content in male chicken calvaria and α-tocopherol (vitamin E) ability to reduce its toxic potential on bone mineralization in offspring. In the experiment carried out once, a solution containing only DMSO, TCDD, TCDD + α-tocopherol, and exclusively α-tocopherol was administrated. Subsequently, on the 5th day after hatching, the mineral composition of the chicken calvaria was evaluated. The results obtained suggest that the use of α-tocopherol contributes to the maintenance of the concentration of calcium, magnesium, and manganese in the chicken calvaria treated with TCDD in the embryonic period. In turn, vitamin E increases the level of zinc. It has been found that α-tocopherol in chicken embryos has a protective effect against disturbance of level of chosen trace elements in the bones of offspring caused by the TCDD.

The Influence of α-Tocopherol on Serum Biochemical Markers During Experimentally Induced Pleuritis in Rats Exposed to Dioxin.

Toxicity of dioxins is wide ranging. Amongst the organs, the liver is the most susceptible to damage by dioxins. Damage caused to liver cells results in promoting inflammatory processes. The aim of this work was to evaluate whether high doses of tocopherol will change the inflammatory response, monitored by biochemical indicators, by improving liver function in rats exposed to tetrachlorodibenzo-p-dioxin (TCDD). The study was conducted on a population of female Buffalo rats. The animals were divided into the following groups: Control Group A-representing physiological norms for the studied diagnostic indicators; Control Group B-subjects were administered a 1% ceragenin solution to induce pleuritis; Study Group 1-where rats were administered α-tocopherol acetate for 3 weeks, after which pleuritis was induced; Study Group 2-rats were administered a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), while 3 weeks later, pleuritis was induced; and Study Group 3-rats were administered a single dose of TCDD and next, were administered α-tocopherol acetate for 3 weeks, followed by pleuritis induction. The results clearly show that administering tocopherol in the course of inflammation causes changes to the distribution and ratio of in the serum protein fractions, including acute phase proteins. The latter proteins are indicative to the improvement in liver function and linked to protein synthesis and stimulation of the antibody-mediated immunity. Moreover, in the course of inflammation caused by exposure of rats to TCDD, tocopherol significantly affected the acute phase protein concentration.