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Background: Erythropoietin (EPO) is a glycoprotein which has a main property, erythropoiesis, but its range of action in the human body is very wide. It has been suggested that EPO acts cytoprotectively for many cell lines against many toxic causes in vitro and in vivo. Our aim was to study the action of EPO on DNA of two cell types, human lymphocytes in vitro and on P388 ascites tumor cells inoculated in BDF1 mice in the presence and absence of the genotoxic agent mitomycin C (MMC). Method: The sister chromatid exchange (SCE) assay was used as it is a very sensitive, simple and rapid method for detecting DNA damage. Proliferation rate indices (PRI) and mitotic indices (MI) were also counted. Results: EPO did not alter the SCE level when it acted alone on both cell lines. MMC as a potent genotoxic agent increased SCE levels in vitro and in vivo. EPO used in combination with MMC significantly decreased SCE levels and increased PRI and MI values induced by MMC alone both in vitro and in vivo. Conclusions: EPO acts protectively against the genotoxic potential of MMC, and this action may have clinical implications. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Background In order to estimate the causes of pediatric morbidity in our area, with particular emphasis on diseases with a genetic background, we retrospectively categorized the admissions of all children hospitalized in the Department of Pediatrics of the University General Hospital of Alexandroupolis, in the area of Evros, Thrace, Greece over the three year period 2005-2007. Finally, in order to guide health care administrators to improve the delivery of pediatric health care services, we estimated the percentage of hospitalized children who were uninsured and the type of health insurance of those who had medical coverage. Patients and Methods The causes of admission, as recorded in the medical records were categorized in terms of the major organ and/or system involved and/or the underlying pathology, with emphasis on diseases with a genetic background. Duplicate admissions, i.e., admissions of the same child for the same underlying disease were excluded. Additional information recorded was age, sex, and type of health insurance of all admitted children. Distribution of the causes of admission by study year was compared by chi-square. A p value < 0.05 was considered significant. Results Over the study period, there were 4,947 admissions in 2,818 boys and 2,129 girls. Respiratory diseases were the most common accounting for 30%, while infectious diseases followed with 26.4%. The frequency of chromosomal abnormalities among the hospitalized children was only 0.06%. However, if we consider diseases with an underlying genetic background, this percentage rises to 5%. Approximately 10.3% of the admitted children had no health insurance. Conclusions The percentage of children hospitalized in our area due to a disease with an underlying genetic background was 5%. This percentage pertains to a Department of Pediatrics that has no inpatient subspecialty units and which is located within a General hospital, because hospitalizations for genetic diseases are more frequent in specialized pediatric hospitals, with competence in clinical genetics. The double figure of uninsured children is worrisome and dictates the need for governmental efforts for universal pediatric health coverage in our country.

Background/Objectives: DPP4 is an enzyme with multiple natural substrates and probable involvement in various mechanisms. It constitutes a drug target for the treatment of diabetes II, although, also related to other disorders. While a number of drugs with competitive inhibitory action and covalent binding capacity are available, undesired side effects exist partly attributed to drug kinetics, and research for finding novel, potent, and safer compounds continues. Despite the research, a low number of uncompetitive and non-competitive inhibitors, which could be of worth for pharmaceutical and mechanism studies, was mentioned. Methods: In the present study sixteen 3-(benzo[d]thiazol-2-yl)-2-aryl thiazolidin-4-ones were selected for evaluation, based on structural characteristics and docking analysis and were tested in vitro for DPP4 inhibitory action using H-Gly-Pro-amidomethyl coumarin substrate. Their mode of inhibition was also in vitro explored. Results: Twelve compounds exhibited IC 50 values at the nM range with the best showing IC 50 = 12 ± 0.5 nM, better than sitagliptin. Most compounds exhibited a competitive mode of inhibition. Inhibition modes of uncompetitive, non-competitive, and mixed type were also identified. Docking analysis was in accordance with the in vitro results, with a linear correlation of logIC 50 with a Probability of Binding Factor(PF) derived using docking analysis to a specific target box and to the whole enzyme. According to the docking results, two probable sites of binding for uncompetitive inhibitors were highlighted in the wider area of the active site and in the propeller loop. Conclusions: Potent inhibitors with IC 50 at the nM range and competitive, non-competitive, uncompetitive, and mixed modes of action, one better than sitagliptin, were found. Docking analysis was used to estimate probable sites and ways of binding. However, crystallographic or NMR studies are needed to elucidate the exact way of binding especially for uncompetitive and non-competitive inhibitors.

Introduction: Maternal infections such as chorioamnionitis could impact fetal lung development by altering cell proliferation and apoptosis. Chorioamnionitis favors the multiple pleiotropic cytokines production such as LIF (leukemia inhibitory factor) and an inflammation-related protein p53. The cytokine production can lead to lung tissue damage and lung disease development., Aim: The aim of the study is to evaluate the expression and the interaction of pro-anti-inflammatory proteins LIF and p53 on fetal lungs of all developmental stages after chorioamnionitis exposure., Methods: Lung tissue was obtained from stillborn fetuses through elective abortion or miscarriage and was examined. This immuno-histochemical study aimed to evaluate the expression of pro-anti-inflammatory proteins LIF, and p53 on fetal lung tissues exposed to chorioamnionitis during three different stages of fetal lung development. Moreover, the interaction between LIF and p53 on inflammatory lung tissue was evaluated., Results: The comparison analysis of p53 rates in the three different stages showed that the p53 rate was significantly higher in the saccular stage compared to pseudogladular stage and canalicular stage, respectively (p-value: 0.05). The comparison analysis of LIF rates in the three different stages showed that the LIF rate was significantly higher in pseudogladular stage compared to the canalicular stage and saccular stage, respectively. No significant association between p53 and LIF was detected during the study duration period (p-value: 0.082)., Conclusion: The relationship between the two cytokines p53 and LIF interferes with the inflammation process. The result of their relation affects differently each stage of lung development as the cells maintain a different potential for differentiation and survival. Consequently, the extent of inflammation has a different importance at each stage., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Bioethics and Ethics Committee of Medical School of Aristotle University of Thessaloniki issued approval 2.691, dated February 27, 2019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kymioni et al.)

Erythropoietin (EPO), a hormone secreted mainly by the kidney, exerts its biological function by binding to its cell-surface receptor (EpoR). The presence of EPO and EpoR in the male and female reproductive system has been verified. Therefore, some of the key properties of EPO, such as its antioxidant and antiapoptotic effects, could improve the fertilizing capacity of spermatozoa. In the present study, the effect of two different concentrations of EPO (10 mIU/μL and 100 mIU/μL) on bovine sperm-quality parameters was evaluated during a post-thawing 4-h incubation at 37 °C. EPO had a positive effect on sperm motility, viability, and total antioxidant capacity. Moreover, EPO inhibited apoptosis, as it reduced both BCL2-associated X apoptosis regulator (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and cleaved cysteine-aspartic proteases (caspases) substrate levels in a dose-dependent manner. In addition, EPO induced sperm capacitation and acrosome reaction in spermatozoa incubated in capacitation conditioned medeia. These results establish a foundation for the physiological role of EPO in reproductive processes and hopefully will provide an incentive for further research in order to fully decipher the role of EPO in sperm physiology and reproduction.

Background: An ongoing debate has been raised on whether is better to use total or free calcidiol as a screening test in the population., Methods: In winter and summer, free calcidiol, total calcitriol, and vitamin D binding protein (DBP) concentrations were determined by immunoenzymatic assays in 326 adults (161 males, 165 females). These included 99 osteoporotic patients, 53 type 1 and 51 type 2 diabetics, and 123 athletic healthy persons, all from northern Greece., Results: In the whole sample, free calcidiol mean concentrations differed significantly (p < 0.001) between males (5.53 pg/ml) and females (4.68 pg/ml). Free calcidiol was significantly greater in the athletic healthy group (6.02 pg/ml) than in the three patient groups, and lowest in the osteoporosis group (3.69 pg/ml). Total calcitriol mean concentration did not differ significantly between genders in the whole sample (p = 0.896) or in the study groups, except for type 2 diabetics (males 38.33 pg/ml, females 54.52 pg/ml, p = 0.001). It was significantly less in the osteoporotics (34.61 pg/ml) than in the athletic healthy group (41.65 pg/ml, p = 0.037) and type 1 diabetics (43.73 pg/ml, p = 0.030), whereas it did not differ significantly between the other study groups. The DBP mean concentrations were not significantly different between genders in the whole sample and the study groups nor among the study groups (p = 0.467)., Conclusion: Comparisons with our previously reported results of total calcidiol suggest the measurement of free calcidiol offers nothing more than that, and total calcitriol is not a sensitive measure for assessing vitamin D status., Competing Interests: None.

Reactive Oxygen Species (ROS), primarily produced by cellular metabolism, are highly reactive molecules that modify cellular compounds. During sperm preparation in Assisted Reproductive Techniques (ARTs), intrinsic and extrinsic sources of ROS can impact spermatozoa's oxidative status. The modification of the media with compounds that enhance sperm quality characteristics is of great significance. The current study investigated the effect of pterostilbene, a phenolic compound, on bovine sperm quality. Cryopreserved spermatozoa from six bulls were thawed, supplemented with pterostilbene (0, 10 μΜ, 25 μΜ) and incubated for 60 min and 240 min. Spermatozoa were analyzed in terms of motility, viability, acrosomal status and intracellular concentration of superoxide anion in each time point. The incubation of spermatozoa with 25 μΜ pterostilbene resulted in the preservation of quality parameters through superoxide anion mitigation, while its presence in capacitating conditions resulted in higher percentage of acrosome-reacted spermatozoa. The results of the present study indicate that the addition of pterostilbene prevents oxidative insult to spermatozoa and preserves the sperm quality parameters.

Background: Vitamin D deficiency is recognised as a pandemic in the developed world. However, the importance of prudent sun exposure tends to be overlooked, which is responsible for this pandemic., Methods: We investigated the vitamin D status in 326 adults, 165 females and 161 males: 99 Osteoporosis patients, 53 Type 1 Diabetes patients, 51 Type 2 Diabetes patients, and 123 Athletic Healthy individuals, from Northern Greece, through the measurement of total calcidiol in winter and summer by immunoenzymatic assay., Results: In the Whole Sample 23.31% had severe deficiency, 13.50% mild deficiency, 17.48% insufficiency, and 45.71% adequacy at the end of winter. Mean concentrations differed significantly (p <0.001) between males and females. The prevalence of deficiency in the young was significantly lower than in the middle-aged (p = 0.004) and in the elderly (p <0.001), while it was significantly lower (p = 0.014) in the middle-aged than in the elderly. The best vitamin D status was found in the Athletic Healthy individuals, followed by the Type 1 and Type 2 Diabetic patients, while Osteoporotic patients had the poorest status. The difference in mean concentrations between winter and summer was significant (p <0.001)., Conclusions: Vitamin D status deteriorated with increasing age and it was better in males than in females. Our findings suggest that outdoor physical activity in a Mediterranean country can cover the vitamin D needs of the young and the middle-aged, but not of the elderly, without the need for dietary supplements., Competing Interests: No potential conflict of interest was reported by the authors

The aim of the present study was to examine the genotoxicity induced by water-soluble fractions of particulate matter (PM) and its potential relation with heavy metals. For this purpose, the genotoxicity induced on human peripheral lymphocytes by water-soluble PM 2.5 (particles with aerodynamic diameter ≤ 2.5 μm) collected from the indoor air of various workplaces in Greece (n = 20), was examined by the Sister Chromatid Exchange (SCE) induction assay and assessed in relation to the concentrations of the heavy metals Cu, Pb, Mn, Ni, Co, Zn, Cr, and Cd. The number of SCEs per metaphase (SCEs/metaphase), as an indicator of genotoxicity, the proliferation rate index (PRI), as an indicator of cytostaticity, and the mitotic index (MI), as an indicator of cytotoxicity, were measured and assessed in three water-soluble fractions of PM 2.5 : the total water-soluble fraction WS A (filtered through 0.45 μm), the dissolved fraction WS B (filtered through 0.22 μm), and the non-chelexed dissolved fraction WS C (filtered through Chelex-100 resin). Results showed statistically significant number of SCEs/metaphase in all water-soluble PM 2.5 fractions in relation to the control with large variabilities across the workplaces as a result of variations in indoor conditions, sources, and/or activities. The concentrations of genotoxicity were evaluated in terms of mass-normalized genotoxicity (SCEs/mg PM 2.5 ), that represents the genotoxic potency of particles, and air volume-normalized genotoxicity (SCEs/m 3 air), that reflects the inhalation risk for people working or spending much time in these microenvironments. Correlation and linear regression analyses were further employed in order to investigate the potential relationships between genotoxicity and the water-soluble concentrations of PM 2.5 -bounded heavy metals. According to the results, the highest mass-normalized genotoxicity values were found for PM 2.5 from the photocopying center, whereas the highest air volume-normalized genotoxicity was found in tavern-2. Significant positive correlations between the genotoxicity and water-soluble metals were derived, highlighting the role that heavy metals play in the genotoxicity of indoor PM 2.5 . Among the targeted metals, Zn and Pb were found to be good predictors of the genotoxicity of water-soluble PM 2.5.

In this work, novel chrysin-loaded poly( ε -caprolactone) and poly(3-hydroxybutyrate) microcarriers were synthesized according to a modified oil-in-water single emulsion/solvent evaporation method, utilizing poly(vinyl alcohol) surfactant as stabilizer and dispersing agent for the emulsification, and were evaluated for their physico-chemical and morphological properties, loading capacity and entrapment efficiency and in vitro release of their load. The findings suggest that the novel micro-formulations possess a spherical and relatively wrinkled structure with sizes ranging between 2.4 and 24.7 µm and a highly negative surface charge with z -potential values between (-18.1)-(-14.1) mV. The entrapment efficiency of chrysin in the poly( ε -caprolactone) and poly(3-hydroxybutyrate) microcarriers was estimated to be 58.10% and 43.63%, whereas the loading capacity was found to be 3.79% and 15.85%, respectively. The average release percentage of chrysin was estimated to be 23.10% and 18.01%, respectively. The novel micromaterials were further biologically evaluated for their hemolytic activity through hemocompatibility studies over a range of hematological parameters and cytoxicity against the epithelial human breast cancer cell line MDA-MB 231. The poly( ε -caprolactone) and poly(3-hydroxybutyrate) microcarriers reached an IC 50 value with an encapsulated chrysin content of 149.19 µM and 312.18 µM, respectively, and showed sufficient blood compatibility displaying significantly low (up to 2%) hemolytic percentages at concentrations between 5 and 500 µg·mL -1 .

Background: CYP17A1 is involved in the steroidogenesis of dehydroepiandrosterone and androstenedione. CYP17A is a target for the hormonal treatment of prostate cancer (PCa)., Objectives: To investigate the role of CYP17A1 as a driver of PCa growth., Materials and Methods: We examined the expression of CYP17A1 and of androgen receptors (AR) in PCa specimens and in PCa cell lines., Results: CYP17A1 was strongly expressed in the cytoplasm of PCa cells (median 50% of cancer cells, range 0-100%). The nuclear AR expression in cancer cells was directly related with CYP17A1 (p < 0.0001, r = 0.51). The hormone dependent 22Rv1 cell line expressed the CYP17A1 and AR protein and mRNA, in contrast to the PC3 and DU145 cell lines (p < 0.0001). Testosterone and dexamethasone induced nuclear expression of AR and this effect was abolished by abiraterone. CYP17A1 levels were not affected by the incubation with testosterone, while abiraterone significantly reduced its expression. Abiraterone reduced the growth rate and migration of testosterone stimulated 22Rv1 cells., Conclusions: CYP17A1 is strongly expressed in half about of human prostate carcinomas, implying an intracellular androgen synthesis by cancer cells. Abiraterone effectively blocked nuclear accumulation of AR and suppressed CYP17A1 expression. CYP17A1 may function as a biomarker to select the best hormonal anticancer therapy., (Copyright © 2019 by S. Karger AG, Basel.)

Cultured human lymphocytes were treated with vitamins K 1 and B 1 , potential anticancer agents, either alone or in combination with irinotecan, a semisynthetic analogue of camptothecin. The frequency of sister chromatid exchanges (SCEs) was measured as an indicator of genotoxicity and the proliferation rate index (PRI) and mitotic index (MI) was measured as indicators of cytostatic effect. Vitamin K 1 alone did not induce SCEs at the concentrations tested and combined with irinotecan does not increase SCE rates induced by irinotecan alone. Vitamin B 1 significantly increased SCEs and, in combination with irinotecan, increased rates further (p < 0.05). Vitamin K 1 decreased PRI and MI in combination with irinotecan, there were further increases in MI. At a low concentration, vitamin B 1 reduced the levels of SCE and increased PRI induced by irinotecan. The use of these vitamins in combination with antitumor agents might reduce clinical side effects of the antineoplastics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The bioactivity of the extractable organic matter (EOM) of particulate matter (PM) exhausted from major urban combustion sources, including residential heating installations (wood-burning fireplace and oil-fired boiler) and vehicular exhaust from gasoline and diesel cars), was investigated in vitro by employing multiple complementary cellular and bacterial assays. Cytotoxic responses were investigated by applying the MTT ((3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide)) bioassay and the lactate dehydrogenase (LDH) release bioassay on human lung cells (MRC-5). Sister Chromatids Exchange (SCE) genotoxicity was measured on human peripheral lymphocytes. Lipid peroxidation potential via reactive oxygen species (ROS) was evaluated on E. coli bacterial cells by measuring the malondialdehyde (MDA) end product. Furthermore, the DNA damage induced by the organic PM fractions was evaluated by the reporter (β-galactosidase) gene expression assay in the bacterial cells, and, by examining the fragmentation of chromosomal DNA on agarose gel electrophoresis. The correlations between the source PM-induced biological endpoints and the PM content in polycyclic aromatic hydrocarbons (PAHs), as typical molecular markers of combustion, were investigated. Fireplace wood smoke particles exhibited by far the highest content in total and carcinogenic PAHs followed by oil boilers, diesel and gasoline emissions. However, in all bioassays, the total EOM-induced toxicity, normalized to PM mass, was highest for diesel cars equipped with Diesel Particle Filter (DPF). No correlation between the toxicological endpoints and the PAHs content was observed suggesting that cytotoxicity and genotoxicity are probably driven by other extractable organic compounds than the commonly measured unsubstituted PAHs. Clearly, further research is needed to elucidate the role of PAHs in the biological effects induced by both, combustion emissions, and ambient air particles., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: Tocolytic drugs are used widely in order to prevent preterm birth. Ritodrine, is the only food and drug administration (FDA) approved drug for tocolytic use. We estimated the cytogenetic effect of ritodrine administered as maternal therapy, alone or in combination with smoking, in women and their neonates., Methods: Lymphocyte and fibroblasts cultures were evaluated and three indices were analyzed; sister chromatid exchanges (SCEs), proliferation rate index (PRI) and mitotic index (MI) as well as average generation time (AGT) and population doubling time (PDT). Campothacin (CPT-11) was used as a positive control., Results: Administration of ritodrine up to a month revealed significant reduction of SCEs/cell in neonates in the presence or absence of the mutagenic agent. A statistical significant increase on SCEs, for mothers and neonates, was noticed in neonate's lymphocytes when tocolytic therapy was over a month. Ritodrine revealed a cytoprotective action against smoking when the two factors were combined, but the synergistic action of ritodrine with smoking increased genotoxicity, cytostaticity and cytotoxicity of neonates after long administration (1-3 months)., Conclusions: The time-depended genotoxic, cytostatic and cytotoxic action of ritodrine alone or in combination with smoking suggests that its administration should not exceed the time period of a month.

We studied the effects of three newly synthesized steroidal derivatives of nitrogen mustards, alone or in combination with caffeine, on sister chromatid exchange (SCE) frequencies and on human lymphocyte proliferation kinetics. The agents have as alkylator functionalities either P-N,N-bis(2-chloroethyl)aminophenyl-buturate (CHL) or P-N,N-bis(2-chloroethyl)aminophenyl-acetate (PHE), esterified with a modified steroidal nucleus. An enhancement of SCE frequency was seen with compounds which contain either PHE or CHL as alkylators and are esterified with a steroidal nucleus having added a cholestene group in the 17-position of the D-ring. The exocyclic insertion of an -NHCO- group in the D-ring of the steroidal nucleus esterified with PHE (amide ester of PHE) gave a compound showing increased SCE frequency. Enhanced cytogenetic damage was observed when lymphocytes were exposed in vitro to caffeine. The compounds, alone or in combination with caffeine, caused a concentration-dependent increase in SCE frequencies and cell division delays, and caffeine was found to act synergistically with the steroidal alkylators., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: The examination of the genotoxic, cytostatic and cytotoxic effects of smoking during pregnancy., Method: Lymphocyte cultures of peripheral blood were received from 20 women who smoked during pregnancy as well as umbilical cord blood of their newborns. Fluorescence Plus Giemsa staining technique was used in order to perform cytogenetic analyses for three indices, Sister Chromatid Exchanges (SCEs), Proliferation Rate Index (PRI) and Mitotic Index (MI). To reveal any underlying chromosome instability, CPT-11 was used as a positive control., Results: Newborns whose mothers smoke during pregnancy had increased SCEs levels on their lymphocytes when they were exposed to the mutagenic agent CPT-11 (p < 0.01) compared with newborns lymphocytes exposed to the same agent with non-smoking mothers. Also, mothers smoking during pregnancy had increased SCE levels when their lymphocytes were exposed to CPT-11 (p < 0.01) compared with non smoking mothers whose lymphocytes were exposed to the same agent. In both groups newborns appeared as having decreased (p < 0.01) spontaneous SCEs levels compared with the corresponding SCE rates of their mothers. Decreases of PRIs and MIs are observed in mothers compared to their newborns., Conclusion: Smoking during pregnancy can promote cytogenetic damage in newborn's DNA, causing chromosome instability. The clinical importance of this indirect damage lies in the fact that this type of damage can act synergistically with other environmental and/or chemical mutagenic substances possibly leading to carcinogenicity.

We studied the effect of five newly synthesized steroidal derivatives of nitrogen mustards. These derivatives have as alkylators either P-N, N-bis(2-chloroethyl)aminophenyl-butyrate (CHL) or P-N, N-bis(2-chloroethyl)aminophenyl-acetate (PHE) groups esterified with different modified steroidal nuclei. We examined them alone or in combination, on sister chromatid exchange rates and on human lymphocyte proliferation kinetics. The antitumor activity of these compounds, alone or in combination, was also tested on Leukemia P388-bearing mice. A pronounced cytogenetic and antineoplastic action was demonstrated by the compounds that contain either PHE or CHL as alkylators and are esterified with a steroidal nucleus having added a cholestene group in the 17 position of the D-ring. The exocyclical insertion of an -NHCO- group in the D-ring of the steroidal nucleus esterified with PHE (amide ester of PHE) yielded a compound demonstrating a distinct cytogenetic and antineoplastic effect. In contrast, the ketone group in the D-ring being inserted endocyclically in the steroidal nucleus (androstene) esterified with either CHL or with PHE gave negative cytogenetic and antineoplastic effects. However, the combined action of cholestene esterified with either CHL or with PHE in combination with either the androstene ester of PHE or with the androstene ester of CHL, respectively, gave synergistic cytogenetic and antineoplastic effects. Also the amide ester of PHE in combination with the androstene ester of CHL gave distinct cytogenetic and antineoplastic effects in a synergistic manner.

Background: Modified steroidal derivatives (PK11-PK14) of p-bis(2-chloroethyl)aminophenyl propenate (PK15) were used to study their antitumour activity on Lewis lung carcinoma (LLC) and their effect on sister chromatid exchanges (SCEs) and human lymphocyte proliferation kinetics., Materials and Methods: LLC was tested in this study. C57BL mice were used for in vivo chemotherapy evaluation and the antitumour activity was assessed. Lymphocyte cultures were used to study the genotoxic effect in vitro., Results: PK15 and PK11 were the most effective against LLC, causing significant inhibition of tumour growth. PK11 and PK15 induced significant increase in SCE rates. A correlation was observed between the cytogenetic effect and the antitumour effectiveness., Conclusion: The order of the antitumour effectiveness of PK11-PK15 resembled the order of the cytogenetic damage induced by the same compounds in vitro.

Food coloring agents, amaranth, erythrosine and tartrazine have been tested at 0.02-8mM in human peripheral blood cells in vitro, in order to investigate their genotoxic, cytotoxic and cytostatic potential. Amaranth at the highest concentration (8mM) demonstrates high genotoxicity, cytostaticity and cytotoxicity. The frequency of SCEs/cell was increased 1.7 times over the control level. Additionally, erythrosine at 8, 4 and 2mM shows a high cytotoxicity and cytostaticity. Finally, tartrazine seems to be toxic at 8 and 4mM. No signs of genotoxicity were observed. Reversely, tartrazine showed cytotoxicity at 1 and 2mM. Furthermore, spectroscopic titration studies for the interaction of these food additives with DNA showed that these dyes bind to calf thymus DNA and distinct isosbestic points are observed clearly suggesting binding of the dyes to DNA. Additionally DNA electrophoretic mobility experiments showed that these colorants are obviously capable for strong binding to linear dsDNA causing its degradation. PCR amplification of all DNA fragments (which previously were pre-treated with three different concentrations of the colorants, extracted from agarose gel after separation and then purified), seems to be attenuated with a manner dye concentration-dependent reflecting in a delayed electrophoretic mobility due to the possible binding of some molecules of the dyes. Evaluation of the data and curves were obtained after quantitative and qualitative analysis of the lanes of the gel by an analyzer computer program. Our results indicate that these food colorants had a toxic potential to human lymphocytes in vitro and it seems that they bind directly to DNA., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

This research aimed to study children's psychopathology and unintentional accidents in Thrace, northern Greece. We examined whether there was a correlation between each risk factor of the research and the dependent variables: 1) minor accidents, 2) serious accidents that required Emergency Room attendance (ER accidents), 3) serious accidents that led to hospital admission (admission accidents). High school children (n = 1,516) completed an anonymous questionnaire regarding the cause of their accident, as well as the "Strengths and difficulties questionnaire" (SDQ) by Goodman. The results indicate that sex, conduct disorders, hyperactivity, and abnormal score in SDQ were important risk factors for minor injuries and continued to be important risk factors for ER accidents. Sex, conduct disorders, hyperactivity, peer-problems, and abnormal score in SDQ were important risk factors for the most serious accidents (admission accidents). Because major accidents can result in serious health problems or disability, attention should be paid to the risk factors found.

Tourniquets are often used to provide a bloodless operating field. However, they carry the risk of adverse effects caused by DNA damage from the free radicals generated during postischemic reperfusion of the blood. The aim of this study was to evaluate the cytogenetic damage caused by postischemic reperfusion on peripheral lymphocytes of five women and six men undergoing total knee arthroplasty "bloodless" operation using samples received before, during, immediately, and 1 h after the operations. The sister chromatid exchange assay was applied to peripheral blood lymphocyte cultures and the levels of sister chromatid exchanges were analyzed as a quantitative index of genotoxicity, along with the values of mitotic index and proliferation rate index as qualitative indices of cytotoxicity and cytostaticity, respectively. We observed that postischemic reperfusion induced cytogenetic damages specifically through reperfusion. DNA effects were most pronounced after tourniquet release and declined afterward without returning to preischemic baseline values. Our findings suggest the presence of a functional association between postischemic reperfusion and cytogenetic damage that may have important clinical implications.

Purpose: The purpose of the present study was the investigation of antileukemic effect of amiodarone in leukemia P388 BDF1 bearing mice and its genotoxic and cytostatic effect in cultured normal human lymphocytes., Methods: Leukemia P388 was used in this study. BDF1 mice were used for chemotherapy evaluation in vivo. The antitumor activity was assessed by the oncostatic parameter T/C, representing the increase of life span of drug-treated animals vs. controls. Lymphocyte cultures were used to study the genotoxic and cytostatic effect in vitro, expressed by enhanced sister chromatid exchange (SCE) and reduced proliferation rate indices (PRIS)., Results: Amiodarone was found to exert antileukemic potency against leukemia P388 bearing mice at all three different treatment schedules used, yielding T/C values of 155%, 163% with one cure and 230%. In the in vitro cytogenic experiments, significant increase of SCE rates by amiodarone was observed at 0.2 μM, while at the same concentration significant suppression of PRIS was achieved., Conclusion: According to the National Cancer Institute (NCI), a compound is characterized as potential chemotherapeutic deserving further evaluation if it produces T/C values≥125%. On the other hand the SCE assay has predictive value as a clinical assay for drugs exhibiting a strong correlation between cell killing and induction of SCEs. Further studies are warranted to clarify the structure-activity relationship of amiodarone.

Unlabelled: Child injuries are a growing global public health problem and the aim of this research was to study child accidents, their causes and risk factors in a northern part of Greece, Thrace., Methods: 1,516 high school children completed an anonymous questionnaire regarding the cause, type, activity before the accident, and result of their accident., Results: The Chi square method showed a high correlation between accidents and variables such as gender (OR .55, 95% CI: .437-.687, P < .001), grade (P < .05), maternal education level (P < .001), paternal education level (P < .001), and social group each child belongs to (P < .001). The odds ratio was 3.3 (95% CI: 1.760-6.296) for Non-natives compared with Native Christians and Native Muslims. The latter had half odds in comparison with Native Christians (OR .4, 95% CI: .328-.545)., Conclusions: Young boys (7th grade), non-natives, and children whose parents received higher education were at greater risk of being injured.

Introduction: The aim of this study was to design new potentially antineoplastic agents by combining nitrogen mustard with steroidal skeleton, in an effort to improve specificity and simultaneously to reduce systemic toxicity. The steroidal part is aimed to act as a biological platform enabling the alkylating moiety to approach its site of action by altering its physicochemical properties., Materials and Methods: The compounds tested have, as alkylating agents, either p-N,N-bis(2-chloroethyl)aminophenyl-butyrate or p-N,N-bis(2-chloroethyl)aminophenyl-acetate esterified with a modified steroidal nucleus. The four newly synthesized compounds were compared on a molar basis, regarding their ability to induce sister chromatid exchanges and modify proliferation rate indices in cultured human lymphocytes. Life span of BDF1 mice inoculated with L1210 leukemia was also estimated (antileukemic activity)., Results: A compound having p-N,N-bis(2-chloroethyl)aminophenyl-acetate as the alkylator and two ketone groups in the steroidal part demonstrated the highest statistically significant enhancement of sister chromatid exchanges and suppression of proliferation rate indices, and also caused significant antineoplastic activity. The other compounds proved less active., Conclusion: These results suggest that cytogenetic and antileukemic activity of alkylating steroidal esters depends on the configuration of the whole molecule and the appropriate combination of the alkylator with the steroidal molecule.

Objective: The aim of this study was to investigate the frequency of sister chromatid exchanges (SCEs), the presence of cytostaticity, cytotoxicity, and therefore, the possible genetic instability in patients with chronic renal failure (CRF) in human cultured peripheral blood lymphocytes., Methods: Peripheral blood lymphocytes were cultured from 32 patients with CRF (average 55.2 years) and 18 healthy blood donors (average 44.6 years), and the SCE method was applied afterward. The increase in SCE frequency was evaluated as an immediate DNA damage index, while the reduction in the values of the proliferating rate indices was evaluated as a cytostatic index and the mitotic indices as a cytotoxic index was also measured., Results: A significant increase in the SCE frequencies along with a significant reduction in mitotic indices was observed in patients with CRF compared with the controls. It is notable that there was no significant difference in SCE levels among patients with CRF and cancer, and patients with CRF alone., Conclusions: This study illustrates increased genetic instability in patients with CRF. These results could also be of a great importance in early diagnosis to prognosticate a possible generation of neoplasm in the future.