Effects of secondary biological treatment plant effluent administration, as drinking water, to rats' urogenital system in relation to cadmium and lead accumulation.

The aim of this study was to examine the effect of the secondary biological treatment plant effluent administration on the kidneys, urinary bladder, and testis of Wistar rats in relation to lead (Pb) and cadmium (Cd) accumulation, since such an effluent is used for irrigation of edible plants. Male Wistar rats, randomly assigned into 5 groups, were treated with domestic sewage effluent (DSE) for 24 months. Cadmium and lead concentrations in the DSE, rats' tissues, and urine were estimated by means of atomic spectroscopy. Lead was rapidly accumulated in high amounts in rats' kidney and to a lesser extent in the testis whereas Cd concentration was raised in all tissues examined. Deposition of Cd and Pd in the kidney of the rats resulted in profound damage over time. The results showed that long-term administration to DSE as drinking water exposes living organisms to urogenital stress related to heavy metal concentration and pH of the effluent.

Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats.

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney's relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats' blood and malondialdehyde levels in rats' urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood's antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons' histology from cisplatin's toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.

The increased expression of the inducible Hsp70 (HSP70A1A) in serum of patients with heart failure and its protective effect against the cardiotoxic agent doxorubicin.

The aim of this study was to examine the potential association between the expression of Hsp70 protein and heart failure and to investigate the possible protective effect of Hsp70 against the doxorubicin-induced toxicity. Initially, at clinical level, the expression levels of the inducible Hsp70 were quantified in serum from patients with heart failure. Our results showed that in heart failure, Hsp70 concentration appeared to be increased in blood sera of patients compared to that of healthy individuals. The enhanced expression of Hsp70 in serum of patients with heart failure seemed to be associated with various features, such as gender, age and the type of heart failure, but not with its etiology. Next, in our study at cellular level, we used primary cell cultures isolated from embryos of Hsp70-transgenic mice (Tg/Tg) overexpressing human HSP70 and wild-type mice (F1/F1). After exposure to a wide range of doxorubicin concentrations and incubation times, the dose- and time-dependent toxicity of the drug, which appeared to be reduced in Tg/Tg cells, was demonstrated. In addition, doxorubicin administration appeared to result in a dose- and time-dependent decrease in the activity of two of the major endogenous antioxidant enzymes (SOD and GPx). The increased activity of these enzymes in Tg/Tg cells compared to the control F1/F1 cells was obvious, suggesting that the presence of Hsp70 confers enhanced tolerance against DOX-induced oxidative stress. Overall, it has been indicated that Hsp70 protein exerts a very important protective action and renders cells more resistant to the harmful effects of doxorubicin.

Lipidome of plasma lipoproteins and liver is zinc- modulated in High fat diet treated mice.

Zinc (Zn) and Zn-transcription Factors regulate the metabolic pathways of lipids and glucose, consequently nutritional zinc deficiency or excess, activates stress pathways and deranges the hepatic metabolism of lipids. High fat diet (HFD) also leads to lipids' profile disorders as well as to intracellular free radicals (FR) accumulation and finally to metabolic stress-syndrome. Study of nutritional Zn effects on the lipidome of plasma lipoproteins and liver, in HFD-mice, was the aim of the present research. Three Zn enriched HF-Diets as follows, 3 mg/kg feed (Zn deficient diet), 30 mg/kg feed (Zn sufficient diet), 300mgZn /kg feed (Zn excess diet) (Mucedola s.r.l Italy-55% cal) were applied respectively to three groups of male wild type (wt) mice (Hybrid F1/F1),C57Bl/6xCBA, one month old, for 10 weeks. Accordingly, mice body weight rate and 1H-NMR spectrum analysis of liver extracts and plasma HDL and non-HDL lipoproteins were evaluated at the end of the experimental period. It is concluded that Zn sufficient diet (30 mg/Kg Feed) creates a highly protective lipidomic profile on plasma and liver lipoproteins of HFD-mice, related to significantly increased antiatherogenic indicators in lipids' composition, compared to mice in nutritional Zn deficiency or excess.

Impact of major earthquakes on the incidence of acute coronary syndromes - A systematic review of the literature.

Natural disasters such as tsunami, hurricanes, and earthquakes may have a negative impact on cardiac health. The aim of our systematic review is to evaluate the impact of earthquakes on the incidence of acute coronary syndromes and cardiac mortality and to examine the impact of the time of earthquakes on the incidence of acute coronary syndromes. MEDLINE and Cochrane databases were searched for studies assessing the impact of earthquakes on acute coronary syndromes from inception until December 20, 2017. Reference lists of all included studies and relevant review studies were also searched. A total of 26 studies on 12 earthquake disasters were included in the systematic review. The existing data show a significant negative impact of the Great East Japan, Christchurch, Niigata-Chuetsu, Northridge, Great Hanshin-Awaji, Sichuan, Athens, Armenia, and Noto Peninsula earthquakes on the incidence of acute coronary syndromes. By contrast, studies on the Newcastle, Loma Prieta, and Thessaloniki earthquakes did not show a significant correlation with myocardial infarction and cardiac mortality. In conclusion, earthquakes may be associated with increased incidence of acute coronary syndromes and cardiovascular mortality. There are conflicting data about the impact of the timing of earthquakes on the occurrence of acute coronary syndromes. Preventive measures to promote the adjustment of healthcare systems to treat cardiovascular diseases after natural disasters should be immediately implemented particularly in high-risk regions.

Modulation of cisplatin cytotoxic activity against leiomyosarcoma cells by epigallocatechin-3-gallate.

The aim of this study was to investigate the cytotoxic effect cisplatin in combination with epigallocatechin-3-gallate (EGCG) on leiomyosarcoma cells (LMS cells) in order to identify a less toxic but equally effective alternative. Assays for cell proliferation, colony formation efficiency, induction of apoptosis and cell cycle arrest were performed using the IC50 of cisplatin (8.6 µΜ) as a reference value and a concentration of EGCG (30 µΜ) that caused a non-significant reduction in cell proliferation. Pre-treatment of cells with EGCG for 24 h before the addition of cisplatin increased cytotoxicity up to 8.5% (p < 0.05) and the number of apoptotic cells by 40%. Epigallocatechin-3-gallate failed to alter S-phase cell cycle arrest induced by cisplatin and to modulate cisplatin effects on mitochondrial function. These results indicate that pre-treatment with EGCG could be used as an adjunctive therapy to maximise effectiveness of chemotherapy.

Effects of smoking on heart rate at rest and during exercise, and on heart rate recovery, in young adults.

INTRODUCTION: There is an established link between smoking, abnormal heart rate (HR) values, and impaired cardiovascular health in middle-aged or older populations. The purpose of this study was to examine the effects of smoking on resting HR and on HR responses during and after exercise in young adults. METHODS: A sample of 298 young adults (159 men), aged 20-29 years old, were selected from a large population of health-science students based on health status, body mass index, physical activity, and smoking habit. All subjects underwent a maximal Bruce treadmill test and their HR was recorded during, at peak, and after termination of exercise. RESULTS: Smokers had significantly higher resting HR values than non-smokers. Both female and male smokers showed a significantly slower HR increase during exercise. Female smokers failed to reach their age-predicted maximum HR by 6.0 bpm and males by 3.6 bpm. The actual maximum HR achieved (HRmax) was significantly lower for both female smokers (191.0 bpm vs.198.0 bpm) and male smokers (193.2 bpm vs.199.3 bpm), compared to non-smokers. Heart rate reserve was also significantly lower in female (114.6 bpm vs. 128.1 bpm) and male smokers (120.4 bpm vs. 133.0 bpm). During recovery, the HR decline was significantly attenuated, but only in female smokers. Females had a higher resting HR and showed a higher HR response during sub-maximal exercise compared to males. CONCLUSIONS: Smoking was found to affect young smokers' HR, increasing HR at rest, slowing HR increase during exercise and impairing their ability to reach the age-predicted HRmax. In addition, smoking was associated with an attenuated HR decline during recovery, but only in females.

Zinc inhibits apoptosis and maintains NEP downregulation, induced by ropivacaine, in HaCaT cells.

Zinc (Zn), a cell-protective metal against various toxic compounds, is the key agent for neutral endopeptidase (NEP) functional structure. NEP is a zinc metalloenzyme which degrades endogenous opioids and is expressed in human keratinocytes (HaCaT). Ropivacaine, a widely used opiate local anaesthetic, exerts cell toxic and apoptotic effects against HaCaT cells. The aim of the present study is to investigate whether zinc modulates the effects of ropivacaine on proliferation, viability, apoptosis and NEP expression in HaCaT cells. To investigate the role of ropivacaine in NEP function, HaCaT cells overexpressing NEP were generated via cell transfection with plasmids carrying NEP cDNA. Ropivacaine's anti-proliferative effect was tested by Neubauer's chamber cell counting, and induction of cell death was demonstrated by trypan blue exclusion assay. Apoptosis due to ropivacaine was tested via DNA fragmentation and poly-ADP-ribose-polymerase (PARP) cleavage. NEP and PARP expression was performed by western blot analysis. Results showed that zinc (15 µΜ) inhibited proliferation and cell death induction by ropivacaine (0.5, 1 and 2 mM) (p < 0.05) as well as apoptosis induced by the drug (0.5 and 1 mM) in HaCaT cells. Ropivacaine (1.0, 2.0 and 5.0 mM) downregulated NEP expression in the presence of zinc (15 µΜ) while NEP overexpression enhanced ropivacaine's apoptotic effect. In conclusion, the abilities of zinc to inhibit the toxic and apoptotic effects of ropivacaine, to maintain NEP downregulation induced by the drug and, consequently, to enhance its anaesthetic result suggest that zinc may have a significant role in pain management and tissue protection.

Smoking and physical activity interrelations in health science students. Is smoking associated with physical inactivity in young adults?

BACKGROUND: Smoking and physical inactivity constitute a major public health concern for Greece. The purpose of this study was to examine smoking behaviour and physical activity (PA) in Greek health science students. METHODS: A standardised questionnaire and the Greek version of IPAQ-short were given to 2000 health science students, randomly selected from five higher education institutions, in order to record smoking behaviour and PA status. All healthy young adults aged 19-30 years old were eligible. The final cohort size of the study was 1651 students (690 men). RESULTS: In the overall population, smoking prevalence was 37.6%, with 23.1% being heavy smokers (=21 cig/day). Smoking prevalence did not differ significantly between sexes, but heavy smoking was more prevalent in males. Age at smoking initiation was negatively associated with the daily number of cigarettes smoked (smoking volume), but only in females. The prevalence of health-enhancing PA (high PAclass) was only 14.2%, while 45.4% of the study population was classified as insufficiently active (low PAclass). Males were more physically active than females. Logistic regression analysis showed a strong inverse association between smoking and PA that was more pronounced in males. Smoking was associated with significantly decreased odds of being either moderately or highly physically active. Smoking volume was also negatively related with PA, but this relation was more pronounced in females. CONCLUSION: Smoking prevalence and rates of physical inactivity are considerably high in Greek health science students. Smoking was strongly and inversely associated with PA in this sample of Greek young adults.

Expression levels of matrix metalloproteinase (MMP)-9 and its specific inhibitor TIMP-1, in septic and aseptic arthritis of the knee.

PURPOSE: In cases of septic knee arthritis, there is excess of matrix metalloproteinases (MMPs) over tissue inhibitors of metalloproteinases (TIMPs), due to enhanced expression and activation that are induced by bacteria in comparison with rheumatic or degenerative arthritis. The aim of this study was to explore the expression levels of synovial gelatinase MMP-9 and its specific inhibitor TIMP-1 in septic and aseptic arthritis and their potential use as additional aids to clinical investigation. METHODS: Gelatin zymography and western blot analysis were applied in effusions from knees of the patients with septic (SA-10 patients), rheumatic (RA-10 patients) and osteoarthritis (OA-10 patients). RESULTS: Zymographic analysis revealed that all samples contained latent MMP-2 activity, albeit activated MMP-2 appeared in more of the septic than aseptic effusions. MMP-9 was not detected in osteoarthritic synovial fluid samples. Only trace amounts of MMP-9 activity were detected in 4 of 10 patients with RA, whereas higher MMP-9 levels were evident in all samples from SA (P = 0.0241). In immunoblotting assays, samples from SA showed significantly higher levels of MMP-9 compared with samples from RA (P = 0.0052), confirming zymographic results. Although no significant difference in TIMP-1 levels was observed, the estimated MMP-9/TIMP-1 ratio of septic effusions was significantly higher compared with aseptic ones (P = 0.0029). CONCLUSIONS: The data presented suggest enhanced expression and activation of MMP-9 in septic native knee arthritis compared with aseptic. The presence of high levels of MMP-9 with concomitantly increased MMP-9/TIMP-1 ratio and activated gelatinases in effusions, independent of neutrophilic counts, may be indicative for infection.

Changes in copper and zinc plasma concentrations during the normal menstrual cycle in women.

OBJECTIVE: To investigate whether there is a fluctuation of the copper and zinc plasma levels during the menstrual cycle and if this correlates to the physiological fluctuations of estradiol and progesterone plasma concentrations in eumenorrhoic women. METHODS: We studied 14 eumenorrhoic women. Copper (Cu), zinc (Zn), estradiol (E2) and progesterone (Prg) plasma concentrations, during time of menstruation (time 1), midfollicular phase (time 2), time of ovulation (time 3) and midluteal phase (time 4) were determined. RESULTS: We observed significant changes in both copper plasma concentrations and zinc plasma concentrations during the four times studied (p < 0.05). The changes of Cu during the various phases correlated negatively with the changes in E2 (r > 0.5, p < 0.05), whereas the changes of Zn correlated positively with those of E2 (r > 0.8, p < 0.05). We were unable to demonstrate any statistically significant correlation between Cu and Prg or Zn and Prg. CONCLUSIONS: This study indicates that there is a cyclic fluctuation of Cu and Zn concentrations in plasma during the menstrual cycle, in healthy eumenorrhoic women. This cyclic fluctuation might be due to the cyclic fluctuation of plasma levels of E2.

Criterion-related validity of the short International Physical Activity Questionnaire against exercise capacity in young adults.

BACKGROUND: Self-reported physical activity (PA) is well associated with cardiorespiratory fitness and exercise capacity. The short International Physical Activity Questionnaire (IPAQ-short) is a frequently used instrument for cross-national assessments of PA in adults. The purpose of this study was to validate IPAQ-short against exercise capacity in Greek young adults. DESIGN AND METHODS: One hundred and thirteen men and 105 women, aged 20-29 years, were randomly selected from a larger population of young health-science students. A Greek version of IPAQ-short (IPAQ-Gr) was administered to all participants before their exercise capacity evaluation with a maximal Bruce treadmill test. Multiple regression and correlation analyses were used to examine the associations between all IPAQ-Gr outcomes with exercise capacity based on maximal treadmill time. RESULTS: Spearman's correlations for total and vigorous PA against maximal treadmill time were significant in all groups examined, ranging from 0.35 to 0.43. Moderate and walking PA correlations were poor and nonsignificant, ranging from near-zero values to 0.19. In multiple linear regression analysis, only sex, smoking, and vigorous PA from all personal and log-transformed IPAQ-Gr data were significantly associated with maximal treadmill time. Partial correlation analysis for the overall population, adjusted for sex and smoking, showed that total PA (r=0.37) and vigorous PA (r=0.47) were significantly associated with exercise capacity. CONCLUSION: IPAQ-Gr was tested against exercise capacity and showed acceptable validity properties in Greek young adults. Total and vigorous weekly PA expenditure were well associated with exercise capacity, presenting significant validity correlations against maximal treadmill time.

Reliability measures of the short International Physical Activity Questionnaire (IPAQ) in Greek young adults.

INTRODUCTION: The short International Physical Activity Questionnaire (IPAQ-short) has frequently been used for national and international comparable physical activity (PA) prevalence studies. The purpose of this paper is to describe a Greek version of IPAQ-short (IPAQ-Gr) and present its reliability properties in Greek young and healthy adults. METHODS: Two hundred and eighteen health science students of the Athens Technological Educational Institute, aged 19-29 years, were randomly selected and participated in the study. An intra-examiner reliability study over time (8 and 30 days apart) was carried out to assess IPAQ-Gr repeatability. An inter-examiner reliability study was also performed to assess the consistency of IPAQ-Gr outcomes between examiners. At the same time, an intra-examiner reliability study using an independent sample of 175 medical students at the University of Ioannina was carried out in order to examine multi-centre IPAQ-Gr reliability. Intra-class correlation coefficients for IPAQ scores and kappa statistics and percent agreement for physical activity classification were used in the analysis. RESULTS: Intra-class correlation coefficients (ICCs) between day-1 and day-9 assessments for IPAQ total and vigorous PA were high in all groups examined (0.84 to 0.93). ICCs for walking PA, moderate PA and sitting hours were lower, but still good (0.69 to 0.81). Repeatability of IPAQ-Gr outcomes after one-month re-administration was high for total and vigorous PA (0.87, 0.81) and good for moderate (0.66) and walking PA (0.75). Inter-examiner reliability data showed that all correlations between examiners were greater than 0.70, up to 0.87 (paired t-test, p=NS), with the exception of moderate PA, where correlations were weaker (0.58 to 0.64). Similar results were found when intra-examiner correlations were compared between educational institutes (multi-centre inter-examiner reliability of IPAQ). CONCLUSIONS: IPAQ-Gr was found to present acceptable reliability properties in Greek young adults. IPAQ-Gr showed high repeatability values for total and vigorous PA, and good for moderate and walking PA.

Evidence for association of SLC7A9 gene haplotypes with cystinuria manifestation in SLC7A9 mutation carriers.

Cystinuria is a complex genetic disorder. In the present study, we report on the strict linkage disequilibrium of SLC7A9 mutations with the wild type SLC7A9 haplotype of 15 single nucleotide polymorphisms (SNPs) and their effect on cystinuria manifestation and classification. Specifically, screening for mutations and polymorphisms was performed in the family members of ten cystinuric patients with SLC7A9 gene mutations. The molecular genetic and clinical data of cystinuric patients and their relatives were combined to construct the SLC7A9 SNP haplotypes and evaluate the manifestation of the disorder in carriers for a SLC7A9 gene mutation. It was found that all carriers of a SLC7A9 mutation manifested cystinuria if their normal allele had non-wild type nucleotides in two or more of the identified polymorphic sites. Subsequently, the polymorphic background of the SLC7A9 gene probably affects the expression of the disorder in SLC7A9 mutation carriers and points to a revised genetic classification of cystinuric patients.

Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine.

Local anesthetics inhibit cell proliferation and induce apoptosis in various cell types. Ropivacaine, a unique, novel tertiary amine-type anesthetic, was shown to inhibit the proliferation of several cell types including keratinocytes. We found that Ropivacaine could inhibit the proliferation and induce apoptosis in an immortalized human keratinocyte line, HaCaT, in a dose- and time-dependent manner and with the deprivation of serum. The dose-dependent induction of apoptosis by ropivacaine was demonstrated by DNA fragmentation analysis and the proteolytic cleavage of a caspase-3 substrate-poly (ADP-ribose) polymerase (PARP). In addition, ropivacaine downregulated the expression of clusterin/ apoliporotein J, a protein with anti-apoptotic properties, in a dose-dependent manner, which well correlated with the induction of apoptosis of HaCaT cells. To investigate the role of clusterin/apoliporotein J in ropivacaine-induced apoptosis, HaCaT cells overexpressing clusterin/apoliporotein J were generated and compared to cells expressing the well established anti-apoptotic Bcl-2 protein. Ectopic overexpression of the secreted form of clusterin/apoliporotein J or Bcl-2 decreased the sensitivity of HaCaT cells to toxic effects of ropivacaine as demonstrated by DNA fragmentation, the proteolytic cleavage of PARP and by a reduction in procaspase-3 expression. Furthermore, the downregulation of endogenous clusterin/apolipoprotein J levels by ropivacaine suggested that this might be one mechanism by which ropivacaine induced cell death in HaCaT cells. In conclusion, the ability of ropivacaine to induce antiproliferative responses and to suppress the expression of the anti-apoptotic protein clusterin/apolipoprotein J, combined with previously reported anti-inflammatory activity and analgesic property of the drug, suggests that ropivacaine may have potential utility in the local treatment of tumors.