Re-evaluation of the existing health-based guidance values for copper and exposure assessment from all sources.

Copper is an essential micronutrient and also a regulated product used in organic and in conventional farming pest management. Both deficiency and excessive exposure to copper can have adverse health effects. In this Scientific Opinion, the EFSA 2021 harmonised approach for establishing health-based guidance values (HBGVs) for substances that are regulated products and also nutrients was used to resolve the divergent existing HBGVs for copper. The tightly regulated homeostasis prevents toxicity manifestation in the short term, but the development of chronic copper toxicity is dependent on copper homeostasis and its tissue retention. Evidence from Wilson disease suggests that hepatic retention is indicative of potential future and possibly sudden onset of copper toxicity under conditions of continuous intake. Hence, emphasis was placed on copper retention as an early marker of potential adverse effects. The relationships between (a) chronic copper exposure and its retention in the body, particularly the liver, and (b) hepatic copper concentrations and evidence of toxicity were examined. The Scientific Committee (SC) concludes that no retention of copper is expected to occur with intake of 5 mg/day and established an Acceptable Daily Intake (ADI) of 0.07 mg/kg bw. A refined dietary exposure assessment was performed, assessing contribution from dietary and non-dietary sources. Background copper levels are a significant source of copper. The contribution of copper from its use as plant protection product (PPP), food and feed additives or fertilisers is negligible. The use of copper in fertilisers or PPPs contributes to copper accumulation in soil. Infant formula and follow-on formula are important contributors to dietary exposure of copper in infants and toddlers. Contribution from non-oral sources is negligible. Dietary exposure to total copper does not exceed the HBGV in adolescents, adults, elderly and the very elderly. Neither hepatic copper retention nor adverse effects are expected to occur from the estimated copper exposure in children due to higher nutrient requirements related to growth.

Correlation between expression of CatSper1,2 and sperm parameters in the gamma irradiated adult mouse testis.

Propose: CatSper protein channels are responsible for the entry of Ca2+ into sperm cells. These proteins play an important role in motility and male fertility. So it is important to find out whether or not environmental factors, such as gamma radiation, have an effect on the expression of Catsper genes. In this study, we investigated the effects of gamma radiation on the expression of CatSper1 and CatSper2 genes. Materials and methods: Twenty-one male NMRI mice were divided into three groups: a control group without gamma radiation, and two experimental groups; Group 1 treated with 1 Gy of gamma radiation, and Group 2 treated with a higher dose of 2 Gy gamma radiation. Testes were removed from all groups of animals 35 days following irradiation and the testicular tissue, processed and embedded in paraffin blocks for sectioning and histological examination. Sperm samples were also taken from the epididymis for microscopic. Sperm parameters such as sperm count, morphology, motility, and viability rates were analyzed. Expression of CatSper genes was evaluated using Real-time PCR. Data were analyzed using the SPSS software and ANOVA test. Results: Our results showed that after treatment with gamma radiation, testes morphology was changed. Epididymal sperm count, motility, and morphology rates were significantly affected in both experimental groups compared to the control group. The relative expressions of CatSper 1 and 2 genes were significantly reduced in the irradiated mice (1 Gy and 2 Gy) than non-irradiated ones. Conclusions: Gamma radiations not only change testes histology and sperm parameters, but also decrease the expression of CatSper 1 and 2 genes in male mice.

The prevalence of metabolic syndrome increases with serum high sensitivity C-reactive protein concentration in individuals without a history of cardiovascular disease: a report from a large Persian cohort.

Background Metabolic syndrome is defined by a clustering of cardiovascular risk factors and is associated with a heightened inflammatory state. A raised serum high-sensitivity C-reactive protein, a marker of inflammation, is also known to associate with cardiovascular risk. We have investigated the relationship between the presence of metabolic syndrome and serum high-sensitivity C-reactive protein concentration in a large representative Persian population cohort without a history of cardiovascular disease. Methods The MASHAD study population cohort comprised 9778 subjects, who were recruited from the city of Mashhad, Iran, between 2007 and 2008. Several cardiovascular risk factors were measured in this population without cardiovascular disease. Individuals were categorized into quartiles of serum high-sensitivity C-reactive protein concentration: first quartile - 0.72 (0.59-0.85) (median [range]) mg/L, second quartile - 1.30 (1.14-1.4) mg/L, third quartile - 2.29 (1.92-2.81) mg/L and fourth quartile - 6.63 (4.61-11.95) mg/L, respectively. The prevalence of metabolic syndrome in each quartile was determined using either International Diabetes Federation or Adult Treatment Panel III criteria. Results The prevalence of metabolic syndrome was highest in the fourth quartile for serum high-sensitivity C-reactive protein (1220 subjects [50.0%]), and significantly higher than that in the first quartile (reference group) (634 subjects [25.9%]) ( P < 0.001). A positive smoking habit (OR, 1.47 [1.26-1.70], P < 0.001) and the presence of either metabolic syndrome-International Diabetes Federation (OR, 1.35 [1.18-1.55], P < 0.001) or metabolic syndrome-ATPIII (OR, 1.40 [1.18-1.50], P < 0.001) were strong predictors of a fourth quartile for serum high-sensitivity C-reactive protein concentration. Conclusions There was a significant association between high concentrations of serum high-sensitivity C-reactive protein and the presence of metabolic syndrome among individuals without a history of cardiovascular disease in our Persian cohort.

Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide.

The cytoprotective effects of erythropoietin (EPO) and an EPO-related nonerythropoietic analog, pyroglutamate helix B surface peptide (pHBSP), were investigated in an in vitro model of bovine aortic endothelial cell injury under normoxic (21% O2) and hypoxic (1% O2) conditions. The potential molecular mechanisms of these effects were also explored. Using a model of endothelial injury (the scratch assay), we found that, under hypoxic conditions, EPO and pHBSP enhanced scratch closure by promoting cell migration and proliferation, but did not show any effect under normoxic conditions. Furthermore, EPO protected bovine aortic endothelial cells from staurosporine-induced apoptosis under hypoxic conditions. The priming effect of hypoxia was associated with stabilization of hypoxia inducible factor-1α, EPO receptor upregulation, and decreased Ser-1177 phosphorylation of endothelial nitric oxide synthase (NOS); the effect of hypoxia on the latter was rescued by EPO. Hypoxia was associated with a reduction in nitric oxide (NO) production as assessed by its oxidation products, nitrite and nitrate, consistent with the oxygen requirement for endogenous production of NO by endothelial NOS. However, while EPO did not affect NO formation in normoxia, it markedly increased NO production, in a manner sensitive to NOS inhibition, under hypoxic conditions. These data are consistent with the notion that the tissue-protective actions of EPO-related cytokines in pathophysiological settings associated with poor oxygenation are mediated by NO. These findings may be particularly relevant to atherogenesis and postangioplasty restenosis.

Cytokine profiles in overweight and obese subjects and normal weight individuals matched for age and gender.

Background Obesity is associated with a state of systemic inflammation, mediated by adipose tissue-derived cytokines that may also have metabolic effects, including an effect on insulin resistance. The aim of this study was to compare the serum profile of pro- and anti-inflammatory cytokines in obese and non-obese subjects. Methods A total of 242 subjects who were either overweight or obese (body mass index [BMI] ≥ 25 kg/m2) and non-obese subjects (body mass index <25 kg/m2), were recruited in Mashhad in northeastern Iran. The concentrations of serum interleukin-1α, -1ß, -2, -4, -6, -8 and -10 (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8 and IL-10), were measured in all subjects, together with serum vascular endothelial growth factor, interferon-γ, epidermal growth factor, monocyte chemoattractant protein-1 and tumour necrosis factor-α. Results The groups differed significantly with respect to measures of adiposity and fasted lipid profile. Serum pro-inflammatory cytokines interferon-γ and interleukin-1α, and anti-inflammatory cytokines, interleukin-10, and epidermal growth factor were significantly different between obese and non-obese individuals, as was serum high-sensitivity C-reactive protein. Multivariate regression showed that waist circumference was significantly and independently related to serum monocyte chemoattractant protein-1concentrations ( P = 0.001). Conclusion Despite significant differences in several cytokines between the groups, only monocyte chemoattractant protein-1appeared to be independently related to a measure of adiposity in this population sample from Iran.

Serum Hsp70 Antigen: Early Diagnosis Marker in Perinatal Asphyxia.

BACKGROUND: Perinatal asphyxia is an important cause of mortality and permanent neurological and developmental deficit. Early and accurate diagnosis would help to establish the likely prognosis and may also help in determining the most appropriate treatment. Studies in experimental animal models suggest that a protein called Hsp70 may be a good and potentially useful marker of cellular stress that may be clinically useful in determining the presence of neonatal asphyxia. OBJECTIVES: Regarding the importance of early and accurate diagnosis of asphyxia, we conducted this study, which is the first investigation of the comparison of the serum Hsp70 antigen level between asphyxiated and healthy infants. PATIENTS AND METHODS: In this observational study, the serum concentrations of Hsp70 antigen were compared between neonates suffering from perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria for the cases were neonates who had reached term and had at least two clinical criteria of asphyxia. Exclusion criteria were babies with gestational age < 37 weeks, infants with congenital abnormalities or positive blood culture. Exclusion criteria in this group were the requirement to hospital stay during first week of the life or babies whose mothers had difficulties during pregnancy or delivery. Term neonates without major anomalies who had asphyxia during delivery were enrolled in the first six hours after delivery, and control group consisted of healthy term neonates without problems and normal delivery process in the first week of life. The cord blood was taken during labor to measure Hsp70 antigen level by using an in-house ELISA (The enzyme-linked immunosorbent assay). RESULTS: The median values of serum anti Hsp70 titers were significantly higher in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 - 1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58% and specificity 76% based on ROC curve. CONCLUSIONS: A significant difference between the serum concentrations of Hsp70 of the control and patient group was observed in this study. It is inferred serum concentrations of Hsp70 antigen may be a useful marker for the early diagnosis of that prenatal hypoxia.

Micronutrient intake and the presence of the metabolic syndrome.

BACKGROUND: Dietary micronutrients have been proposed to protect against oxidative damage and related clinical complications. AIMS: We aimed to compare the micronutrient intake between individuals with and without metabolic syndrome (MS). MATERIALS AND METHODS: This cross-sectional study included 3800 men and women who were aged between 35 and 65 years. The diagnosis of the MS was based on International Diabetes Federation criteria. Dietary intake of participants was assessed using a questionnaire for 24 h dietary recall. Student's t-test and Mann-Whitney U-tests were used for comparing the micronutrient intake of subjects with or without the MS and the odds ratio for the presence of the MS was calculated for each micronutrient by control for total energy intake adjusted by the residue method. RESULTS: The mean age of MS subjects and the control group was 48.8 ± 7.9 years and 47.6 ± 7.6 years, respectively. Energy-adjusted intake of vitamin E (P < 0.05), B2 (P < 0.01), and B12 (P < 0.05) was higher in normal women compared with women with MS. Energy-adjusted intake of vitamin B1 was significantly higher in women with MS. After logistic regression analysis, no significant association between micronutrient intake and MS was shown. CONCLUSION: We found no significant association between micronutrient intake and MS.

Curcuminoids modulate pro-oxidant-antioxidant balance but not the immune response to heat shock protein 27 and oxidized LDL in obese individuals.

Curcuminoids have potentially important functional qualities including anti-inflammatory and antioxidant properties. In this randomized double-blind placebo-controlled cross-over trial, the effects of a curcuminoid supplement on serum pro-oxidant-antioxidant balance (PAB) and antibody titres to Hsp27 (anti-Hsp27) and oxLDL (anti-oxLDL) were investigated. Thirty obese individuals were randomized to receive either curcuminoids (1 g/day) or placebo for a period of 30 days. After a wash-out period of 2 weeks, subjects were crossed over to the alternate regimen for another 30 days. Serum PAB along with anti-Hsp27 and anti-oxLDL titres was measured at the beginning and at the end of each study period. There was no significant carry-over effect for any of the assessed parameters. Curcuminoid supplementation was associated with a significant decrease in PAB (p = 0.044). However, no significant change was observed in serum concentrations of anti-Hsp27 or anti-oxLDL (p > 0.05). These findings suggest that oral curcuminoids supplementation (1g/day) is effective in reducing oxidative stress burden, though this needs to be validated in larger study populations.