Mercury Transfer During Pregnancy and Breastfeeding: Hair Mercury Concentrations as Biomarker

Hair mercury (HHg) concentration is a biomarker of exposure that is widely used to assess environmental contamination by fish methylmercury and neurodevelopment in children. In the Rio Madeira basin (Brazilian Amazon), total HHg concentrations in 649 mother–infant pairs were measured at birth (prenatal exposure) and after 6 months of exclusive breastfeeding; these mother–infant pairs were from high fish-eating communities (urban, n?=?232; rural, n?=?35; and Riverine, n?=?262) and low fish-eating tin-miner settlers (n?=?120). Differences in kinetics were seen between Hg exposure from fish consumption and environmental exposure to a tin-ore mining environment. Overall maternal HHg concentrations (at childbirth and after 6 months of lactation) were higher than those of infant HHg. However, the relative change in HHg after 6 months of lactation showed that mothers decreased HHg while infants increased HHg. The relative change showed a consistently higher increase for girls than boys with a statistical significance only in high fish-eating mothers. The correlation coefficients between maternal and newborn hair were high and statistically significant for mothers living in urban (r?=?0.66, p?<?0.001), rural (r?=?0.89, p?<?0.001), and Riverine (r?=?0.89, p?<?0.001) communities not for tin miner settlers (r?=?0.07, p?=?0.427). After 6 months of exclusive breastfeeding, correlation coefficients showed high correlation coefficients and statistical significance for all groups (urban, r?=?0.73, p?<?0.001; rural, r?=?0.88, p?<?0.001; Riverine, r?=?0.91, p?<?0.001) except for Tin miners (r?=??0.07, p?=?0.428). A linear model analysis was used to assess the longitudinal associations of maternal total HHg and total HHg at birth (0 days) and 6 months of age in exclusively breastfed infants. Regression analysis significantly predicted HHg in newborn from maternal HHg for high fish-eating maternal-infant pairs. Conclusion: The concentration of mercury accumulated in newborn tissues (in utero and during breastfeeding) relevant to both, maternal sources and infant exposure, can be reliably assessed from maternal hair.     

Effects of Obesity and Body Fat Distribution on Lipids and Lipoproteins in Nondiabetic American Indians: The Strong Heart Study

Objectives: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Research Methods and Procedures: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high‐density lipoprotei in (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/lipoproteins. Results: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m²) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m²), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = ?0.24, p < 0.001). There was a significant but weak relation with apoAI (r = ?0.14 p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14 p < 0.001) and negatively related to HDL cholesterol (r = ?0.23, p < 0.001) and apoAI (r = ?0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = ?0.35, p < 0.001) and apoAI (r = ?0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = ?0.36 p < 0.001). In both women and men there was an inverted U‐shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (?1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (?0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. Discussion: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.     

Interrelations and associations of serum levels of steroids and pituitary hormones with markers of insulin resistance,inflammatory activity,and renal function in men and women aged >70 years in an 8-year longitudinal study of opposite-sex twins

Background: The physiological serum levels of steroids and pituitary hormones in older men and women have been sparsely reported in the literature.Objectives: The aims of this study were to investigate the normal variation and sex differences in steroids and pituitary hormones in those aged >70 years, and to study the interrelation between these hormones and indicators of the metabolic syndrome, inflammatory activity, and renal function.Methods: The investigation comprised a population-based sample of pairs of white opposite-sex twins from the Swedish Twin Registry. At baseline in 1996 and at the 8-year follow-uup in 2004, serum levels of progesterone, cortisol, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, creatinine, C-reactive protein (CRP), and urea were analyzed. Serum levels of insulin and cystatin were analyzed only at the follow-up.Results: The study sample included 219 men and 183 women aged 71 to 80 years (mean [SD], 74.5 [2.5] years) at baseline in 1996, and 127 men and 135 women at follow-uup in 2004. At baseline, in both men and women, the variation of progesterone in serum was positively correlated with that of estradiol (men: r = 0.226, P < 0.01; women: r = 0.115, P = NS), testosterone (men: r = 0.178, P < 0.01; women: r = 0.315, P < 0.001), and cortisol (men: r = 0.314, P < 0.001; women: r = 0.296, P < 0.001). The values of progesterone and other steroid hormones were associated with markers of insulin resistance (iie, insulin, waist circumference), inflammatory activity (ie, CRP) for progesterone (men: r = 0.267, P < 0.001; women: r = 0.150, P < 0.05), and renal function (ie, creatinine) for progesterone (men: r = 0.424, P < 0.001; women: r = 0.212, P < 0.01). Estradiol and prolactin were associated with insulin resistance, inflammation, and renal function. Furthermore, progesterone was associated with prolactin (men: r = 0.275, P < 0.001; women: r = 0.172, P < 0.05).. Among both men and women, there was a strong correlation between testosterone and estradiol (men: r = 0.753, P < 0.001; women: r = 0.526, P < 0.001); in women, there was also a link between testosterone and cortisol at follow-up (r = 0.340, P < 0.01). For progesterone, there was a significant correlation between the values of the co-twins (in 1996: r = 0.16, P < 0.05; in 2004: r = 0.45, P < 0.001). Higher serum levels of progesterone (2.0 [0.7] nmol/L in men and 1.7 [0.8] nmol/L in women) and prolactin (6 [5] μg/L in men and 8 [10] μg/L in women) were found among those who were deceased at follow-up compared with survivors (progesterone: 1.8 [0.5] nmol/L in men and 1.4 [0.6] nmol/L in women, P < 0.01; prolactin: 4 [3] μg/L in men and 5 [2] μg/L in women, P < 0.001).Conclusions: In this study of opposite-sex Swedish twins aged >70 years, there was a sex difference in the serum levels of steroids and pituitary hormones between men and women. Progesterone and other steroid hormones were associated with markers of insulin resistance, inflammatory activity, and renal function. Progesterone and prolactin levels were associated with increased risk of mortality in this sample.     

Assessment of Treg/Th17 axis role in immunopathogenesis of chronic injuries of mustard lung disease

Purpose: Sulfur mustard (SM) lung is a heterogeneous disease associated with abnormal inflammatory immune responses. The Th17/Treg axis imbalance is associated with the pathogenesis of chronic inflammatory pulmonary disease. We aimed to determine the distribution of different Th17 and Treg cells in patients with SM lung and chronic obstructive pulmonary disease (COPD) and evaluate the clinical implications in this homeostasis. Methods: In this analytical cross-sectional study, CD4?⁺?Foxp3^+?Treg and CD4⁺?IL-17^+?Th17 cells were measured in peripheral blood mononuclear cells (PBMCs) and transbronchial biopsy (TBB) samples of 15 SM-exposed patients, 12 COPD and 13 healthy controls (HCs). The potential correlation between the ratio of Th17/Tregs and lung function was evaluated with multivariate logistic regression (MLR) analysis. Results: The frequency of CD4?⁺?FoxP3⁺?Tregs and CD4?⁺?IL-17⁺?Th17 was increased ～1.7-fold (8.71/4.95) and ～2.7-fold (1.028/0.371) respectively, in the PBMC of SM patients compared with the health controls (p?<?0.001). The results indicated that there were increases in the frequency of Th17 and Tregs cells in the patients with COPD versus the HC, that is, ～2.6-fold (0.987/0.371) and ～1.4-fold (7.12/4.95), respectively; but they did not reach to SM level (p?≥?0.05). Moreover, in the TBB samples, the CD4?⁺?IL-17^+?Th17 and CD4⁺?FoxP3^+?Tregs numbers were significantly higher in SM and COPD patients than HC (p?<?0.05). The Th17 and Treg cells were inversely correlated with forced expiratory volume in 1s (FEV1%) (r?=??0.351, p =?0.001; r?=??0.344, p?=?0.021) and FEV1/FVC (r?=??0.44, p?=?0.001; r?=??0.302, p?=?0.011), respectively. Instead, positive correlations were found between Treg/Th17 ratios and forced FEV1%pred (r?=?0.156, p?=?0.007), as well as FEV1/FVC ratio (r?=?0.334, p?=?0.006). Conclusions: The imbalance of Th17/Treg has a key role in immunopathogenesis of chronic phase of mustard lung disease.     

Insights into CX3CL1/Fractalkine during experimental Trypanosoma cruzi infection

Trypanosoma cruzi triggers a progressive myocarditis in mammalians through activation and recruitment of leukocytes and release of inflammatory mediators. The chemokine CX3CL1 has been highlighted for its potential role in the parasite controlling in end-pathological status of infected hosts. This study investigated the systemic and cardiac release of CX3CL1 in experimental T. cruzi infection and how this chemokine correlates with endothelin-1 and TNF. Male Fisher rats (n = 20) were infected, or not, by the Y strain of T. cruzi and parasitemia was daily evaluated and immunoassays performed in the cardiac tissue macerated supernatant and in serum to evaluate CX3CL1, endothelin, and TNF production on days 5 and 15 of infection. T. cruzi infection induced a higher serum and cardiac production of these mediators on days 5 and 15 of infection. In both periods of infection, respectively, CX3CL1 showed a positive correlation with TNF (r = 0.833, p < 0.001 and r = 0.723, p < 0.001) and endothelin-1 (r = 0.801, p < 0.05 and r = 0.857, p < 0.001), which reinforce its participation in the T. cruzi-induced myocarditis development.     

Proinflammatory,anti-inflammatory cytokines and adiponkines in students with central obesity

Several studies have investigated the correlation between central obesity and inflammatory cytokines and the anti-inflammatory cytokine adiponectin. But, the correlation between central obesity and the anti-inflammatory cytokines IL-4, IL-5 has not been studied yet. Thus, we aimed to study the IL-4 and IL-5 correlation to central obesity in adolescent Egyptian girls among proinflammatory and anti-inflammatory cytokines. The study was carried out on 86 obese adolescent girls (BMI > 95 percentile) divided into two groups according to central obesity. The group I with waist to hip ratio <0.8 as a control and group II with waist to hip ratio >0.8 (central obesity). There was a significant increase in TNF-alpha (p < 0.0001), and IL-1β (p < 0.0001), as proinflammatory cytokines in group II, as compared to their corresponding group I. Group II showed a significant increase in the anti-inflammatory cytokines IL-4 and IL-5 than group I at (p < 0.0001) and (p < 0.0005) respectively. In addition there was a significant decrease in the anti-inflammatory adiponectin and an increase in the inflammatory leptin levels in group II at (p < 0.0001) and (p < 0.0001) respectively in comparison to group I. A high positive correlation has been observed between waist to hip ratio, leptin, TNF-α, IL-1-β, IL-4 and IL-5 at (r = 0.331, p < 0.03), (r = 0.559, p < 0.001), (r = 0.435, p < 0.004), (r = 0.509, p < 0.001), (r = 0.550, p < 0.0015), in group II respectively and a high negative one with adiponectin at (r = ?0.410, p < 0.0001). We concluded that central obesity lowers adiponectin plasma level through increasing proinflammatory adipokines such as TNF-α, IL-1β, leptin. Further studies are needed to explore the positive correlation we found between central obesity and the anti-inflammatory cytokines IL-4 and IL-5 known to be associated with bronchial asthma.     

Neovascularization of coronary tunica intima (DIT) is the cause of coronary atherosclerosis. Lipoproteins invade coronary intima via neovascularization from adventitial vasa vasorum, but not from the arterial lumen: a hypothesis

ABSTRACT: BACKGROUND: An accepted hypothesis states that coronary atherosclerosis (CA) is initiated by endothelial dysfunction due to inflammation and high levels of LDL-C, followed by deposition of lipids and macrophages from the luminal blood into the arterial intima, resulting in plaque formation. The success of statins in preventing CA promised much for extended protection and effective therapeutics. However, stalled progress in pharmaceutical treatment gives a good reason to review logical properties of the hypothesis underlining our efforts, and to reconsider whether our perception of CA is consistent with facts about the normal and diseased coronary artery. Analysis To begin with, it must be noted that the normal coronary intima is not a single-layer endothelium covering a thin acellular compartment, as claimed in most publications, but always appears as a multi-layer cellular compartment, or diffuse intimal thickening (DIT), in which cells are arranged in many layers. If low density lipoprotein cholesterol (LDL-C) invades the DIT from the coronary lumen, the initial depositions ought to be most proximal to blood, i.e. in the inner DIT. The facts show that the opposite is true, and lipids are initially deposited in the outer DIT. This contradiction is resolved by observing that the normal DIT is always avascular, receiving nutrients by diffusion from the lumen, whereas in CA the outer DIT is always neovascularized from adventitial vasa vasorum. The proteoglycan biglycan, confined to the outer DIT in both normal and diseased coronary arteries, has high binding capacity for LDL-C. However, the normal DIT is avascular and biglycan-LDL-C interactions are prevented by diffusion distance and LDL-C size (20 nm), whereas in CA, biglycan in the outer DIT can extract lipoproteins by direct contact with the blood. These facts lead to the single simplest explanation of all observations: (1) lipid deposition is initially localized in the outer DIT; (2) CA often develops at high blood LDL-C levels; (3) apparent CA can develop at lowered blood LDL-C levels. This mechanism is not unique to the coronary artery: for instance, the normally avascular cornea accumulates lipoproteins after neovascularization, resulting in lipid keratopathy. Hypothesis Neovascularization of the normally avascular coronary DIT by permeable vasculature from the adventitial vasa vasorum is the cause of LDL deposition and CA. DIT enlargement, seen in early CA and aging, causes hypoxia of the outer DIT and induces neovascularization. According to this alternative proposal, coronary atherosclerosis is not related to inflammation and can occur in individuals with normal circulating levels of LDL, consistent with research findings.     

Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy

Background

Increasing evidence indicates a pathogenic role of deregulated autophagy in rheumatoid arthritis (RA). We examined the relationship between autophagy and inflammatory parameters in patients with RA receiving biologic therapy.

Methods

In 72 patients with RA and 20 healthy control subjects (HC), autophagosome levels were determined by the mean fluorescence intensity (MFI) of autophagosomotropic dye incorporated into circulating immune cells, and p62 expression levels in immune cells were measured by flow cytometry. We used immunoblotting to examine protein expression of LC3-II and p62 in peripheral blood mononuclear cells.

Results

Patients with RA had significantly higher levels of autophagosome reflected by MFI of Cyto-ID in circulating lymphocytes, monocytes, and granulocytes (median values, 3.6, 11.6, and 64.8, respectively) compared with HC (1.9, 6.0, and 35.8; respectively) (all p?<?0.001). p62 MFI levels in lymphocytes and granulocytes from patients with RA (17.1 and 8.6, respectively) were significantly lower than those in the corresponding cells from HC (20.2, p?<?0.05; and 13.1, p?<?0.001, respectively). Significantly higher levels of LC3-II protein expression in contrast to lower p62 protein levels were observed in patients with RA than in HC. The autophagosome levels in immune cells were significantly correlated with inflammatory parameters in patients with RA, and they were significantly decreased with disease remission after treatment with tumor necrosis factor-α inhibitors or interleukin-6 receptor inhibitor.

Conclusions

Elevated autophagy with significant correlation to inflammation suggests the involvement of autophagy in RA pathogenesis. The effectiveness of biologic therapy might be partly related to the downregulation of autophagy expression.

     

Circulating microparticles in patients with coronary heart disease and its correlation with interleukin-6 and C-reactive protein

Microparticles (MPs) are vesicles released from activated or apoptotic cells. MP derive from various cells, most notably platelets, but also leucocytes, lymphocytes, erythrocytes, and endothelial cells. The aim of this study was to investigate endothelial MP (EMP), platelet MP (PMP), lymphocyte MP and monocyte MP and TF-positive MPs (TF⁺ MPs) in patients with coronary heart disease (CHD), and to evaluate the correlation of these MPs with Interleukin-6 (IL-6) and C-reactive protein (CRP). Different cell-derived MPs and TF⁺ MPs were analyzed by flow cytometry in 40 patients with myocardial infarction (MI), 30 unstable angina (UA), 20 stable angina (SA) and 20 healthy individuals, and IL-6 and CRP were determined by ELISA and special protein analyzer, respectively. Compared with SA and control, EMP and PMP was significantly elevated in MI and UA (P < 0.001), and TF⁺ MPs was significantly elevated in MI and UA (P < 0.001). EMP and PMP correlated with IL-6 (r = 0.822, P < 0.001 and r = 0.567, P < 0.001; respectively) or CRP level (r = 0.597, P < 0.001 and r = 0.66, P < 0.001; respectively). Different cell-derived MPs in CHD may indicate the different pathophysiological changes in vessels, and MPs may both participate in the development of thrombosis and enhance the vascular inflammation.     

Association of Increased Hair Calcium Levels and Enhanced Augmentation Index (AIx): a Marker of Arterial Stiffness

Arterial stiffness is involved in the pathophysiology of cardiovascular disease, and the degree of arterial stiffness is associated with the extent of vascular calcification. This study aimed to investigate the association of hair calcium levels with augmentation index (AIx), a simple, non-invasive measurement for arterial stiffness. Healthy Koreans (male, n?=?34, female, n?=?70) were enrolled in this study. Anthropometric parameters, lipid profiles, fasting glucose, hair mineral levels, and AIx were measured. Pearson/partial correlations and multivariate linear regression analyses were used to assess the relationship between hair calcium levels and AIx. AIx positively correlated with hair calcium levels (r?=?0.275, p?=?0.005), age (r?=?0.283, p?=?0.004), systolic blood pressure (r?=?0.282, p?=?0.004), low-density lipoprotein (LDL)-cholesterol (r?=?0.255, p?=?0.009), and hair magnesium (r?=?0.196, p?=?0.046), and negatively correlated with heart rate (r?=?-0.563, p?<?0.001) and fasting glucose (r?=?-0.262, p?=?0.005). Hair calcium levels significantly correlated with hair magnesium (r?=?0.926, p?<?0.001). Significant relationship between AIx and hair calcium levels was maintained after adjustment for sex, age, height, hear rate, blood pressure, total cholesterol, LDL-cholesterol, fasting glucose, and hair magnesium (r?=?0.244, p?=?0.018). Logistic regression model showed that AIx increased with the increment of hair calcium levels; log-AIx increased by 0.403% (95% CI: 0.139–0.515, p?=?0.001) per unit change in log-hair calcium level (sex-adjusted). After adjustment for all the variables above together with triglyceride and high-density lipoprotein-cholesterol, increased significance of the association was 0.513% (p?=?0.016)]. This study supports the presence of the independent positive relationship between hair calcium levels and AIx. It suggests the possibility that hair calcium levels may be a useful index for reflecting arterial stiffness.     

The relationship between arterial wall stiffness and left ventricular dysfunction

Objectives

The purpose of this study was to explore the relationship between left ventricular (LV) dysfunction and arterial wall stiffening.

Methods

A total of 218 patients over the age of 45 diagnosed with hypertension in Jinan City and hospitalised between 2010 and 2011 were included in this study. LV function was evaluated using echocardiography (ECHO). Blood pressure was monitored with an automated tonometric device, and the parameters of arterial wall stiffness were measured. In addition, the metabolic parameters of blood samples, such as glucose and lipids, were also determined using the Cobas E601 analyser.

Results

Stiffness parameter beta positively correlated with LV diastolic function (E/Em ratio) (r?=?0.255, p?<?0.001). LV end-diastolic diameter not only related to the E/Em ratio (r?=?0.196, p?=?0.009) but also with beta (r?=?0.220, p?=?0.002). The stiffness parameter beta was an early indicator of E/Em ratio as determined by multiple regression analysis (R ²?=?0.381, p?<?0.01). Age, blood pressure and fasting blood glucose contributed to stiffness parameter beta (p?<?0.05), as well as the E/Em ratio (p?<?0.01).

Conclusions

Our findings suggested that LV dysfunction may have a direct relationship to arterial stiffening, independently of having similar risk factors. In addition, arterial stiffness can be an independent predictor of LV diastolic function, suggesting that the severity of arterial stiffness directly correlates with the severity of LV dysfunction.     

Dynamic thiol/disulphide homeostasis as indicator of oxidative stress in automotive workers

Abstract

Purpose: To examine thiol-disulphide homeostasis auto painters.

Materials and methods: A total of 115 male workers, including 60 auto painters workers and 55 reference group, of the painting and assembly line units respectively, were included in the study. Thiol-disulphide parameters and ischaemia-modified albumin (IMA) of groups were determined. Urinary hippuric acid, (HA) phenol, hexanedione, trichloroacetic acid, arsenic and blood lead and manganese were analysed.

Results: The median urinary HA level was significantly higher in auto painters when compared to the reference group [(2461 (1212) vs. 520 (513) µgr/L), (p?<?0.001)] . The mean disulphide level [19.7 (4.3) vs 0.15.1(4.1) μmol/L, (p?<?0.001)], the disulphide/native thiol ratio [4.72 (1.47) vs. 3.13 (1.21, (p?<?0.001)] and the disulphide/total thiol ratio [4.31 (1.23) vs. 2.94 (1.06), (p?<?0.001)] were higher in auto painters when compared to the reference group. There was a statistically significant positive correlation between urinary HA and disulphide concentrations (r?=?0.536 and p?<?0.001), disulphide/native thiol ratio (r?=?0.564 and p?<?0.001) and the disulphide/total thiol ratio (r?=?0.564 and p?<?0.001) and IMA (r?=?0.396 and p?<?0.001).

Conclusion: The results presented in this study showed that oxidative stress can be associated with occupational exposure to toluene denoted by alteration of thiol disulphide homeostasis and ischaemia-modified albumin levels.     

Binge alcohol promotes hypoxic liver injury through a CYP2E1–HIF-1α-dependent apoptosis pathway in mice and humans

Binge drinking, a common pattern of alcohol ingestion, is known to potentiate liver injury caused by chronic alcohol abuse. This study was aimed at investigating the effects of acute binge alcohol on hypoxia-inducible factor-1α (HIF-1α)-mediated liver injury and the roles of alcohol-metabolizing enzymes in alcohol-induced hypoxia and hepatotoxicity. Mice and human specimens assigned to binge or nonbinge groups were analyzed for blood alcohol concentration (BAC), alcohol-metabolizing enzymes, HIF-1α-related protein nitration, and apoptosis. Binge alcohol promoted acute liver injury in mice with elevated levels of ethanol-inducible cytochrome P450 2E1 (CYP2E1) and hypoxia, both of which were colocalized in the centrilobular areas. We observed positive correlations among elevated BAC, CYP2E1, and HIF-1α in mice and humans exposed to binge alcohol. The CYP2E1 protein levels (r = 0.629, p = 0.001) and activity (r = 0.641, p = 0.001) showed a significantly positive correlation with BAC in human livers. HIF-1α levels were also positively correlated with BAC (r = 0.745, p < 0.001) or CYP2E1 activity (r = 0.792, p < 0.001) in humans. Binge alcohol promoted protein nitration and apoptosis with significant correlations observed between inducible nitric oxide synthase and BAC, CYP2E1, or HIF-1α in human specimens. Binge-alcohol-induced HIF-1α activation and subsequent protein nitration or apoptosis seen in wild type were significantly alleviated in the corresponding Cyp2e1-null mice, whereas pretreatment with an HIF-1α inhibitor, PX-478, prevented HIF-1α elevation with a trend of decreased levels of 3-nitrotyrosine and apoptosis, supporting the roles of CYP2E1 and HIF-1α in binge-alcohol-mediated protein nitration and hepatotoxicity. Thus binge alcohol promotes acute liver injury in mice and humans at least partly through a CYP2E1–HIF-1α-dependent apoptosis pathway.     

Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes

Although iron is a first-line pro-oxidant that modulates clinical manifestations of various systemic diseases, including diabetes, the individual tissue damage generated by active oxidant insults has not been demonstrated in current animal models of diabetes. We tested the hypothesis that oxidative stress is involved in the severity of the tissues injury when iron supplementation is administered in a model of type 1 diabetes. Streptozotocin (Stz)-induced diabetic and non-diabetic Fischer rats were maintained with or without a treatment consisting of iron dextran ip at 0.1 mL day^?1 doses administered for 4 days at intervals of 5 days. After 3 weeks, an extensive increase (p < 0.001) in the production of reactive oxygen species (ROS) in neutrophils of the diabetic animals on iron overload was observed. Histological analysis revealed that this treatment also resulted in higher (p < 0.05) tissue iron deposits, a higher (p < 0.001) number of inflammatory cells in the pancreas, and apparent cardiac fibrosis, as shown by an increase (p < 0.05) in type III collagen levels, which result in dysfunctional myocardial. Carbonyl protein modification, a marker of oxidative stress, was consistently higher (p < 0.01) in the tissues of the iron-treated rats with diabetes. Moreover, a significant positive correlation was found between ROS production and iron pancreas stores (r = 0.42, p < 0.04), iron heart stores (r = 0.54, p < 0.04), and change of the carbonyl protein content in pancreas (r = 0.49, p < 0.009), and heart (r = 0.48, p < 0.02). A negative correlation was still found between ROS production and total glutathione content in pancreas (r = ?0.50, p < 0.03) and heart (r = ?0.45, p < 0.04). In conclusion, our results suggest that amplified toxicity in pancreatic and cardiac tissues in rats with diabetes on iron overload might be attributed to increased oxidative stress.     

Relationship between environmental factors,yeasts and coliforms in the Yodo River

The relationship between microbial populations, the numbers of yeasts, bacteria and coliforms, and temperature, pH, DO, COD, BOD, NH₄- NO₂, NO₃N and Total-P has been investigated by using 12 water samples collected from four stations on the Yodo River, Osaka, Japan. Total yeast counts had a positive response to increased pollution of NH₄N and Total-P in water. There were significant positive correlations between the size of the yeast population and the concentration of some nutrients, with total phosphate Pearson's correlation coefficient r=0.780 (p<0.01) and NH₄N Spearman's correlation r=0.515 (p<0.10). The number of yeast cells also correlated with that of coliforms (r=0.911, p<0.01) at all stations except the estuary one. Traditionally, coliforms in water have been used as an indicator of the extent of water pollution, but yeast can be a better indicator when the water include an area susceptible to saltwater.     

Lead Accumulation as Possible Risk Factor for Primary Open-Angle Glaucoma

The objective of this study was to investigate the relationship between preeclampsia and iodine levels and magnesium concentration in the blood of subjects in the northeast Anatolia region where iodine deficiency is common. Blood specimens were obtained from 24 preeclamptic and 16 healthy pregnant women. Iodine levels in blood were determined by the Foss method based on the Sandell–Kolthoff reaction. Serum protein-bound iodine (PBI) levels and magnesium concentration in maternal blood were lower in patients with severe preeclampsia compared to normal pregnant women (8.46?±?1.22 vs. 11.46?±?1.71 μg/dL, p?<?0.001, 1.63?±?0.05 vs. 1.86?±?0.05 mg/dL, p?<?0.001, respectively). Serum PBI levels and magnesium concentration in umbilical cord blood were higher in patients with severe preeclampsia than in normal pregnant women (8.84?±?1.9 vs. 7.33?±?1.07 μg/dL, p?<?0.05, 2.48?±?0.03 vs. 2.02?±?0.01 mg/dL, p?<?0.001, respectively). There was a positive correlation between the serum PBI levels in maternal blood and magnesium concentration in maternal blood in patients with severe preeclampsia (r?=?0.41, p?<?0.05). Thus, iodine may be one factor contributing to the pathophysiology of preeclampsia. Iodine supplementation may be effective therapy in preeclamptic in pregnant women.     

Does dietary arsenic and mercury affect cutaneous bleeding time and blood lipids in humans?

Fish species may contain considerable amounts of trace elements, such as selenium (Se), arsenic (As), and mercury (Hg). The present study investigated the relationships between dietary intake of these elements and cutaneous bleeding time and blood lipids in 32 healthy volunteers. For 6 wk, one group (n=11) consumed approx 250 g Se-rich fish daily, providing them with an average Se intake of 115±31 μg Se/d, Hg intake of 18±8 μg/d, and As intake of 806±405 μg/d, all values analyzed in 4-d duplicate food collections. To study the effect of Se alone, one group (n=11) included Se-rich bread in their normal diet, giving them a Se intake (135±25 μg/d) that was comparable to the fish group. A control group (n=10) ate their normal diet, providing 77±25 gmg Se/d, 3.1±2.5 μg Hg/d, and 101±33 μg As/d. The dietary As load strongly correlated both with bleeding times and changes in bleeding times (r=0.48,p<0.01 andr=0.54,p<0.002, respectively). Dietary Hg showed a positive correlation with LDL-cholesterol (r=0.55,p<0.01), whereas dietary Hg in the fish group showed a strong negative relationship with HDL-cholesterol (r=?0.76,p<0.01). Selenium seemed to have only a modest effect on bleeding time. Our results suggest that mercury and arsenic from fish may be factors contributing to or modifying some of the known effects of fish ingestion.     

Selenium concentration in blood and hair of holstein dairy cows

Four-hundred Holstein cows in 40 dairy farms in north Greece were included in this study, and blood (n=400), black hair (n=400), white hair (n=40), and feed (n=40) samples were obtained. Although the feeding regime in these farms was similar, the selenium content of feeds was variable. The Se content of concentrate feeds was 0.104±0.086 mg/kg dry matter (DM), and of silage, it was 0.025±0.018 mg/kg. A significantly positive correlation was found between the Se concentration in black hair and the Se concentration in blood (r ²=0.610, p<0.001), the Se concentration in white hair and the Se concentration in blood (r ²=0.770, p<0.001), and the Se concentration in white hair and the Se concentration in black hair (r ²=0.921, p<0.001). The Se concentration in white hair was significantly smaller than that in black hair (p<0.001).     

Difference of immune cell infiltration between stable and unstable carotid artery atherosclerosis

Atherosclerotic plaque instability contributes to ischaemic stroke and myocardial infarction. This study is to compare the abundance and difference of immune cell subtypes within unstable atherosclerotic tissues. CIBERSORT was used to speculate the proportions of 22 immune cell types based on a microarray of atherosclerotic carotid artery samples. R software was utilized to illustrate the bar plot, heat map and vioplot. The immune cell landscape in atherosclerosis was diverse, dominated by M2 macrophages, M0 macrophages, resting CD4 memory T cells and CD8 T cells. There was a significant difference in resting CD4 memory T cells (p = 0.032), T cells follicular helper (p = 0.033), M0 (p = 0.047) and M2 macrophages (p = 0.012) between stable and unstable atherosclerotic plaques. Compared with stable atherosclerotic plaques, unstable atherosclerotic plaques had a higher percentage of M2 macrophages. Moreover, correlation analysis indicated that the percentage of naïve CD4 T cells was strongly correlated with that of gamma delta T cells (r = 0.93, p < 0.001), while memory B cells were correlated with plasma cells (r = 0.85, p < 0.001). In summary, our study explored the abundance and difference of specific immune cell subgroups at unstable plaques, which would aid new immunotherapies for atherosclerosis.     

Cholesterol Forms and Traditional Lipid Profile for Projection of Atherogenic Dyslipidemia: Lipoprotein Subfractions and Erythrocyte Membrane Cholesterol

Atherogenic dyslipidemia characterized by abnormal changes in plasma lipid profile such as low high-density lipoprotein (HDL) and increased triglyceride (TG) levels is strongly associated with atherosclerotic diseases. We aimed to evaluate the levels of pro- and antiatherogenic lipids and erythrocyte membrane cholesterol (EMC) content in normo- and dyslipidemic subjects to investigate whether EMC content could be a useful marker for clinical presentation of atherogenic dyslipidemia. Low-density lipoprotein (LDL), HDL and their subfraction levels and erythrocyte lipid content were determined in 64 normolipidemic (NLs), 42 hypercholesterolemic (HCs) and 42 mixed-type dyslipidemic subjects (MTDs). Plasma atherogenic lipid indices [small–dense LDL (sdLDL)/less-dense HDL (LHDL), TC/HDL-C, TG/HDL-C and Apo B/AI] were higher in MTDs compared to NLs (p < 0.001). The highest sdLDL level was observed in HCs (p < 0.01). Despite a slight increase in EMC level in dyslipidemic subgroups, the difference was not statistically significant. A significant negative correlation, however, was observed between EMC and sdLDL/LHDL in HCs (p < 0.035, r = ?0.386). Receiver operating characteristic curves to predict sdLDL level showed that TG and EMC levels had higher area under curve values compared to other parameters in HCs. We showed that diameters of larger LDL and HDL particles tend to shift toward smaller values in MTDs. Our results suggest that EMC content and TG levels may be a useful predictor for sdLDL level in hypercholesterolemic patients.