Evaluating the association between opium abuse, blood lead levels, and the complexity of coronary artery disease.

Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and blood lead levels (BLLs) and the CAD complexity. We evaluated patients with acute coronary symptoms who underwent coronary angiography, and those with >50% stenosis in at least one of the coronary arteries were included. Furthermore, Synergy between PCI with Taxus and Cardiac Surgery I (SYNTAX I) score and BLLs were measured. Based on the opium abuse, 95 patients were subdivided into opium (45) and control (50) groups. Differences in demographics and CAD risk factors were insignificant between the two groups. The median BLLs were remarkably higher in the opium group than in controls (36 (35.7) and 20.5 µg/dL (11.45), respectively, p = 0.003). We also revealed no significant differences in SYNTAX score between the two groups (15.0 (9.0) and 17.5 (14.0), respectively, p = 0.28). Additionally, we found no significant correlation between BLLs and the SYNTAX scores (p = 0.277 and r = -0.113). Opium abuse was associated with high BLLs. Neither opium abuse nor high BLLs were correlated with the complexity of CAD. Further studies are warranted to establish better the relationship between opium abuse, BLLs, and CAD.

[Lead exposure aggravates Aß1-42-induced microglial activation and copper ion accumulation in microglial cells].

OBJECTIVE: To investigate the effect of lead (Pb) exposure on Aß1-42-induced microglial activation and copper ion accumulation in microglial cells and explore the regulatory mechanism of Pb-induced aggravation of Alzheimer's disease (AD)-like pathology. METHODS: Cultured microglial BV2 cells were treated with different concentrations of Aß1-42, lead acetate or their combination for 12 h, and the changes in cell viability and morphology were evaluated. Immunofluorescence assay was performed to detect iNOS and oxidative stress level in the treated cells, and the release of inflammatory factors was detected using ELISA. Western blotting and inductively coupled plasma-mass spectrometry (ICP-MS) were used to detect the expressions of CTR1 and ATP7A proteins and copper content in the cells. RESULTS: Treatment with 15 and 20 µmol/L Aß1-42 for 12 h significantly lowered the viability of BV2 cells. Treatment with Aß1-42 at 10 µmol/L for 12 h obviously increased the release of iNOS, TNF-α and IL-6 in the cells (P<0.05), and its combination with 15 or 20 µmol/L lead acetate more strongly lowered BV2 cell viability (P<0.05). Compared with 10 µmol/L Aß1-42 treatment alone, 10 µmol/L Aß1-42 combined with 10 µmol/L lead acetate for 12 h caused more obvious microglial activation, as manifested by enlarged cell bodies, increased cell protrusions and elongation, enhanced release of iNOS, TNF-α, IL-6, IL-1ß and ROS, and increased intracellular copper ion accumulation and expression of copper transporter CTR1 (P<0.05). Compared with the conditioned medium from activated BV2 cells, which caused obvious injuries in hippocampal neuron HT22 cells (P<0.001), the medium from BV2 cells treated with NAC and the copper ion chelating agent TM caused milder injuries in HT22 cells (P<0.05). CONCLUSION: Lead exposure aggravates neuronal damage caused by Aß1-42-treated microglial cells by increasing copper ion accumulation, oxidative stress, and inflammatory factor release to trigger microglial activation.

Early Lead Exposure Associated with Molar Hypomineralization.

Purpose: The purpose of this study was to determine the association between prenatal and early life exposure to lead and the presence of molar hypomineralization (MH) in a group of Mexican children. Methods: A subset of participants of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENTS) cohort study was examined for the presence of molar hypomineralization using European Academy of Pedi- atric Dentistry (EAPD) criteria. Prenatal lead exposure was assessed by K-ray fluorescence measurements of patella and tibia lead and by maternal blood lead levels by trimester and averaged over trimesters. Postnatal exposure was assessed by levels of maternal blood lead at delivery and child blood lead at 12 and 24 months. Results: A subset of 506 subjects from the ELEMENT cohorts (nine to 18 years old) were examined for MH; 87 subjects (17.2 percent) had MH. Maternal blood lead levels in the third trimester (odds ratio [OR] equals 1.08; 95 percent confidence interval [95% CI] equals 1.02 to 1.15) and averaged over three trimesters (OR equals 1.10; 95% CI equals 1.02 to 1.19) were significantly associated with MH status. None of the maternal bone lead or the child's blood lead parameters was significantly associated with the presence of MH (P>0.05). Conclusions: This study documents a significant association between prenatal lead exposure especially in late pregnancy and the odds of molar hypomineralization.

Long-term indoor gunshot exposure of special police forces induces bronchitic reactions and elevated blood lead levels-The Berlin shooting range study.

BACKGROUND: Gunshot emissions contain toxic elements that can harm those frequently exposed, such as police officers. Several years ago, police indoor firing ranges were closed by the Berlin municipality in response to police officer health complaints, and an investigation was launched into the possible respiratory health risks of frequent gunshot emission exposure. We, therefore, conducted an exploratory cross-sectional study to investigate clinical and functional parameters of respiratory health as well as the burden of trace elements in policemen with long-term high exposure to indoor gunshot emissions, compared to low-exposure and control groups. METHODS: We conducted lung function tests and collected blood and urine samples from Berlin police officers and government employees who were divided into three subject groups based on exposure to gunshot emissions: high exposure (n = 53), low exposure (n = 94) and no exposure (n = 76). Lung function was examined using body plethysmography. Blood and urine samples were tested via inductively coupled plasma mass spectrometry for the presence of common gunshot powder elements (antimony, lead and manganese). Exposure and symptoms were assessed using records as well as questionnaires. RESULTS: Higher exposure was associated with more respiratory symptoms during gun shooting practice (64% vs. 21%, P < 0.001) compared to the low-exposure group. Headache, cough, discoloured mucous and shortness of breath were also more common as were some other symptoms. The cough symptomatology of the high-exposure group also persisted significantly longer (median: 0.67 vs. 0.01 days, range: 0 to 5 days, P = 0.029) compared to the low-exposure group. They also showed a lower forced expiratory volume in 1 s/forced vital capacity quotient (Tiffeneau index), P = 0.018 between the three groups and P = 0.005 for the high-exposure group, a possible marker of early, subclinical bronchial obstruction. We observed increased blood lead concentrations depending on subject's age (+1.2% per year, 95% confidence interval: 0.5-1.9%, P < 0.001) and cumulative gunshot exposure (+0.34% per 100 000 shots, 0.02-0.66%, P = 0.037). CONCLUSIONS: These first results suggest that long-term exposure to indoor gunshot emissions induces bronchitic reactions due to repeated irritation of the airways. Higher levels of exposure lead to more negatively impacted lung function and higher blood lead levels with the possible reason that more frequent exposure may mean shorter regeneration phases for the respiratory mucous membrane. We recommend a reduction of exposure to gunshot emissions in order to decrease symptoms and avoid any-even small-deterioration in spirometry.

Public and occupational health risks related to lead exposure updated according to present-day blood lead levels.

Lead is an environmental hazard that should be addressed worldwide. Over time, human lead exposure in the western world has decreased drastically to levels comparable to those among humans living in the preindustrial era, who were mainly exposed to natural sources of lead. To re-evaluate the potential health risks associated with present-day lead exposure, a two-pronged approach was applied. First, recently published population metrics describing the adverse health effects associated with lead exposure at the population level were critically assessed. Next, the key results of the Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) were summarized and put in perspective with those of the published population metrics. To our knowledge, SPHERL is the first prospective study that accounted for interindividual variability between people with respect to their vulnerability to the toxic effects of lead exposure by assessing the participants' health status before and after occupational lead exposure. The overall conclusion of this comprehensive review is that mainstream ideas about the public and occupational health risks related to lead exposure urgently need to be updated because a large portion of the available literature became obsolete given the sharp decrease in exposure levels over the past 40 years.

Levels of Lead in Residential Drinking Water and Iron Deficiency among Patients with End Stage Kidney Disease.

Background: Although those with kidney disease may have heightened susceptibility to heavy metal toxicity, whether low levels of drinking water lead contamination have clinical consequence is unknown. Methods: Given that lead toxicity is known to associate with iron deficiency, we merged data from the Environmental Protection Agency (EPA) Safe Drinking Water Information and United States Renal Data Systems to examine whether municipal 90th percentile drinking water lead levels associate with iron deficiency among incident dialysis patients. Iron deficiency was defined across thresholds of transferrin saturation (<10% and 20%) and ferritin (<100 and <200 ng/ml), and simultaneous transferrin saturation <20% and ferritin <200 ng/ml, all obtained within 30 days of dialysis initiation. The average 90th percentile of drinking water lead samples per patient city of residence over a 5-year period before dialysis initiation was examined at the <1 µg/L level of detection, and at the 25th, 50th, and 100th percentile of the EPA's actionable level (15 µg/L). Results: Among 143,754 incident ESKD patients, those in cities with drinking water lead contamination had 1.06 (95% CI, 1.03 to 1.09), 1.06 (95% CI, 1.02 to 1.10), and 1.07 (95% CI, 1.03 to 1.11) higher adjusted odds of a transferrin saturation <20%, ferritin <200 ng/ml, and simultaneous transferrin saturation <20% and ferritin <200 ng/ml, respectively. These associations were apparent across the range of lead levels found commonly in the United States and were significantly greater among Black patients (multiplicative interaction P values between lead and race <0.05). Conclusions: Even exposure to low levels of lead contamination, as commonly found in US drinking water, may have adverse hematologic consequence in patients with advanced kidney disease. These associations are particularly evident among Black people and, although consistent with other environmental injustices facing minorities in the United States, might reflect a greater susceptibility to lead intoxication.

Lung cancer incidence among workers biologically monitored for occupational exposure to lead: a cohort study.

OBJECTIVE: Earlier studies have reported increased risks of lung, kidney and brain cancers for exposure to lead. The International Agency for Research on Cancer (IARC) Working Group evaluated inorganic lead and its compounds probably carcinogenic to humans. This study aimed to assess the association between blood lead level in occupational exposure and risk of lung cancer. METHODS: The study was based on the follow-up of lung cancer incidence during 1973-2014 among 20 729 employees biologically monitored for their occupational lead exposure in 1973-1983. Duration of employment in the monitored work was assessed using records from the Finnish Centre for Pensions; and potential confounding by other occupational carcinogens using longitudinal information on the occupation in censuses and the Finnish National Job-Exposure Matrix (FINJEM). Occupation- and gender-specific prevalence of regular tobacco smoking and the socioeconomic status were also utilized in the adjustments for potential confounding. RESULTS: Positive trends were found for the elevated blood lead levels on the lung cancer risk. Among employees with the duration of employment of ≥60 months, the relative risk (RR) of lung cancer was 1.72 [95% confidence interval (CI) 1.28-2.31] for mean blood lead 1.0-1.9 µmol/L and RR 2.63 (95% CI 1.71-4.05) for mean blood lead ≥2.0 µmol/L, compared with mean lead <0.5 µmol/L. The studied potential confounders did not explain the findings on the increased risk for lead exposure. CONCLUSIONS: The current study lends support to the findings that exposure to lead increases lung cancer risk. Increased risks were seen already at rather low blood lead levels.

Effects of heavy metals in acute ischemic stroke patients: A cross-sectional study.

ABSTRACT: Cerebrovascular disease is the second commonest cause of mortality globally and among the commonest causes of disability. However, research executed to probe the heavy metal exposure-stroke incidence relationship is scarce. Accordingly, we executed our study to probe the relationship of heavy metal concentrations (ie, concentrations of lead [Pb], mercury [Hg], cadmium [Cd], and arsenic) in the serum and urine of acute ischemic stroke (AIS) patients with several patient variables.For enrollment, we chose patients who had a first AIS within 7 days after the onset of a stroke. Thus, 33 newly diagnosed patients with AIS were recruited. We determined the aforementioned metals' concentrations by executing inductively coupled plasma mass spectrometry. We also gauged the association between such metal concentrations and patient variables by employing Spearman correlation coefficient. To examine the differences in metal concentrations between the different variables, we implemented an independent Mann-Whitney U test.In our cohort analysis, we noted serum Pb and Cd concentrations to be positively correlated with serum creatinine and hemoglobin. Serum and urine Cd concentrations had a negative correlation with impaired HbA1c in AIS patients. Urine Hg had a positive correlation with C-reactive protein in the participants. Participants who smoked or consumed alcohol had significantly higher Pb and Cd levels in serum than did those who neither smoked nor drank. Patients with AIS who smoked or consumed alcohol had high levels of serum Pb and serum Cd than did those who did not. Patients with AIS who consumed alcohol had significantly higher Pb and Hg urine concentrations than did those who did not.Our study indicated that serum Cd and Pb elevation increased the AIS risk in southern Taiwan patients.

Neuroprotective effects of Lippia javanica (Burm.F.) Spreng. Herbal tea infusion on Lead-induced oxidative brain damage in Wistar rats.

BACKGROUND: Though Lippia javanica (Burm.f.) Spreng antioxidant activity has been demonstrated, its effect in protecting the brain from lead (Pb)-induced oxidative damage is unknown. This study investigated the effect of L. javanica against Pb-induced oxidative stress, inflammation, apoptosis and acetylcholinesterase activity in rat's brain. METHODS: L. javanica herbal tea infusion was prepared, its phytochemical constituent was revealed by liquid chromatography-Mass spectrometer (LC-MS) and was administered simultaneously with Pb. Four groups of male Wistar rats (n = 5/group) were used: control received distilled water; Pb-acetate group received 50 mg Pb/ Kg bodyweight (bw), treatment group received 50 mg Pb/ Kg Pb-acetate + 5 ml/kg bw L. javanica and L. javanica group received 5 ml/Kg bw of L. javanica tea infusion only. After 6 weeks of treatment, oxidative status, acetylcholinesterase activity, inflammation and apoptosis was assessed in brain tissue which was also histologically examined. RESULTS: Mean brain and heart weight was reduced (p < 0.05) while liver and spleen weights were increased (p < 0.05) in Pb exposed animals but were prevented by L. juvanica treatment. Treatment with L. javanica increased (p < 0.05) overall brain antioxidant status (glutathione and superoxide dismutase activities) and reduced lipid peroxidation (p < 0.05) compared to the Pb exposed animals. Pro-inflammatory cytokine tumour necrotic factor-alpha, pro-apoptosis Bax protein and anticholinesterase activity were reduced (p < 0.05) in Pb-L. javanica treated animals compared to the Pb exposed group. Histological examination confirmed neuroprotective effects of L. javanica as evidenced by reduced apoptosis/necrosis and inflammation-induced vacuolization and oedema in the hippocampus. The L. javanica treatment alone had no detrimental effects to the rats. LC-MS analysis revealed L. javanica to be rich in phenolics. CONCLUSIONS: This study demonstrated that L. javanica, rich in phenolics was effective in reducing Pb-induced brain oxidative stress, inflammation, apoptosis, acetylcholinesterase activity and neuronal damage.

Environmental exposure to lead, mercury, and cadmium is not associated with abnormal kidney function in Korean adolescents.

BACKGROUND: We aimed to elucidate the relationship between environmental exposure to lead (Pb), mercury (Hg), and cadmium (Cd) which were measured in blood and the kidney function of adolescents. METHODS: Cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey from 2010 to 2017. Statistical procedures were performed to analyze the Korean population of adolescents aged 12-17 years. Regression analysis was performed, and covariates included age, sex, body mass index, smoking status, and other heavy metal levels. RESULTS: The median blood levels of Pb, Hg, and Cd were 1.165 µg/dL, 1.805 µg/L, and 0.304 µg/L, respectively. Adolescents with Pb levels in the highest quartile (> 1.454 µg/dL) had a 3.35 mL/min/1.73 m2-lower estimated glomerular filtration rate using creatinine (eGFRcr) (95% confidence interval (CI), -6.03 to -0.68 mL/min/1.73 m2) compared to those in the lowest quartile (< 0.856 µg/dL) in the unadjusted model. However, there was no association between the blood Pb level and eGFRcr in the adjusted model. Levels of Hg and Cd were not associated with eGFRcr in either model. High blood levels of all three heavy metals were not associated with the risk of hypertension. CONCLUSIONS: There was no association between increased blood levels of Pb, Hg, and Cd; eGFRcr; and increased risk of hypertension in Korean adolescents who were exposed to relatively low levels of heavy metals.

Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica.

BACKGROUND: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. OBJECTIVES: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). METHODS: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (µg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (µg/g) and blood (MnB) (µg/L), and blood lead (PbB) (µg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. RESULTS: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: ß = -0.79 (95%CI = -1.51, -0.08) and ß = -0.29 (95%CI = -0.62, -0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (ß = 0.04 (95%CI = 0.00, 0.07 per 1 µg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. DISCUSSION: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.

Association between occupational lead exposure and immunotoxicity markers: A systematic review and meta-analysis.

Recent evidences suggest the role of chronic lead (Pb) exposure in altering immunological parameters. Present study aimed to systematically review existing literature and synthesize quantitative evidence on the association between chronic Pb exposure and changes in immunological markers. Observational studies reporting immunological markers such as leukocyte derivative counts (CD3+, CD4+, CD8+, CD45+, CD56+, lymphocyte, and total leukocyte), cytokine, Immunoglobulin (Igs), C-reactive protein (CRP) among Pb-exposed and unexposed controls were systematically searched from PubMed, Scopus and Embase digital databases from inception to January 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered during systematic review. Mean differences in the immunological markers between Pb-exposed and control groups were pooled using random-effects model. The heterogeneity was assessed using Cochran-Q test and I2 statistic. The review included forty studies reporting immunological markers in Pb-exposed and unexposed control groups. The occupational Pb-exposed group exhibited significantly higher BLL, impaired immunological markers, characterized by a marginal lowering in lymphocyte count, lymphocyte subsets (CD3+, CD4+, CD4+/CD8+ ratio), IFN-γ and IgG levels, while CD8+, IgM, IgA, IgE, and cytokines (IL-4, IL-6, IL-10, and TNF-α) exhibited a trend of higher values in comparison to the control group. Further, inflammatory marker viz., total leukocyte count was significantly higher among Pb-exposed. The included studies exhibited high levels of heterogeneity. In conclusion, Occupational Pb exposure alters the immunological markers such as the circulating cytokines and leukocyte counts. However, high-quality, multicentered studies are required to strengthen present observations and further understand the Pb's role on the immune system. Prospero Registration ID: CRD42021228252.

Melatonin Protects Tobacco Suspension Cells against Pb-Induced Mitochondrial Dysfunction.

Recent studies have shown that melatonin is an important molecule in plant physiology. It seems that the most important is that melatonin effectively eliminates oxidative stress (direct and indirect antioxidant) and switches on different defence strategies (preventive and interventive actions) during environmental stresses. In the presented report, exogenous melatonin potential to protect Nicotiana tabacum L. line Bright Yellow 2 (BY-2) exposed to lead against death was examined. Analyses of cell proliferation and viability, the level of intracellular calcium, changes in mitochondrial membrane potential (ΔΨm) as well as possible translocation of cytochrome c from mitochondria to cytosol and subsequent caspase-like proteolytic activity were conducted. Our results indicate that pretreatment BY-2 with melatonin protected tobacco cells against mitochondrial dysfunction and caspase-like activation caused by lead. The findings suggest the possible role of this indoleamine in the molecular mechanism of mitochondria, safeguarding against potential collapse and cytochrome c release. Thus, it seems that applied melatonin acted as an effective factor, promoting survival and increasing plant tolerance to lead.

Antioxidant status in relation to heavy metals induced oxidative stress in patients with polycystic ovarian syndrome (PCOS).

Polycystic ovary syndrome (PCOS) is a global health concern for women of reproductive age, as 6.5% of women worldwide are affected by this syndrome. PCOS is marked by hyperandrogenism, anovulation, menstrual abnormalities, and polycystic ovaries. Metals such as arsenic, cadmium, lead and mercury are considered to be systemic toxicants/human carcinogens and seem to have devastating effects on humans, even at minimal exposures. One of the probable aetiological factors for PCOS has been identified as oxidative stress. In view of the probable associations among oxidative stress, metal toxicity and PCOS, the present study examined the role of heavy metals in the generation of oxidative stress among females. This prospective study included 106 women (56 women diagnosed with PCOS and 50 women who were not diagnosed with PCOS as control women). There were no significant differences in the sociodemographic characteristics between the two groups except for the irregularity of menses and the presence of acne. The serum As, Cd, Pb, and Hg levels increased and the serum glutathione (GSH) and superoxide dismutase (SOD) levels diminished significantly in the PCOS group compared to the control group at P < 0.001. The SOD levels were negatively correlated with the As and Pb levels at P < 0.05. Additionally, the PCOS group exhibited a strong negative correlation between the GSH and As levels (P < 0.01), GSH and Pb levels (P < 0.05) and GSH and Hg levels (P < 0.01). Furthermore, the As levels were positively correlated with increased levels of Cd, Pb and Hg among PCOS women. Significant positive correlations were observed between Pb and Cd and between Cd and Hg at P < 0.001. The outcome of the study provides clear insight into the role of metal-induced oxidative stress, which plays a vital role in the pathophysiology underlying PCOS and suggests the use of these markers as prognostic tools to reduce the consequences of high-risk exposure to these metals among females.

Multibiomarker approach to assess the magnitude of occupational exposure and effects induced by a mixture of metals.

Metals and metalloids including lead (Pb), arsenic (As) and manganese (Mn) can occur as mixtures in occupational contexts, such as mines. These chemicals are all known to be neurotoxic and provoke changes in heme metabolism also known to induce neurotoxicity. The objective of this work was to propose a multi-biomarker (BM) methodology to screen subjects exposed to the mixture of Pb, As and Mn and assess the severity of their exposure/effects, in an individual basis. The urinary levels of the metals, dela-aminolevulinic acid (ALA) and porphyrins were determined in Portuguese miners and in a control group. The combination of Pb and As urinary levels had the highest capability to identify subjects occupationally exposed to this mixture in mines, as evaluated through Receiver Operating Characteristic (ROC) (A = 98.2%; p < 0.05), allowing that 94.2% of 86 studied subjects were properly identified and the generation of an equation indicating the odd of a subject be considered as exposed to the metal mixture. The combination of urinary ALA and porphyrins revealed to be best one to be applied in the assessment of subjects with high, intermediate, and low magnitudes of exposure/effects, with 95.7% of 46 miners classified correctly according to their severity sub-group and allowing to generate equations, which can be applied in new subjects. The proposed methodology showed a satisfactory performance, evaluating in an integrated manner the magnitude of exposure/effects of the exposed workers, may contributing to improve the control of their health.

Interaction of Smoking and Lead Exposure among Carriers of Genetic Variants Associated with a Higher Level of Oxidative Stress Indicators.

Smoking and lead (Pb) exposure increased oxidative stress in human body, and people with some gene variants may be susceptible to Pb and smoking via oxidative stress. The aim of this study is to evaluate oxidative stress by measuring thiobarbituric acid reactive substances (TBARS) and the relationship of lipid peroxidation markers in Pb workers with different gene polymorphisms (rs4673 and rs1050450) in both smokers and nonsmokers. Blood samples were collected from 267 Pb workers who received their annual health examination in the Kaohsiung Medical University Hospital. Glutathione peroxidase 1 (GPx-1) rs1050450 and cytochrome B-245 Alpha Chain (CYBA) rs4673 single-nucleotide polymorphisms (SNP) were analyzed by specific primer-probes using Real-Time PCR methods. The interaction between blood Pb and smoking increased serum levels of TBARS and the ratio of oxidative low-density lipoprotein and low-density lipoprotein (oxLDL/LDL). Analysis of workers with rs1050450 SNPs showed higher blood Pb levels in the workers with CC genotype than those with CT genotype. Smokers had significantly higher blood Pb, alanine transaminase (ALT), TBARS, and OxLDL levels than nonsmokers. TBARS increased 0.009 nmol/mL when blood Pb increased one µg/dL in smokers compared to nonsmokers. The ratio of OxLDL/LDL increased 0.223 when blood Pb increased one µg/dL in smokers compared to nonsmokers. TBARS levels and the ratio of OxLDL/LDL were positively correlated and interacted between blood Pb and smoking after the adjustment of confounders, suggesting that smoking cessation is an important issue in the Pb-exposed working environment.

Global and gene-specific promoter methylation, and micronuclei induction in lead-exposed workers: A cross-sectional study.

Perturbation of epigenetic regulation is a well-established mechanism for cancer but its role for lead (Pb)-associated toxicity has not been adequately investigated. We aimed to investigate whether occupational Pb exposure is associated with micronuclei (MN) frequency and to further explored the mediating roles of epigenetic gene regulation. All the Pb-exposed workers recruited from a Chinese acid battery factory, blood lead levels (BLLs) and MN frequency in lymphocytes were measured. In addition, methylation levels of seven genes (Line-1, RASSF1A, RUNX3, p16, CYP26C1, hMLH1, p15) were examined among 230 workers. Robust Poisson regression model was used to investigate the association between BLLs and MN frequency. Mediation analysis was used to explore the mediating role of specific DNA methylation. Among total 677 participants, 71% were male, median BLLs was 229.1 µg/L (P25  = 155.5, P75  = 319.3; ranged from 8.9 to 647.7 µg/L), mean MN frequency was 2.5‰ (SD = 1.8‰; ranged from 0 to 9‰). Results from base model, adjusted for age, sex, and body mass index, showed that MN frequency would increase 1.38 (95%confidential interval: 1.34, 1.43) per 100 µg/L increment in BLLs. Using categorized exposure variable analyses, a BLLs dose-response increase in MN frequency was observed: 2.74 (2.13, 3.51), 3.43 (2.73, 4.32), 4.41 (3.89, 5.01) to 6.86 (6.02, 7.81). Mediation analysis indicated that Line-1 methylation significantly mediated 3.6% of the association of BLLs with MN frequency. Occupational Pb exposure induces MN frequency in a dose-response relationship. Part of this association was mediated by Line-1 promotor methylation.

Lactobacillus fermentum CQPC08 protects rats from lead-induced oxidative damage by regulating the Keap1/Nrf2/ARE pathway.

In this experiment, Lactobacillus fermentum CQPC08 (LF-CQPC08) isolated from traditionally fermented pickles was used to study its mitigation effect on lead acetate-induced oxidative stress and lead ion adsorption capacity in rats. In vitro experiments showed that the survival rate in artificial gastric juice and the growth efficiency in artificial bile salt of LF-CQPC08 was 93.6% ± 2.2% and 77.2% ± 0.8%, and the surface hydrophobicity rate was 45.5% ± 0.3%. The scavenging rates of hydroxyl radical, superoxide anion, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) were 47.8% ± 0.9%, 63.9% ± 1.2%, and 83.6% ± 1.5%, respectively, and the reduction power was 107.3 ± 2.8 µmol L-1. LF-CQPC08 could not only adsorb 76.9% ± 1.0% lead ions in aqueous solution but also reduce the lead content in serum, liver, kidneys, and brain tissue of Sprague-Dawley (SD) rats, as well as maintain the cell structure and tissue state of the liver and kidneys. In addition, by examining the indicators of inflammation and oxidation in the serum, liver, and kidneys of SD rats, we found that LF-CQPC08 can reduce the proinflammatory factors interleukin (IL)-1 beta (1ß), IL-6, tumor necrosis factor alpha, and interferon gamma in the body, increase the level of anti-inflammatory factor IL-10, enhance the activity of antioxidant enzymes such as superoxide dismutase and catalase and glutathione levels in serum and organ tissues, and reduce the production of reactive oxygen species and accumulation of lipid peroxide malondialdehyde. LF-CQPC08 can also activate the Keap1/Nrf2/ARE signaling pathway to promote high-level expression of the downstream antioxidants heme oxygenase 1 (HO-1), NAD(P)H : quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase (γ-GCS). As food-grade lactic acid bacteria, LF-CQPC08 has great potential and research value in removing heavy metals from food and alleviating the toxicity of heavy metals in the future.

Changing epidemiology of calcific aortic valve disease: 30-year trends of incidence, prevalence, and deaths across 204 countries and territories.

Calcific aortic valve disease (CAVD) is associated with increased morbidity and mortality. We aimed to elucidate the 30-year epidemiology of CAVD globally. Global CAVD incidence, prevalence, and deaths increased 3.51-, 4.43-, and 1.38-fold from 1990 to 2019, respectively, without any decreasing trends, even after age standardization. In 2019, Slovenia had the highest age-standardized rate (ASR) of CAVD incidence (62.21/100,000 persons) and prevalence (1,080.06/100,000) whereas Cyprus had the highest ASR of deaths (8.20/100,000). Population aging was an important contributor to incidence. Compared with women, more men had CAVD and men had earlier peaks in disease prevalence. High systolic blood pressure, diet high in sodium, and lead exposure were the main risk factors for deaths owing to CAVD. The estimated annual percentage change, a measure to estimate the variation of ASR, was significantly associated with the ASR and sociodemographic index (SDI) in 2019 for incidence and prevalence across all 204 countries and territories (all p<0.0001). With increased lifespan and risk factors, the overall burden of CAVD is high and remains on the rise, with differences by sex, age, and SDI level. Our findings serve to sound the alarm for organizations, institutions, and resources whose primary purpose is to improve human health.