Prolonged feeding with guanidinoacetate,a methyl group consumer,exacerbates ethanol-induced liver injury

AIMTo investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage.METHODSAdult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted.RESULTSContrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol.CONCLUSIONTo conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.     

Proportionate Cancer Mortality in Methyl Methacrylate-Exposed Orthopedic Surgeons Compared to General Surgeons

Methyl methacrylate (MMA), a volatile liquid used to make dentures, hearing aids, joint prostheses, and medical adhesives, has been associated with colorectal carcinomas in acrylic sheet manufacturing workers. A case–control proportionate cancer mortality investigation was conducted to determine cancer death differences in orthopedic surgeons performing total joint replacements (TJRs) (MMA-exposed cases) and general surgeons not performing TJRs (unexposed controls). The American Colleges of Orthopedic Surgeons and General Surgeons provided complete demographic information on 468 male orthopedic surgeons and 1,890 male general surgeons who died during 1991–2001. Decedent data was submitted to the National Death Index for matching with underlying causes of death on state death certificates. Proportionate differences in ages at death, deaths from cancer, and deaths from site-specific cancers were analyzed for statistically significant differences by unpaired, two-tailed t tests for continuous variables and by both proportionate cancer mortality ratios and Yates-corrected chi squares for categorical variables. Orthopedic surgeons died of cancer more often (χ² = 7.699, P = 0.006) and at younger (t = 5.53, P < 0.001) ages (mean = 69.4 years) than general surgeons (mean = 79.2 years). For site-specific cancers, orthopedic surgeons died of esophageal cancer (χ² = 4.372, P = 0.037) and myeloproliferative malignancies (χ² = 4.369, P = 0.037) more often than general surgeons. Orthopedic surgeons are chronically exposed to MMA and are proportionately more likely to die from cancer, especially esophageal and myeloproliferative cancers, than general surgeons. MMA-exposed healthcare workers may be at increased risks of untimely deaths from site-specific malignancies.     

甲基泼尼松龙冲击联合氮芥治疗狼疮性肾炎的观察及护理

目的：观察甲基泼尼松龙（MP）冲击联合氮芥治疗狼疮性肾炎过程中的副作用,探讨有效的护理方式。方法：对收治的103例狼疮性肾炎（LN）,进行甲基泼尼松龙冲击联合氮芥治疗,在加强心理护理,预防和控制感染及针对药物不良反应的特殊护理的基础上,观察该疗法的副作用。结果：氮芥的消化系统反应79例（76.70%）,脱发1例（0.97%）,骨髓抑制31例（30.10%）,出血性膀胱炎0例,停经1例（0.97%）,全身感染4例（3.88%）。结论：严格掌握氮芥的适应证,积极做好并发症的预防预案,正确使用氮芥的注射方法,认真观察、积极处置其副作用,进行合理有效的护理,甲基泼尼松龙冲击联合氮芥治疗狼疮性肾炎是安全、有效的。     

纳米羟基磷灰石人工心脏机械瓣膜对细胞毒性评价

目的用四甲基偶氮唑蓝（MTT）法检测羟基磷灰石（HA）对人脐带内皮细胞可能存在的细胞毒性。方法用MTT比色方法评价材料的细胞毒性。设常温漫提液组和高温浸提液组。两组均设置各自对应的阳性和阴性对照组。将加入浸提液和材料并培养72h后的各组样品分别在倒置相差显微镜下观察细胞在浸提液中及在材料边缘的形态变化及生长状况,以细胞毒性实验来评价生物材料生物相容性。参照国际标准化组织（ISO）制定的细胞毒性实验的标准,即ISO10993—5：1992（医疗器械生物学评价细胞毒性实验体外法》之评价标准和要求。结果材料浸提液与细胞共培养组24h时观察常温浸提液、高温浸提液及阴性对照组的HUVEC细胞形态、数量,各实验组与阴性对照组差异无统计学意义。结论HA材料对人脐带内皮细胞生长抑制反应级别为1级或0级,无明显毒性作用,有良好的细胞相容性。     

Polychlorinated biphenyls, lead, and mercury are associated with liver disease in American adults: NHANES 2003-2004

Background

High-level occupational exposures to some industrial chemicals have been associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, the potential role of low-level environmental pollution on liver disease in the general population has not been evaluated.

Objective

We determined whether environmental pollutants are associated with an elevation in serum alanine aminotransferase (ALT) activity and suspected NAFLD in U.S. adults.

Methods

This cross-sectional cohort study evaluated adult participants without viral hepatitis, hemochromatosis, or alcoholic liver disease from the National Health and Nutrition Examination Survey (NHANES) for 2003–2004. ALT elevation was defined in men as ≥ 37 IU/L (age18–20 years) and ≥ 48 IU/L (age ≥ 21 years) and in women as ≥ 30 IU/L (age 18–20 years) and ≥ 31 IU/L (age ≥ 21 years). Adjusted odds ratios (ORs) for ALT elevation were determined across exposure quartiles for 17 pollutant subclasses comprising 111 individual pollutants present with at least a 60% detection rate. Adjustments were made for age, race/ethnicity, sex, body mass index, poverty income ratio, and insulin resistance. Individual pollutants from subclasses associated with ALT elevation were subsequently analyzed.

Results

The overall prevalence of ALT elevation was 10.6%. Heavy metals and polychlorinated biphenyls (PCBs) were associated with dose-dependent increased adjusted ORs for ALT elevation. Within these subclasses, increasing whole-blood levels of lead and mercury and increasing lipid-adjusted serum levels of 20 PCBs were individually associated with ALT elevation.

Conclusions

PCB, lead, and mercury exposures were associated with unexplained ALT elevation, a proxy marker of NAFLD, in NHANES 2003–2004 adult participants.     

Blood Mercury Concentrations in CHARGE Study Children with and without Autism

Background

Some authors have reported higher blood mercury (Hg) levels in persons with autism, relative to unaffected controls.

Objectives

We compared blood total Hg concentrations in children with autism or autism spectrum disorder (AU/ASD) and typically developing (TD) controls in population-based samples, and determined the role of fish consumption in differences observed.

Methods

The Childhood Autism Risk from Genetics and the Environment (CHARGE) Study enrolled children 2–5 years of age. After diagnostic evaluation, we analyzed three groups: AU/ASD, non-AU/ASD with developmental delay (DD), and population-based TD controls. Mothers were interviewed about household, medical, and dietary exposures. Blood Hg was measured by inductively coupled plasma mass spectrometry. Multiple linear regression analysis was conducted (n = 452) to predict blood Hg from diagnostic status controlling for Hg sources.

Results

Fish consumption strongly predicted total Hg concentration. AU/ASD children ate less fish. After adjustment for fish and other Hg sources, blood Hg levels in AU/ASD children were similar to those of TD children (p = 0.75); this was also true among non-fish eaters (p = 0.73). The direct effect of AU/ASD diagnosis on blood Hg not through the indirect pathway of altered fish consumption was a 12% reduction. DD children had lower blood Hg concentrations in all analyses. Dental amalgams in children with gum-chewing or teeth-grinding habits predicted higher levels.

Conclusions

After accounting for dietary and other differences in Hg exposures, total Hg in blood was neither elevated nor reduced in CHARGE Study preschoolers with AU/ASD compared with unaffected controls, and resembled those of nationally representative samples.     

Atmospheric mercury in Changbai Mountain area, northeastern China II. The distribution of reactive gaseous mercury and particulate mercury and mercury deposition fluxes

Reactive gaseous mercury (RGM) and particulate mercury (Hgp) concentrations in ambient air from a remote site at Changbai Mountain area in northeastern China were intermittently monitored from August 2005 to July 2006 totaling 93 days representing fall, winter-spring and summer season, respectively. Rainwater and snow samples were collected during a whole year, and total mercury (THg) in rain samples were used to calculate wet depositional flux. A throughfall method and a model method were used to estimate dry depositional flux. Results showed mean concentrations of RGM and Hgp are 65 and 77 pg m⁻³. Compared to background concentrations of atmospheric mercury species in Northern Hemisphere, RGM and Hgp are significantly elevated in Changbai area. Large values for standard deviation indicated fast reactivity and a low residence time for these mercury species. Seasonal variability is also important, with lower mercury levels in summer compared to other seasons, which is attributed to scavenging by rainfall and low local mercury emissions in summer. THg concentrations ranged from 11.5 to 15.9 ng L⁻¹ in rainwater samples and 14.9-18.6 ng L⁻¹ in throughfall samples. Wet depositional flux in Changbai area is calculated to be 8.4 μg m⁻² a⁻¹, and dry deposition flux is estimated to be 16.5 μg m⁻² a⁻¹ according to a throughfall method and 20.2 μg m⁻² a⁻¹ using a model method.     

Effect of Ca on the H NMR chemical shift of the methyl signal of oversulphated chondroitin sulphate,a contaminant in heparin

The chemical shift of the methyl signal of oversulphated chondroitin sulphate (OSCS) is dependent on the type and concentration of the counterion. When OSCS is present as a contaminant in heparin sodium, the reported methyl ¹H chemical shift is 2.15 ± 0.02 ppm. In this report, a value of 2.18 ± 0.01 ppm is reported for the OSCS in the presence of Ca²⁺. The chemical shift of the methyl signal of pure OSCS varies linearly from 2.13 ppm to 2.18 ppm with increasing amounts of Ca²⁺, until reaching the saturation point of four Ca²⁺ ions per OSCS disaccharide unit, which contains four sulphate groups (a 1:1 ratio between sulphate groups and Ca²⁺). This Ca²⁺ effect can be used for OSCS identification as well as to facilitate quantification.     

Mallory-Denk body pathogenesis revisited

This editorial reviews the recent evidence showing that Mallory-Denk bodies (MDBs) form in hepatocytes as the result of a drug-induced shift from the 26s proteasome formation to the immunoproteasome formation. The shift is the result of changes in gene expression induced in promoter activation, which is induced by the IFNγ and TNFα signaling pathway. This activates TLR 2 and 4 receptors. The TLR signaling pathway stimulates both the induction of a cytokine proinflammatory response and an up regulation of growth factors. The MDB- forming hepatocytes proliferate as a result of the increase in growth factor expression by the MDB- forming cells, which selectively proliferate in response to drug toxicity. All of these mechanisms are induced by drug toxicity, and are prevented by feeding the methyl donors SAMe and betaine, supporting the epigenetic response of MDB formation.     

Developmental neurotoxicants in e-waste: an emerging health concern

Objective

Electronic waste (e-waste) has been an emerging environmental health issue in both developed and developing countries, but its current management practice may result in unintended developmental neurotoxicity in vulnerable populations. To provide updated information about the scope of the issue, presence of known and suspected neurotoxicants, toxicologic mechanisms, and current data gaps, we conducted this literature review.

Data sources

We reviewed original articles and review papers in PubMed and Web of Science regarding e-waste toxicants and their potential developmental neurotoxicity. We also searched published reports of intergovernmental and governmental agencies and nongovernmental organizations on e-waste production and management practice.

Data extraction

We focused on the potential exposure to e-waste toxicants in vulnerable populations—that is, pregnant women and developing children—and neurodevelopmental outcomes. In addition, we summarize experimental evidence of developmental neurotoxicity and mechanisms.

Data synthesis

In developing countries where most informal and primitive e-waste recycling occurs, environmental exposure to lead, cadmium, chromium, polybrominated diphenyl ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons is prevalent at high concentrations in pregnant women and young children. Developmental neurotoxicity is a serious concern in these regions, but human studies of adverse effects and potential mechanisms are scarce. The unprecedented mixture of exposure to heavy metals and persistent organic pollutants warrants further studies and necessitates effective pollution control measures.

Conclusions

Pregnant women and young children living close to informal e-waste recycling sites are at risk of possible perturbations of fetus and child neurodevelopment.