Toxic trace elements at gastrointestinal level

Many trace elements are considered essential [iron (Fe), zinc (Zn), copper (Cu)], whereas others may be harmful [lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As)], depending on their concentration and chemical form. In most cases, the diet is the main pathway by which they enter our organism. The presence of toxic trace elements in food has been known for a long time, and many of the food matrices that carry them have been identified. This has led to the appearance of legislation and recommendations concerning consumption. Given that the main route of exposure is oral, passage through the gastrointestinal tract plays a fundamental role in their entry into the organism, where they exert their toxic effect. Although the digestive system can be considered to be of crucial importance in their toxicity, in most cases we do not know the events that occur during the passage of these elements through the gastrointestinal tract and of ascertaining whether they may have some kind of toxic effect on it. The aim of this review is to summarize available information on this subject, concentrating on the toxic trace elements that are of greatest interest for organizations concerned with food safety and health: Pb, Cd, Hg and As.     

The influence of humic acid on the toxicity of nano‐ZnO and Zn2+ to the Anabaena sp.

This study explored the effects of humic acid (HA) on the toxicity of ZnO nanoparticles (nano‐ZnO) and Zn²⁺ to Anabaena sp. Typical chlorophyll fluorescence parameters, including effective quantum yield, photosynthetic efficiency and maximal electron transport rate, were measured by a pulse‐amplitude modulated fluorometer. Results showed that nano‐ZnO and Zn²⁺ could inhibit Anabaena sp. growth with the EC₅₀ (concentration for 50% of maximal effect) of 0.74 ± 0.01 and 0.3 ± 0.01 mg/L, respectively. In the presence of 3.0 mg/L of HA, EC₅₀ of nano‐ZnO increased to 1.15 ± 0.04 mg/L and EC₅₀ of Zn²⁺ was still 0.3 ± 0.01 mg/L. Scanning electron microscopy observation revealed that HA prevented the adhesion of nano‐ZnO on the algae cells due to the increased electrostatic repulsion. The generation of intracellular reactive oxygen species and cellular lipid peroxidation were significantly limited by HA. Nano‐ZnO had more damage to the cell membrane than Zn²⁺ did, which could be proven by the malondialdehyde content in Anabaena sp. cells. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 895–903, 2015.     

Volatile organic compounds from fungi isolated after hurricane katrina induce developmental defects and apoptosis in a Drosophila melanogaster model

In previous work, our laboratory developed a Drosophila model for studying the adverse effects of fungal volatile organic compounds (VOCs) emitted by growing cultures of molds. In this report, we have extended these studies and compared the toxic effects of fungal VOCs emitted from living cultures of four molds isolated after Hurricane Katrina from a flooded home in New Orleans. Strains of Aspergillus, Mucor, Penicillium, and Trichoderma were grown with wild‐type larvae and the toxic effects of volatile products on the developmental stages of Drosophila larvae were evaluated. Furthermore, heterozygous mutants of Drosophila carrying the apoptotic genes, reaper and dronc, were used to assess the role of apoptosis in fungal VOCs mediated toxicity. Third‐instar larvae of Drosophila carrying these apoptotic genes were exposed to fungal VOCs emitted from growing mold cultures for 10 days. The larval strains carrying apoptopic genes survived longer than the control wild type larvae; moreover, of those that survived, heterozygous reaper and dronc strains progressed to pupae and adult phases more rapidly, suggesting that fungal VOCs may induce apoptotic changes in flies. These data lend support to the use of Drosophila as an inexpensive and genetically versatile toxicological model to investigate the mechanistic basis for some of the human illnesses/symptoms associated with exposure to mold‐contaminated indoor air, especially after hurricanes. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 614–620, 2015.     

CD8+ T cells undergo activation and programmed death-1 repression in the liver of aged Ae2a,b?/? mice favoring autoimmune cholangitis

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of unknown etiopathogenesis showing progressive autoimmune-mediated cholangitis. In PBC patients, the liver and lymphocytes exhibit diminished expression of AE2/SLC4A2, a Cl⁻/HCO₃⁻ anion exchanger involved in biliary bicarbonate secretion and intracellular pH regulation. Decreased AE2 expression may be pathogenic as Ae2_a,b^−/− mice reproduce hepatobiliary and immunological features resembling PBC. To understand the role of AE2 deficiency for autoimmunity predisposition we focused on the phenotypic changes of T cells that occur over the life-span of Ae2_a,b^−/− mice. At early ages (1-9 months), knockout mice had reduced numbers of intrahepatic T cells, which exhibited increased activation, programmed-cell-death (PD)-1 expression, and apoptosis. Moreover, young knockouts had upregulated PD-1 ligand (PD-L1) on bile-duct cells, and administration of neutralizing anti-PD-L1 antibodies prevented their intrahepatic T-cell deletion. Older (≥10 months) knockouts, however, showed intrahepatic accumulation of cytotoxic CD8⁺ T cells with downregulated PD-1 and diminished apoptosis. In-vitro DNA demethylation with 5-aza-2′-deoxycytidine partially reverted PD-1 downregulation of intrahepatic CD8⁺ T cells from aged knockouts. Conclusion: Early in life, AE2 deficiency results in intrahepatic T-cell activation and PD-1/PD-L1 mediated deletion. With aging, intrahepatic CD8⁺ T cells epigenetically suppress PD-1, and their consequential expansion and further activation favor autoimmune cholangitis.     

An amino acid substitution in the putative second extracellular loop of RBC band 3 accounts for the Froese blood group polymorphism

BACKGROUND: The low incidence RBC antigen Fr(a) has been excluded from 17 of the 25 established blood group systems. Previous genetic analysis assigned the gene controlling Fr(a) expression to the same chromosomal region as the solute carrier family 4, anion exchanger member 1 gene (SLC4A1). Because SLC4A1 encodes RBC band 3 and controls the expression of Diego blood group system antigens, the possible relationship of Fr(a) to the Diego blood group system was investigated by molecular analysis of SLC4A1. STUDY DESIGN AND METHODS: Blood samples were obtained from the members of two unrelated Mennonite kindreds segregating for Fr(a). DNA was extracted, amplified by PCR using intronic primer sets flanking exons 11-20 of SLC4A1, and screened by single-strand conformation polymorphism (SSCP) analysis. Those exons displaying SSCPs were subjected to DNA sequence analysis. RESULTS: An exon 13 SSCP mobility shift was observed in the DNA from all Fr(a+) persons that was not seen in the DNA from Fr(a-) family members or control subjects. Linkage between the exon 13 SSCP and FR:(a) was established, with peak lods = 3.62 at theta = 0.00 for combined paternal and maternal meioses. DNA sequencing revealed a GAG --> AAG mutation that underlies a Glu480Lys substitution in RBC band 3. CONCLUSIONS: A point mutation in exon 13 of SLC4A1 accounting for a Glu480Lys substitution in band 3 controls Fr(a) expression. On the basis of these our results, the International Society of Blood Transfusion Working Party on Terminology for Red Cell Surface Antigens has assigned Fr(a) to the Diego blood group system, with the designation DI20.     

不同时相应用高张盐对失血性休克犬复苏效果的影响

目的比较不同时相应用高张盐对失血性休克犬复苏效果的影响.方法采用修订的Wiggers法复制犬失血性休克模型后,将实验动物随机分为两组,分别于休克后10分钟(组1)、70分钟(组2)给予6 ml/kg 7.5%NaCl右旋糖酐溶液(HSD)静推,5分钟内输完.分别在基础期、休克期及复苏后测定氧运输参数、BD(碱缺失)及乳酸的变化.结果应用高张盐复苏后,组1犬氧耗量(VO2)、氧输送量(DO2)、氧摄取率(O2ER)、BD及乳酸等值均较组2改善明显(P＜0.01或0.05).结论早期应用高张盐,可通过有效改善全身有氧代谢,以达到改善休克的目的.用液越早,疗效越好,维持时间越长.     

Inhibition of dentin matrix‐bound cysteine cathepsins by potassium fluoride

Matrix metalloproteinases (MMPs) and cysteine cathepsins (CCs) can break down unprotected type I collagen fibrils in dentin matrix. This study investigated the use of potassium fluoride (KF) as a potential inhibitor of MMPs and CCs in dentin. Demineralized dentin beams were divided into groups (n = 10 in each group) and incubated in artificial saliva (AS, control), either alone or with one of seven concentrations of KF (6–238 mM fluoride) for 1, 7, and 21 d. After 21 d, all groups were further aged in AS for 6 months. Total MMP activity was screened using the colorimetric MMP assay. The activities of MMP‐2 and MMP‐9 were investigated using gelatin zymography. At the end of each incubation, changes in loss of dry mass and CC‐mediated or total dissolution of collagen peptides were measured via precision weighing, C‐terminal crosslinked telopeptide of type I collagen (CTX), and hydroxyproline (HYP) assays. The beams were examined using scanning electron microscopy. After 21 d, total MMP activities, dry mass loss, and CTX release for the groups exposed to 179 and 238 mM fluoride were significantly lower compared with the control group. After 6 months, all groups showed similar total MMP activity, dry mass loss, and HYP release, and CTX levels were significantly lower when the fluoride concentration was ≥24 mM. Calcium fluoride (CaF₂)‐like precipitates were observed over the beams. In summary, KF significantly inhibited the catalytic activity of dentin matrix‐bound CCs but did not seem to be effective for MMP‐mediated activity.     

检测乙酰胆碱酯酶的双光子荧光探针的设计、合成及生物学评价

目的 设计并合成用于检测乙酰胆碱酯酶（acetylcholinesterase，AChE）的双光子荧光探针，并考察探针对AChE的成像检测性能。方法 经酯化、取代等多步有机反应合成探针，并通过¹H-NMR、¹³C-NMR和ESI-MS确认结构。考察探针与AChE发生响应后的荧光信噪比、灵敏度、特异性、酶动力学和双关子吸收截面积数值等指标；研究探针可否用于AChE抑制剂的体外筛选；利用单-双光子成像试验考察探针在细胞和组织水平上对AChE活力变化的检测能力。结果 通过¹H-NMR、¹³C-NMR和ESI-MS确认了产物的结构。体外试验表明探针与AChE响应后的荧光信噪比为15倍，检测限达到0.23 U·mL^–1，并具有很强的特异性和优良的酶亲合能力，在波长820 nm有最优的双光子吸收；探针可用于AChE抑制剂的体外筛选；探针通过单-双光子成像技术可对细胞和组织水平上的AChE活力变化进行成像检测，并且组织成像检测深度可达110 μm。结论 本研究成功开发了可用于AChE检测的双光子荧光探针，有潜力成为可用于活体中检测AChE活力的双光子成像试剂。     

An evaluation of the RNase H inhibitory effects of Vietnamese medicinal plant extracts and natural compounds

Context: Acquired immune deficiency syndrome (AIDS) is a severe pandemic disease especially prevalent in poor and developing countries. Thus, developing specific, potent antiviral drugs that restrain infection by human immunodeficiency virus type 1 (HIV-1), a major cause of AIDS, remains an urgent priority.

Objective: This study evaluated 32 extracts and 23 compounds from Vietnamese medicinal plants for their inhibitory effects against HIV-1 ribonuclease H (RNase H) and their role in reversing the cytopathic effects of HIV.

Materials and methods: The plants were air-dried and extracted in different solvent systems to produce plant extracts. Natural compounds were obtained as previously published. Samples were screened for RNase H inhibition followed by a cytopathic assay. Data were analyzed using the Microsoft Excel.

Results and discussion: At 50?μg/mL, 11 plant extracts and five compounds inhibited over 90% of RNase H enzymatic activity. Methanol extracts from Phyllanthus reticulatus and Aglaia aphanamixis leaves inhibited RNase H activity by 99 and 98%, respectively, whereas four extracts showed modest protection against the cytopathic effects of HIV.

Conclusion: The screening results demonstrated that the butanol (BuOH) extract of Celastrus orbiculata leaves, methanol (MeOH) extracts of Glycosmis stenocarpa stems, Eurya ciliata leaves, and especially P. reticulatus leaves showed potential RNase H inhibition and protection against the viral cytopathic effects of HIV-1. Further chemical investigations should be carried out to find the active components of these extracts and compounds as potential anti-HIV drug candidates.     

Characterization of indoor air contaminants in a randomly selected set of commercial nail salons in Salt Lake County,Utah, USA

Air samples were collected in 12 randomly selected commercial nail salons in Salt Lake County, Utah. Measurements of salon physical/chemical parameters (room volume, CO₂ levels) were obtained. Volatile organic compound (VOC) concentrations were collected using summa air canisters and sorbent media tubes for an 8-h period. Multivariate analyses were used to identify relationships between salon physical/chemical characteristics and the VOCs found in the air samples. The ACGIH^® additive mixing formula was also applied to determine if there were potential overexposures to the combined airborne concentrations of chemicals monitored. Methyl methacrylate was detected in 58% of the establishments despite having been banned for use in nail products by the state of Utah. Formaldehyde was found above the NIOSH REL^® (0.016?ppm) in 58% of the establishments. Given the assortment of VOCs to which nail salon workers are potentially exposed, a combination of engineering as well as personal protective equipment is recommended.