How does formal and informal industry contribute to lead exposure? A narrative review from Vietnam, Uruguay, and Malaysia.

INTRODUCTION: Lead industries are one of the major sources of environmental pollution and can affect human through different activities, including industrial processes, metal plating, mining, battery recycling, etc. Although different studies have documented the various sources of lead exposure, studies highlighting different types of industries as sources of environmental contamination are limited. Therefore, this narrative review aims to focus mainly on lead industries as significant sources of environmental and human contamination. CONTENT: Based on the keywords searched in bibliographic databases we found 44 relevant articles that provided information on lead present in soil, water, and blood or all components among participants living near high-risk areas. We presented three case scenarios to highlight how lead industries have affected the health of citizens in Vietnam, Uruguay, and Malaysia. SUMMARY AND OUTLOOK: Factories conducting mining, e-waste processing, used lead-acid battery recycling, electronic repair, and toxic waste sites were the primary industries for lead exposure. Our study has shown lead exposure due to industrial activities in Vietnam, Uruguay, Malaysia and calls for attention to the gaps in strategic and epidemiologic efforts to understand sources of environmental exposure to lead fully. Developing strategies and guidelines to regulate industrial activities, finding alternatives to reduce lead toxicity and exposure, and empowering the public through various community awareness programs can play a crucial role in controlling exposure to lead.

Narrative review of lead poisoning in humans caused by industrial activities and measures compatible with sustainable industrial activities in Republic of Zambia.

Lead (Pb) pollution and human exposure to Pb, is an important issue for the international community to address being associated with 0.90 million deaths from long-term effects. The Republic of Zambia is a typical mineral resource-rich country, with long-standing mining and smelting activities of metals including Pb in several parts of the country. This narrative review provides a comprehensive overview of previous papers that have assessed human exposure to Pb and related health effects in Zambia. Environmental remediation methods that should be applied locally, ways to reduce Pb exposure of the population, and issues that need to be addressed by various sectors are discussed. Environmental remediation methods using locally available and affordable materials are needed to ensure both sustainable industrial activities and pollution prevention. In the Zambian mining towns, including Kabwe, various research activities have been conducted, including environmental monitoring, human biomonitoring and health impact assessments. The town of Kabwe, which was one of Zambia's largest Pb mining area in the 20th century, continues to have formal and informal Pb-related industries and is known as one of the most polluted areas in the world. For example, despite the World Health Organization asserting that "For an individual with a blood Pb concentration ≥ 5 µg/dL, appropriate action should be taken to terminate exposure", there are reports of blood Pb levels in Kabwe children exceeding 100 µg/dL. While Pb pollution is a global issue, not many places have such continuous and comprehensive research has been conducted, and there is much to be learned from the knowledge accumulated in these areas. Because the high levels of Pb accumulation in humans and the adverse health effects were clarified, we consider that it is important to combine mining activities, which are a key industry, with measures to prevent environmental pollution.

Use of formalin-fixed paraffin-embedded tumor tissue as a DNA source in molecular epidemiological studies of pediatric CNS tumors.

Formalin-fixed paraffin-embedded tissue (FFPET) samples are a potential source of DNA for molecular epidemiological studies. However, the use of FFPET samples can be restricted by the yield and quality of DNA isolated. The aim of this study was to examine whether FFPET biopsies from pediatric central nervous system tumors were a feasible alternative to archival frozen tissue when characterizing common gene polymorphisms. DNA was isolated from 50 frozen pediatric central nervous system tumor biopsies and matched FFPET samples. Real-time polymerase chain reaction (PCR) was used to quantify DNA and characterize GSTT1, GSTM1, GSTP1, and MTHFR gene polymorphisms. The use of whole-genome amplification (WGA) to increase DNA yields was also investigated. The results showed that DNA isolated from FFPET samples was more fragmented and provided smaller yields than DNA isolated from frozen samples. Attempts to increase the DNA yield from FFPET using WGA were unsuccessful. DNA from FFPET samples was successfully genotyped for the GSTP1 Ile105Val and MTHFR 677 C>T polymorphisms in 98% of samples and was 100% concordant with the results from frozen tissue. However, DNA from FFPET performed poorly in real-time PCR assays for GSTM1 and GSTT1 deletion polymorphisms. Our investigations show that DNA extracted from FFPET is substantially fragmented and not readily amplified using WGA. In addition, careful validation of PCR assays should be carried out due to the variable amplification of fragmented FFPET DNA.

TSG-6 modulates the interaction between hyaluronan and cell surface CD44.

Interactions between CD44 and hyaluronan are implicated in the primary adhesion of lymphocytes to endothelium at inflammatory locations. Here we show that preincubation of hyaluronan with full-length recombinant TSG-6 or its Link module domain (Link_TSG6) enhances or induces the binding of hyaluronan to cell surface CD44 on constitutive and inducible cell backgrounds, respectively. These effects are blocked by CD44-specific antibodies and are absent in CD44-negative cells. Enhancement of CD44-mediated interactions of lymphoid cells with hyaluronan by TSG-6 proteins was seen under conditions of flow at shear forces that occur in post-capillary venules. Increases in the number of rolling cells were observed on substrates comprising TSG-6-hyaluronan complexes as compared with a substrate containing hyaluronan alone. In ligand competition experiments, cell surface-bound TSG-6-hyaluronan complexes were more potent than hyaluronan alone in inhibiting cell adhesion to immobilized hyaluronan. Link_TSG6 mutants with impaired hyaluronan binding function had a reduced ability to modulate ligand binding by cell surface CD44. However, some mutants that exhibited close to wild-type hyaluronan binding were found to have either reduced or increased activity, suggesting that some amino acid residues outside of the hyaluronan binding site might be involved in protein self-association, potentially leading to the formation of cross-linked hyaluronan fibers. In turn, cross-linked hyaluronan could increase the binding avidity of CD44 by inducing receptor clustering. The ability of TSG-6 to modulate the interaction of hyaluronan with CD44 has important implications for CD44-mediated cell activity at sites of inflammation, where TSG-6 is expressed.

Role of the extracellular and cytoplasmic domains of CD44 in the rolling interaction of lymphoid cells with hyaluronan under physiologic flow.

CD44 can function as an adhesion receptor that mediates leukocyte rolling on hyaluronan (HA). To study the contributions of different domains of the standard isoform of CD44 to cell rolling, a CD44-negative mouse T lymphoma AKR1 was transfected with wild type (WT) or mutated cDNA constructs. A parallel flow chamber was used to study the rolling behavior of CD44 transfectants on immobilized HA. For CD44WT transfectants, the fraction of cells that rolled and the rolling velocity was inversely proportional to the amount of cell surface CD44. When the cytoplasmic domain distal to Gly(305) or sequences that serve as binding sites for cytoskeletal linker proteins, were deleted or replaced with foreign sequences, no significant changes in the rolling behavior of mutant cells, compared with the transfectant expressing CD44WT, were observed. Transfectants lacking 64 amino acids of the cytoplasmic tail distal to Cys(295) adhered to HA but showed enhanced rolling at low shear forces. When 83 amino acids from the "non-conserved" membrane-proximal region of the CD44 extracellular domain were deleted, cells adhered firmly to the HA substrate and did not roll at any fluid shear force tested. Unlike wild type cells that exhibited a nearly homogeneous distribution of CD44 on a smooth cell surface, cells expressing the non-conserved region deletion mutant accumulated CD44 in membrane protrusions. Disruption of the actin cytoskeleton with cytochalasin B precluded the formation of membrane protrusions, however, treated cells still adhered firmly to HA and did not roll. We conclude that interaction between the cytoplasmic domain of CD44 and the cytoskeleton is not required for cell rolling on immobilized ligand. The strong effect of deletion of the non-conserved region of the extracellular domain argues for a critical role of this region in CD44-dependent rolling and adhesion interactions with HA under flow.

Hyaluronan binding properties of a CD44 chimera containing the link module of TSG-6.

CD44, a cell-surface receptor for the extracellular matrix glycosaminoglycan hyaluronan, can mediate leukocyte rolling on hyaluronan substrates and has been implicated in leukocyte migration to sites of inflammation. CD44-mediated binding to hyaluronan is of low affinity, and effective cell/matrix interaction depends on multiple interactions with the multivalent ligand. We replaced the Link module of CD44 with the homologous region of TSG-6, a hyaluronan-binding protein secreted in response to inflammation whose Link module has a higher affinity for ligand. Monoclonal antibodies raised against the CD44/TSG-6 chimera recognized recombinant human TSG-6 and native mouse TSG-6 and blocked hyaluronan binding to these proteins. Cells expressing the CD44/TSG-6 molecule bound hyaluronan with higher avidity than cells expressing CD44. This resulted in changes in the hyaluronan binding properties characteristic of cells expressing CD44 such as requirements for threshold levels of receptor expression and for hyaluronan of high molecular mass. In parallel plate flow assays used to model leukocyte rolling, cells expressing CD44/TSG-6 failed to roll on hyaluronan. Instead, they stuck and remained "tethered" to the substrate under fluid flow. This result argues that the low affinity of CD44 for its ligand is important for rolling, an early phase of leukocyte extravasation from the blood.