OBJECTIVEThe relationship between polymorphisms of ALAD and VDR genes and individual susceptibility of lead poisoning was investigated in children highly-exposed to lead.

METHODFour hundred and sixty-nine children were recruited into this study and the blood lead, ZPP, hemoglobin as well as three physical developmental indexes (head circumference, height and weight) were measured. VDR and ALAD gene polymorphisms were analyzed by the methods of PCR-RFLP.

RESULTSThe subjects with ALAD2 allele had higher ZPP level (10.12 micro mol/L vs 12.87 micro mol/L) (P = 0.017). The subjects with B allele has larger head circumference than only with b allele (51.19 cm vs 50.75 cm) (P = 0.028).

CONCLUSIONSIt was suggested that the ALAD gene polymorphism modified the relationship between blood lead and ZPP and the VDR gene variants influenced the skull development in children living under lead-polluted environment. The polymorphism of ALAD and VDR genes might serve as the molecular inherited factors modifying the susceptibility of lead poisoning.

Alleles ; Body Height ; drug effects ; genetics ; Body Weight ; drug effects ; genetics ; Child ; China ; epidemiology ; Environmental Pollution ; adverse effects ; Female ; Gene Frequency ; Genotype ; Humans ; Lead ; adverse effects ; blood ; Lead Poisoning ; epidemiology ; etiology ; genetics ; Male ; Polymorphism, Genetic ; Porphobilinogen Synthase ; genetics ; Receptors, Calcitriol ; genetics

OBJECTIVEIn order to minimize lead pollution and to protect the identified individuals with high blood lead level from lead contamination, an epidemiological study was carried on children living around the village and township-owned lead industries in Tianying town.

METHODSEnvironmental monitoring: lead levels in air, soil, drinking water and crops were measured. Biological monitoring: 959 children aged 5 - 12 years were selected from villages where the lead smelters located near the residential areas and the battery disassembling was done in some families. The control children (207 pupils) were from other villages without lead exposure. Blood lead, ZnPP and teeth lead were determined. Height, weight and head circle of children and IQ scores were measured.

RESULTSThe environment was seriously polluted. The average lead concentrations in air and soils were 8.5 times and 10 times of the MACs (national health standard) respectively. Eighty-five per cent the air samples with lead concentrations higher than the national health standard. Local crops and wheat at farmers' home were also contaminated by lead dust, with. Lead content being 24 times higher than the standard. The mean blood lead and ZnPP levels of children lived in the polluted areas were 496 microgram/L and 9.41 microgram/g Hb respectively. The lead exposure caused adverse effects on children's IQ and physical development.

CONCLUSIONIt is necessary to remove and reduce currently active sources of lead pollution in the community and to increase public awareness of potential health effects of lead exposure.

Air Pollutants ; analysis ; Child ; Child Development ; drug effects ; Child, Preschool ; China ; Crops, Agricultural ; chemistry ; Environmental Monitoring ; methods ; Environmental Pollution ; adverse effects ; analysis ; Female ; Health Status ; Humans ; Industrial Waste ; adverse effects ; analysis ; Lead ; adverse effects ; blood ; Male ; Soil Pollutants ; analysis ; Suburban Health ; standards ; Urban Health ; standards

Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor-kappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.
Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Bortezomib ; pharmacology ; therapeutic use ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; drug effects ; Drug Screening Assays, Antitumor ; Humans ; Multiple Myeloma ; drug therapy ; metabolism ; pathology ; NF-kappa B ; metabolism ; Signal Transduction ; drug effects ; Structure-Activity Relationship ; Ubiquitin-Protein Ligases ; genetics ; metabolism