ABSTRACT
In the natural environment, toxicant effects can be monitored by the signature mRNA expression patterns of genes that they generate in test organisms. The specificity and sensitivity of these transcriptome-based bioassays to a given toxicant can be confounded by temporal changes in biomarker mRNA expression, effects of other toxicants and hardness ions, and non-linear mRNA expression responses of genes. This study provides the foundation for the development of a transcriptomic-based bioassay for bioavailable Cd in the freshwater alga, Chlamydomonas reinhardtii. It characterizes: (1) the Cd regulation of nine genes with respect to their mRNA induction kinetics; (2) the effects of two additional metals common to freshwaters, Cu2+ and Pb2+, and (3) the relationships between metal bioaccumulation and the transcriptomic responses. Quantitative real time PCR was used to monitor mRNA levels of nine Cd-induced genes following an exposure to 0.01, 0.11 and 1.16 µM Cd2+. Several distinct mRNA expression patterns were observed with time. While the presence of Cu2+ and Pb2+ decreased Cd biouptake, mRNA levels increased for six genes, showing lack of Cd2+ specificity. Nonetheless, the transcriptomic effects of binary metal exposures rarely adhered to a simple additive model based on single metal exposures; rather most exhibited synergistic or antagonistic interactions. While none of these genes could be used as a specific Cd biomarker, the signature mRNA expression profile obtained from a select subset of Cd sensitive genes was a useful biomarker of sublethal effects.
Subject(s)
Cadmium/toxicity , Chlamydomonas reinhardtii/drug effects , Gene Expression Profiling , Water Pollutants, Chemical/toxicity , Biomarkers/metabolism , Cadmium/chemistry , Chlamydomonas reinhardtii/genetics , Chlamydomonas reinhardtii/metabolism , Copper/chemistry , Copper/metabolism , Copper/toxicity , Drug Interactions , Lead/chemistry , Lead/metabolism , Lead/toxicity , RNA, Messenger/metabolism , Transcription, Genetic/drug effects , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/metabolismABSTRACT
We evaluated retrospectively the treatment of 44 open femur fractures occurring between the lesser trochanter and the distal femoral physis in 43 children aged 16 years and younger. Fractures that involved the physis or that were a consequence of gunshot wounds were excluded. There were 25 grade I, 9 grade II, and 9 grade III fractures. The mean age at injury was 9.5 years. Ninety percent of the fractures were automobile related. More than 70% of the children had associated injuries. The average time to healing for all fractures in this study was 17 weeks. Our data indicate that there is a statistically significant increased time to heal with increasing age of the child (p = 0.04). Additionally, grade III fractures healed more slowly than grade I or II fractures (p = 0.0006). Fractures treated with external fixation took longer to unite than those treated with other methods (p = 0.05). The presence of complications increased the time to fracture union (p = 0.00001). Grade III injuries were the most difficult to manage; 50% of the fractures in this group developed osteomyelitis and 20% malunited. In contrast, none of the fractures in either the grade I or II groups developed deep infection. After aggressive debridement, grade I and grade II fractures may be stabilized with age-appropriate fixation methods. Grade III injuries should be managed with vigorous debridement and vigilance, as these injuries are prone to deep infection and malunion. The optimal method of skeletal stabilization in grade III fractures remains unresolved.
