Lead Exposure and Developmental Disabilities in Preschool-Aged Children.

CONTEXT: Lead is a preventable environmental toxin that has been previously associated with deficits in cognition, academic performance, attention, and behavior in children. Very few studies, however, have examined the relationship between exposure to lead and documented developmental disabilities. OBJECTIVE: This study examined the relative risk of lead exposure on developmental disabilities in preschool-aged children. DESIGN: A statewide lead surveillance data set containing blood lead level (BLL) was integrated with another statewide data set containing developmental disability classifications for special education placement for preschool-aged children. PARTICIPANTS: The participants were the 85 178 children (average age 2.6 years) whose records in both data sets were able to be linked. Forty-six percent of the participants had an identified developmental disability. MAIN OUTCOME MEASURE: Developmental disability classification served as the main outcome measure. RESULTS: A high BLL, defined as 5 µg/dL or more, was associated with significantly increased risk for developmental disabilities (risk ratio [RR] = 1.04; 95% CI = 1.01-1.08), particularly intellectual disability (RR = 1.58, 95% CI = 1.10-2.25) and developmental delay (DD; RR = 1.11, 95% CI = 1.06-1.17). CONCLUSIONS: The results of this study are consistent with previous research identifying an association between lead exposure and numerous intellectual and educational outcomes and demonstrate that high BLL is associated with meeting eligibility criteria for developmental disabilities in young children. Continued research, surveillance, and prevention efforts are needed to further reduce the negative impacts of lead on individuals and society. Reducing or eliminating lead exposure would improve outcomes for individual children (eg, better academic performance) and reduce the burden to society (eg, lower enrollments in special education systems).

Enantioselective supercritical fluid chromatography-tandem mass spectrometry method for simultaneous estimation of risperidone and its 9-hydroxyl metabolites in rat plasma.

AIM: Objective of the current work was to develop a 'green chemistry' compliant selective and sensitive supercritical fluid chromatography-tandem mass spectrometry method for simultaneous estimation of risperidone (RIS) and its chiral metabolites in rat plasma. Methodology & results: Agilent 1260 Infinity analytical supercritical fluid chromatography system resolved RIS and its chiral metabolites within runtime of 6 min using a gradient chromatography method. Using a simple protein precipitation sample preparation followed by mass spectrometric detection achieved a sensitivity of 0.92 nM (lower limit of quantification). With linearity over four log units (0.91-7500 nM), the method was found to be selective, accurate, precise and robust. CONCLUSION: The method was validated and was successfully applied for simultaneous estimation of RIS and 9-hydroxyrisperidone metabolites (R & S individually) after intravenous and per oral administration to rats.

Quantitative proteomics for identifying biomarkers for tuberculous meningitis.

INTRODUCTION: Tuberculous meningitis is a frequent extrapulmonary disease caused by Mycobacterium tuberculosis and is associated with high mortality rates and severe neurological sequelae. In an earlier study employing DNA microarrays, we had identified genes that were differentially expressed at the transcript level in human brain tissue from cases of tuberculous meningitis. In the current study, we used a quantitative proteomics approach to discover protein biomarkers for tuberculous meningitis. METHODS: To compare brain tissues from confirmed cased of tuberculous meningitis with uninfected brain tissue, we carried out quantitative protein expression profiling using iTRAQ labeling and LC-MS/MS analysis of SCX fractionated peptides on Agilent's accurate mass QTOF mass spectrometer. RESULTS AND CONCLUSIONS: Through this approach, we identified both known and novel differentially regulated molecules. Those described previously included signal-regulatory protein alpha (SIRPA) and protein disulfide isomerase family A, member 6 (PDIA6), which have been shown to be overexpressed at the mRNA level in tuberculous meningitis. The novel overexpressed proteins identified in our study included amphiphysin (AMPH) and neurofascin (NFASC) while ferritin light chain (FTL) was found to be downregulated in TBM. We validated amphiphysin, neurofascin and ferritin light chain using immunohistochemistry which confirmed their differential expression in tuberculous meningitis. Overall, our data provides insights into the host response in tuberculous meningitis at the molecular level in addition to providing candidate diagnostic biomarkers for tuberculous meningitis.

Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery.

Esophageal squamous cell carcinoma (ESCC) is among the top ten most frequent malignancies worldwide. In this study, our objective was to identify potential biomarkers for ESCC through a quantitative proteomic approach using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. We compared the protein expression profiles of ESCC tumor tissues with the corresponding adjacent normal tissue from ten patients. LC-MS/MS analysis of strong cation exchange chromatography fractions was carried out on an Accurate Mass QTOF mass spectrometer, which led to the identification of 687 proteins. In all, 257 proteins were identified as differentially expressed in ESCC as compared to normal. We found several previously known protein biomarkers to be upregulated in ESCC including thrombospondin 1 (THBS1), periostin 1 (POSTN) and heat shock 70 kDa protein 9 (HSPA9) confirming the validity of our approach. In addition, several novel proteins that had not been reported previously were identified in our screen. These novel biomarker candidates included prosaposin (PSAP), plectin 1 (PLEC1) and protein disulfide isomerase A 4 (PDIA4) that were further validated to be overexpressed by immunohistochemical labeling using tissue microarrays. The success of our study shows that this mass spectrometric strategy can be applied to cancers in general to develop a panel of candidate biomarkers, which can then be validated by other techniques.