Protein coronas on gold nanorods passivated with amphiphilic ligands affect cytotoxicity and cellular response to penicillin/streptomycin.

We probe how amphiphilic ligands (ALs) of four different types affect the formation of protein coronas on gold nanorods (NRs) and their impact on cellular response. NRs coated with cetyltrimethylammonium bromide were ligand exchanged with polyoxyethylene[10]cetyl ether, oligofectamine, and phosphatidylserine (PS). Protein coronas from equine serum (ES) were formed on these NR-ALs, and their colloidal stability, as well as cell uptake, proliferation, oxidative stress, and gene expression, were examined. We find that the protein corona that forms and its colloidal stability are affected by AL type and that the cellular response to these NR-AL-coronas (NR-AL-ES) is both ligand and corona dependent. We also find that the presence of common cell culture supplement penicillin/streptomycin can impact the colloidal stability and cellular response of NR-AL and NR-AL-ES, showing that the cell response is not necessarily inert to pen/strep when in the presence of nanoparticles. Although the protein corona is what the cells see, the underlying surface ligands evidently play an important role in shaping and defining the physical characteristics of the corona, which ultimately impacts the cellular response. Further, the results of this study suggest that the cellular behavior toward NR-AL is mediated by not only the type of AL and the protein corona it forms but also its resulting colloidal stability and interaction with cell culture supplements.

Suicidal ideation among low-income women on family assistance programs.

Low-income women face significant adversities. Many of the adversities they contend with have been associated with suicidal ideation in other groups. However little is known about low-income women's suicidal ideation and its correlates. The purpose of this study was to evaluate prevalence of and risk factors associated with suicidal ideation in a randomly drawn sample of 2,112 women ranging in age from 18 to 59 years and enrolled in family assistance programs. As in other studies of low-income women, this group had high rates of mental and physical health problems. Yet, the overall prevalence rate of suicidal ideation was not substantially higher than those found in other populations. Emotional difficulties, substance abuse/dependence, physical limitations, having been arrested, and injuries were associated with suicidal ideation. Increasing numbers of adversities were associated with increasing prevalence of suicidal ideation. Employment and pregnancy were inversely associated with suicidal ideation when controlling for adverse events. This study provided important information on prevalence and risk factors associated with suicidal ideation among low income women on family assistance programs as well as suggested areas for future work to improve the health of these women.

Gene expression and target tissue dose in the rat epidermis after brief JP-8 and JP-8 aromatic and aliphatic component exposures.

Exposures of jet propulsion fuel 8 (JP-8) to human and laboratory animal skin have resulted in skin irritation. JP-8 is a mixture of aromatic and aliphatic hydrocarbons, which in some cases have also been shown to be irritating to the skin. In an attempt to determine if aromatic or aliphatic components could mimic the JP-8-induced gene expression response, we exposed rats to JP-8, undecane (UND), tetradecane (TET), trimethylbenzene (TMB), and dimethylnaphthalene (DMN) for 1 h and examined the epidermis to characterize the gene expression response. We also measured the concentrations of the JP-8 components in the epidermis with gas chromatography/mass spectrometry after 1-h exposures to JP-8 and pure components to determine if differences in potency could be identified. Changes in gene expression, compared to sham treatment, were studied with microarray techniques and analyzed for changes in gene ontology categories. UND and TMB exposures caused the greatest number of changes in transcript levels compared to DMN and TET. When only the specific functional and signaling pathways that were changed by JP-8 were considered, these pathways were nearly all activated by the components, but to different extents. After pure component exposures, the epidermal concentrations of the components showed no significant differences, although the differences in magnitude of either total or pathway-specific gene expression differed by a factor of 10-fold. We conclude that no single component that we studied mimicked the gene expression resulting from the JP-8 exposure but that UND had the most similar responses. These data suggest that there are differences in potency between the four components studied.

Effects of brief cutaneous JP-8 jet fuel exposures on time course of gene expression in the epidermis.

The jet fuel jet propulsion fuel 8 (JP-8) has been shown to cause an inflammatory response in the skin, which is characterized histologically by erythema, edema, and hyperplasia. Studies in laboratory animal skin and cultured keratinocytes have identified a variety of changes in protein levels related to inflammation, oxidative damage, apoptosis, and cellular growth. Most of these studies have focused on prolonged exposures and subsequent effects. In an attempt to understand the earliest responses of the skin to JP-8, we have investigated changes in gene expression in the epidermis for up to 8 h after a 1-h cutaneous exposure in rats. After exposure, we separated the epidermis from the rest of the skin with a cryotome and isolated total mRNA. Gene expression was studied with microarray techniques, and changes from sham treatments were analyzed and characterized. We found consistent twofold increases in gene expression of 27 transcripts at 1, 4, and 8 h after the beginning of the 1-h exposure that were related primarily to structural proteins, cell signaling, inflammatory mediators, growth factors, and enzymes. Analysis of pathways changed showed that several signaling pathways were increased at 1 h and that the most significant changes at 8 h were in metabolic pathways, many of which were downregulated. These results confirm and expand many of the previous molecular studies with JP-8. Based on the 1-h changes in gene expression, we hypothesize that the trigger of the JP-8-induced, epidermal stress response is a physical disruption of osmotic, oxidative, and membrane stability which activates gene expression in the signaling pathways and results in the inflammatory, apoptotic, and growth responses that have been previously identified.

Characterization of the skin penetration of a hydrocarbon-based weapons maintenance oil.

Break-Free CLP is a commercial petroleum-based liquid used for cleaning, lubricating, and protecting firearms that is used in the United States by military personnel, police, and individual gun owners for maintaining a wide variety of firearms. According to its material safety data sheet (MSDS), Break-Free CLP is predominately polyalphaolefin oil but also contains dibasic ester and isoparaffinic hydrocarbons; all of these ingredients are known to induce skin irritation in laboratory animals. Studies completed in our labs found that repeated topical application of Break-Free CLP to the backs of CD-1 mice produced evidence of systemic effects. Studies were conducted to characterize the dermal penetration of Break-Free CLP in mouse, rat, and pig skin to provide insight on possible factors or causes of skin irritation and systemic effects observed in previous studies. Mouse skin was 37 times more permeable to Break-Free CLP than pig skin and 6 times more permeable than rat skin. Flux measurements from static diffusion cells showed an inverse correlation with mouse, rat, and pig skin thickness. The concentration of Break-Free CLP in mouse skin was 4.5 times higher than the amount found in rat skin and about 17 times higher than the amount absorbed by pig skin. These results support the idea that Break-Free CLP causes skin irritation and systemic effects in the mouse by both penetrating through and accumulating in the skin. The findings for rat and pig skin are probably most representative of Break-Free CLP flux into and through unprotected human skin and suggest that dermal toxicity studies in CD-1 mice overestimate the risk to humans. These results, nevertheless, suggest that persons handling or using Break-Free CLP should protect the skin from possible exposure.

Validity of women's self-reports of cancer screening test utilization in a managed care population.

This study was undertaken to examine the validity of self-reported data on breast and cervical cancer screening behavior. An abbreviated version of the Behavioral Risk Factor Surveillance System telephone survey, including questions on mammography, clinical breast examination (CBE), and Papanicolaou test utilization, was administered to a sample of 480 women aged 40-74 years, enrolled in Kaiser Permanente Colorado for at least 5 years. Screening information reported in the telephone interview was compared with that abstracted from respondents' medical records. The vast majority of women had a mammogram, CBE, and Pap test according to both self-report and medical record. Sensitivity for determining whether her last test was within 2 years (3 years for Pap test) exceeded 95% for all, whereas specificities were <55%. The percentage of overall agreement between self-reported and recorded information was 88.4% (kappa = 0.62) for mammography, 87.9% (kappa = 0.45) for CBE, and 87.2% (kappa = 0.54) for Pap test. Pearson correlations between self-reported and recorded information for specific time interval since most recent mammogram, CBE, and Pap test were 0.72, 0.58, and 0.65, respectively. Correlation increased greatly when time interval was allowed to vary by +/-1 year. In most cases of disagreement, the self-report underestimated the time since last screening. These results suggest that self-reporting of breast and cervical cancer screening is fairly accurate in this managed care population, although women tend to underestimate the time since their last screening.

Gene expression in rat skin induced by irritating chemicals.

Occupational skin disease is the second most significant cause of occupational disease, after accidents. Irritation from occupational chemicals such as solvents, hydrocarbons, and surfactants are one cause of this disease. Gene expression studies provide useful information about normal processes in the skin and responses of the skin to exogenous chemicals. We exposed rats, cutaneously, to sodium lauryl sulfate (SLS, 1% and 10% aqueous solution), m-xylene (pure liquid), and d-limonene (pure liquid) for 1 h and measured transcriptional responses at the end of the exposure and 3 h later for comparison with untreated skin samples. Total skin RNA was isolated and analyzed using the Affymetrix RatTox U34 array. Using the Affymetrix software, we found that 234 of approximately 850 genes were detected as present in at least 80% of the normal skin samples. The largest number of these genes was related to metabolism, oxidative/cellular stress, and signal transduction. Limonene caused the largest change in mRNA levels with a total of 34 increased transcripts and 4 decreased transcripts. Xylene treatment resulted in 6 increased transcripts and 14 decreased transcripts, while 10% SLS caused 5 transcripts to increase and 17 to decrease. Only two transcripts were observed to change in skin following a 1% SLS exposure. Sodium lauryl sulfate transcript changes increased with dose and were maximum at 4 h. Limonene transcript changes were more numerous at 1 h than at 4 h. The observed differences may reflect different mechanisms of irritation.

Molecular and histological responses in rat skin exposed to m-xylene.

Solvents, surfactants, cutting fluids, hydrocarbons, and oils cause skin irritation by incompletely understood mechanisms. This study examined histological and molecular changes in rodent skin caused by brief topical exposures to m-xylene. At 0, 1, 2, 4, and 6 h after 1-h exposure, skin samples were removed and analyzed for histopathological changes and interleukin-1 alpha (IL-1 alpha) and inducible nitric oxide synthase (iNOS) protein levels. Histopathological changes (epidermal-dermal separation and granulocyte infiltration) and increases in IL-1 alpha and iNOS protein expression occurred during our observation period. IL-1 alpha levels increased by 80% immediately after exposure and iNOS levels increased about 60% 4 hours after exposure. Our study demonstrates that dermal exposure to m-xylene promotes IL-1 alpha and iNOS production in skin and these proteins may serve as early indicators of skin irritation.

Underascertainment of child maltreatment fatalities by death certificates, 1990-1998.

OBJECTIVE: Child fatality review teams have emerged across the United States in the past decade to address the concern that systems of child protection, law enforcement, criminal justice, and medicine do not adequately assess the circumstances surrounding child fatality as a result of maltreatment. METHODS: We compared data collected by a multidisciplinary child fatality review team with vital records for all children who were aged birth to 16 years and died in Colorado between January 1, 1990, and December 1, 1998. Odds ratios and 95% confidence intervals for ascertainment by the death certificate were estimated using logistic regression. RESULTS: Only half of the children who died as a result of maltreatment had death certificates that were coded consistently with maltreatment. Black race and female gender were associated with higher ascertainment, whereas death in a rural county was associated with lower ascertainment. Deaths resulting from violent causes (eg, shaking, blunt force trauma, striking) were more likely to be ascertained than those that involved acts of omission (eg, neglect and abandonment, drowning, fire). The most common perpetrators of maltreatment were parents. However, maltreatment by an unrelated perpetrator was 8.71 times (95% confidence interval: 3.52-21.55) more likely to be ascertained than maltreatment by a parent. CONCLUSIONS: The degree of underascertainment found in this study is of concern because most national estimates of child maltreatment fatality in the United States are derived from coding on death certificates. In addition, the patterns recognized in this study raise concern about systematic underascertainment that may affect children of specific sociodemographic groups.