An investigation of the relationship between antemortem and postmortem drug concentrations in blood

In the field of postmortem toxicology, principles from pharmacology and toxicology are combined in order to determine if exogenous substances contributed to ones death. In order to make this determination postmortem and (whenever available) antemortem blood samples may be analyzed. This project focused on evaluating the relationship between postmortem and antemortem blood drug levels, in order to better define an interpretive framework for postmortem toxicology. To do this, it was imperative to evaluate the differences in antemortem and postmortem drug concentrations, determine the role microbial activity and evaluate drug stability. Microbial studies determined that the bacteria Escherichia coli and Pseudomonas aeruginosa could use the carbon structures of drugs as a source of food. This would suggest prior to sample collection, microbial activity could potentially affect drug levels. This process however would stop before toxicologic evaluation, as at autopsy blood samples are stored in tubes containing the antimicrobial agent sodium fluoride. Analysis of preserved blood determined that under the current storage conditions sodium fluoride effectively inhibited microbial growth. Nonetheless, in many instances inconsistent drug concentrations were identified. When comparing antemortem to postmortem results, diphenhydramine, morphine, codeine and methadone, all showed significantly increased postmortem drug levels. In many instances, increased postmortem concentrations correlated with extended postmortem intervals. Other drugs, such as alprazolam, were likely to have concentration discrepancies when short antemortem to death intervals were coupled with extended postmortem intervals. While still others, such as midazolam followed the expected pattern of metabolism and elimination, which often resulted in decreased postmortem concentrations. The importance of drug stability was displayed when reviewing the clonazepam/ 7-aminoclonazepam data, as the parent drug commonly converted to its metabolite even when stored in the presence of a preservative. In instances of decreasing postmortem drug concentrations the effect of refrigerated storage could not be ruled out. A stability experiment, which contained codeine, produced data that indicated concentrations could continue to decline under the current storage conditions. The cumulative data gathered for this experiment was used to identify concentration trends, which subsequently aided in the development of interpretive considerations for the specific analytes examined in the study.

Risk factors and associations for hepatitis C infection among Hispanic/Latino intravenous drug users in Miami-Dade County, Florida

Hepatitis C infection (HCV) continues to disproportionately affect Hispanics/Latinos in the United States. Hispanic/Latino intravenous drug users (IDUs), because of their risky injection and sexual behaviors, are prone to HCV infection and rapid transmission of the virus to others via several routes. With a prevalence rate of approximately 75% among IDUs, it is imperative that transmission of HCV be prevented in this population. This study aims to examine the associations between demographic, injection and sexual risk factors to HCV infection in a group Hispanic/Latino IDUs in Miami-Dade County, Florida. Preliminary unadjusted results in this sample reveal that age (OR=4.592, p=0.004), weekly injection (OR=5.171, p=0.000), daily injection frequency (OR=3.856, p=0.000) and use of a dirty needle (OR=2.320, p= 0.006) were all significantly associated with HCV infection. Being born outside the U.S. was significantly negatively associated with HCV infection (OR=0.349, p=0.004). Additionally, having two or more sex partners in the past three months (OR=0.472, p=0.014) was negatively associated with HCV infection. After adjusting for all other variables, older age (AOR=7.470, p=0.006), weekly injection (AOR=3.238, p=0.007) and daily injection frequency (AOR=2.625, p=0.010) were all significantly associated with HCV infection. Being born outside the U.S. (AOR=0.369, p=0.019) was a significant protective factor for HCV infection, along with having two or more sex partners in the past three months (AOR=0.481, p=0.037). When analyzing the significant variables in a backward regression model, having 2 or more sex partners in the past three months was not significant at the p

Qualitative Responses to Pre-employment Drug Testing in the Foodservice Industry

Employee substance abuse has long time been a topic of concern for the hospitality industry. Operating under the assumption that drug-users, and associated undesirable behavior, can be eliminated from the hiring process, many operations have adopted pre-employment drug-testing policies. Despite being represented across the industry as a major target of effort and resources, it is suggested that the perceived sensitive-nature of the subject has somewhat hindered access to qualitative information. The purpose of this research was to assess and explore the attitudes, beliefs and perceptions of both management and employees in the foodservice industry regarding pre-employment drug-testing and its impact on work performance. Through the use of a phenomenological survey, qualitative data was collected then used to identify themes in participants’ perceptions of such screening policies and their effects. Results and implications of these findings are discussed.

Drug Abuse in the Hospitality Industry

Drug and alcohol abuse in the hospitality industry is an ongoing problem, reflective of business as a whole. A series of surveys were conducted at national drug rehabilitation centers seeking information from patients currently or formerly employed in the hotel and restaurant industry. The author identifies a number of problem indicators and makes recommendations relevant to resolutions.

Specific Increase in MDR1 Mediated Drug-Efflux in Human Brain Endothelial Cells following Co-Exposure to HIV-1 and Saquinavir

Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can augment the expression of these transporters, it is not known whether concomitant exposure to virus and anti-retroviral drugs can increase drug-efflux functions in HBMVEC. Our in vitro studies showed that exposure of HBMVEC to HIV-1 significantly up-regulates both MDR1 gene expression and protein levels; however, no significant increases in either MRP-1 or MRP-2 were observed. Furthermore, calcein-AM dye-efflux assays using HBMVEC showed that, compared to virus exposure alone, the MDR1 mediated drug-efflux function was significantly induced following concomitant exposure to both HIV-1 and saquinavir (SQV). This increase in MDR1 mediated drug-efflux was further substantiated via increased intracellular retention of radiolabeled [3H-] SQV. The crucial role of MDR1 in 3H-SQV efflux from HBMVEC was further confirmed by using both a MDR1 specific blocker (PSC-833) and MDR1 specific siRNAs. Therefore, MDR1 specific drug-efflux function increases in HBMVEC following co-exposure to HIV-1 and SQV which can reduce the penetration of HPIs into the infected brain reservoirs of HIV-1. A targeted suppression of MDR1 in the BBB may thus provide a novel strategy to suppress residual viral replication in the CNS, by augmenting the therapeutic efficacy of HAART drugs.