The relationship of thymulin activity, immune parameters of HIV disease progression and substance use in a cohort of HIV seropositive alcohol and drug users

Zinc is essential for the activity of thymulin, a thymic hormone involved in T-lymphocyte differentiation and activation. Zinc deficiency is widespread in populations with HIV infection, and HIV+ drug users are particularly susceptible to zinc deficiency and immune suppression. This dissertation explored the relationship of zinc-bound active thymulin to plasma zinc, CD4+ and CD8+ cell count, the CD4+/CD8+ ratio, and drug use in HIV-infected drug users. Zinc-bound active thymulin was assessed in plasma of HIV+ drug users who were participating in a 30 month zinc supplementation trial. Plasma from 80 participants at the 12 month visit, and 40 of these same participants, randomly selected, at the baseline visit were assessed for zinc-bound active thymulin levels using a modification of the rosette inhibition assay. Thymulin activity was directly associated with CD4+ cell count (β = 0.127, p = 0.002) and inversely associated with cocaine use (β = −0.908, p = 0.026; R2 = 0.188, p = 0.019) independent of HIV viral load, age, gender and antiretroviral use. An increase in thymulin activity was 1.4 times more likely when CD4+ cell count increased (OR = 1.402, 95%CI: 1.006–1.956), independent of change in viral load, antiretroviral use, and age. Participants who used cocaine consistently, were 7.6 times less likely to have an increase in thymulin activity (OR = 0.133, 95%CI: 0.017–1.061). There was a direct correlation between change in plasma zinc and change in zinc-bound active thymulin (r = 0.243, p = 0.13). Analysis of CD4+ cell count decline in 222 participants in the zinc supplementation trial across the 30 months showed that both crack cocaine use and heavy alcohol use accelerated CD4+ cell count decline. Thymulin activity is directly associated with HIV disease progression, measured by CD4+ cell count, and is depressed with cocaine use independent of antiretroviral use and HIV viral load. Cocaine and heavy alcohol accelerate CD4+ cell count decline. The effect of cocaine on thymic output requires further evaluation as a mechanism for the association of cocaine use with faster HIV disease progression.

Treatment attrition among racial /ethnic minority adolescents participating in a brief motivational intervention for substance use problems: The influence of individual, social, cultural, and treatment factors

The present study has the primary aim of examining the predictors of treatment attrition among racial/ethnic minority adolescents with substance use problems. This study explores the potential differential influence of specific individual, social, cultural, and treatment factors on treatment attrition within three racial/ethnic subgroups of adolescents. Participants: A unique feature of the study is the use of a racial/ethnic minority sample (N=453), [U.S.-born Hispanics (n = 262), Foreign-born Hispanics (n = 117), and African-Americans (n = 74)]. Multivariate logit analyses were used to examine the influence of specific factors on treatment attrition among the full sample of adolescents, as well as within each racial/ethnic subgroup. Consistent with expectations, multivariate logit analyses reveal that, the specific factors associated with attrition varied across the three racial/ethnic subgroups. Having parents with problem substance use, being on the waitlist, and being court mandated to treatment emerged as predictors of attrition among the US-born Hispanics, while only Conduct Disorder was significantly associated with greater attrition among foreign-born Hispanics. Finally, among African-Americans, parental crack/cocaine use, parental abstinence from alcohol, and being on the waitlist were predictive of attrition. Multiple factors were associated with treatment attrition among racial/ethnic minority adolescents with specific factors differentially predicting attrition within each racial/ethnic subgroup. African-American youth were more than twice as likely as their Hispanic counterparts to leave treatment prematurely. It is critically important to understand the predictors of attrition among racial/ethnic minority youth in order to better meet the needs of youth most at risk of dropping out. ^

Treatment attrition among racial/ethnic minority adolescents participating in a brief motivational intervention for substance use problems : the influence of individual, social, cultural, and treatment factors

The present study has the primary aim of examining the predictors of treatment attrition among racial/ethnic minority adolescents with substance use problems. This study explores the potential differential influence of specific individual, social, cultural, and treatment factors on treatment attrition within three racial/ethnic subgroups of adolescents. Participants: A unique feature of the study is the use of a racial/ethnic minority sample (N=453), [U.S.-born Hispanics (n = 262), Foreign-born Hispanics (n = 117), and African- Americans (n = 74)]. Multivariate logit analyses were used to examine the influence of specific factors on treatment attrition among the full sample of adolescents, as well as within each racial/ethnic subgroup. Consistent with expectations, multivariate logit analyses reveal that, the specific factors associated with attrition varied across the three racial/ethnic subgroups. Having parents with problem substance use, being on the waitlist, and being court mandated to treatment emerged as predictors of attrition among the US-born Hispanics, while only Conduct Disorder was significantly associated with greater attrition among foreign-born Hispanics. Finally, among African-Americans, parental crack/cocaine use, parental abstinence from alcohol, and being on the waitlist were predictive of attrition. Multiple factors were associated with treatment attrition among racial/ethnic minority adolescents with specific factors differentially predicting attrition within each racial/ethnic subgroup. African-American youth were more than twice as likely as their Hispanic counterparts to leave treatment prematurely. It is critically important to understand the predictors of attrition among racial/ethnic minority youth in order to better meet the needs of youth most at risk of dropping out.

A phenomenology of crack abuse

The aim of this dissertation is to identify, describe, and explain the common experiences defining the crack abuser's life-world. Its method is phenomenological. Using basic cybernetic premises, a neurophysiologically oriented phenomenological framework concerning the constitution of thoughts, memories, and perceptions is first written. The framework is designed to hypothetically represent the neuropathology of crack abuse within a perspective that prescinds and describes the constitution, flow, and interdependence of experience. After the framework is written, the dissertation outlines the neuro-psychopharmacology of crack abuse and delimits crack abusers as a specific group within the more general population of cocaine users. It then represents the neuropathology of crack abuse within its phenomenological framework and uses the first-person accounts of forty-two crack dependents to actualize a phenomenological sketch of the crack abuser's life-world. The ethnographies afford the possibility of writing a “thick” description of the crack abuser's daily life—one that communicates the substance, order, and subjective and cultural dimensions of the dependent's defining experiences. ^ The dissertation's goals are successfully realized. The framework written and the ethnographies recorded and transcribed, the dissertation is able to identify, describe, and to a certain extent explain some of the common experiences defining the crack abusers life-world. The dissertation concludes that the crack abuser's life-world is organized around three primary and four secondary experiences. His primary experiences include: (1) an almost complete, yet fleeting, satisfaction of the ego's innate insufficiency and sublime, erotic-like stimulation of its core, (2) a fundamental inclination and expansion of the uniquely oriented euphoria-dysphoria dynamic that vivifies and orients the flow of consciousness, and (3) a change in the ego's innate structure. His secondary experiences include: (a) a characteristic aiming of projects, actions, and conduct toward the procurement and consumption of crack, (b) a denigration in the hold of legitimations and institutionalizations on the thematic field, (c) a strict alignment and a contraction in the scope of logical types pointing to the salient experiences within the stock of knowledge, and (d) for some crack abusers, ontological insecurity, despair, and exhaustion. ^

Crack tip stress study for elastic-perfectly plastic materials with some applications

The problems of plasticity and non-linear fracture mechanics have been generally recognized as the most difficult problems of solid mechanics. The present dissertation is devoted to some problems on the intersection of both plasticity and non-linear fracture mechanics. The crack tip is responsible for the crack growth and therefore is the focus of fracture science. The problem of crack has been studied by an army of outstanding scholars and engineers in this century, but has not, as yet, been solved for many important practical situations. The aim of this investigation is to provide an analytical solution to the problem of plasticity at the crack tip for elastic-perfectly plastic materials and to apply the solution to a classical problem of the mechanics of composite materials.^ In this work, the stresses inside the plastic region near the crack tip in a composite material made of two different elastic-perfectly plastic materials are studied. The problems of an interface crack, a crack impinging an interface at the right angle and at arbitrary angles are examined. The constituent materials are assumed to obey the Huber-Mises yielding condition criterion. The theory of slip lines for plane strain is utilized. For the particular homogeneous case these problems have two solutions: the continuous solution found earlier by Prandtl and modified by Hill and Sokolovsky, and the discontinuous solution found later by Cherepanov. The same type of solutions were discovered in the inhomogeneous problems of the present study. Some reasons to prefer the discontinuous solution are provided. The method is also applied to the analysis of a contact problem and a push-in/pull-out problem to determine the critical load for plasticity in these classical problems of the mechanics of composite materials.^ The results of this dissertation published in three journal articles (two of which are under revision) will also be presented in the Invited Lecture at the 7$\rm\sp{th}$ International Conference on Plasticity (Cancun, Mexico, January 1999). ^

Correlation of detector dog alerts to cocaine decomposition products found in illicit forensic specimens

The volatile chemicals which comprise the odor of the illicit drug cocaine have been analyzed by adsorption onto activated charcoal followed by solvent elution and GC/MS analysis. A series of field tests have been performed to determine the dominant odor compound to which dogs alert. All of our data to date indicate that the dominant odor is due to the presence of methyl benzoate which is associated with the cocaine, rather than the cocaine itself. When methyl benzoate and cocaine are spiked onto U.S. currency, the threshold level of methyl benzoate required for a canine to signal an alert is typically 1-10 $\mu$g. Humans have been shown to have a sensitivity similar to dogs for methyl benzoate but with poorer selectivity/reliability. The dominant decomposition pathway for cocaine has been evaluated at elevated temperatures (up to 280$\sp\circ$C). Benzoic acid, but no detectable methyl benzoate, is formed. Solvent extraction and SFE were used to study the recovery of cocaine from U.S. currency. The amount of cocaine which could be recovered was found to decrease with time. ^

The New Transatlantic Bonanza: Cocaine on Highway 10.

The 10th Parallel marine and aerial routes linking South America and West Africa harbor a long history of trade between the two continents. More recently, these routes have become one of the preferred routes used by Latin American traffickers for shipping multi-tons of cocaine destined for the growing European market. The Parallel’s growing importance in cocaine trafficking has made it known as cocaine “Highway 10” among law enforcement. Latin American cocaine trafficking organizations, particularly the Colombian ones, have established stable bases in West Africa, controlling and developing the route. West African facilitators, Nigerians as well as an increasing number of nationals from all countries where shipments are stocked, have developed a stronger capacity for taking over more ambitious and lucrative role in the business as transporters, partners, and final buyers. In one case (Guinea), the West African partner had already started developing his own trafficking and manufacturing capacity, reproducing the patterns that made Colombia the business model of the drug industry. In this reshaped context, of particular concern is the role played by the Colombian FARC (Fuerzas Armadas Revolucionarias de Colombia) as provider of cocaine shipments to West African cocaine entrepreneurs, as well as the impact of drug trafficking money on the financing of terrorist and rebel groups operating in the Sahel-Saharan belt.

Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.

The Creation and Evaluation of Novel Canine Training Aids for Cocaine Using Molecularly Encapsulated Sol-Gel Polymers and an Investigation of Canine Field Accuracy

Biological detectors, such as canines, are valuable tools used for the rapid identification of illicit materials. However, recent increased scrutiny over the reliability, field accuracy, and the capabilities of each detection canine is currently being evaluated in the legal system. For example, the Supreme Court case, State of Florida v. Harris, discussed the need for continuous monitoring of canine abilities, thresholds, and search capabilities. As a result, the fallibility of canines for detection was brought to light, as well as a need for further research and understanding of canine detection. This study is two-fold, as it looks to not only create new training aids for canines that can be manipulated for dissipation control, but also investigates canine field accuracy to objects with similar odors to illicit materials. It was the goal of this research to improve upon current canine training aid mimics. Sol-gel polymer training aids, imprinted with the active odor of cocaine, were developed. This novel training aid improved upon the longevity of currently existing training aids, while also provided a way to manipulate the polymer network to alter the dissipation rate of the imprinted active odors. The manipulation of the polymer network could allow handlers to control the abundance of odors presented to their canines, familiarizing themselves to their canine’s capabilities and thresholds, thereby increasing the canines’ strength in court. The field accuracy of detection canines was recently called into question during the Supreme Court case, State of Florida v. Jardines, where it was argued that if cocaine’s active odor, methyl benzoate, was found to be produced by the popular landscaping flower, snapdragons, canines will false alert to said flowers. Therefore, snapdragon flowers were grown and tested both in the laboratory and in the field to determine the odors produced by snapdragon flowers; the persistence of these odors once flowers have been cut; and whether detection canines will alert to both growing and cut flowers during a blind search scenario. Results revealed that although methyl benzoate is produced by snapdragon flowers, certified narcotics detection canines can distinguish cocaine’s odor profile from that of snapdragon flowers and will not alert.

The creation and evaluation of novel canine training aids for cocaine using molecularly encapsulated sol-gel polymers and an investigation of canine field accuracy

Biological detectors, such as canines, are valuable tools used for the rapid identification of illicit materials. However, recent increased scrutiny over the reliability, field accuracy, and the capabilities of each detection canine is currently being evaluated in the legal system. For example, the Supreme Court case, State of Florida v. Harris, discussed the need for continuous monitoring of canine abilities, thresholds, and search capabilities. As a result, the fallibility of canines for detection was brought to light, as well as a need for further research and understanding of canine detection. This study is two-fold, as it looks to not only create new training aids for canines that can be manipulated for dissipation control, but also investigates canine field accuracy to objects with similar odors to illicit materials. ^ It was the goal of this research to improve upon current canine training aid mimics. Sol-gel polymer training aids, imprinted with the active odor of cocaine, were developed. This novel training aid improved upon the longevity of currently existing training aids, while also provided a way to manipulate the polymer network to alter the dissipation rate of the imprinted active odors. The manipulation of the polymer network could allow handlers to control the abundance of odors presented to their canines, familiarizing themselves to their canine’s capabilities and thresholds, thereby increasing the canines’ strength in court.^ The field accuracy of detection canines was recently called into question during the Supreme Court case, State of Florida v. Jardines, where it was argued that if cocaine’s active odor, methyl benzoate, was found to be produced by the popular landscaping flower, snapdragons, canines will false alert to said flowers. Therefore, snapdragon flowers were grown and tested both in the laboratory and in the field to determine the odors produced by snapdragon flowers; the persistence of these odors once flowers have been cut; and whether detection canines will alert to both growing and cut flowers during a blind search scenario. Results revealed that although methyl benzoate is produced by snapdragon flowers, certified narcotics detection canines can distinguish cocaine’s odor profile from that of snapdragon flowers and will not alert.^