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Director's Report to the National Advisory Council on Drug Abuse - September, 2010



Research Findings - Research on Medical Consequences of Drug Abuse and Co-Occurring Infections (HIV/AIDS, HCV)

Human Immunodeficiency Virus Type 1 clade B and C Tat Differentially Induce Indoleamine 2, 3-dioxygenase and Serotonin in Immature Dendritic Cells: Implications for NeuroAIDS

Human immunodeficiency virus type 1 (HIV-1) is commonly associated with immune dysfunctions and the suppression of antigen-presenting cells. This results in immune alterations, which could lead to impaired neuronal functions, such as neuroAIDS. The neurotoxic factor kynurenine (KYN), the rate-limiting enzyme indoleamine 2, 3-dioxygenase (IDO), serotonin (5-HT), and serotonin transporter (5-HTT) may play a role in tryptophan deficiency and serotogenic dysfunction in neuroAIDS. HIV-1 transactivator regulatory protein (Tat) is known to play a major role in immune dysfunction. Previous studies suggest that HIV-1 B and C clades differentially manifest neuronal dysfunctions in the infected host. In the present study an examination was conducted of the effect of HIV-1 B and C clade-derived Tat on IDO and 5-HTT gene and protein expressions by dendritic cells as studied by quantitative polymerase chain reaction (qPCR) and Western blot. In addition, the intracellular IDO expression, IDO enzyme activity, and the levels of 5-HT and KYN were also measured. Results indicate that HIV-1 clade B Tat up-regulates IDO and down-regulates 5-HTT gene and protein expressions. Further, HIV-1 clade B Tat caused a reduction of 5-HT with simultaneous increase in KYN levels as compared to HIV-1 clade C Tat. These studies suggest that HIV-1 clade B and C Tat proteins may play a differential role in the neuropathogenesis of HIV-associated dementia (HAD) or HIV-associated neurocognitive disorder (HAND). Samikkannu T, Rao KV, Gandhi N, Saxena SK, Nair MP. Human immunodeficiency virus type 1 clade B and C Tat differentially induce indoleamine 2,3-dioxygenase and serotonin in immature dendritic cells: Implications for neuroAIDS. J Neurovirol. 2010 Jul 6. [Epub ahead of print].

Randomized, Controlled Clinical Trial of Zinc Supplementation to Prevent Immunological Failure in HIV-infected Adults

Adequate zinc is critical for immune function; however, zinc deficiency occurs in >50% of human immunodeficiency virus (HIV)-infected adults. The authors examined the safety and efficacy of long-term zinc supplementation in relation to HIV disease progression. A prospective, randomized, controlled clinical trial was conducted involving 231 HIV-infected adults with low plasma zinc levels (<0.75 mg/L), who were randomly assigned to receive zinc (12 mg of elemental zinc for women and 15 mg for men) or placebo for 18 months. The primary end point was immunological failure. HIV viral load and CD4(+) cell count were determined every 6 months. Questionnaires, pill counts, and plasma zinc and C-reactive protein levels were used to monitor adherence to study supplements and antiretroviral therapy. Intent-to-treat analysis used multiple-event analysis, treating CD4(+) cell count <200 cells/mm(3) as a recurrent immunological failure event. Cox proportional hazard models and the general-linear model were used to analyze morbidity and mortality data. Zinc supplementation for 18 months reduced 4-fold the likelihood of immunological failure, controlling for age, sex, food insecurity, baseline CD4(+) cell count, viral load, and antiretroviral therapy (relative rate, 0.24; 95% confidence interval, 0.10-0.56; P<.002). Viral load indicated poor control with antiretroviral therapy but was not affected by zinc supplementation. Zinc supplementation also reduced the rate of diarrhea by more than half (odds ratio, 0.4; 95% confidence interval, 0.183-0.981; P=.019), compared with placebo. There was no significant difference in mortality between the 2 groups. This study demonstrated that long-term (18-month) zinc supplementation at nutritional levels delayed immunological failure and decreased diarrhea over time. This evidence supports the use of zinc supplementation as an adjunct therapy for HIV-infected adult cohorts with poor viral control. Trial registration. ClinicalTrials.gov identifier: NCT00149552. Baum MK, Lai S, Sales S, Page JB, Campa A. Randomized, controlled clinical trial of zinc supplementation to prevent immunological failure in HIV-infected adults. Clin Infect Dis 2010; 50(12): 1653-1660.

Alcohol Use Accelerates HIV Disease Progression

The effects of alcohol abuse on HIV disease progression have not been definitively established. A prospective, 30-month, longitudinal study of 231 HIV(+) adults included history of alcohol and illicit drug use, adherence to antiretroviral therapy (ART), CD4(+) cell count, and HIV viral load every 6 months. Frequent alcohol users (two or more drinks daily) were 2.91 times (95% CI: 1.23-6.85, p = 0.015) more likely to present a decline of CD4 to < or=200 cells/microl, independent of baseline CD4(+) cell count and HIV viral load, antiretroviral use over time, time since HIV diagnosis, age, and gender. Frequent alcohol users who were not on ART also increased their risk for CD4 cell decline to < or=200 cells/mm(3) (HR = 7.76: 95% CI: 1.2-49.2, p = 0.03). Combined frequent alcohol use with crack-cocaine showed a significant risk of CD4(+) cell decline (HR = 3.57: 95% CI: 1.24-10.31, p = 0.018). Frequent alcohol intake was associated with higher viral load over time (beta = 0.259, p = 0.038). This significance was maintained in those receiving ART (beta = 0.384, p = 0.0457), but not in those without ART. Frequent alcohol intake and the combination of frequent alcohol and crack-cocaine accelerate HIV disease progression. The effect of alcohol on CD4(+) cell decline appears to be independent of ART, through a direct action on CD4 cells, although alcohol and substance abuse may lead to unmeasured behaviors that promote HIV disease progression. The effect of alcohol abuse on viral load, however, appears to be through reduced adherence to ART. Baum MK, Rafie C, Lai S, Sales S, Page JB, Campa A. Alcohol use accelerates HIV disease progression. AIDS Res Hum Retroviruses. 2010; 26(5): 511-518.

Methadone, Buprenorphine, and Street Drug Interactions With Antiretroviral Medications

While street drugs appear unlikely to alter the metabolism of antiretroviral (ARV) medications, several ARVs may induce or inhibit metabolism of various street drugs. However, research on these interactions is limited. Case reports have documented life-threatening overdoses of ecstasy and gamma-hydroxybutyrate after starting ritonavir, an ARV that inhibits several metabolic enzymes. For opioid addiction, methadone or buprenorphine are the treatments of choice. Because a number of ARVs decrease or increase methadone levels, patients should be monitored for methadone withdrawal or toxicity when they start or stop ARVs. Most ARVs do not cause buprenorphine withdrawal or toxicity, even if they alter buprenorphine levels, with rare exceptions to date including atazanavir/ritonavir associated with significant increases in buprenorphine and adverse events related to sedation and mental status changes in some cases. There are newer medications yet to be studied with methadone or buprenorphine. Further, there are many frequently used medications in treatment of complications of HIV disease that have not been studied. There is need for continuing research to define these drug interactions and their clinical significance. Gruber VA, McCance-Katz EF. Methadone, buprenorphine, and street drug interactions with antiretroviral medications. Curr HIV/AIDS Rep. 2010; 7(3): 152-160.

A Critical Function of Toll-Like Receptor-3 In the Induction of Anti-Human Immunodeficiency Virus Activities In Macrophages

Summary Toll-like receptor-3 (TLR-3) recognizes double-stranded RNA and induces multiple intracellular events responsible for innate anti-viral immunity against a number of viral infections. Activation of TLR-3 inhibits human immunodeficiency virus (HIV) replication, but the mechanism(s) underlying the action of TLR-3 activation on HIV are largely unknown. The authors demonstrate that treatment of monocyte-derived macrophages with poly I:C, a synthetic ligand for TLR-3, significantly inhibited HIV infection and replication. Investigation of the mechanisms showed that TLR-3 activation resulted in the induction of type I interferon inducible antiviral factors, including APOBEC3G and tetherin, the newly identified anti-HIV cellular proteins. In addition, poly I:C-treated macrophages expressed increased levels of CC chemokines, the ligands for CCR5. Furthermore, TLR-3 activation in macrophages induced the expression of cellular microRNAs (miRNA-28, -125b, -150, -223 and -382), the newly identified intracellular HIV restriction factors. These findings indicate that TLR-3-mediated induction of multiple anti-HIV factors should be beneficial for the treatment of HIV disease where innate immune responses are compromised by the virus. Zhou Y, Wang X, Liu M, Hu Q, Song L, Ye L, Zhou D, Ho W. A critical function of toll-like receptor-3 in the induction of anti-human immunodeficiency virus activities in macrophages. Immunology. 2010 Jul 16. [Epub ahead of print].

Noninvasive Markers of Liver Fibrosis Are Highly Predictive of Liver-Related Death In a Cohort of HCV-Infected Individuals With and Without HIV Infection

Noninvasive markers of liver fibrosis correlate with the stage of liver fibrosis, but have not been widely applied to predict liver-related mortality. The authors assessed the ability of two indices of liver fibrosis, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fib-4, and two markers of extracellular matrix metabolism, hyaluronic acid (HA) and YKL40, to predict liver mortality in a prospective cohort of hepatitis C virus (HCV)-infected individuals with and without HIV coinfection. These were compared with two established prognostic scores, the Child-Pugh-Turcotte (CPT) and model of end-stage liver disease (MELD) scores. A total of 303 subjects, of whom 207 were HIV positive at study entry, were followed up for a mean period of 3.1 years. There were 33 deaths due to liver disease. The ability of each test and score to predict 3-year liver mortality was expressed as the area under the receiver operator curve. The area under the receiver operator curve 95% confidence intervals were: HA 0.92 (0.86-0.96), CPT 0.91 (0.79-0.96), APRI 0.88 (0.80-0.93), Fib-4 0.87 (0.77-0.92), MELD 0.84 (71-0.91). In multivariate analyses HA, APRI, and fib-4 were independent predictors of mortality when included in models with MELD or CPT. Noninvasive markers of liver fibrosis are highly predictive of liver outcome in HCV-infected individuals with and without HIV coinfection. These markers seem to have a prognostic value independent of CPT and MELD. Nunes D, Fleming C, Offner G, Craven D, Fix O, Heeren T, Koziel MJ, Graham C, Tumilty S, Skolnik P, Stuver S, Horsburgh CR Jr, Cotton D. Noninvasive markers of liver fibrosis are highly predictive of liver-related death in a cohort of HCV-infected individuals with and without HIV infection. Am J Gastroenterol. 2010; 105(6): 1346-1353. Epub 2010 Feb 23.

Decreased Kidney Function in a Community-based Cohort of HIV-Infected and HIV-Negative Individuals in Rakai, Uganda

High prevalences of reduced glomerular filtration rate (GFR) have been reported from HIV-infected individuals in sub-Saharan Africa when initiating antiretroviral therapy. However little is known about natural history HIV-related kidney disease or about background rates of reduced GFR in HIV-negative individuals in this region. The authors estimated GFR from first and last available stored serum samples from 1202 HIV-infected and 664 age-matched and sex-matched HIV-negative individuals in a community-based cohort of HIV-infected and HIV-negative individuals in Rakai, Uganda, between 1994 and 2003. The prevalence and incidence of mildly (60-89 ml.min.1.73 m) and moderately (<60 ml.min.1.73 m) reduced GFR using standard analytical methods was assessed. At baseline, 8.4% of HIV-infected and 4.7% of HIV-negative individuals had mildly or moderately reduced GFR (P = 0.002). During follow-up, the rates of decline to a lower GFR category were of 32.4 and 20.3 per 1000 person-years in HIV-infected and HIV-negative subjects, respectively (P = 0.019). In an unselected community sample of HIV-infected individuals followed in Rakai, Uganda, before the availability of antiretroviral therapy, the prevalence of decreased GFR and the incidence of a decline in GFR category during follow-up were both significantly higher in HIV-infected subjects compared with HIV-negative subjects, although moderately reduced GFR was uncommon. Lucas GM, Clarke W, Kagaayi J, Atta MG, Fine DM, Laeyendecker O, Serwadda D, Chen M, Wawer MJ, Gray RH. Decreased Kidney Function in a Community-based Cohort of HIV-Infected and HIV-Negative Individuals in Rakai, Uganda. J Acquir Immune Defic Syndr. 2010 Jul 6. [Epub ahead of print].

Clinic-Based Treatment of Opioid-Dependent HIV-Infected Patients Versus Referral To An Opioid Treatment Program: A Randomized Trial

Opioid dependence is common in HIV clinics. Buprenorphine-naloxone (BUP) is an effective treatment of opioid dependence that may be used in routine medical settings. The objective of this study was to compare clinic-based treatment with BUP (clinic-based BUP) with case management and referral to an opioid treatment program (referred treatment). The study design was a single-center, 12-month randomized trial. Participants and investigators were aware of treatment assignments. (ClinicalTrials.gov registration number: NCT00130819). The study site was an HIV clinic in Baltimore, Maryland. Patients were 93 HIV-infected, opioid-dependent participants who were not receiving opioid agonist therapy and were not dependent on alcohol or benzodiazepines. Clinic-based BUP included BUP induction and dose titration, urine drug testing, and individual counseling. Referred treatment included case management and referral to an opioid-treatment program. Initiation and long-term receipt of opioid agonist therapy, urine drug test results, visit attendance with primary HIV care providers, use of antiretroviral therapy, and changes in HIV RNA levels and CD4 cell counts. The average estimated participation in opioid agonist therapy was 74% (95% CI, 61% to 84%) for clinic-based BUP and 41% (CI, 29% to 53%) for referred treatment (P < 0.001). Positive test results for opioids and cocaine were significantly less frequent in clinic-based BUP than in referred treatment, and study participants receiving clinic-based BUP attended significantly more HIV primary care visits than those receiving referred treatment. Use of antiretroviral therapy and changes in HIV RNA levels and CD4 cell counts did not differ between the 2 groups. This was a small single-center study, follow-up was only moderate, and the study groups were unbalanced in terms of recent drug injections at baseline. Management of HIV-infected, opioid-dependent patients with a clinic-based BUP strategy facilitates access to opioid agonist therapy and improves outcomes of substance abuse treatment. Lucas GM, Chaudhry A, Hsu J, Woodson T, Lau B, Olsen Y, Keruly JC, Fiellin DA, Finkelstein R, Barditch-Crovo P, Cook K, Moore RD. Clinic-based treatment of opioid-dependent HIV-infected patients versus referral to an opioid treatment program: A randomized trial. Ann Intern Med. 2010; 152(11): 704-711.

HIV Risk Behavior Before and After HIV Counseling and Testing In Jail: A Pilot Study

Incarceration represents an opportunity to deliver HIV counseling and testing (C&T) services to persons at increased risk of infection. However, jails can be chaotic with rapid turnover of detainees. A pilot study to investigate the feasibility of comparing the effect of different approaches to HIV C&T in jail on subsequent HIV risk behaviors among persons testing HIV negative was conducted. Consecutive cohorts of new detainees were recruited with 132 subjects completing standard HIV C&T and 132 subjects completing rapid testing with an individualized counseling session. Risk behavior was assessed and compared at baseline and 6 weeks after jail release. Among the 264 male participants, pre-incarceration substance use and sexual risk were common. The follow-up visit was completed by 59% of eligible participants. There were no differences in post-release HIV risk behavior between the 2 arms but there was an overall decrease in risk behavior after jail release for the cohort. In addition, all participants in the rapid arm received rapid HIV test results compared with participants receiving 28% of conventional test results. Jail incarceration represents an important public health opportunity to deliver HIV C&T. This study demonstrated (1) feasibility in delivering rapid HIV testing combined with individualized counseling to jail detainees, (2) improved test result delivery rates, and (3) success with evaluating risk behaviors during the transition from jail to the community. Further research is needed to determine the optimal approach to HIV C&T in jail with the goal of increasing awareness of HIV serostatus and decreasing HIV risk behavior. Beckwith CG, Liu T, Bazerman LB, DeLong AK, Desjardins SF, Poshkus MM, Flanigan TP. HIV Risk Behavior Before and After HIV counseling and testing in Jail: a pilot study. Acquired Immune Defic Syndr. 2010 Apr 1:53(4): 485-490.

Virology and Clinical Sequelae of Drug-Resistant HBV In HIV-HBV-Coinfected Patients On Highly Active Antiretroviral Therapy

Several of the nucleoside/nucleotide analogues used to treat HIV also inhibit HBV replication, with lamivudine being the oldest of this group. Thus, prior to licensing of tenofovir, many HIV-HBV-coinfected individuals received lamivudine as the only drug active against HBV as part of an anti-HIV regimen, which set the stage for the emergence of drug-resistant HBV. In coinfected persons, lamivudine-resistant HBV develops more rapidly than in HBV-monoinfected persons, but it is not known if this is true for the newer agents. Owing to overlapping reading frames of the HBV polymerase and surface antigens, drug-resistant changes in HBV Pol can lead to mutations in the envelope. This review discusses studies of drug-resistant HBV in HIV-infected persons including drug-resistant mutations that have been identified and clinical sequelae of these mutations. Thio CL. Virology and clinical sequelae of drug-resistant HBV in HIV-HBV-coinfected patients on highly active antiretroviral therapy. Antivir Ther. 2010; 15(3 Pt B): 487-491.

Hepatitis C Virus Risk Behaviors Within the Partnerships of Young Injecting Drug Users

Young injection drug users (IDU) are at high risk for hepatitis C virus (HCV). Assessments have been conducted to evaluate the implications of partner perceptions regarding their injecting partner. An HCV positive status was associated with decreased odds of engaging in receptive needle/syringe sharing (RNS) or ancillary equipment sharing (AES) with that partner, a cross sectional study between 2003 to 2007 in San Francisco, 212 participant (under age 30) IDUs who were HCV antibody negative reported on 492 injecting partnerships measured by self-report regarding perceptions of receptive (RNS) or ancillary (AES) sharing. The odds of engaging in RNS were significantly lower for relationships in which the participant reported that his/her partner was HCV positive; an association that was attenuated when adjusted for reusing one's own needle/syringe (adjusted OR 0.57; 95% CI 0.28-1.15) (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.25-0.95). The odds of engaging in AES were lower for participants who did not know the HCV status of their partner, only among non-sexual partnerships (OR 0.47; 95% CI 0.29-0.76). A partner's perception that their partner is HCV positive was associated with decreased RNS, increased HCV testing and thus, partner disclosure may be warranted. Perception of one's AES was common and was decreased only among non-sexual partnerships in which the HCV status of the partner was unknown. These assessments show the value of interventions to reduce AES in young IDU and the need that they be widespread. Hahn JA, Evans JL, Davidson PJ, Lum PJ, Page K. Hepatitis C Virus Risk behaviors within the partnerships of young injecting drug users. Addiction. 2010; 105(7): 1254-1264.

Are Young Injection Drug Users Ready and Willing To Participate In Preventive HCV Vaccine Trials?

The participation of high risk HCV seronegative injection drug users (IDUs) will be needed to evaluate the efficacy of preventive HCV vaccines. To guide clinical trial planning, these investigators have assessed willingness of young IDU in San Francisco to participate in HCV vaccine efficacy trials and have evaluated knowledge of vaccine trial concepts: placebo, randomization and blinding. During 2006 and 2007, a total of 67 participants completed the survey. A substantial proportion (88%) would definitely (44%) or probably (44%) be willing to participate in a randomized trial, but knowledge of vaccine trial concepts was low. Reported willingness to participate in an HCV vaccine trial decreased with increasing trial duration, with 67% of participants surveyed willing to participate in a trial of 1 year duration compared to 43% of participants willing to participate in a trial of 4 years duration. Willingness to enroll in HCV vaccine trials was higher in young IDU than reported by most at-risk populations in HIV vaccine trials. Educational strategies will be needed to ensure understanding of key concepts prior to implementing HCV vaccine trials. Levy V, Evans JL, Stein ES, Davidson PJ, Lum PJ, Hahn JA, Page K. Are young injection drug users ready and willing to participate in preventive HCV vaccine trials? Vaccine. 2010 Jul 16.

Dissolution of Arterial Platelet Thrombi In Vivo With A Bifunctional Platelet Gpiiia49-66 Ligand Which Specifically Targets the Platelet Thrombus

Patients with HIV-1 immune-related thrombocytopenia have a unique antibody (Ab) against integrin GPIIIa49-66 capable of inducing oxidative platelet fragmentation via Ab activation of platelet NADPH oxidase and 12-lipoxygenase releasing reactive oxygen species. Using a phage display single-chain antibody (scFv) library, a novel human monoclonal scFv Ab against GPIIIa49-66 (named A11) capable of inducing fragmentation of activated platelets was developed. In this study, the authors investigated the in vivo use of A11. The authors show that A11 does not induce significant thrombocytopenia or inhibit platelet function. A11 can prevent the cessation of carotid artery flow produced by induced artery injury and dissolve the induced thrombus 2 hours after cessation of blood flow. In addition, A11 can prevent, as well as ameliorate murine middle cerebral artery stroke, without thrombocytopenia or brain hemorrhage. To further optimize the anti-thrombotic activity of A11, the authors produced a bifunctional A11-plasminogen 1st kringle agent (SLK), which homes to newly deposited fibrin strands within and surrounding the platelet thrombus, reducing effects on non-activated circulating platelets. Indeed, SLK is able to completely reopen occluded carotid vessels 4 hours after cessation of blood flow, whereas A11 had no effect at 4 hours. Thus, a new anti-thrombotic agent was developed for platelet thrombus clearance. Zhang W, Li YS, Nardi MA, Dang S, Yang J, Ji Y, Li Z, Karpatkin S, Wisniewski T. Dissolution of arterial platelet thrombi in vivo with a bifunctional platelet GPIIIa49-66 ligand which specifically targets the platelet thrombus. Blood. 2010 Jun 4. [Epub ahead of print].

Magnetic Nanoformulation of Azidothymidine 5'-triphosphate for Targeted Delivery Across the Blood-Brain Barrier

Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood-brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. The authors report herein development of magnetic azidothymidine 5'-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. The authors hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, the authors anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS. Saiyed ZM, Gandhi NH, Nair MP. Magnetic nanoformulation of azidothymidine 5'-triphosphate for targeted delivery across the blood-brain barrier. Int J Nanomedicine. 2010; 5: 157-166.

Pubertal Timing and Smoking Initiation In Adolescent Females: Differences By Race

The purpose of this study was to examine whether (a) early pubertal timing effects on smoking onset existed for both White and Black girls and (b) whether the association between pubertal timing and smoking onset was moderated by race. Participants included 264 girls (14.9 +/- 2.2 years, 164 White, and 100 Black) at the baseline report of a longitudinal study of whom 153 reported smoking and age at first cigarette. Kaplan-Meier analysis stratified by racial group showed a significant difference between the pubertal timing groups for Black girls only. After accounting for covariates using Cox regression, there was no significant interaction between pubertal timing and racial group. There was a main effect of pubertal timing indicating that late maturers were at significantly lower risk for smoking initiation compared with the early and on-time groups, but the early and on-time groups were not significantly different from each other. Results point to equal risk of early smoking onset for early and on-time maturers of both racial groups, indicating the need for smoking prevention in early adolescence for both White and Black females. Negriff S, Dorn LD, Huang B. Pubertal timing and smoking initiation in adolescent females: differences by race. Nicotine Tob Res. 2010; 12(7): 748-755. Epub 2010 May 19.

Association of Anxiety and Depressive Symptoms and Adiposity Among Adolescent Females, Using Dual Energy X-Ray Absorptiometry

The purpose of this study is to evaluate the association between anxiety and depressive symptoms and obesity among adolescent females using objective measures of adiposity and evaluate for moderating effects of race and age. This is a cross-sectional analysis of 198 females aged 11, 13, 15, and 17 years (mean = 14.6, standard deviation = 2.2). Adiposity measures include BMI, BMI Z score, percentage body fat from dual energy X-ray absorptiometry (DXA), and fat distribution (fat mass upper vs lower body regions from DXA). Symptoms of anxiety are measured with the State-Trait Anxiety Inventory and depressive symptoms with the Children's Depression Inventory. Trait anxiety and depressive symptoms are positively associated with BMI and percentage body fat. No interaction of anxiety/ depressive symptoms with race or age on measures of adiposity was detected. Symptoms of anxiety and depression are associated with percentage body fat among adolescent females, linking psychological distress with a physiological measure of adiposity. Hillman JB, Dorn LD, Bin Huang. Association of anxiety and depressive symptoms and adiposity among adolescent females, using dual energy X-ray absorptiometry. Clin Pediatr (Phila). 2010; 49(7): 671-677. Epub 2010 Mar 31.

Iron Homeostasis and the Inflammatory Response

Iron and its homeostasis are intimately tied to the inflammatory response. The adaptation to iron deficiency, which confers resistance to infection and improves the inflammatory condition, underlies what is probably the most obvious link: the anemia of inflammation or chronic disease. A large number of stimulatory inputs must be integrated to tightly control iron homeostasis during the inflammatory response. In order to understand the pathways of iron trafficking and how they are regulated, this article presents a brief overview of iron homeostasis. A major focus is on the regulation of the peptide hormone hepcidin during the inflammatory response and how its function contributes to the process of iron withdrawal. The review also summarizes new and emerging information about other iron metabolic regulators and effectors that contribute to the inflammatory response. Potential benefits of treatment to ameliorate the hypoferremic condition promoted by inflammation are also considered. Wessling-Resnick M. Iron Homeostasis and the Inflammatory Response. Annu Rev Nutr. 2010; 30: 105-122.


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