Tobacco Smoking, Substance Use, and Mental Health Symptoms in People with HIV in an Urban HIV Clinic.

The prevalence of tobacco smoking among people with HIV (PWH) ranges from 40% to 70%. Additionally, tobacco smoking is higher among low-income individuals, yet few studies have examined tobacco smoking in low socioeconomic status PWH. Using data from a cohort of PWH receiving care in an urban HIV clinic, we characterized factors associated with current and former smoking and with initiation/re-initiation and cessation of tobacco use. Among a study sample of 1,607 PWH, the prevalence of current smoking was 46.6% among men and 46.0% among women. Current smoking in men and women was associated with Medicaid insurance status, substance use, and panic symptoms. In women, but not men, hazardous alcohol use decreased the likelihood of quitting smoking and increased the risk of initiation/re-initiation. Smoking interventions for low-income, urban PWH may need to be tailored to address mental health and substance use comorbidities.

Hair analysis versus conventional methods of drug testing in substance abusers seeking organ transplantation.

As substance abusers need to demonstrate abstinence prior to transplant, valid/reliable drug tests are needed. Patients may deny use, fearing surgery will be delayed. Breath, blood and urine tests have brief detection windows that allow patients to evade detection. Routine laboratory tests do not include all substances of abuse. Hair analysis overcomes these barriers, increasing the likelihood that active users will be identified. This study compared results for alcohol, opioids and cocaine based on 445 self-report, breath, urine and hair samples from 42 patients who had been denied a transplant due to recent substance abuse. Compared to hair toxicology, sensitivity for conventional drug tests was moderate for cocaine and opioids, but poor for alcohol. Of positive hair tests, only half were corroborated through other tests. In contrast, specificity was high across tests and substances, with positive findings from conventional tests confirmed through hair toxicology. Based on a 90-day detection window for hair analysis, two negative tests suggest 6 months of continuous abstinence. Hair testing should be considered as an alternative approach for monitoring substance use in the transplant population, either as a routine procedure or when the veracity of findings from conventional tests is in doubt.

Temperature acclimation alters oxidative capacities and composition of membrane lipids without influencing activities of enzymatic antioxidants or susceptibility to lipid peroxidation in fish muscle.

Cold acclimation of ectotherms results typically in enhanced oxidative capacities and lipid remodeling, changes that should increase the risk of lipid peroxidation (LPO). It is unclear whether activities of antioxidant enzymes may respond in a manner to mitigate the increased potential for LPO. The current study addresses these questions using killifish (Fundulus heteroclitus macrolepidotus) and bluegill (Lepomis macrochirus) acclimated to 5 and 25 degrees C for 9 days and 2 months, respectively. Because the effects of temperature acclimation on pro- and antioxidant metabolism may be confounded by variable activity levels among temperature groups, one species (killifish) was also subjected to a 9-day exercise acclimation. Oxidative capacity of glycolytic (skeletal) muscle (indicated by the activity of cytochrome c oxidase) was elevated by 1.5-fold in killifish, following cold acclimation, but was unchanged in cardiac muscle and also unaffected by exercise acclimation in either tissue. No changes in citrate synthase activity were detected in either tissue following temperature acclimation. Enzymatic antioxidants (catalase and superoxide dismutase) of either muscle type were unaltered by temperature or exercise acclimation. Mitochondria from glycolytic muscle of cold-acclimated killifish were enriched in highly oxidizable polyunsaturated fatty acids (PUFA), including diacyl phospholipids (total carbons:total double bonds) 40:8 and 44:12. Increased oxidative capacity, coupled with elevated PUFA content in mitochondria from cold-acclimated animals did not, however, impact LPO susceptibility when measured with C11-BODIPY. The apparent mismatch between oxidative capacity and enzymatic antioxidants following temperature acclimation will be addressed in future studies.

Population pharmacokinetics and bioavailability of motexafin gadolinium (Xcytrin) in CD1 mice following intravenous and intraperitoneal injection.

Motexafin gadolinium (Xcytrin) is an expanded porphyrin macrocyclic compound under development for the treatment of several types of cancer. Currently clinical trials and non-clinical pharmacology and toxicology studies are ongoing. The goals of this open label, four arm, non-crossover bioavailability study were to explore motexafin gadolinium pharmacokinetics, determine the i.p. bioavailability, and define a pharmacokinetic model suitable for descriptive and predictive use. Mice received one or seven daily i.v. or i.p. injections (40 mg/kg) then blood samples were collected and analyzed. Plasma concentration data were modelled using population pharmacokinetic methods and a two compartment model was the most appropriate model. The stability and predictive performance of the model were evaluated using bootstrap procedures. The accuracy of the predicted concentrations was 8.3%. Motexafin gadolinium was rapidly cleared from the plasma and although T(1/2beta) was 12.9 h there was no accumulation following seven doses. The i.p. bioavailability was 87.4% and higher plasma concentrations were sustainable for a longer period with i.p. dosing. V(c) was larger than the blood volume and the tissue compartment volume was 38% of V(c), suggesting motexafin gadolinium was not widely distributed into less well perfused tissues. The pharmacokinetic profile in this study was similar to that in oncology patients administered multiple doses of motexafin gadolinium. The unbiased model yields reliable parameter estimates and insight into the pharmacokinetics of motexafin gadolinium in mice, is suitable for both descriptive and predictive purposes, and is a valuable tool in the planning, analysis, and interpretation of pharmacology and toxicology studies in mice.

Psychopathology in pregnant drug-dependent women with and without comorbid alcohol dependence.

BACKGROUND: Individuals with comorbid alcohol and drug use disorders are at particularly high risk for a variety of problems, including other psychiatric disorders. In general, patients with comorbid alcohol and drug dependence tend to have more severe dependence problems and often have poorer treatment outcomes than individuals with single disorders. For treatment-seeking pregnant women, psychiatric comorbidity can lead to relapse and premature treatment dropout, with adverse consequences to mother and infant. METHODS: Psychopathology, as measured by the Minnesota Multiphasic Personality Inventory-Revised (MMPI-2), was examined in 170 pregnant women admitted to a comprehensive treatment program for cocaine or opiate dependence. Most were single (75%) and African American (80%), with a mean age of 29 years. Thirty-six met DSM-III-R criteria for both alcohol and drug dependence (alcohol positive), whereas 134 were drug dependent only (alcohol negative). RESULTS: Alcohol-positive women had higher levels of psychopathology than alcohol-negative women, with higher scores on scales 2 (Depression), 4 (Psychopathic Deviance), 8 (Schizophrenia), and 0 (Social Introversion; p < 0.05). The mean MMPI-2 profile for alcohol-positive women was 2-4-8 (Depression-Psychopathic Deviance-Schizophrenia; all T-scores > 65), whereas alcohol-negative women had only a scale 4 increase. CONCLUSIONS: Results suggest that pregnant, drug-dependent women with comorbid alcohol dependence present for treatment with greater psychopathology and thus may require more intense interventions than pregnant, drug-dependent women without comorbid alcohol dependence. Alcohol use by pregnant women is particularly important to address in treatment, because alcohol is a known teratogen associated with mental retardation and behavioral problems.

A twin study on sensation seeking, risk taking behavior and marijuana use.

The contribution of genetic and environmental factors to the covariation between risk-taking and marijuana use was assessed in adolescent twins. Genetic factors were found to significantly influence some traits (i.e. risk-taking attitude), while familial environmental factors were important for others (i.e. sexual promiscuity). For marijuana use, genetic and environmental factors were equally important; however, the association between risk taking and marijuana use may not be comparable for different behaviors. Results suggest that different etiological factors may underlie various risk taking traits which is relevant to both prevention efforts and attempts to identify genes involved in risk taking and shared genetic influences with substance use.

Family history influence on drug abuse severity and treatment outcome.

Influence of parental alcohol/substance abuse on methadone maintenance therapy (MMT) outcome was examined in 164 DSM-III-R opioid dependent adults with no other current DSM Axis I disorder. Family history positive patients had more DSM-III-R opioid dependence symptoms and were more likely to be classified as severely dependent. However, when placed on identical daily doses of methadone (50 mg), they had lower rates of illicit opioid use but higher rates of cocaine use than family history negative patients. Both effects remained significant after adjusting for gender and race. These results suggest that common genetic factors may underlie both susceptibility to heroin dependence and response to therapeutic methadone treatment.

Environmental transmission of DSM-IV substance use disdorders in adoptive and step families.

BACKGROUND: One factor contributing to the 3- to 5-fold increase in risk for substance use disorders (SUDs) among children of alcoholics may be the rearing environment. These influences may include availability of substances, modeling of SUDs, inadequate parenting, or other factors. The contribution of parental environmental influences on offspring with SUDs may be estimated independently of genetic influences through assessment of adoptees raised by nonbiological parents. METHODS: Relative risk of SUDs was assessed in adult adoptees (N = 442) of alcoholic and nonalcoholic adoptive parents as well as in stepchildren (N = 1859) with alcoholic or nonalcoholic stepfathers who participated in the community-based National Longitudinal Alcohol Epidemiologic Survey (NLAES). RESULTS: Rearing by an alcoholic adoptive mother was associated with increased DSM-IV alcohol abuse. Rearing by an alcoholic adoptive father was predictive of adoptees' illicit drug use, as well as DSM-IV drug dependence. Rearing by an alcoholic stepfather was predictive of stepchild DSM-IV alcohol abuse, illicit drug use, and drug dependence, whereas an alcoholic stepmother was associated with increased illicit drug use in the stepchild. Alcoholism in adoptive parents or step parents did not increase risk for offspring DSM-IV alcohol dependence. In both adoptive and biological families, there was a subadditive interaction of mother by father alcoholism such that the rate of substance abuse when both parents were alcoholic was less than that expected based on the additive effects of each alcoholic parent. CONCLUSIONS: Rearing by an alcoholic parent had a greater influence on alcohol abuse by offspring than on alcohol dependence. The increased risk of proband illicit drug use and drug dependence associated with paternal alcoholism suggested nonspecificity of environmental transmission. Both maternal and paternal cultural transmission effects influenced offspring SUDs.

Sensitive high-performance liquid chromatographic assay for motexafin gadolinium and motexafin lutetium in human plasma.

We present new HPLC methods for the quantitation in human plasma of two investigative metallotexaphyrin agents, motexafin gadolinium (Gd-Tex) and motexafin lutetium (Lu-Tex). Each assay uses: the other texaphyrin analogue as an internal standard; protein precipitation with acetonitrile:methanol (50:50, v/v); an ODS reversed-phase column; an isocratic mobile phase of 100 mM ammonium acetate, pH 4.3:acetonitrile:methanol (59:21:20, v/v/v); and absorbance detection at 470 nm. The Gd-Tex assay has a lower limit of quantitation (LLOQ) of 0.01 microM and is linear between 0.01 and 30 microM. The Lu-Tex assay has an LLOQ of 0.1 microM and is linear between 0.1 and 30 microM. The assays are suited for in vivo preclinical studies and clinical trials because they require minimal amounts of plasma, are sensitive, and involve a 30-mm run time. These assays are important tools for evaluating the potential of Gd-Tex and Lu-Tex as a radiation enhancer and photosensitizer, respectively.

A family history and direct interview study of the familial aggregation of substance abuse: the adolescent substance abuse study.

The adolescent substance abuse (ASA) study collected information concerning drug use and psychopathology on male adolescent probands in treatment for substance abuse and also on matched control adolescents, as well as all available family members of both groups. Information was obtained through direct interview and the family history method of assessment. Both methods revealed greater alcohol and drug use, conduct disorder (CD) and antisocial personality disorder (ASP) in the relatives of treatment probands as compared with control relatives. These results suggest familial transmission, not only for alcohol abuse, but also for non-alcohol substance abuse. Familial transmission for CD and ASP is also evident for both male and female relatives, although the prevalence of these disorders is significantly greater in males than females.

The familial aggregation of depressive symptoms, antisocial behavior, and alcohol abuse.

This study describes results from an ongoing family study of adolescent boys and their families designed to investigate potential risk factors for substance abuse. The adolescent treatment probands have severe drug and alcohol related problems and were recruited through a residential rehabilitation program. To date, the sample includes 251 individuals: 39 male probands and their families and 34 control families matched for age and geographic location (zip code). Probands and participating family members are given a structured interview which assesses alcohol and drug problems, and various psychiatric symptoms. The purpose of the present study was to examine the coaggregation of depressive symptoms, antisocial behavior, and alcohol misuse. Multivariate pedigree analyses were performed using a model that allowed for the estimation of vertical familial transmission, residual sibling resemblance, and assortative mating. Spouse correlations were estimated at .57, .21, and .31 for antisocial behavior, depressive symptoms, and alcohol abuse, respectively. Residual sibling environment (i.e., sibling resemblance unaccounted for by parent-offspring transmission) was not found for alcohol problem symptoms, but did contribute to resemblance for antisocial behavior and depressive symptoms. The proportion of variance accounted for by vertical familial transmission was estimated at approximately 30 to 40%. More important, correlations among the transmissible family factors for these psychiatric syndromes ranged from .58 to .73, suggesting substantial overlap among the underlying familial antecedents for these disorders.

Localization and efficacy analysis of the phototherapeutic lutetium texaphyrin (PCI-0123) in the murine EMT6 sarcoma model.

Lutetium texaphyrin (PCI-0123) is a pure, water-soluble photodynamic therapy (PDT) agent that is activated by tissue-penetrating far red light. The sensitizer is highly fluorescent and exhibits a strong, broad emission signal at 750 nm. In vitro cellular uptake studies revealed an increase in sensitizer retention with incubation time. Confocal laser scanning microscopy demonstrated that the intracellular localization site of PCI-0123 is the lysosomes. Ensuing illumination of the EMT6 cells led to lysosomal breakup, extensive cytoplasmic blebbing and subsequent cell death. Noninvasive spectral imaging analysis of PCI-0123 fluorescence depicted selective drug uptake, compared to surrounding normal tissue, in EMT6 mammary sarcomas syngeneic to BALB/c mice. The PCI-0123 PDT was shown to effectively treat the EMT6 murine sarcoma. Irradiation (732 nm light) 3 h postintravenous injection of 10 mumol PCI-0123 per kg gave 100% cures (no evidence of cancer), whereas light exposure at 5 h resulted in 75% cures. Hematoxylin and eosin histologic examination of photoirradiated tumors indicated apoptosis of the EMT6 neoplasms at early times post-PDT progressing, with time, to extensive necrotic areas. Gel electrophoresis of extracted photoirradiated tumors showed the typical apoptotic DNA ladder pattern that increased in intensity following PDT treatment.

Genetic and environmental architecture of human aggression.

A meta-analysis was performed on data from 24 genetically informative studies by using various personality measures of aggression. There was a strong overall genetic effect that may account for up to 50% of the variance in aggression. This effect was not attributed to methodological inadequacies in the twin or adoption designs. Age differences were important. Self-report and parental ratings showed genes and the family environment to be important in youth; the influence of genes increased but that of family environment decreased at later ages. Observational ratings of laboratory behavior found no evidence for heritability and a very strong family environment effect. Given that almost all substantive conclusions about the genetics of personality have been drawn from self or parental reports, this last finding has obvious and important implications for both aggression research in particular and personality research.