Blood lead levels in glue sniffers

The aim of this study was to investigate blood levels of lead (Pb) among adolescents with glue sniffing in Turkey. Blood Pb levels were measured in 30 adolescent glue sniffers by atomic absorption spectrophotometry and compared with those of the 30 healthy adolescents. The Pb contents of various glue preparations marketed in Turkey and used by the abusers were also measured. Blood Pb levels were significantly higher in the study group when compared to the control group. Pb was detected at considerably high levels in the contents of all the various glue preparations most commonly used by the cases in the study group. The increased blood Pb levels in glue sniffers may be related to the high lead contents of glues marketed in Turkey. The blood Pb levels and signs of Pb toxicity should be investigated in examination of glue sniffers.     

Assessment of DNA damage in glue sniffers by use of the alkaline comet assay

Toluene is used widely, not only in industry, but also in households where toluene exposure and abuse can occur. To estimate the genotoxic risk of toluene exposure, DNA damage was determined in peripheral lymphocytes of 20 glue sniffers and 20 age-matched controls by use of the alkaline comet assay. Urinary hippuric acid and o-cresol excretion rates, which are used as a marker for toluene exposure, were also measured in sniffers and compared with historical control values. The increase in genetic damage in sniffers was statistically significant as compared to control subjects (P<0.0001). The mean values of the hippuric acid and o-cresol excretion rate for glue sniffers was 73- and 1582-fold higher, respectively, than in controls and confirms the putative exposure. Education of the general public and efforts to keep adolescents away from volatile solvent-based products, which may lead to a desire of sniffing in the future, would be advisable.     

Determination of urinary hippuric acid and o-cresol levels as biological indicators of toluene exposure in shoe-workers and glue sniffers.

In this study, groups exposed to toluene either intentionally (glue sniffers) or unintentionally (shoe-workers) were compared. The groups were evaluated in terms of urinary levels of the toluene metabolites hippuric acid and o-cresol. Results were also compared with control values. Hippuric acid levels were determined by high performance liquid chromatography and o-cresol levels by gas liquid chromatography. The levels of hippuric acid and o-cresol were found to be statistically significantly higher in glue sniffers than in shoe-workers (p <0.001) or controls (p <0.001). In addition, the differences between the levels of urinary hippuric acid and o-cresol in the shoe-workers and in the controls were statistically significant (p <0.05 and p <0.001, respectively). These results suggest that extremely high levels of urinary hippuric acid and o-cresol indicate massive exposure to toluene.     

Solvent encephalopathy.

Nineteen children aged 8-14 years were admitted over a six-year period with an acute encephalopathy due to toluene intoxication. Seven had a history of euphoria and hallucinations. The remainder presented with coma (4), ataxia (3), convulsions (3), and behaviour disturbance with diplopia (2), A history of glue sniffing was elicited in 14, but in the remainder toluene assay confirmed the diagnosis. Thirteen children recovered completely; five still had psychological impairment and personality change on discharge from hospital but were lost to follow-up, and one has a persistent cerebellar ataxia one year after the acute episode, despite absence of further exposure. Toluene inhalation is an important cause of encephalopathy in children and may lead to permanent neurological damage. Diagnosis is most important if further damage due to continued abuse is to be prevented, and toluene assay is a valuable aid to diagnosis.     

Upregulation of SOCS-3 and PIAS-3 Impairs IL-12-Mediated Interferon-Gamma Response in CD56+ T Cells in HCV-Infected Heroin Users

Background

CD56⁺ T cells are abundant in liver and play an important role in host innate immunity against viral infections, including hepatitis C virus (HCV) infection, a common infection among heroin abusers. We thus investigated the in vivo impact of heroin use or heroin use plus HCV infection on the CD56⁺ T cell frequency and function.

Methodology/Principal Findings

A total of 37 heroin users with (17) or without (20) HCV infection and 17 healthy subjects were included in the study. Although there was no significant difference in CD56⁺ T cell frequency in PBMCs among three study groups, CD56⁺ T cells isolated from the heroin users had significantly lower levels of constitutive interferon-gamma (IFN-γ) expression than those from the normal subjects. In addition, when stimulated by interleukin (IL)-12, CD56⁺ natural T cells from HCV-infected heroin users produced significantly lower levels of IFN-γ than those from the normal subjects. This diminished ability to produce IFN-γ by CD56⁺ T cells was associated with the increased plasma HCV viral loads in the HCV-infected heroin users. Investigation of the mechanisms showed that although heroin use or heroin use plus HCV infection had little impact on the expression of the key positive regulators (IL-12 receptors, STAT-1, 3, 4, 5, JAK-2, and TYK-2) in IL-12 pathway, heroin use or heroin use plus HCV infection induced the expression of suppressor of cytokine signaling protein-3 (SOCS-3) and protein inhibitors of activated STAT-3 (PIAS-3), two key inhibitors of IL-12 pathway.

Conclusion/Significance

These findings provide compelling in vivo evidence that heroin use or heroin use plus HCV infection impairs CD56⁺ T cell-mediated innate immune function, which may account for HCV infection and persistence in liver.     

Micronucleus formation and DNA damage in buccal epithelial cells of Indian street boys addicted to gasp 'Golden glue'

Genotoxicity of glue sniffing/huffing and tobacco use has been examined in 302 street boys (median age 13 years) and 50 age-matched control school boys who were neither tobacco nor glue users. All the street boys were tobacco users. In addition, 155 were addicted to gasp an industrial adhesive popularly known as 'Golden glue'. Micronucleus (MN) frequency was determined as a measure of chromosomal breakage in exfoliated buccal epithelial cells (BECs) and DNA double strand breaks were quantitatively assessed by counting γ-H2AX foci using immunofluorescence microscopy. Micronucleated cell frequencies (MCFs) in BEC of glue non-addicted (only tobacco) and addicted (tobacco plus glue) street boys were 1.87 ± 1.06‰ and 4.04 ± 2.55‰ respectively, which were significantly higher than that of control (0.32 ± 0.11‰, p<0.0001). Similarly, the numbers γ-H2AX foci in nuclei of BEC were 2.3- and 5.2-times more than control in glue non-addicted and addicted street boys respectively (p<0.0001). Spearman's rank correlation revealed a strong positive association between years of glue addiction with MCFs and γ-H2AX foci numbers, and the association between glue addiction and chromosomal and DNA damage remained positive and significant after controlling income, spending on addiction and loss of appetite as potential confounders in multivariate logistic regression analysis. Thus, addiction to tobacco among the street children in India is associated with chromosomal and DNA damage in BECs and the severity of these changes is significantly increased by the habit of sniffing/huffing of industrial glue.     

Catecholamine and MHPG plasma levels,platelet MAO activity,and3H-imipramine binding in heroin and cocaine addicts

This work evaluated in a population of heroin and heroin plus cocaine human addicts:

1. Norepinephrine (NE), epinephrine (Epi), and 3-methoxy-4-hydroxyphenylglycol (MHPG) (the principal metabolite of brain NE) plasma levels;
2. Monoamine oxidase (MAO) activity; and
3. ³H-imipramine specific binding to the amine carrier in platelets.

NE plasma levels were significantly lower in the short-term heroin user groups (1–3 and 4–6 yr), a finding not observed in both the long-term heroin user (>6 yr) and heroin plus cocaine user (>6 yr) groups. Epi levels changed in a similar manner, except that a significant increase was noted in heroin plus cocaine abusers. Conversely, dopamine and MHPG plasma levels increased with the duration of heroin use, and even more with cocaine abuse. Platelet MAO activity increased in all groups. Specific³H-imipramine binding sites showed an increase after 3 yr of heroin abuse and in all heroin plus cocaine addicts. In conclusion, short-term use of heroin decreases NE or Epi release, but with prolonged use, a slow adpatation occurs. In contrast, cocaine inhibits the neuronal Epi uptake, even in a situation of long duration of abuse. Probably the amine levels additionally regulate the amine carrier, resulting in changes that show a different pattern from major depression. These drugs of abuse may also influence directly or indirectly related enzymatic systems.     

HCV and HIV Infection among Heroin Addicts in Methadone Maintenance Treatment (MMT) and Not in MMT in Changsha and Wuhan,China

Objective

To compare HCV and HIV infection among heroin addicts in MMT and not in MMT in two large cities in central China.

Methods

A total of 541 heroin addicts were recruited from MMT clinics and voluntary detoxification centers in Changsha and Wuhan, China. Structured questionnaires collected data on their socio-demographics, clinical status, risk behaviors, and their knowledge of HIV. Their HIV serostatus and Hepatitis C virus (HCV) serostatus were determined by testing antibodies in blood serum.

Results

We observed a higher prevalence of HCV infection among MMT heroin addicts (82.3%) than that in the non-MMT group (50.6%). However, our findings indicated that the heroin addicts in MMT had less drug or sexual HIV/HCV risk behaviors and more knowledge about HIV than non-MMT addicts. The heroin addicts in MMT had a significantly higher percentage of individuals who always used condoms (44.9%) compared with patients in the non-MMT group (14.6%, p = 0.039), and they had more knowledge about HIV than non-MMT individuals (p<.001). The percentage of HIV-positive addicts in the MMT group (0.7%) and non-MMT group (0.8%) were almost same.

Conclusion

Our study indicated that the rate of HCV infection among heroin addicts among MMT or non-MMT settings in central China is very high. The non-MMT heroin addicts have higher risk of becoming infected with HCV in the future, while at present they have lower rates of HCV infection than MMT heroin addicts. Although rates of HIV infection among MMT and non-MMT heroin addicts are low now, they are all at great risk of becoming infected with HIV in the future, especially for non-MMT heroin addicts. We should use the MMT sites as a platform to improve the control of HCV and HIV infection in heroin addicts.     

Clonidine improved laboratory-measured decision-making performance in abstinent heroin addicts

Background

Impulsivity refers to a wide spectrum of actions characterized by quick and nonplanned reactions to external and internal stimuli, without taking into account the possible negative consequences for the individual or others, and decision-making is one of the biologically dissociated impulsive behaviors. Changes in impulsivity may be associated with norepinephrine. Various populations of drug addicts all performed impulsive decision making, which is a key risk factor in drug dependence and relapse. The present study investigated the effects of clonidine, which decreased norepinephrine release through presynaptic alpha-2 receptor activation, on the impaired decision-making performance in abstinent heroin addicts.

Methodology/Principal Findings

Decision-making performance was assessed using the original version of Iowa Gambling Task (IGT). Both heroin addicts and normal controls were randomly assigned to three groups receiving clonidine, 0, 75 µg or 150 µg orally under double blind conditions. Psychiatric symptoms, including anxiety, depression and impulsivity, were rated on standardized scales. Heroin addicts reported higher scores on the Barratt Impulsiveness Scale and exhibited impaired decision-making on the IGT. A single high-dose of clonidine improved the decision-making performance in heroin addicts.

Conclusions/Significance

Our results suggest clonidine may have a potential therapeutic role in heroin addicts by improving the impaired impulsive decision-making. The current findings have important implications for behavioral and pharmacological interventions targeting decision-making in heroin addiction.     

Exercise decreases speedball self-administration

Aims

Epidemiological studies report that individuals who exercise are less likely to abuse drugs. Preclinical studies report that exercise, in the form of treadmill or wheel running, reliably decreases the self-administration of psychomotor stimulants and opioids. To date, preclinical studies have only examined the effects of exercise on responding maintained by individual drugs and not by combinations of multiple drugs. This limits the translational appeal of these studies because polydrug abuse is common among substance abusing populations. The purpose of this study was to examine the effects of exercise on the self-administration of speedball, a combination of cocaine and heroin that is frequently encountered in intravenous drug abusing populations.

Main methods

Female rats were obtained at weaning and assigned to sedentary or exercising conditions. Sedentary rats were housed in standard cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed in similar cages with an activity wheel. After 6 weeks, rats were implanted with intravenous catheters and trained to self-administer cocaine, heroin, and dose combinations of cocaine and heroin (i.e., speedball) on a progressive ratio schedule of reinforcement.

Key findings

Doses of speedball maintained greater levels of responding than corresponding doses of cocaine and heroin alone. Importantly, responding maintained by cocaine, heroin, and speedball was lower in exercising rats than sedentary rats.

Significance

These data indicate that exercise decreases the self-administration of speedball and suggest that exercise may reduce the abuse of drug combinations that have traditionally been resistant to treatment.     

A method for generating natural and user-defined sniffing patterns in anesthetized or reduced preparations

Sniffing has long been thought to play a critical role in shapingneural responses to odorants at multiple levels of the nervoussystem. However, it has been difficult to systematically examinehow particular parameters of sniffing behavior shape odorant-evokedactivity, in large part because of the complexity of sniffingbehavior and the difficulty in reproducing this behavior inan anesthetized or reduced preparation. Here we present a methodfor generating naturalistic sniffing patterns in such preparations.The method involves a nasal ventilator whose movement is controlledby an analog command voltage. The command signal may consistof intranasal pressure transients recorded from awake rats andmice or user-defined waveforms. This "sniff playback" devicegenerates intranasal pressure and airflow transients in anesthetizedanimals that approximate those recorded from the awake animaland are reproducible across trials and across preparations.The device accurately reproduces command waveforms over an amplituderange of approximately 1 log unit and up to frequencies of approximately12 Hz. Further, odorant-evoked neural activity imaged duringsniff playback appears similar to that seen in awake animals.This method should prove useful in investigating how the parametersof odorant sampling shape neural responses in a variety of experimentalsettings.     

柠檬术后止呕作用的临床研究

目的观察柠檬果临床止呕的疗效。方法随机抽取术后伴呕吐患者180例,分为3组,每组60例,男女各半。对照组肌注胃复安,柠檬皮组使用柠檬果皮划痕榨汁嗅闻,柠檬汁组口含柠檬汁或浸泡柠檬丝口服。观察3组止呕的最佳时间和作用程度。结果3种方法比较,以柠檬果皮划痕榨汁嗅闻达到止呕的效果最好。结论柠檬果皮划痕榨汁嗅闻可以在大手术后呕吐患者中使用,其方法简单,无副作用,值得推广应用。     

Cost-Effectiveness of Buprenorphine and Naltrexone Treatments for Heroin Dependence in Malaysia

Aims

To aid public health policymaking, we studied the cost-effectiveness of buprenorphine, naltrexone, and placebo interventions for heroin dependence in Malaysia.

Design

We estimated the cost-effectiveness ratios of three treatments for heroin dependence. We used a microcosting methodology to determine fixed, variable, and societal costs of each intervention. Cost data were collected from investigators, staff, and project records on the number and type of resources used and unit costs; societal costs for participants’ time were estimated using Malaysia’s minimum wage. Costs were estimated from a provider and societal perspective and reported in 2004 US dollars.

Setting

Muar, Malaysia.

Participants

126 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial in Malaysia (2003–2005) receiving counseling and buprenorphine, naltrexone, or placebo for treatment of heroin dependence.

Measurements

Primary outcome measures included days in treatment, maximum consecutive days of heroin abstinence, days to first heroin use, and days to heroin relapse. Secondary outcome measures included treatment retention, injection drug use, illicit opiate use, AIDS Risk Inventory total score, and drug risk and sex risk subscores.

Findings

Buprenorphine was more effective and more costly than naltrexone for all primary and most secondary outcomes. Incremental cost-effectiveness ratios were below $50 for primary outcomes, mostly below $350 for secondary outcomes. Naltrexone was dominated by placebo for all secondary outcomes at almost all endpoints. Incremental treatment costs were driven mainly by medication costs, especially the price of buprenorphine.

Conclusions

Buprenorphine appears to be a cost-effective alternative to naltrexone that might enhance economic productivity and reduce drug use over a longer term.     

Pathways to Age of Onset of Heroin Use: A Structural Model Approach Exploring the Relationship of the COMT Gene,Impulsivity and Childhood Trauma

Background

The interaction of the association of dopamine genes, impulsivity and childhood trauma with substance abuse remains unclear.

Objectives

To clarify the impacts and the interactions of the Catechol -O-methyltransferase (COMT) gene, impulsivity and childhood trauma on the age of onset of heroin use among heroin dependent patients in China.

Methods

202 male and 248 female inpatients who meet DSM-IV criteria of heroin dependence were enrolled. Impulsivity and childhood trauma were measured using BIS-11 (Barratt Impulsiveness Scale-11) and ETISR-SF (Early Trauma Inventory Self Report-Short Form). The single nucleotide polymorphism (SNP) rs737866 on the COMT gene-which has previously been associated with heroin abuse, was genotyped using a DNA sequence detection system. Structural equations model was used to assess the interaction paths between these factors and the age of onset of heroin use.

Principal Findings

Chi-square test indicated the individuals with TT allele have earlier age of onset of heroin use than those with CT or CC allele. In the correlation analysis, the severity of childhood trauma was positively correlated to impulsive score, but both of them were negatively related to the age of onset of heroin use. In structure equation model, both the COMT gene and childhood trauma had impacts on the age of onset of heroin use directly or via impulsive personality.

Conclusions

Our findings indicated that the COMT gene, impulsive personality traits and childhood trauma experience were interacted to impact the age of onset of heroin use, which play a critical role in the development of heroin dependence. The impact of environmental factor was greater than the COMT gene in the development of heroin dependence.     

Anatomical contributions to odorant sampling and representation in rodents: zoning in on sniffing behavior

Odorant sampling behaviors such as sniffing bring odorant molecules into contact with olfactory receptor neurons (ORNs) to initiate the sensory mechanisms of olfaction. In rodents, inspiratory airflow through the nose is structured and laminar; consequently, the spatial distribution of adsorbed odorant molecules during inspiration is predictable. Physicochemical properties such as water solubility and volatility, collectively called sorptiveness, interact with behaviorally regulable variables such as inspiratory flow rate to determine the pattern of odorant deposition along the inspiratory path. Populations of ORNs expressing the same odorant receptor are distributed in strictly delimited regions along this inspiratory path, enabling different deposition patterns of the same odorant to evoke different patterns of neuronal activation across the olfactory epithelium and in the olfactory bulb. We propose that both odorant sorptive properties and the regulation of sniffing behavior may contribute to rodents' olfactory capacities by this mechanism. In particular, we suggest that the motor regulation of sniffing behavior is substantially utilized for purposes of "zonation" or the direction of odorant molecules to defined intranasal regions and hence toward distinct populations of receptor neurons, pursuant to animals' sensory goals.     

Heroin Use Is Associated with Suppressed Pro-Inflammatory Cytokine Response after LPS Exposure in HIV-Infected Individuals

Background

Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens.

Methods

Treatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1) using heroin 2) receiving methadone opioid substitution 3) using heroin over 1 year ago and 4) controls (never used opioids). Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 β, IL-6, IL-10, IFN-α, IFN-γ and TNF-α) was determined using multiplex beads assay.

Results

Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05). After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable.

Conclusion

The cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution.     

布氏田鼠在不同光周期下对陌生个体尿液和粪便的气味辨别

研究了成年布氏田鼠在10min内,对不同光照周期下（长光照：LD;短光照：SD）陌生雌／雄个体尿液和粪便两种单一个体气味源的气味行为反应,实验发现：所有雌雄被试鼠对LD气味源比SD气味源表现出更多的嗅闻行为。LD和SD被试鼠对同性／异性尿液气味的嗅闻行为没有表现出明显的差别,但LD被试雄鼠对陌生雌鼠粪便的嗅闻频次显多于SD被试雄鼠,从嗅闻行为特征量（嗅闻行为占所有行为的百分比）来看,所有LD和SD被试雌,雄鼠对尿液的嗅 明显多于粪便,除SD粪便气味外,被试鼠对异性气味源的嗅闻明显多于同性,实验结果表明：作为两种个体气味源,尿液和粪便都带有季节性信息,而且是具有性别特性的。异性的个体气味源比同性的个体气味源更具吸引力;长光照动物的个体气味比短光照动物的气味更具吸引力。     

HSV-2 Infection as a Cause of Female/Male and Racial/Ethnic Disparities in HIV Infection

Objectives

To examine the potential contribution of herpes simplex virus 2 (HSV-2) infection to female/male and racial/ethnic disparities in HIV among non-injecting heroin and cocaine drug users. HSV-2 infection increases susceptibility to HIV infection by a factor of two to three.

Methods

Subjects were recruited from entrants to the Beth Israel drug detoxification program in New York City 2005-11. All subjects reported current use of heroin and/or cocaine and no lifetime injection drug use. A structured questionnaire was administered and serum samples collected for HIV and HSV-2 testing. Population-attributable risk percentages (PAR%s) were calculated for associations between HSV-2 infection and increased susceptibility to HIV.

Results

1745 subjects were recruited from 2005-11. Overall HIV prevalence was 14%. Females had higher prevalence than males (22% vs. 12%) (p<0.001), African-Americans had the highest prevalence (15%), Hispanics an intermediate prevalence (12%), and Whites the lowest prevalence (3%) (p<.001). There were parallel variations in HSV-2 prevalence (females 86%, males 51%, African-Americans 66%, Hispanics 47%, Whites 36%), HSV-2 prevalence was strongly associated with HIV prevalence (OR  =  3.12 95% CI 2.24 to 4.32). PAR%s for HSV-2 as a cause of HIV ranged from 21% for Whites to 50% for females. Adjusting for the effect of increased susceptibility to HIV due to HSV-2 infection greatly reduced all disparities (adjusted prevalence  =  males 8%, females 11%; Whites 3%, African-Americans 10%, Hispanics 9%).

Conclusions

Female/male and racial/ethnic variations in HSV-2 infection provide a biological mechanism that may generate female/male and racial/ethnic disparities in HIV infection among non-injecting heroin and cocaine users in New York City. HSV-2 infection should be assessed as a potential contributing factor to disparities in sexually transmitted HIV throughout the US.     

Seasonal and perennial changes in the distribution of water in the sapwood of conifers in a sub-frigid zone

An analysis was made of progressive changes in patterns of cavitation in the sapwood of three species of conifer (Larix kaempferi, Abies sachalinensis, and Picea jezoensis) that were growing in a sub-frigid zone. In all three conifers, all tracheids of the newly forming outermost annual ring were filled with water or cytoplasm during the period from May to August. However, many tracheids in the transition zone from earlywood to latewood lost water in September, presumably through drought-induced cavitation. Cavitated tracheids tended to be continuously distributed in a tangential direction. Subsequently, some earlywood tracheids of the outermost annual ring lost water during the period from January to March. This was associated with freeze-thaw cycles. In the second and third annual rings from the cambium of all three conifers, the lumina of most tracheids in the transition zone from earlywood to latewood contained no water. In contrast, some latewood tracheids near the annual ring boundary and many earlywood tracheids retained water in their lumina. The third annual ring had more cavitated tracheids than the second annual ring. Our observations indicated that cavitation progressed gradually in the tracheids of the conifers and that they were never refilled once cavitation had occurred. The region involved in water transport in conifers did not include the entire sapwood and differed among annual rings.     

Search for new natural sources of morphinans

Codeine, medically the most widely used opiate, is mostly derived from morphine, isolated from opium and poppy straw (Papaver somniferum, opium poppy). Morphine, however, is greatly misused by illegal conversion into its diacetyl-derivative: heroin. The discovery of an efficient alternative medicine or a source for codeine other than opium poppy may contribute to a curtailment of the heroin market. No major adverse properties should be present in such a new medicine or codeine source. In this paper the search for the latter is discussed with regards to the natural occurrence of morphinan derivatives and the biosynthetic pathways in available plants. Economic and social problems connected with the introduction of a new biological source for opiates are reviewed.